No full-text available
To read the full-text of this research,
you can request a copy directly from the authors.
Chronic Kidney Disease Associated With Environmental Toxins and Exposures
Abstract
People are exposed to various potentially toxic agents and conditions in their natural and occupational environments. These agents may be physical or chemical, may enter the human body through oral, inhalational, or transdermal routes, and may exert effects on all organ systems. Several well-known as well as lesser known associations exist between chronic kidney disease (CKD) and both environmental agents and conditions, such as heavy metals, industrial chemicals, elevated ambient temperatures, and infections. The effects of these agents may be modulated by genetic susceptibility and other comorbid conditions and may lead to the development of acute and CKD. In this article, we present environmental factors that are associated with CKD.
... Experimental evidence suggests that exposure to heavy metals may cause oxidative stress, inflammation, and lipid peroxidation in organs. Low chronic exposure to Cd, Pb, and Hg can cause both renal proximal tubular damage and a decrease in GFR [9][10][11][12]. Heavy metals including As, Cd, Pb, and Hg deplete major antioxidants of cells, particularly thiol-containing antioxidants and enzymes, which may cause an increase in production of reactive oxygen species (ROS). ...
... It was determined that mean cigarette consumption per day of ESRD patients undergoing dialysis, ESRD patients not on dialysis, and the control group were 2.09 ± 6.00 (10)(11)(12)(13)(14)(15)(16)(17)(18)(19)(20) cigarettes/day (n = 5, 11.53%), 3.33 ± 7.58 cigarettes/day (n = 5, 16.13%), and 2.50 ± 8.09 cigarettes/day (n = 4, 12.43%), respectively, and the differences between the groups were not statistically significant. All individuals in the patient and control groups stated that they did not consume alcohol at all ( Table 1). ...
... However, the pathophysiological mechanism underlying these detrimental effects is not fully understood. Moreover, the effects of hemodialysis on oxidative stress and heavy-metal exposure are other points to be clarified in ESRD patients [9][10][11][12]. Therefore, in this study, we focused on the evaluation of the changes in heavy-metal levels, DNA damage, and oxidative-stress markers among ESRD patient, both in those undergoing dialysis and in those not undergoing dialysis, compared with healthy controls. ...
Chronic kidney disease (CKD), a common progressive renal failure characterized by the permanent loss of functional nephrons can rapidly progress to end-stage renal disease, which is known to be an irreversible renal failure. In the therapy of ESRD, there are controversial suggestions about the use of regular dialysis, since it is claimed to increase oxidative stress, which may increase mortality in patients. In ESRD, oxidative-stress-related DNA damage is expected to occur, along with increased inflammation. Many factors, including heavy metals, have been suggested to exacerbate the damage in kidneys; therefore, it is important to reveal the relationship between these factors in ESRD patients. There are very few studies showing the role of oxidative-stress-related genotoxic events in the progression of ESRD patients. Within the scope of this study, genotoxic damage was evaluated using the comet assay and 8-OHdG measurement in patients with ESRD who were undergoing hemodialysis. The biochemical changes, the levels of heavy metals (aluminum, arsenic, cadmium, lead, and mercury) in the blood, and the oxidative biomarkers, including superoxide dismutase (SOD), catalase (CAT), glutathione peroxidase (GPx), and malondialdehyde (MDA) levels were evaluated, and their relationship with genotoxic damages was revealed. Genotoxicity, oxidative stress, and heavy-metal levels, except mercury, increased significantly in all renal patients. DNA damage, 8OHdG, and MDA significantly increased, and GSH significantly decreased in patients undergoing dialysis, compared with those not having dialysis. The duration and the severity of disease was positively correlated with increased aluminum levels and moderate positively correlated with increased DNA damage and cadmium levels. In conclusion, this study revealed that the oxidative-stress-related DNA damage, and also the levels of Al and Cd, increased in ESRD patients. It is assumed that these changes may play an important role in the progression of renal damage. Approaches for reducing oxidative-stress-related DNA damage and heavy-metal load in ESRD patients are recommended.
... The mechanisms of PM-induced renal damage have not been fully understood, yet the urinary system is well-known to be highly susceptible to environmental toxins, such as drugs, heavy metals and ionising radiation (Finn, 1977;Kim, 2017;Möhner et al., 2017;Pesch et al., 2000;D. O. Schlondorff, 2008;Soderland et al., 2010). In mice exposed to ultrafine particles from motorcycle exhaust emissions twice a day for 10 days, an increased concentration of ultrafine PM was found in the kidney (Wardoyo et al., 2018). ...
... Acute PM exposure causes direct injury in proximal tubules, while chronic PM exposure may induce interstitial nephritis and renal fibrosis resulting in the elevation of biomarkers of kidney damage (i.e. haematuria, albuminuria), changes in haemodynamics, and hypertension (Al Suleimani et al., 2017;Kim, 2017;Navarro-Moreno et al., 2009;Soderland et al., 2010;Tavera Busso et al., 2018). High PM dosage induces more pathological features to both glomerular and tubular compartments in the kidney, including loss of glomerular integrity due to glomerular atrophy, loss of epithelial cells, increased Bowman's space, significant oedema, and tubular dilation and vacuolation (Al Suleimani et al., 2017;Wardoyo et al., 2018). ...
... PM2.5 in occupational solvents (e.g. paints, mineral oils and asbestos) may even increase the risk of malignant renal diseases (Möhner et al., 2017;Pesch et al., 2000), and augment underlying kidney damage and thus, instigate progression to end-stage kidney disease (Soderland et al., 2010). ...
Airborne particulate matter (PM) comprises both solid and liquid particles, including carbon, sulphates, nitrate, and toxic heavy metals, which can induce oxidative stress and inflammation after inhalation. These changes occur both in the lung and systemically, due to the ability of the small-sized PM (i.e. diameters ≤2.5 μm, PM2.5) to enter and circulate in the bloodstream. As such, in 2016, airborne PM caused ∼4.2 million premature deaths worldwide. Acute exposure to high levels of airborne PM (eg. during wildfires) can exacerbate pre-existing illnesses leading to hospitalisation, such as in those with asthma and coronary heart disease. Prolonged exposure to PM can increase the risk of non-communicable chronic diseases affecting the brain, lung, heart, liver, and kidney, although the latter is less well studied. Given the breadth of potential disease, it is critical to understand the mechanisms underlying airborne PM exposure-induced disorders. Establishing aetiology in humans is difficult, therefore, in-vitro and in-vivo studies can provide mechanistic insights. We describe acute health effects (e.g. exacerbations of asthma) and long term health effects such as the induction of chronic inflammatory lung disease, and effects outside the lung (e.g. liver and renal change). We will focus on oxidative stress and inflammation as this is the common mechanism of PM-induced disease, which may be used to develop effective treatments to mitigate the adverse health effect of PM exposure.
... Though the population burden and patient-level progression of CKD due to certain factors, such as hypertension and diabetes, are well-established, 44,45 only a limited number of studies have examined relationships with environmental variables, such as ambient air pollution or water quality. [46][47][48][49] To examine how integration of spatial structure to modeling affects resulting coefficients, we performed a spatial modeling casestudy exploring associations between countyaggregated CKD prevalence and a measure of overall county-level environmental quality, the EQI. EQI has been utilized extensively as a predictor variable in epidemiological literature [50][51][52][53][54][55] but not in relation to CKD prevalence. ...
... [62][63][64] Bayesian spatial regressions are powerful tools that support broad flexibility in modeling by allowing borrowed strength across geographic and temporal domains. 64 The effect of environmental exposures on CKD prevalence is beginning to be understood, [46][47][48][49] and those environmental factors with less clearly understood relationships with CKD, such as heat exposure, air pollution, water quality, and other environmental toxins or exposures, have potential to be clarified more accurately via spatial models. Environmental exposures are not only difficult to measure with reasonable certainty but also can vary strongly temporally (e.g., by season or exposures due to one-time disasters) and across geography. ...
Geospatial modeling methods in population-level kidney research have not been used to full potential because few studies have completed associative spatial analyses between risk factors and exposures and kidney conditions and outcomes. Spatial modeling has several advantages over traditional modeling, including improved estimation of statistical variation and more accurate and unbiased estimation of coefficient effect direction or magnitudes by accounting for spatial data structure. Because most population-level kidney research data are geographically referenced, there is a need for better understanding of geospatial modeling for evaluating associations of individual geolocation with processes of care and clinical outcomes. In this review, we describe common spatial models, provide details to execute these analyses, and perform a case-study to display how results differ when integrating geographic structure. In our case-study, we used U.S. nationwide 2019 chronic kidney disease (CKD) data from Centers for Disease Control and Prevention’s Kidney Disease Surveillance System and 2006 to 2010 U.S. Environmental Protection Agency environmental quality index (EQI) data and fit a nonspatial count model along with global spatial models (spatially lagged model [SLM]/pseudo-spatial error model [PSEM]) and a local spatial model (geographically weighted quasi-Poisson regression [GWQPR]). We found the SLM, PSEM, and GWQPR improved model fit in comparison to the nonspatial regression, and the PSEM model decreased the positive relationship between EQI and CKD prevalence. The GWQPR also revealed spatial heterogeneity in the EQI-CKD relationship. To summarize, spatial modeling has promise as a clinical and public health translational tool, and our case-study example is an exhibition of how these analyses may be performed to improve the accuracy and utility of findings.
... 7,13 Although the aetiology of CKDu still remains unknown, it is thought to be a disease of multifactorial origin primarily resulting from environmental factors. 9,14,15 Identification of potential risk factors is therefore crucial in mitigating exposures and ultimately reduction of disease associated morbidity and mortality. 7,16 In Africa, CKD is an increasingly important public health problem with risk factors that include communicable and noncommunicable diseases. ...
... A comprehensive understanding key environmental factors is essential for the development of public health interventions to reduce the devastating impact of CKD in the region. Considering the environmental factors implicated in CKDu reported in different affected areas, [7][8][9][10]14,15,38,39 highlighting the range of risk factors may be of value in unravelling the causes of CKD/CKDu, and in the effort to develop prevention strategies. 16,38 As noted above (Figure 2), genetics, infectious diseases, rural residence, drinking water, low SES, malnutrition, farming and exposure to agrochemicals, heavy metals, traditional herbal agents and Ochratoxin A were identified as potential contributors to CKD/CKDu in the region. ...
During the last two decades, an epidemic of a severe form of chronic kidney disease (CKD) unrelated to traditional risk factors (diabetes and hypertension) has been recognized in low‐ to middle‐income countries. CKD of unknown aetiology (CKDu) mainly affects young working‐age adults, and has become as an important and devastating public health issue. CKDu is a multifactorial disease with associated genetic and environmental risk factors. This review summarizes the current epidemiological evidence on the burden of CKDu and its probable environmental risk factors contributing to CKD in Africa. PubMed/Medline and the African Journals Online databases were searched to identify relevant population‐based studies published in the last two decades. In the general population, the burden of CKD attributable to CKDu varied from 19.4% to 79%. Epidemiologic studies have established that environmental factors, including genetics, infectious agents, rural residence, low socioeconomic status, malnutrition, agricultural practise and exposure to agrochemicals, heavy metals, use of traditional herbs, and contaminated water sources or food contribute to the burden of CKD in the region. There is a great need for epidemiological studies exploring the true burden of CKDu and unique geographical distribution, and the role of environmental factors in the development of CKD/CKDu.
image
... Exposure to environmental metals, which can occur through air, food, drinking water, and soil (Soderland et al. 2010), is prevalent in daily life, especially in mineral-contaminated areas. Exposure to inorganic metal elements can adversely affect human health, and the kidney is one of the major target organs in metal exposure due to its characteristics of glomerular and tubular changes (Barbier et al. 2005;Orr and Bridges 2017). ...
... Renal tubular dysfunction is the most common manifestation of chronic cadmium and arsenic exposure, mainly through mechanisms including oxidative stress, DNA methylation, histone acetylation, impaired DNA repair, and apoptosis (Scott et al. 1993;Bork et al. 2010;Kim et al. 2015;Nair et al. 2015). The natural existence of heavy metals along with mining and smelting activities may increase both workers' and nearby residents' kidney damage risks, as metals accumulated in human kidneys are difficult to degrade (Soderland et al. 2010). People are naturally exposed to multiple metals, and synergistic or antagonistic effects caused by metal mixtures could be much more complex than previously thought (Braun et al. 2016;Shelley et al. 2012;Lin et al. 2014;Tsai et al. 2017). ...
Previous studies have indicated that exposure to a single toxic metal can cause renal tubular damage, while evidence about the effects of multimetal exposure on renal tubular damage is relatively limited. We aimed to evaluate the relationships of multimetal coexposure with renal tubular damage in adults in heavy metal-polluted rural regions of China. A cross-sectional study of 1918 adults in China’s heavy metal-contaminated rural regions was conducted. Inductively coupled plasma–mass spectrometry (ICP–MS) was used to measure the plasma levels of 18 metals in participants, and immune turbidimetry was used to measure sensitive biological indicators, reflecting renal tubular damage (including retinol-binding protein and β2-microglobulin). Least absolute shrinkage and selection operator (LASSO) penalized regression analysis, logistic and linear regression analysis, restricted cubic spline (RCS) regression analysis and the Bayesian kernel machine regression (BKMR) method were used to explore associations of multimetal coexposure with renal tubular damage risk or renal tubular damage indicators. Plasma selenium, cadmium, arsenic, and iron were identified as the main plasma metals associated with renal tubular damage risk after dimensionality reduction. Multimetal regression models showed that selenium was positively associated, and iron was negatively associated with renal tubular damage risk or its biological indicators. Multimetal RCS analyses additionally revealed a non-linear relationship of selenium with renal tubular damage risk. The BKMR models showed that the metal mixtures were positively associated with biological indicators of renal tubular damage when the metal mixtures were above the 50th percentile of concentration. Our findings indicated that natural exposure to high levels of multimetal mixtures increases the risk of renal tubular damage. Under the conditions of multimetal exposure, selenium was positively associated, and iron was negatively associated with renal tubular damage risk or its biological indicators.
... Chronic kidney disease with unknown cause (CKDu) has recently been reports in people from poor communities in Meso-America (Garcia-Trabanino et al. 2015), Sri Lanka (Chandrajith et al. 2011;Jayasumana et al. 2015) and India (Ganguli 2016). Initially CKDu was suspected to be an occupational disease associated with exposures in the agricultural workplace, such as heat stress and dehydration (Garcia-Trabanino et al. 2015), pesticide spraying (Rajapakse et al. 2016), heavy metals and agrochemicals (Soderland et al. 2010) or use of NSAIDs (Gooch et al. 2007). Non-agricultural workers and other community members could also be at risk of CKDu, as environmental contamination from heavy metals and pesticides residues (Agampodi et al. 2018;Soderland et al. 2010) or use of folk medicines containing heavy metals or aristolochic acid (Debelle et al. 2008) may be contributing to the disease. ...
... Initially CKDu was suspected to be an occupational disease associated with exposures in the agricultural workplace, such as heat stress and dehydration (Garcia-Trabanino et al. 2015), pesticide spraying (Rajapakse et al. 2016), heavy metals and agrochemicals (Soderland et al. 2010) or use of NSAIDs (Gooch et al. 2007). Non-agricultural workers and other community members could also be at risk of CKDu, as environmental contamination from heavy metals and pesticides residues (Agampodi et al. 2018;Soderland et al. 2010) or use of folk medicines containing heavy metals or aristolochic acid (Debelle et al. 2008) may be contributing to the disease. Spraying pesticides without personal protective equipment (PPE) or working with contaminated soil have been suggested as likely exposure pathways for pesticides (Jayasumana et al. 2017). ...
Background
Chronic kidney disease with unknown cause (CKDu) is prevalent in tropical and agricultural communities, however, its aetiology remains unclear. The objective of this study was to examine the association between pesticide exposures and the risk of kidney function loss using four waves of the National Health and Nutrition Examination Survey (NHANES) to identify a pathological pathway.
Methods
We pooled data from four cross-sectional waves of NHANES, providing 41,847 participants in total. Sub-population analyses for 2,4-dichlorophenoxyacetic acid (2,4-D), 3,5,6- trichloropyridinol, 3-phenoxybenzoic acid (3-PBA) and Malathion were conducted using. Logistic regression to estimate the odds ratios (ORs) and 95% CIs of the association between log-pesticide levels and kidney function.
Results
We found that Malathion acid increased the risk of low kidney function among the Malathion sub-population (aOR = 1.26, 95% CI = 1.01–1.56) in the adjusted model. Significantly increased risk of low kidney function was not found among the 2,4-D (aOR = 0.88, 95% CI = 0.72–1.09), 3,5,6-trichloropyridinol (aOR = 0.96, 95% CI = 0.83–1.12) and 3-PBA (aOR = 1.03, 95% CI = 0.94–1.13) subpopulations.
Conclusions
Our findings provide evidence of altered kidney function in people exposed to Malathion, highlighting the need to focus on Malathion acid as a potential cause of renal injury or chronic kidney disease.
... Some nephrotoxic substances such as Balkan aristholic acid found in star fruit (Averrohea carabola.L) and some herbal remedies are also thought to cause chronic kidney disease. [5] Other causes are NSAIDs, and the infections are leptosporis, malaria, leprosy, and other rare causes are heat stroke and subsequent rhabdomyolysis. Because the kidneys are vital organs and excrete not only toxic substances from the body but also have other endocrine and hemostatic functions, in order to learn about the risk factors for the kidneys in our society, we conducted a study entitled "Explanation of patients with renal insufficiency". ...
... According to epidemiological studies, the prevalence of chronic kidney disease in various countries varies from 10 to 16% at different stages (these cases have been recorded in adults). [5,6] From the global Reports about chronic kidney Disease, it is indicated that 30-40% of people have Diabetes Mellitus, 25-30% hypertension, and age understood to be a risk factor. [1,2,7] Nephrologic syndrome affects a variety of processes that lead to the onset of pathological processes, including: 1. GFR deficiency (azotemia), 2. Changes in urine sedimentation, 3. Abnormal protein excretion (protein urea), 4. Urine Volume change (Polyuria, oliguria, and anuria), 5. High blood pressure and edema, 6. Abnormality of electrolytes, 7. Some have fever and pain. ...
BACKGROUND: Chronic kidney disease is a global health problem, affecting the majority of countries in the world. Its prevalence is approximately 10% and is associated mainly with Diabetes mellitus and hypertension. It is a condition in which the kidneys function or structural changes or GFR is reduced from / 1.7 sq.m 60ml / min for three months or longer and it is the leading cause of death in hospitals after cardiovascular disease, tuberculosis and malaria. OBJECTIVES: Determine the Risk factors of chronic kidney disease, such as age, sex, Family history, Drug use, smoking, and socioeconomic status, and concurrent Disease, such as hypertension and Diabetes mellitus associated with chronic renal insufficiency. METHODS: This is a Descriptive cross-sectional study conducted in Nishtar National Kidney and Rukhan Teaching Hospitals Jalalabad, Afghanistan, and was performed on 103 patients under Hemodialysis Departments from March through December 2019 and collect data from Individual health histories, Demographic characteristics (age, sex, Body weight, Height, Place of Residence and others factors) on social conditions and risk factors. A physical examination was performed, along with laboratory tests (blood chemistry) to measure renal function and detect markers for renal damage, the history of certain diseases and the presence or absence of certain habits have been investigated. RESULT: The study included a total of 103 patients with chronic renal insufficiency. 61 (59.2%) were Males and 42 (40.8%) females with no significant difference in the number of gender. The majority of the patients were men and residents of Nangarhar province with an average age of (Mean± SD) 40.53 ± 18.06 years. The majority of patients were married, illiterate and of mid-level socioeconomic status. Three out of every four patients with renal insufficiency had a history of high blood pressure, as well as kidney stones, Diabetes mellitus and Dyslipidemia. In terms of habits, the use of other types of tobacco (such as naswar), smoking and the use of certain drugs have been found to be very addictive. CONCLUSIONS: Chronic kidney Disease is alarming in communities, among both young and older age, men and women. Health services must be properly aligned to manage increased burden of chronic kidney disease, and preventive strategies should be implemented in a practical way.
... KDIGO (2020) criteria for CKD are elevation in markers of kidney damage (proteinuria) or GFR <60 ml/min per 1.73 m2 for >3 months (table 2). Though diabetes and hypertension are the most typical causes of kidney diseases, there is increased recognition of CKD that is associated with environmental toxins and exposures (Soderland et al., 2010). (3); none for AKD Albuminuria categories (3) and GFR categories (6) Classification by prognosis AKI with stages (3); none for AKD Risk categories; albuminuria and GFR categories Abbreviations: AKD, acute kidney diseases and disorders; AKI, acute kidney injury; CKD, chronic kidney disease; GFR, glomerular filtration rate; Different case definitions have been used in describing the acute presentation of CKDu since there was no consensus for a common case definition (Fischer et al., 2017). ...
Chronic kidney disease of uncertain etiology (CKDu) is a primary tubulointerstitial disease manifest with minimal or absent albuminuria in the early stages. The literature review suggests multiple environmental factors pose a risk in causing CKDu in addition to traditional elements. Serum creatinine and albuminuria have been used for many decades to measure glomerular function and damage, respectively. However, the diagnosis and management of CKDu mostly rely on serum creatinine, which is a delayed marker that indicates disease after substantial renal damage. Molecular biomarkers are potential candidates to improve the outcomes of kidney diseases. Furthermore, cytokine biomarkers can be used to explore the pathogenesis and to differentiate phenotypes of kidney diseases. This thesis clinically validated biomarkers for early detection of CKDu and complications arising from renal failure.
We evaluated serum creatinine, serum cystatin C and albumin creatinine ratio (ACR) over dipstick proteinuria for CKDu screening. In addition, we described the clinicopathological profiles of the chronic interstitial nephritis (CIN), acute interstitial nephritis (AIN), and subclinical phenotypes of CKDu before evaluating biomarkers. Candidate renal biomarkers (n=27) were measured on 78 stage 1-4 CKDu (early stages) patients to evaluate biomarker manifestation in the disease state and to interpret the pathophysiology. Selected eight urinary biomarkers from 27 candidates were measured in cases and four different controls to identify the best marker panel to differentiate CKDu from other chronic kidney diseases. Serum transforming growth factor-beta-1 (TGF-β1) and creatinine were measured in CKDu patients with different phenotypes and healthy controls to differentiate phenotypes. Also, a clinical trial was conducted to evaluate the effectiveness of prednisolone and doxycycline on AIN presentation. Only biopsy proven CKDu cases were used in the biomarker validation process. All biomarkers were quantified by the Luminex assay except ACR and serum creatinine.
Serum creatinine and ACR were recommended for population screening purposes in Sri Lanka based on accessibility to the tests in the endemic regions. Upregulation of neutrophil gelatinase-associated lipocalin (NGAL), retinol-binding protein-4 (RBP-4), β2-microglobulin (β2-MG), Cystatin C, and α1-microglobulin (α1-MG) and fatty acid-binding protein-1 (FABP-1), TGF-β1 and Collagen-IV in early stages of CKDu suggest active ongoing renal fibrosis and tubular damage. Whereas downregulated interleukins IL-6, IL-10, and pentraxin (PTX-3) indicate a low-grade inflammation. Moreover, serum osteoprotegerin (OPG), parathyroid hormone (PTH), Renin, and fibroblast growth factor 23 (FGF-23) were also downregulated, suggesting a low prevalence of mineral bone disease and cardiovascular events in early CKDu. Osteopontin (OPN), kidney injury molecule-1 (KIM1), and RBP4 combination distinguishes CKDu from known causes of CKD with both sensitivity and specificity ≥0.93. Urinary α1-MG is the best candidate to detect Subclinical cases when creatinine is normal. Serum TGF β1 is a potential biomarker to differentiate AIN from CIN phenotypes. Steroid therapy for AIN presentation may delay the progression of CKDu.
In conclusion, this thesis identified potential biomarkers for the early detection of CKDu and its’ renal complications. However, none of the biomarkers are pathognomonic for CKDu, and need to be interpreted with clinical justification. Further case-control and cohort studies are warranted before clinical use of these biomarkers.
... These factors can cause health issues such as dehydration, exposure to bacteria and viruses, temperature changes, or exposure to chemicals. The kidneys play a crucial role in maintaining body balance and waste management, making them highly vulnerable to toxic effects caused by environmental hazards" [15,16]. "Environmental toxins, which we are unintentionally exposed to through oral, inhalational, or transdermal routes, are a common yet underappreciated cause of kidney injury" [17,18]. ...
The kidneys play a vital role in our overall health and well-being. Their ability to filter waste, reabsorb essential nutrients and maintain a balance of fluids and electrolytes in our body is essential for our health. However, various factors such as age-related changes, exposure to toxins, and lifestyle habits can contribute to a decline in kidney function, leading to potential health issues. Therefore, it is crucial to identify the risk factors that can cause kidney damage and take early interventive measures to slow down the progression of chronic kidney disease. By raising awareness of these risk factors, we can work towards preventing the development of chronic kidney disease and reducing the incidence of end-stage renal disease. It is important to note that several Review Article 8 of these risk factors are modifiable, and early diagnosis and treatment of kidney disease can prevent severe complications. Through regular checkups , identifying these risk factors through panels of tests, and taking a proactive approach towards our health, we can ensure that we maintain healthy kidney function and prevent potential health problems. In conclusion, by taking a constructive approach towards our health and being aware of the risk factors that can cause kidney damage, we can work towards maintaining healthy kidney function and preventing chronic kidney disease. Let us prioritize our health and make changes to our lifestyle habits to reduce the risk of kidney disease and ensure our long-term well-being.
... While RPTEC oxidative and conjugation enzymes have the capacity to metabolize and dispose of foreign substances, there is the potential for chemical-induced injury to this important site within the kidney nephron. Functional capacity and reserve of the kidney is substantial but over time, repeated injury can eventually cause clinical symptomology and evidence of injury observed by biomarkers in urine and serum [3]. Although the causes of chronic kidney disease (CKD) vary, the insidious nature of long-term damage prior to detection often leave clinicians in a difficult position for therapeutic treatment and reversal. ...
Renal proximal tubule epithelial cells (RPTECs) are a primary site for kidney injury. We created two RPTEC lines from CD-1 mice immortalized with hTERT (human telomerase reverse transcriptase) or SV40 LgT antigen (Simian Virus 40 Large T antigen). Our hypothesis was that low-level, repeated exposure to subcytotoxic levels of 0.25–2.5 μM cisplatin (CisPt) or 12.5–100 μM aflatoxin B1 (AFB1) would activate distinctive genes and pathways in these two differently immortalized cell lines. RNA-seq showed only LgT cells responded to AFB1 with 1139 differentially expressed genes (DEGs) at 72 h. The data suggested that AFB1 had direct nephrotoxic properties on the LgT cells. However, both the cell lines responded to 2.5 μM CisPt from 3 to 96 h expressing 2000–5000 total DEGs. For CisPt, the findings indicated a coordinated transcriptional program of injury signals and repair from the expression of immune receptors with cytokine and chemokine secretion for leukocyte recruitment; robust expression of synaptic and substrate adhesion molecules (SAMs) facilitating the expression of neural and hormonal receptors, ion channels/transporters, and trophic factors; and the expression of nephrogenesis transcription factors. Pathway analysis supported the concept of a renal repair transcriptome. In summary, these cell lines provide in vitro models for the improved understanding of repeated renal injury and repair mechanisms. High-throughput screening against toxicant libraries should provide a wider perspective of their capabilities in nephrotoxicity.
... Exposures to Pb and Cd, and in combination with Hg and Cu, have been reported to increase the serum alanine aminotransferase (ALT) and alkaline phosphatase (ALP) activities, reduce haemoglobin concentrations, and total serum protein levels in animals (Al-Attar, 2011;Tomaszewska et al., 2015). Nephrotoxicity due to exposure to these metals along with As, chromium (Cr), and uranium (U) have been characterised by reduced glomerular filtration rate (GFR), and elevated serum urea and creatinine levels (Soderland et al., 2010;Pollack et al., 2015;Orr and Bridges, 2017). Exposure to metals in early life, even at a low environmental concentration, is a specific concern since children are known to be more susceptible to metal toxicity than adults, are particularly sensitive owing to developing organs and biologic systems, and such toxicity can be associated with life-long disease and disability (de Burbure et al., 2006;Landrigan et al., 2018). ...
Environmental exposure to multiple metals and metalloids is widespread, leading to a global concern relating to the adverse health effects of mixed-metals exposure, especially in young children living around industrial areas. This study aimed to quantify the concentrations of essential and potentially toxic elements in blood and to examine the potential associations between multiple elements exposures, growth determinants, and liver and kidney function biomarkers in children living in several industrial areas in Dhaka, Bangladesh. The blood distribution of 20 trace elements As, Ag, Bi, Br, Cd, Co, Cr, Cu, I, Mn, Hg, Mo, Ni, Pb, Se, Sb, Tl, V, U, and Zn, growth determinants such as body mass index and body fats, blood pressure, liver and kidney injury biomarkers including serum alanine aminotransferase and alkaline phosphatase activities, serum calcium, and creatinine levels, blood urea nitrogen, and hemoglobin concentrations, and glomerular filtration rate were measured in 141 children, aged six to 16 years. Among these elements, blood concentrations of Ag, U, V, Cr, Cd, Sb, and Bi were measured below LOQs and excluded from subsequent statistical analysis. This comprehensive study revealed that blood concentrations of these elements in children, living in industrial areas, exceeded critical reference values to varying extents; elevated exposure to As, Pb, Br, Cu, and Se was found in children living in multiple industrial areas. A significant positive association between elevated blood Tl concentration and obesity (β = 0.300, p = 0.007) and an inverse relationship between lower As concentration and underweight (β = -0.351, p < 0.001) compared to healthy weight children indicate that chronic exposure to Tl and As may influence the metabolic burden and physical growth in children. Concentration-dependent positive associations were observed between the blood concentrations of Cu, Se, and Br and hepatic- and renal dysfunction biomarkers, an inverse association with blood Mo and I level, however, indicates an increased risk of Cu, Se, and Br-induced liver and kidney toxicity. Further in-depth studies are warranted to elucidate the underlying mechanisms of the observed associations. Regular biomonitoring of elemental exposures is also indispensable to regulate pollution in consideration of the long-term health effects of mixed-elements exposure in children.
... Research shows frequent cutaneous contact with fuel causes skin irritation. 38 The health consequences of long-term exposure to fuel derivatives are determined by a variety of parameters, including the concentration of the chemical component and the duration of exposure. Contact with gasoline vapors may cause a variety of ailments, including headaches, nausea, and respiratory tract allergies. ...
Trace elements mediate critical biological events by functioning as cofactors or catalysts for numerous enzymes and as centers for enzyme and protein structure stabilization. As a result, imbalances in trace element metabolism and homeostasis (deficiency or excess) may play a role in a number of disorders. The aim of this study was to investigate the blood concentration of essential trace elements of fuel station workers blood in AL-Ramadi city compared with any people who didn’t work in fuel station (control) by measurement of zinc (Zn), copper (Cu), iron (Fe) because they have negative effects on metabolism and considered to be carcinogenic factors. Total 50 male fuel workers and 50 control from ten fuel stations at Al-Ramadi City- Iraq, were participated in the present study. The levels of Zn, Cu and Fe in serum were measured spectrophotometrically by using laboratory kits. The result clarified that there was a significant increase in zinc, copper and iron mean (p 0.05) in fuel workers group compared to control group. Age had a significant correlation with copper levels and no correlation with zinc and iron. The daily hours of exposure showed no significant correlation with zinc, copper and iron. There was a significant increase in zinc levels in smokers compared to nonsmokers; copper and iron showed no correlation with smoking. The years of work in fuel stations significantly correlated with zinc and copper levels, while it showed no correlation with iron levels. The results of this study showed that there is no significant correlation between zinc, copper and the worker’s weight, while it showed a significant weak positive correlation between iron and the worker’s weight (p 0.05). There was a significant increase in copper levels in the workers with chronic illnesses compared to healthy workers, while zinc and iron had no correlation with chronic illnesses. The conclusion of study is the role of the increase of trace elements on the health of the fuel workers group, attention to use of safety gloves and face mask is recommended for fuel workers and a long follow-up to the studied group is necessary to discover the developments. Also, it is highly recommended to reduce the working hours for fuel workers in order to decrease the accumulative effects of benzene exposure and to allow the body to detoxify the blood.
... The kidney is also highly susceptible to environmental toxins [4][5][6][7]. The role of tobacco smoking as a prominent risk factor in the development of chronic kidney disease is widely recognised, encompassing both direct and indirect impacts on renal health [8][9][10]. ...
High-fat diet (HFD) consumption and tobacco smoking are risk factors for chronic kidney disease. E-cigarettes have gained significant popularity among younger populations worldwide, especially among overweight individuals. It is unclear whether vaping interacts with HFD consumption to impact renal health. In this study, Balb/c mice (male, 7 weeks old) were fed a pellet HFD (43% fat, 20 kJ/g) for 16 weeks when exposed to nicotine or nicotine-free e-vapour from weeks 11 to 16. While HFD alone increased collagen Ia and IV depositions, it did not cause significant oxidative stress and inflammatory responses in the kidney itself. On the other hand, e-vapour exposure alone increased oxidative stress and damaged DNA and mitochondrial oxidative phosphorylation complexes without significant impact on fibrotic markers. However, the combination of nicotine e-vapour and HFD increased inflammatory responses, oxidative stress-induced DNA injury, and pro-fibrotic markers, suggesting accelerated development of renal pathology. Nicotine-free e-vapour exposure and HFD consumption suppressed the production of mitochondrial OXPHOS complexes and extracellular matrix protein deposition, which may cause structural instability that can interrupt normal kidney function in the future. In conclusion, our study demonstrated that a HFD combined with e-cigarette vapour exposure, especially when containing nicotine, can increase susceptibility to kidney disease.
... Young individuals are more susceptible to heavy metal toxicity [22][23][24][25]. The bioaccumulation of lead in the human body interferes with proper mitochondrial functioning, while chronic exposure to cadmium can lead to lung cancer, prostatic proliferative lesions, bone fractures, and hypertension [26][27][28][29][30][31]. Contamination by heavy metals in drinking water has received significant attention due to its strong toxicity even at low concentrations. ...
This study aimed to measure the levels of heavy metals in water samples from the Alau dam, an important source of water for the surrounding areas, using Atomic Absorption spectrometer methods. The metals analyzed were Cu, Zn, Mn, Fe, and Cr, which can have significant environmental and health impacts. The results showed that the mean concentrations of these metals in the middle of the dam were generally higher than those on the side of the dam, with Cu having the highest mean concentration at 0.067 mg/L. The results also showed a range of concentrations for each metal, with Fe having the widest range of 0.003-0.20 mg/L. These findings are important for understanding the potential exposure of individuals and the environment to heavy metals from the Alau dam. Exposure to high levels of heavy metals in water can cause various health problems such as kidney damage, nervous system damage, and cancer, and can also lead to bioaccumulation in the food chain, affecting entire ecosystems. The results of this study provide important information on the concentration of heavy metals in Alau dam and highlight the need for regular monitoring to ensure that the water is safe for human use and does not negatively impact the environment. This information can be used to inform policy decisions and environmental management strategies aimed at minimizing the risks associated with exposure to heavy metals.
... Wastewater treatment plants and rainwater runoff are primarily responsible for the occurrence of xenobiotics in freshwater (Ahlborg et al. 1992;Anetor et al. 2008;Cataudella et al. 2012). The removal of xenobiotics from wastewater by wastewater treatment facilities is frequently insufficient, allowing xenobiotics to infiltrate public sewers, enter the food chain, and directly damage people (Rosas and Eskenazi 2008;Neal and Guilarte 2012), as well as contributing to micropollutant pollution of aquatic bodies (Julvez and Grandjean 2009;Soderland et al. 2010;Descamps and Deschamps 2012). Even though colonies of bacteria and other microorganisms have been discovered to be successful in breaking down particular xenobiotics, activated sludge is typically insufficient for this task. ...
Among the major concerns associated globally with aquaculture or fish farming, top-notch and prime one is the treatment and management of xenobiotics. Aquatic ecosystems are heavily and negatively impacted by these chemicals. Xenobiotics impact aquaculture industry in a number of ways, be it the decline in the production or remaining in the system for so long that it hampers treatment and management. Because of its presence for a large time in waterbodies, these compounds can build up in food chains via the consumption of aquaculture products. There are good reports where these chemicals build-up in human body leading to cancers. One of the main agendas of xenobiotic management is its degradation. Degradation involves bioremediation (bioattenuation, biostimulation, and bioaugmentation). Burkholderia, Bacillus, Pseudomonas, Sphingomonas, Kocuria, Chromohalobacter, and Achromobacter have been reported to play a critical role in the degradation of these compounds. Bioremediation process can be improved with advancements in molecular biological techniques like genome editing, which allows the modification of microbial strains with an increased capacity for digesting several xenobiotics simultaneously and/or at a quick rate the bioremediation process can be improved.KeywordsXenobioticDegradationBioremediationGenome editing
... Cytotoxic effects of petroleum products are exerted on most of body organs of humans and animals such as the liver and kidney [23]. Exposure to benzene for a long period of time could cause nephrotoxicity and hepatotoxicity and the seriousness of poisoning caused by benzene depends on the amount, rout, and length of time of exposure, as well as the age and preexisting medical condition of the exposed person [24]. ...
... Tubulointerstitial nephritis is characterized by a hetero-geneous group of acute or chronic abacterial, nondestructive lesions of the renal tubules and interstitium, with the spread of the inflammatory process to all structures of the renal tissue [38]. One of the nosological forms of tubulointerstitial kidney damage is tubulointerstitial and tubular lesions caused by drugs and heavy metals [39]. These forms of renal pathologies may result from living in the zone of influence of uranium mining deposits, as it is known that uranium has a toxic effect on the kidneys both as a heavy metal and as an alpha-emitting radionuclide. ...
The increase in uranium mining in Kazakhstan has brought with it a number of problems. Reducing the negative impact of radiation-toxic factors on the health of workers and the population in uranium mining regions is one of them. This article presents a pilot population health study in which we developed approaches to support residents living near an operating uranium mining enterprise. The purpose of the current study was to assess the impact of technogenic factors on the health of those living near the Syrdarya uranium ore province. Data collected from 5605 residents from the village of Bidaykol (the main group)—which is located 4 km from the uranium mining enterprise—and the village of Sunakata (the control group), which is located in the Kyzylorda region, were analyzed. A bidirectional cohort study was conducted. The prevalence of acute and chronic diseases among the residents of Bidaykol was 1.3 times higher than that in the control group. The structure of morbidity was dominated by pathologies of the genitourinary system (27%), the circulatory system (14.4%), and the respiratory system (11.9%). Relative risks (RR > 1) were identified for most classes of diseases, the highest being for diseases of the blood (RR = 2.6), skin (RR = 2.3), and genitourinary system (RR = 1.9). In the main group, renal pathologies were the most frequent class in the age group of 30–40 years, occurring mainly in women. In addition, they had a direct dependence on the duration of residence in the territory of the uranium ore province. Further studies into the interaction between the technogenic factors associated with uranium mining enterprises and the development of diseases of the urinary system are needed. This will make it possible to determine ways to prevent these pathologies in the population.
... Endemic chronic kidney disease of unknown aetiology (CKDu) which is prevalent in Sri Lanka and many other tropical countries rank amongst diabetes mellitus and essential hypertension in causing chronic kidney disease (CKD) [1][2][3][4][5]. This condition in Sri Lanka and Nicaragua shares many demographical and clinicopathological similarities that young male agricultural workers who perform strenuous labour in hot and humid working conditions are the worst affected [6,7]. ...
Background
Patients presenting with acute interstitial nephritis (AIN) of unknown aetiology, probably the earliest presentation of chronic kidney disease of unknown aetiology (CKDu), have been treated with oral prednisolone and doxycycline by physicians in Sri Lanka. This trial assessed the effectiveness of prednisolone and doxycycline based on eGFR changes at 6 months in patients with AIN of unknown aetiology.
Method
A randomized clinical trial with a 2 × 2 factorial design for patients presenting with AIN of unknown aetiology ( n = 59) was enacted to compare treatments with; A-prednisolone, B-doxycycline, C-both treatments together, and D-neither. The primary outcome was a recovery of patients’ presenting renal function to eGFR categories: 61–90 ml/min/1.73m ² (complete remission– CR) to 31–60 ml/min/1.73m ² (partial remission– PR) and 0–30 ml/min/1.73m ² no remission (NR) by 6 months. A secondary outcome was progression-free survival (not reaching < 30 ml/min/1.73m ² eGFR), by 6–36 months. Analysis was by intention to treat.
Results
Seventy patients compatible with a clinical diagnosis of AIN were biopsied for eligibility; 59 AIN of unknown aetiology were enrolled, A = 15, B = 15, C = 14 and D = 15 randomly allocated to each group. Baseline characteristics were similar between groups. The number of patients with CR, PR and NR, respectively, by 6 months, in group A 3:8:2, group B 2:8:3 and group C 8:5:0 was compared with group D 8:6:1. There were no significant differences found between groups A vs. D ( p = 0.2), B vs. D ( p = 0.1) and C vs. D ( p = 0.4).
In an exploratory analysis, progression-free survival in prednisolone-treated (A + C) arms was 0/29 (100%) in comparison to 25/30 (83%) in those not so treated (B + D) arms, and the log-rank test was p = 0.02, whereas no such difference found ( p = 0.60) between doxycycline-treated (B + C) arms 27/29 (93%) vs those not so treated (A + D) arms 27/30 (90%).
Conclusion
Prednisolone and doxycycline were not beneficial for the earliest presentation of CKDu at 6 months. However, there is a potential benefit of prednisolone on the long-term outcome of CKDu. An adequately powered steroid trial using patients reaching < 30 ml/min/1.73m ² eGFR by 3 years, as an outcome is warranted for AIN of unknown aetiology.
Trial registration
Sri Lanka Clinical Trial Registry SLCTR/2014/007, Registered on the 31st of March 2014.
... 1 The majority of them are made up of hydrocarbons (aromatic, saturated, and unsaturated) and non-hydrocarbons (N, S, O2, vanadium, and nickel). 2 poisoning is dependent on the amount, route, and length of time of exposure, as well as the exposed person's age and pre-existing medical condition. 16 The most typically requested tests for heart and liver investigations are lipid profile and liver function tests (LFTs). 17 As a result, the goal of this study was to determine the impact of gasoline exposure combined with smoke on the lipid profile parameters and liver function tests in gasoline station workers in Zakho, Duhok City, Kurdistan ...
Introduction: The rapid and recent rise in the pandemic of cardiovascular disease implies that the environment plays a significant role. Numerous biological systems, such as the cardiovascular, blood-forming organs, liver, and kidneys, can be affected by gasoline and smoking. Because filling station employees, repair service workers, gasoline truck drivers, and refinery workers are all at a greater risk of being exposed to gasoline fumes. Even though gasoline and smoking have been investigated for so many years, few studies have looked into the effects of gasoline exposure combined with smoking on a variety of physiological mechanisms. As a result, we propose that combining gasoline exposure with smoking is a risk factor for cardiovascular diseases and impaired hepatic function.
Methods: The study included 95 male adult volunteers who worked with gasoline and were exposed to different fuel derivatives as study group and age and sex-matched seemingly healthy non-exposed people as the controls. Questionnaire interviews were used to collect socio-demographic data and a standard technique was used to collect the blood samples. The levels of cholesterol, HDL4, LDL-C, triglyceride, and VLDL were measured, as well as for liver enzymes ALP, AST, ALT, indirect bilirubin, direct bilirubin, and total bilirubin were measured.
Results: Our data suggest that smoking with gasoline exposure causes an increase in total and bad cholesterol levels, as well as a significant shift concerning the control group in lipid profile and liver enzymes. the exposed group had higher levels of ALP, and AST and significantly increased. In the nonsmoker exposed group D-bilirubin decreased in comparison to the control and exposed smoker group.
Conclusion: This research concluded that the liver enzymes (ALP, AST, ALT) were higher among workers who smoke and are exposed to gasoline than in control subjects, similarly, the bad cholesterol also increase. Therefore, people who smoke and are handled with gasoline are at a higher risk of having heart and hepatic diseases.
... [11] Hg and Cd have been demonstrated to be nephrotoxins at high levels of exposures (e.g., exposure occurring at smelters). [11,19] However, the impact of low level exposure (or non-industrial) on the risk of renal disease is not clear. [20] In this cross-sectional study in Chinese individuals aged >80 years, we found that low Cd and Hg exposure (or non-industrial) were associated with increased risk of CKD after adjusting for confounding factors and this association was further confirmed by a number of subgroup analyses (e.g., with the subgroups of sex, education level, and marital status). ...
Background:
The heavy metals cadmium (Cd) and mercury (Hg) are known to be widespread environmental contaminants and high occupational exposure adversely affects the risk of chronic kidney disease (CKD). However, evidence from epidemiological studies linking low Cd and Hg exposure (or non-industrial) to the risk of progression to CKD are conflicting. This study aimed to explore the association of low Cd and Hg exposure with the risk of CKD in Chinese adults aged ≥80 years.
Methods:
The participants were recruited for the Healthy Aging and Biomarkers Cohort Study in 2017, an ongoing perspective survey conducted in longevity areas in China initially involving 3016 older adults. We used logistic regression models to estimate odds ratios (ORs) with 95% confidence intervals of CKD setting Cd and Hg as categorical variables. Logistic regression with restricted cubic spline was used to characterize a dose-response relationships between Cd or Hg concentrations and the risk of CKD in the study population.
Results:
The ORs for the risk of CKD comparing the fourth to the first quartile of blood Cd, blood Hg, urine Cd, and urine Hg were 1.77, 1.57, 2.03, and 1.50, respectively. Restricted cubic spline models showed that blood Cd and urine Hg were significantly linearly correlated with the risk of CKD, while blood Hg and urine Cd were non-linearly correlated with the risk of CKD with a steeper slope at concentrations <2.30 μg/L and 3.30 μg/g creatinine.
Conclusions:
Our findings suggest that even low Cd and Hg exposure (or non-industrial) were associated with increased risk of CKD in Chinese oldest old, although we did not find a significant multiplicative and additive interaction between Cd and Hg levels in relation to the risk of CKD.
... They facilitate the removal of excess metabolites from the body, retain water, and useful substances after reabsorption, regulate water and electrolyte balance, and maintain an acid-base balance. Metals can enter the human body through ingestion and digestion of contaminated food, inhalation of polluted air, and skin contact (Goix et al. 2016;Sabath and Robles-Osorio 2012;Soderland et al. 2010;Wu et al. 2016) and then act on target organs to finally accumulate in the kidneys. As such, the kidneys are highly sensitive to metals, particularly heavy metals such as cadmium (Cd), lead (Pb), and chromium (Cr; (Sabath and Robles-Osorio 2012). ...
Chronic kidney disease, common in older individuals, causes a considerable disease burden worldwide. Although heavy metal exposure is associated with renal impairment, the effects of heavy metal mixtures and metal–metal interactions on renal impairment warrant investigation. We recruited 1674 participants living in northeastern China for a cross-sectional survey (2016–2019). We gathered data on urinary Cr, Cd, Pb, and Mn; β2-microglobulin (β2-MG); and the renal function biomarker N-acetyl-β-D-glycosaminidase (NAG). We also estimated glomerular filtration rates (eGFRs) using the Modification of Diet in Renal Disease equation (eGFR-MDRD) and the Chronic Kidney Disease Epidemiology Collaboration equation (eGFR-EPI). Generalized linear models were used to explore the association of each metal with the renal function biomarkers. We used quantile g-computation and Bayesian kernel machine regression (BKMR) to explore the overall effects of the metal mixtures and BKMR and multivariate linear regression to investigate the effects of metal–metal interactions on renal function. Metal mixture levels were positively associated with NAG, eGFR-EPI, and eGFR-MDRD but not β-2MG levels. Cd–Cr, Cd–Mn, and Cd–Pb were antagonistically associated with NAG overall. In women, the association of β-2MG with Cd–Mn, Cd–Pb, and Cd–Cr was synergistic, whereas that with Cr–Mn was antagonistic. In men, the association of eGFR-MDRD with Cd–Pb was antagonistic but that with Cd–Cr was synergistic. Overall and in women, the association of eGFR-MDRD with Cd–Cr was antagonistic. Finally, the association of eGFR-EPI with Cd–Cr was synergistic, but that with Cd–Pb was antagonistic. For β-2MG, there was a three-way Cd–Cr–Pb synergistic interaction in men and a four-way Cd–Cr–Mn–Pb interaction in women. Exposure to heavy metals is associated with renal function biomarkers, and metal–metal interactions exert synergistic or antagonistic effects on this association. Additional epidemiological studies considering the combined effects and interactions of multiple pollutants simultaneously are warranted.
Graphical Abstract
... 23 Agrochemicals like 2,4 D and paraquat dichlorate, non-steroidal antiinflammatory drugs(NSAID), heavy metal exposure are associated with acute kidney injury. 23,24,25 Studies suggest that in obesity, adipose tissue may contribute to renal damage by oxidative stress, abnormal plasma lipid, coagulation abnormalities, endothelial dysfunction, inflammation and insulin resistance. 26,27 Smoking is associated with CKD, the possible mechanism includes increased blood pressure and heart rate, cell proliferation, fibronectin, arteriosclerosis of renal artery and arterioles, increased production of growth factors like angiotensin II, endothelin-I, transforming Growth Factor-1, oxidative stress, tubular toxicity, increased aggregation of platelet and vasopressin mediated antidiuresis. ...
Aim: To assess the risk factors for renal dysfunction in a heterogeneous population. To determine the age and sex wise distribution of eGFR and Urinary spot Protein- Creatinine ratio (UPCR) in a heterogeneous population. To estimate the lipid profile and thyroid profile and assess their role as risk factor in renal dysfunction. Introduction: Chronic Kidney Disease (CKD), is a major health problem in India. As per the Kidney Diseases Improving Global Outcomes (KDIGO) 2012, CKD is defined1 as abnormalities of kidney structure or function present for more than three months. Thyroid hormones were also found to influence GFR, tubular secretion and absorption.16,17One study has shown that normal to high levels of Thyroid Stimulating Hormone (TSH) and normal to low levels of free triiodothyronine (FT3) were associated with increased risk of CKD in euthyroid subjects.18 It is also said that high level of serum free thyroxine (FT4) was associated with increased risk of CKD rather than TSH and FT3.There was also associated rapid decline in eGFR.19Many studies have found that hypothyroidism is associated with dyslipidemia and renal dysfunction.
... The effects of agents might be controlled by genetic susceptibility and comorbid conditions may lead to chronic kidney disease. 22 To overcome these complications and for improvement in physical function, a welldeveloped exercise plan can be developed after dialysis in the ward and guide home exercise plan to meet the need of these patients. Moreover, there is very little research on these specific strengthening exercises on dialysis patients and their effects on quality of life. ...
Background: Diabetic nephropathy becomes a disease with a high mortality rate in this modern era of technology. Dialysis in diabetic patients affects kidney functioning is the most common treatment for end-stage renal failure but had different musculoskeletal complications due to bone mineral metabolisms like muscular cramping, atrophy and muscular weakness, restless leg syndrome and limb pain that lowers the quality of life and physical function. Objective: To evaluate the effects of low-impact strengthening exercises on limb pain, strength, glycemic control, hypertension and quality of life of patients with end-stage renal disease. Methods: The randomized controlled study was designed to check the effectiveness of low-impact strengthening exercises on patients involved in the treatment and control group. Using non-probability purposive sampling, data was collected from different hospitals in Faisalabad by providing treatment for six consecutive weeks. Outcomes of measures were pain, strength, glucose level, blood pressure and quality of life which were estimated through the numeric pain rating scale, manual muscle testing, glucometer, sphygmomanometer and kidney disease quality of life questionnaire respectively. Results: Low-impact strengthening exercises in the treatment group showed improvement in muscle strength, blood pressure, glycemic level, pain and quality of life in diabetic patients with end-stage renal disease as compared to the control group. Mean values showed that there was a statistically significant difference in different variables between both groups. Conclusion: It was concluded that there is a statistically significant difference between both groups in the improvement of limb pain and limb muscle strength by low-impact strengthening exercises. These exercises have positive effects on diabetic patients with end-stage renal disease in the treatment group as compared to the control group.
... Epidemiological evidence suggests the role of environmental toxins in kidney diseases. Heavy metals like lead, mercury, arsenic, and cadmium are associated with CKD, AKI, tubular disorders (Fanconi syndrome), and glomerular diseases (80). Kuzḿa et al. demonstrated an association between eGFR decline and CKD development with medium-and short-term exposure to higher air pollution levels (81). ...
The social determinants of health (SDoH) are the non-medical factors that influence kidney health outcomes directly or indirectly in a substantial manner and include conditions in which people are born, grow, work, live, and age. Many such challenges in lower- and middle- income countries have an unfavourable impact on kidney health. These conditions potentially influence economic policies and systems, development agendas, social norms, social policies, and political systems. In addition, many political and legal factors also determine and modify the ultimate outcome in patients with kidney disease. Legal factors that ensure universal health care, promote gender and racial equality, prevent malpractices and regulate strict laws in the field of kidney transplantation are the paramount determinants for the provision of necessary kidney care. Converging lines of evidence have supported the impact of social variables such as socioeconomic resources, social inclusion, housing conditions, educational attainment, and financial status on kidney health, particularly affect vulnerable and disadvantaged groups and result in challenges in kidney care delivery. Furthermore, the climate is an important SDoH that plays a crucial role in the occurrence, prevalence, and progression of kidney diseases as highlighted by the presence of higher prevalence of chronic kidney disease in hot tropical countries. The rising incidence of water and vector-borne diseases causing acute kidney injury is another consequence of disruptive environmental and climate change which is detrimental to kidney health. Political risk factors such as conflict also have a devastating influence on kidney health. The relationship between SDoH and kidney health outcomes requires more clarity. Gaps in the current knowledge need to be identified to inform the development of appropriate interventions to address upstream socio-economic risk factors for kidney disease.
... In addition to the well-known risk factors for renal injuries, such as aging, diabetes mellitus, and hypertension, some environmental chemicals have also been shown to be important risk factors for renal injury. 9,10,11 With the ever-increasing use of synthetic compounds in all aspects of daily life, the health risks from environmental toxins and pollutants becomes increasingly important. In particular, as the kidneys are responsible for excreting waste products from the body, they are exposed to toxins and pollutants in the blood, and they are therefore susceptible to the adverse effects stemming from this exposure. ...
Concentraciones séricas de citocinas proinflamatorias en niños de una comunidad agrícola de México con alto riesgo de enfermedad renal crónica
... According to a 2020 study, awareness of CKD remains low among care providers (Wolide et al. 2020) even though early diagnosis can greatly improve long term prognosis (Nickolas et al. 2004;Coresh et al. 2005;James et al. 2014;Colberg et al. 2016). The risk factor for the kidney diseases, however, remain unclear, though both genetic and environmental factors such as diabetes, high blood pressure cardiovascular disease, smoking, obesity, family history and congential kidney are all known risk factors (Soderland et al. 2010;Levin et al. 2017). Various studies, from different countries, have indicated that exposure to potentially toxic elements is an important etiological factor for kidney disease (Wimalawansa 2016;Diyabalanage et al. 2017). ...
The Akaki River in the Upper Awash Basin, which flows through Addis Ababa, the capital city of Ethiopia, has been highly polluted by sewage from factories and residential areas. A population-based cross-sectional study was used to assess the association between trace elements and kidney injury from residents living in polluted areas downstream (Akaki-Kality) versus upstream (Gullele) in Sub-Cities of Addis Ababa. A total of 95 individuals (53 from Akaki-Kality and 42 from Gullele) were included in the study. Kidney injury molecule 1 (KIM-1), lead, arsenic, cadmium, cobalt, lead, manganese, zinc, iron, copper, chromium and nickel were evaluated in residents’ urine and nail samples. A large proportion (74%) of the sample population contained KIM-1, including 81% residents in Akaki-Kality and 64% residents in Gullele. KIM-1 was, however, not significantly different (p = 0.05) between the two Sub-Cities, with median of 0.224 ng/mL in Akaki-Kality and 0.152 ng/mL in Gullele. Most of the analyzed elements, except Pb, As, Cd and Co, were found in all of the nail samples, with median (µg/g) in the range of 442‒714 Fe, 97.0‒246 Zn, 11.6‒24.1 Mn, 4.49‒5.85 Cu, 1.46‒1.66 Cr and 1.22‒1.41 Ni. The high incidence of KIM-1 indicates a potential for long term renal tubular damage among residents of the Sub-Cities. The concentrations of the elements in nails were, however, not significantly associated (p = 0.05) with the corresponding levels of KIM-1 in urine. Hence, the observed KIM-1 might be related to exposure to toxic substances or factors other than those included in this study.
... These effects can be caused by heavy metals (Tirry et al., 2018). Research on the impacts of cadmium on rice plant habitats has primarily concentrated on the connection between cadmium pollution in paddy soils and cadmium concentrations in rice (Soderland et al., 2010). Because of the many functions that they perform in the cycle of nutrients, the symbiosis of plants, and the detoxification of harmful chemicals used to control plant pests and plant growth, microbial communities play important roles in soil (Ivshina et al., 2014). ...
Soil microbial community is the main indicator having a crucial role in the remediation of polluted soils. These microbes can alter soil pH, organic matter in soils (SOM), soil physic-chemical properties, and potential soil respiration rate via their enzymatic activities. Similarly, heavy metals also have a crucial role in soil enzymatic activities. For this purpose, a number of methods are studied to evaluate the impact of soil pH (a key factor in the formation of biogeographic microbial patterns in bacteria) on bacterial diversity. The effects of pH on microbial activity are glamorous but still unclear. Whereas, some studies also indicate that soil pH alone is not the single key player in the diversity of soil bacteria. Ecological stability is achieved in a pollution-free environment and pH value. The pH factor has a significant impact on the dynamics of microbes’ communities. Here, we try to discuss factors that directly or indirectly affect soil pH and the impact of pH on microbial activity. It is also discussed the environmental factors that contribute to establishing a specific bacterial community structure that must be determined. From this, it can be concluded that the environmental impact on soil pH, reducing soil pH and interaction with this factor, and reducing the effect of soil pH on soil microbial community.
... Although the exact etiology of CKDu is yet to be explained, it is considered a disease of multifactorial origin primarily resulting from environmental factors. 5 Renal damage can progress even in the absence of continuous exposure to the risk factors. Therefore, community screening is of utmost importance in the detection and management of CKDu. ...
... Some metals (such as Pb, Cu, etc.) can enter the body through digestion of contaminated food, inhalation of ambient air pollution, and absorption of dermal contact (Barceloux 1999;Goix et al. 2016;Pacyna and Pacyna 2001;Soderland et al. 2010;Wu et al. 2016). The National Health and Nutrition Examination Survey (NHANES), which was conducted in the America, reported that blood Pb (mean = 0.70 μg/L) is associated with eGFR decline and urinary Pb (0.36 μg/L) is positively associated with eGFR (Sanders et al. 2019); these inconsistent results indicate that the differences between metal concentrations in blood and urine must be considered. ...
Metal exposure contributes significantly to the pathogenesis of kidney dysfunction. However, most studies have focused on metal concentration in a single matrix (i.e., blood or urine), and few have explored the associations of metal clearance and visit-to-visit variability with renal function. We conducted a three-wave repeated-measures study of 201 older adults. Metal clearance and visit-to-visit variability were calculated to reflect, respectively, the body burden and homeostasis of meals. Renal function was measured as the urinary albumin-to-creatinine ratio (UACR) and estimated glomerular filtration rate (eGFR). Linear mixed-effects and Bayesian Kernel Machine Regression models were used to evaluate the effects of single metals and metal mixtures. The blood metal mixture was negatively associated with eGFR, and urinary Cu was positively associated with UACR (β = 0.417). The metal clearance ratios of Cu, Ni, and Sr were significantly and negatively associated with eGFR, and Cu had the largest effect estimate. The variability independent of the mean of urinary Cs was negatively associated with eGFR after adjustments for the individual metal mean concentration (IMM) of urinary Cs. Furthermore, the visit-to-visit variability of blood Sr was significantly and positively associated with UACR and independent of IMM. Among eight meals in blood and urine, urinary Cu contributed the most to the increase in UACR. We firstly proposed metal clearance and visit-to-visit variability, and found the new indicators are associated with kidney dysfunction. This study revealed real-world metal exposure from the perspective of metal mixtures and improved the understanding of the pathophysiology of metal exposure-induced kidney dysfunction.
Graphical Abstract
... idneys are affected by many environmental toxins such as lead, mercury, and industrial chemicals [1].Additionally, the increased intake of processed food leads to consumption of high amounts of simple sugars, phosphorus, salt, and added potassium. This causes increased incidence of chronic kidney diseases [2]. ...
Hypertension is the leading cause of cardiovascular disease in women, and sub-Saharan African (SSA) countries have some of the highest rates of hypertension in the world. Expanding knowledge of causes, management, and awareness of hypertension and its co-morbidities worldwide is an effective strategy to mitigate its harms, decrease morbidities and mortality, and improve individual quality of life. Hypertensive disorders of pregnancy (HDPs) are a particularly important subset of hypertension, as pregnancy is a major stress test of the cardiovascular system and can be the first instance in which cardiovascular disease is clinically apparent. In SSA, women experience a higher incidence of HDP compared with other African regions. However, the region has yet to adopt treatment and preventative strategies for HDP. This delay stems from insufficient awareness, lack of clinical screening for hypertension, and lack of prevention programs. In this brief literature review, we will address the long-term consequences of hypertension and HDP in women. We evaluate the effects of uncontrolled hypertension in SSA by including research on heart disease, stroke, kidney disease, peripheral arterial disease, and HDP. Limitations exist in the number of studies from SSA; therefore, we will use data from countries across the globe, comparing and contrasting approaches in similar and dissimilar populations. Our review highlights an urgent need to prioritize public health, clinical, and bench research to discover cost-effective preventative and treatment strategies that will improve the lives of women living with hypertension in SSA.
Heavy metals are often found in soil and can contaminate drinking water, posing a serious threat to human health. Molecular pathways and curation therapies for mitigating heavy metal toxicity have been studied for a long time. Recent studies on oxidative stress and aging have shown that the molecular foundation of cellular damage caused by heavy metals, namely, apoptosis, endoplasmic reticulum stress, and mitochondrial stress, share the same pathways as those involved in cellular senescence and aging. In recent aging studies, many types of heavy metal exposures have been used in both cellular and animal aging models. Chelation therapy is a traditional treatment for heavy metal toxicity. However, recently, various antioxidants have been found to be effective in treating heavy metal-induced damage, shifting the research focus to investigating the interplay between antioxidants and heavy metals. In this review, we introduce the molecular basis of heavy metal-induced cellular damage and its relationship with aging, summarize its clinical implications, and discuss antioxidants and other agents with protective effects against heavy metal damage.
The design, development and analysis of a planar microstrip sensor operating at 2.4 GHz for the detection of adulteration in liquid samples is presented. The sensor characterises the samples based on the material properties which in turn affects the electric field fringing from the sensing area. In particular, a closed loop microstrip antenna is developed and used for the sensing application. The sensor is designed and analysed using simulation software and the fabricated prototype is experimentally validated. Parametric analysis of the design variables and mathematical modelling of the sensor operations are carried out by analysing the fields generated within the sensor. A case study for adulteration testing is carried out by choosing milk as the sample. Qualitative and quantitative testing using the milk as sample has been carried out experimentally under different test conditions. For quantitative testing, water is added to milk as the adulterant and for qualitative testing, usual chemical adulterants that are mixed with milk are added and the variations in operating frequency and return loss are analysed. From the analysis it could be observed that the shift in the operating frequency and return loss are dependent on the changes in dielectric permittivity of the sample loaded on to the sensor surface. From this analysis, the adulteration rate in milk can be estimated based on the variation in permittivity of the adulterant that is added to the milk. The same procedure can be extended in detecting the adulteration of any liquid samples.
Xenobiotics are foreign agents in a biological system, including the human body. Immoderate use of xenobiotics and lack of adequate disposal technology resulted in the ecosystem’s defilement, including humans, which globally impacts its self-regulating activities. That results in irrevocable effects on the structure and function of an ecosystem. The reason behind the irrevocable effect is the foreign nature because when any product remains unmetabolized it would reach the maximum toxic concentration. For metabolic activity, any prokaryotic or eukaryotic cell requires enzymes, energy to operate these enzymes, and multiple cofactors. This would result in bewildering effects on the soil as it contains both prokaryotic and eukaryotic microflora. Soil microflora plays a prominent role in maintaining soil health and ecosystem functioning that holds the key to sustainable land use in terms of environmental sustainability and food security. To achieve this goal, the assessment of xenobiotic effects on soil microflora is the most crucial step. Bacteria are the most ubiquitous microorganisms and help the soil to maintain nutrients with the help of biogeochemical cycling. So, xenobiotic assessment required two-way interaction that will help to understand the persistence of xenobiotics and microflora activity along with the biodegradation process that leads to changes in soil microflora at the contaminated sites. This assessment can also help to understand the adverse effects of xenobiotics on human health through the food chain. Accumulation of xenobiotics shows slight modifications in metabolic pathways by inducing metabolic pathway disorders resulting in the alteration in xenobiotic-metabolizing enzymes that need to be figured out with the help of bioassay.
Introduction: Chronic kidney disease of unknown aetiology (CKDu) is an emerging public health concern in India. The present study was carried out to investigate the concentrations of potentially toxic heavy metals (Cd, Pb, Ni, Cr, Hg, and As) in locally grown food crops (rice, pulses, and vegetables) in CKDu prevalent areas of Cuttack district, India.
Methods: Exposure risks from food crops were analysed, including estimated daily intake, hazard quotient, hazard index, and carcinogenic risk.
Result: The overall heavy metal concentrations in the crop samples were in the following order: Pb>Ni>Cd>Cr>As>Hg. The mean concentration of heavy metals in different crops were as follows, ranked from highest to lowest: spinach, rice, okra, mustard, potato, carrot, tomato, green gram, black gram. A statistical multivariate analysis revealed that the primary sources of Cd, Pb, Ni, Cr, Hg, and As in crop samples were both natural and human activities. For lead, target hazard quotient (THQ) values in rice were greater than 1, indicating significant noncarcinogenic health risks to both adults and children.
Discussion: While the majority of the crop samples had Pb levels below the permissible level (10⁻⁵), the target carcinogenic risk of Cd was higher than the USEPA threshold value (10⁻⁴), showing a cancer risk to adults and children. This study concluded that long-term intake of locally grown food crops may produce a significant health risk to the local inhabitants, and that of regular heavy metal monitoring is strongly recommended in this region.
High environmental exposure to lead is associated with kidney failure, but the effect of low-level environmental exposure has not been well studied .Objective : The aim of the study was to evaluate the blood lead levels in the serum of patients with renal failure and compare it with those in the control group, as well as to verify its relationship with kidney function. Subjects and Method : The study included 87 people, their ages ranged (17-72 years), 45 of them were diagnosed with chronic kidney disease, while 32 of them were diagnosed with good health. Samples were collected from December 2022 to May 2022 and blood lead levels were estimated using atomic absorption Shimadzu in China, biochemical parameters were measured weight calculated for body mass index divided by height squared in meters, serum creatinine and blood urea by colorimetric methods using Spectrophotometer from Genway company . Results : The average levels of lead in the blood in the group of chronic kidney patients were much higher than it was in the control group (p≤ 0.01).
Arsenic is commonly found in Earth’s crust and ranks 20th in terms of abundance. It can enter the human body through drinking water, inhalation, and diet, but drinking water is the most common source. The toxic effects of arsenic are widespread in both developed and developing countries. Arsenic exposure over a prolonged period can lead to skin, lungs, CNS, and reproductive health disorders. Arsenic is a human carcinogen well known for affecting multiple organs. Recent evidence suggests that arsenic exposure causes reproductive toxicity, which leads to teratogenic and developmental effect. Arsenic exposure at high levels increases the chances of developing diabetes mellitus.KeywordsHealth effectsChronic arsenicMulti-organ damageReproductive toxicityTeratogenicity
The environment is that part of living and non-living nature that surrounds organisms and directly or indirectly affects their existence, development and reproduction.The increase of toxic substances in the environment and the human body beyond the permissible norm leads to a progressive increase in such chronic diseases as: diseases of the respiratory and cardiovascular systems, genetic and congenital malformations, chronic poisoning, malignant tumors, allergies, blood diseases, chronic liver diseases. Chronic kidney disease (CKD) is a global public health problem associated with high rates of morbidity and mortality.It affects > 10% of the total population worldwide, which is > 800 million individuals. Environmental nephrotoxic factors causing CKD can be classified as: (1) metals, (2) air pollution, and (3) exposure to other non-metals. Metals used in industrial processes have been shown to contaminate drinking water, food and soil, thereby increasing the risk of exposure among the general population.In the following sections, we summarize the metals that are known to have a nephrotoxic effect, including arsenic, cadmium, lead, mercury and uranium. a prospective observational study in Taiwan reported that people ingesting ≥ 50 μg/L of As in well water had a 30% increased risk of clinically recognized CKD compared to ≤ 10 μg/L. a cross-sectional study showed that urinary Cd was significantly positively associated with renal tubular biomarkers, including N-acetyl-β-D-glucosaminidase and β2-microglobulin, in the general population in China and Korea.recent studies have investigated the relationship between phthalate exposure and renal function including early renal injury markers such as urine albumin/creatinine ratio and urinary β2-microglobulin (β2M) in different populations.a series of epidemiological studies support the hypothesis that long-term environmental exposure to low-dose melamine can increase the risk of adverse kidney outcomes, including urolithiasis, early renal damage, and the deterioration of kidney function in adults. Most of the epidemiological evidence regarding the association between environmental pollution and kidney disease discussed in this study comes from cross-sectional studies.Studying the interaction between environmental pollutants and genetic factors can help to better understand disease susceptibility, thereby reducing the global burden of morbidity and mortality caused by environmental factors.
Chemicals have been identified as a potential risk factor of renal dysfunction. However, studies that consider both multiple chemicals and non-chemical risk factors, such as hypertension, are rare. In this study, we assessed the associations between exposure to several chemicals, including major metals, phthalates, and phenolic compounds, and the albumin-to-creatinine ratio (ACR). A group of Korean adult women in reproductive age (n = 438, aged between 20 and 49 years), who were previously studied for association of several organic chemicals, was chosen for this purpose. We constructed multivariable linear regression models for individual chemicals and weighted-quantile sum (WQS) mixtures, by hypertension status. Among the study population, approximately 8.5% of the participants exhibited micro/macro-albuminuria (ACR ≥30 mg/g), and 18.5% and 3.9% exhibited prehypertension and hypertension, respectively. Blood cadmium and lead levels showed a stronger association with ACR only among women with prehypertension or hypertension. Among organic chemicals, depending on the statistial model, BP-1 and MEHHP showed a significant association regardless of hypertension status, but most associations disappeared in the (pre)hypertensive group. These findings clearly indicate that hypertension status can modify and may potentiate the association of environmental chemicals with ACR. Our observations suggest that low-level environmental pollutant exposure may have potential adverse effects on kidney function among general adult women. Considering the prevalence of prehypertension in the general population, efforts to reduce exposure to cadmium and lead are necessary among adult women to minimize the risk of adverse kidney function.
In today's society, with the continuous development of manufacturing industries and factories related to chemicals, the amount of heavy metals in the inhaled air of humans, water and even food consumption has increased dramatically. The aim of this study was investigation of relationship between exposure to heavy metals on the increased carcinogenicity risk of kidney and bladder. Databases used to for searched were the Springer, Google Scholar, Web of Science, Science Direct (Scopus) and PubMed. At the end after sieve we selected 20 papers. Identify all relevant studies published 2000-2021. The results of this study showed that exposure to heavy metals due to the bio accumulative properties of these metals can cause kidney and bladder abnormalities and provide the basis through various mechanisms for malignant tumors in these organs. Based on result this study, since a limited number of heavy metals including copper, iron, zinc and nickel in very small amounts as micronutrients play a very important role in the function of enzymes and the body cells biological reactions, but exposure to some of them like arsenic, lead, vanadium and mercury will cause irreversible effects on people's health and cause various diseases including cancers of the liver, pancreas, prostate, breast, kidney and bladder. The kidneys, ureter and bladder are the most important organs in the urinary tract on human. According to the result of this study, the duty of this urinary system is to remove toxins, chemicals and heavy metals from the blood, balance electrolytes, excrete excess fluid, produce urine and transfer it to the bladder. This mechanism causes the kidneys and bladder to be highly associated with these toxins and heavy metals, which can lead to various diseases in these two important organs. According to the finding the reducing exposure to heavy metals in various ways can prevent many diseases related to this system and reduce the incidence of kidney and bladder cancers.
To overcome the safety risks and low utilization efficiency of H2O2 in traditional Fenton processes, in situ production of H2O2 by enzymatic reactions has attracted increasing attention recently. In this study, magnetite-immobilized glucose oxidase (MIG) was prepared to catalyze the heterogeneous Fenton reaction for the removal of trichloroethene from water. The successful immobilization of glucose oxidase on magnetite was achieved with a loading efficiency of 70.54%. When combined with substrate glucose, MIG could efficiently remove 5-50 mg L-1 trichloroethene from water with a final removal efficiency of 76.2% to 94.1% by 192 h. This system remained effective in the temperature range of 15-45 °C and pH range of 3.6-9.0. The removal was slightly inhibited by different cations and anions (influencing degree Ca2+ > Mg2+ > Cu2+ and H2PO4 - > Cl- > SO4 2-) and humic acid. Meanwhile, the MIG could be recycled for 4 cycles and was applicable to other chlorinated hydrocarbons. The results of reactive oxidative species generation monitoring and quenching experiments indicated that H2O2 generated by the enzymatic reaction was almost completely decomposed by magnetite to produce ·OH with a final cumulative concentration of 129 μM, which played a predominant role in trichloroethene degradation. Trichloroethene was almost completely dechlorinated into Cl-, CO2 and H2O without production of any detectable organic chlorinated intermediates. This work reveals the potential of immobilized enzymes for in situ generation of ROS and remediation of organic chlorinated contaminants.
Rationale & objective:
Keratin-based hair straightening treatment is a popular hair styling method. The majority of these products in Israel contain glycolic acid derivatives, which are considered safe when used topically. Systemic absorption of these products is possible and anecdotal reports have described kidney toxicity associated with their use. We report a series of cases of severe AKI following use of hair-straightening treatment occurring in Israel over the past several years.
Study design:
Case series.
Setting & participants:
We retrospectively identified 26 patients from 14 medical centers in Israel who developed severe AKI and reported prior treatment with hair-straightening products between 2019 and 2022.
Findings:
The 26 patients described had a median age of 28.5 years (range, 14-58) and developed severe AKI following hair-straightening procedure. The most common symptoms at presentation were nausea, vomiting, and abdominal pain. Scalp rash was noted in 10 (38%) patients. Two patients developed a recurrent episode of AKI following a repeat hair-straightening treatment. Seven patients underwent kidney biopsies that demonstrated intra-tubular calcium oxalate deposition in six and microcalcification in tubular cells in one. In all biopsies, signs of acute tubular injury were present, and an interstitial infiltrate was noted in four cases. Three patients required temporary dialysis.
Limitations:
Retrospective uncontrolled study, small number of kidney biopsies.
Conclusions:
This study describes cases of acute kidney injury with prior exposure to hair straightening treatments. Acute oxalate nephropathy was the dominant finding on kidney biopsies, which may be related to absorption of glycolic acid derivatives and their metabolism to oxalate. This case series suggests a potential under-recognized cause of AKI in the young healthy population. Further studies are needed to confirm this association and to assess the extent of this phenomenon as well as its pathogenesis.
Chronic kidney disease (CKD) is an established global public health problem that represents a key determinant for poor health outcomes. This chapter presents the available evidence of the distribution of CKD in disadvantaged populations across the globe, with a particular focus on the challenges and opportunities in the detection and treatment of CKD among such populations. Social determinants of health are mostly responsible for health inequities, the unfair and avoidable differences in health status seen within and between countries. Socioeconomic status usually encompasses education, occupation, and income as proxies for measurement of social and economic wellbeing. Apart from aging, there are two main determinants that predispose individuals to developing kidney disease and can be considered inherently biological: genetics and developmental programming. There are several challenges which need to be systematcally addressed in the context of CKD in disadvantaged populations.
Prenatal exposure to arsenic (As), cadmium (Cd), mercury (Hg), and lead (Pb) may be nephrotoxic, yet limited studies have examined subclinical kidney injury biomarkers in children. We assessed whether metal exposure in the second trimester (2T), a crucial time of kidney development, is associated with altered urine kidney injury and function biomarkers in preadolescent children. Analyses included 494 children participating in a birth cohort study in Mexico City. Concentrations of As, Cd, and Pb were measured from pregnant women in 2T blood and urine, and Hg in urine only. Kidney biomarkers were measured from children in urine at age 8–12 years. We assessed the associations between individual metals and (1) kidney biomarkers using linear regression and (2) a multi-protein kidney mixture using weighted quantile sum (WQS) regression. Associations of separate urine and blood metal mixtures with individual kidney biomarkers were assessed via WQS. Within the multi-protein mixture, the association with increased urinary As was predominated by urine alpha-1-microglobulin (A1M), interferon gamma-induced protein 10 (IP10), and fatty acid binding protein 1; the association with increased urinary Cd was predominated by A1M, clusterin, and albumin. The urine metal mixture was associated with increased albumin (0.23 ng/mL; 95% confidence interval (CI): 0.10, 0.37), IP10 (0.15 ng/mL; 95% CI: 0.02, 0.28), and cystatin C (0.17 ng/mL; 95% CI: 0.04, 0.31); these associations were mainly driven by urinary As and Cd. We observed null associations between prenatal blood or urine metal mixtures and estimated glomerular filtration rate. Higher prenatal urinary metals, individually and as a mixture were associated with altered kidney injury biomarkers in children. Further research and longer participant follow-up are required to ascertain the risk of kidney disease later in life.
In many cases the social determinants of health need to be assessed through their interaction with environmental factors. This review looks at the impact of physical location and occupation of individuals on their kidney health. It examines the effect of living at high altitude on kidney function and the relationship between extreme cold or hot temperatures and the incidence of kidney injury. It reviews as well the many occupations that have been linked to kidney disease in high-income and low-and-middle-income countries. As a conclusion, this overview proposes preventive recommendations that could be individualized based on weather, altitude, socio-economic level of the country and occupation of the individual.
Bade community in Northern Yobe State has been known as a ‘hotspot’ of chronic kidney disease of unknown source (CKDu). There have been high cases of chronic kidney disease of unknown underlying causes among the population based on hospital records. Despite the various research efforts to uncover the root cause of the disease in the area, the actual aetiology still appeared unknown. This study has reviewed all the research so far carried out regarding the disease so as to provide novel insight that will guide future research. Eleven (11) related peer-reviewed articles that focused directly or indirectly on the disease were surveyed and systematically reviewed. The findings of the relevant published articles totaling (5) were placed within the context of CKDu-related case studies particularly Sri Lankan Nephropathy and other relevant literature. The idea behind this decision is rooted from the similarity of the case as the two affected locales shared in common geography, means of livelihoods (paddy agriculture) and disease pattern. The review revealed that none of the previous investigations has drawn any scientific logical conclusion on the actual aetiology of Bade CKDu. However, previous studies have implicated exposure to heavy metals in various mediums (water and food resources) as potential ‘trigger’ of the disease. Therefore, it is suggested that adopting geospatially-fluent CKDu aetiology scouting approach could help to uncover the underlying cause of the disease in the area. The outcome that will emanate from adopting such type of approach will counter or confirm the existing speculations on the aetiology disease and in turn, will help concerned authorities address the issue.
Acute tubulointerstitial nephritis (ATIN) is a histological diagnosis commonly seen in patients with acute or sub-acute loss of kidney function. This loss of kidney function is often the presenting feature of patients with ATIN. To establish the diagnosis, the clinician must maintain a high index of suspicion for this disease in all patients with acute or sub-acute loss of kidney function. The diagnosis requires careful evaluation of medication history including temporal association with loss of kidney function, evaluation of urine for subtle clues, and often obtaining a kidney biopsy to confirm or refute the diagnosis. Many novel, non-invasive tests are under study but not yet available for clinical use.
Non-immunological causes of tubulointerstitial disease include a wide range of environmental, occupational, and therapeutic exposures. These categories can be roughly divided into heavy metals (e.g., lead, cadmium, uranium), naturally occurring compounds (e.g., aristolochic acid), and therapeutics (e.g., non-steroidal anti-inflammatory drugs, chemotherapeutics agents, lithium, radiation therapy). Additionally, the potential role of toxic exposures in Chronic Kidney Disease of uncertain etiology (CKDu) prevalent in Central America and South Asia is discussed.KeywordsTubulointerstitial nephritisHeavy metalsLeadCadmiumAristolochic acidNephrotoxicityRadiationCKDuMesoamerican nephropathy
Recently published epidemiological and outcome analysis studies have brought to our attention the important role played by acute kidney injury (AKI) in the progression of chronic kidney disease (CKD) to end-stage renal disease (ESRD). AKI accelerates progression in patients with CKD; conversely, CKD predisposes patients to AKI. This research gives credence to older, well-thought-out wisdom that recovery from AKI is often not complete and is marked by residual structural damage. It also mirrors older experimental observations showing that unilateral nephrectomy, a surrogate for loss of nephrons by disease, compromises structural recovery and worsens tubulointerstitial fibrosis after ischemic AKI. Moreover, review of a substantial body of work on the relationships among reduced renal mass, hypertension, and pathology associated with these conditions suggests that impaired myogenic autoregulation of blood flow in the setting of hypertension, the arteriolosclerosis that results, and associated recurrent ischemic AKI in microscopic foci play important roles in the development of progressively increasing tubulointerstitial fibrosis. How nutrition, an additional factor that profoundly affects renal disease progression, influences these events needs reevaluation in light of information on the effects of calories vs. protein and animal vs. vegetable protein on injury and progression. Considerations based on published and emerging data suggest that a pathology that develops in regenerating tubules after AKI characterized by failure of differentiation and persistently high signaling activity is the proximate cause that drives downstream events in the interstitium: inflammation, capillary rarefaction, and fibroblast proliferation. In light of this information, we advance a comprehensive hypothesis regarding the pathophysiology of AKI as it relates to the progression of kidney disease. We discuss the implications of this pathophysiology for developing efficient therapeutic strategies to delay progression and avert ESRD.
The authors aimed to analyze 35 commonly used medicinal plants in India by exploring the possibilities of translocation of lead and cadmium into humans and animals. They collected plant materials from the same sources used by traditional healers and commercial drug manufacturers and estimated lead and cadmium levels in leaf stem bark, roots, and seeds, depending on the medicinal value of the plant portion. The authors determined lead and cadmium content of the digested samples using an atomic absorption spectrophotometer. Lead and cadmium concentrations were higher in aerial parts of the medicinal plants than in the roots. Lead concentration in 54.29% of medicinal plants and cadmium concentration in 77.14% of medicinal plants exceeded the maximum permissible level designated by the World Health Organization. The results indicate that prolonged consumption of such medicinal plants may be detrimental to one's health.
Lead intoxication is a worldwide health problem which frequently affects the kidney. In this work, we studied the effects of chronic lead intoxication (500 ppm of Pb in drinking water during seven months) on the structure, function and biochemical properties of rat proximal tubule cells. Lead-exposed animals showed increased lead concentration in kidney, reduction of calcium and amino acids uptake, oxidative damage and glucosuria, proteinuria, hematuria and reduced urinary pH. These biochemical and physiological alterations were related to striking morphological modifications in the structure of tubule epithelial cells and in the morphology of their mitochondria, nuclei, lysosomes, basal and apical membranes. Interestingly, in addition to the nuclei, inclusion bodies were found in the cytoplasm and in mitochondria. The epithelial cell structure modifications included an early loss of the apical microvillae, followed by a decrement of the luminal space and the respective apposition and proximity of apical membranes, resulting in the formation of atypical intercellular contacts and adhesion structures. Similar but less marked alterations were observed in subacute lead intoxication as well. Our work contributes in the understanding of the physiopathology of lead intoxication on the structure of renal tubular epithelial cell-cell contacts in vivo.
The general methods used to complete measurements of human exposures are identified and illustrations are provided for the cases of indirect and direct methods used for exposure analysis. The application of the techniques for external measurements of exposure, microenvironmental and personal monitors, are placed in the context of the need to test hypotheses concerning the biological effects of concern. The linkage of external measurements to measurements made in biological fluids is explored for a suite of contaminants. This information is placed in the context of the scientific framework used to conduct exposure assessment. Examples are taken from research on volatile organics and for a large scale problem: hazardous waste sites.
Measurements of intake and uptake of cadmium in relation to diet composition were carried out in 57 nonsmoking women, 20-50 years of age. A vegetarian/high-fiber diet and a mixed-diet group were constructed based on results from a food frequency questionnaire. Duplicate diets and the corresponding feces were collected during 4 consecutive days in parallel with dietary recording of type and amount of food ingested for determination of the dietary intake of cadmium and various nutrients. Blood and 24-hr urine samples were collected for determination of cadmium, hemoglobin, ferritin, and zinc. There were no differences in the intake of nutrients between the mixed-diet and the high-fiber diet groups, except for a significantly higher intake of fiber (p < 0.001) and cadmium (p < 0.002) in the high-fiber group. Fecal cadmium corresponded to 98% in the mixed-diet group and 100% in the high-fiber diet group. No differences in blood cadmium (BCd) or urinary cadmium (UCd) between groups could be detected. There was a tendency toward higher BCd and UCd concentrations with increasing fiber intake; however, the concentrations were not statistically significant at the 5% level, indicating an inhibitory effect of fiber on the gastrointestinal absorption of cadmium. Sixty-seven percent of the women had serum ferritin < 30 micrograms/l, indicating reduced body iron stores, which were highly associated with higher BCd (irrespective of fiber intake). BCd was mainly correlated with UCd, serum ferritin, age, anf fibre intake. UCd and serum ferritin explained almost 60% of the variation in BCd.(ABSTRACT TRUNCATED AT 250 WORDS)
To describe trends in blood lead levels for the US population and selected population subgroups during the time period between 1976 and 1991.
Two nationally representative cross-sectional surveys and one cross-sectional survey representing Mexican Americans in the southwestern United States.
Participants in two national surveys that included blood lead measurements: the second National Health and Nutrition Examination Survey, 1976 to 1980 (n = 9832), and phase 1 of the third National Health and Nutrition Examination Survey, 1988 to 1991 (n = 12,119). Also, Mexican Americans participating in the Hispanic Health and Nutrition Examination Survey, 1982 to 1984 (n = 5682).
The mean blood lead level of persons aged 1 to 74 years dropped 78%, from 0.62 to 0.14 mumol/L (12.8 to 2.8 micrograms/dL). Mean blood lead levels of children aged 1 to 5 years declined 77% (0.66 to 0.15 mumol/L [13.7 to 3.2 micrograms/dL]) for non-Hispanic white children and 72% (0.97 to 0.27 mumol/L [20.2 to 5.6 micrograms/dL]) for non-Hispanic black children. The prevalence of blood lead levels 0.48 mumol/L (10 micrograms/dL) or greater for children aged 1 to 5 years declined from 85.0% to 5.5% for non-Hispanic white children and from 97.7% to 20.6% for non-Hispanic black children. Similar declines were found in population subgroups defined by age, sex, race/ethnicity, income level, and urban status. Mexican Americans also showed similar declines in blood lead levels of a slightly smaller magnitude over a shorter time.
The results demonstrate a substantial decline in blood lead levels of the entire US population and within selected subgroups of the population. The major cause of the observed decline in blood lead levels is most likely the removal of 99.8% of lead from gasoline and the removal of lead from soldered cans. Although these data indicate major progress in reducing lead exposure, they also show that the same sociodemographic factors continue to be associated with higher blood lead levels, including younger age, male sex, non-Hispanic black race/ethnicity, and low income level. Future efforts to remove other lead sources (eg, paint, dust, and soil) are needed but will be more difficult than removing lead from gasoline and soldered cans.
A study was conducted of the chemical effects on the human kidney induced by the chronic ingestion of uranium in drinking water. Subjects were divided into two groups: The low-exposure group, whose drinking water was obtained from a municipal water system and contained < 1 microgram uranium/L, and the high-exposure group, whose drinking water was obtained from private drilled wells and contained uranium levels that varied from 2 to 781 micrograms/L. Years of residence varied from 1 to 33 years in the low-exposure group and from 3 to 59 years in the high-exposure group. The indicators of kidney function measured in this study included glucose, creatinine, protein, and beta 2-microglobulin (BMG). The markers for cell toxicity studied were alkaline phosphatase (ALP), gamma-glutamyl transferase (GGT), lactate dehydrogenase (LDH), and N-acetyl-beta-D-glucosaminidase (NAG). Urinary glucose was found to be significantly different and positively correlated with uranium intake for males, females, and pooled data. Increases in ALP and BMG were also observed to be correlated with uranium intake for pooled data. In contrast, the indicators for glomerular injury, creatinine and protein, were not significantly different between the two groups nor was their urinary excretion correlated to uranium intake. These results suggest that at the intakes observed in this study (0.004 microgram/kg to 9 micrograms/kg body wt), the chronic ingestion of uranium in drinking water affects kidney function and that the proximal tubule, rather than the glomerulus, is the site for this interference.
Chinese-herb nephropathy is a progressive form of renal fibrosis that develops in some patients who take weight-reducing pills containing Chinese herbs. Because of a manufacturing error, one of the herbs in these pills (Stephania tetrandra) was inadvertently replaced by Aristolochia fangchi, which is nephrotoxic and carcinogenic.
The diagnosis of a neoplastic lesion in the native urinary tract of a renal-transplant recipient who had Chinese-herb nephropathy prompted us to propose regular cystoscopic examinations and the prophylactic removal of the native kidneys and ureters in all our patients with end-stage Chinese-herb nephropathy who were being treated with either transplantation or dialysis. Surgical specimens were examined histologically and analyzed for the presence of DNA adducts formed by aristolochic acid. All prescriptions written for Chinese-herb weight-reducing compounds during the period of exposure (1990 to 1992) in these patients were obtained, and the cumulative doses were calculated.
Among 39 patients who agreed to undergo prophylactic surgery, there were 18 cases of urothelial carcinoma (prevalence, 46 percent; 95 percent confidence interval, 29 to 62 percent): 17 cases of carcinoma of the ureter, renal pelvis, or both and 1 papillary bladder tumor. Nineteen of the remaining patients had mild-to-moderate urothelial dysplasia, and two had normal urothelium. All tissue samples analyzed contained aristolochic acid-related DNA adducts. The cumulative dose of aristolochia was a significant risk factor for urothelial carcinoma, with total doses of more than 200 g associated with a higher risk of urothelial carcinoma.
The prevalence of urothelial carcinoma among patients with end-stage Chinese-herb nephropathy (caused by aristolochia species) is a high.
Leptospirosis is a re‐emerging infectious disease, affecting both animals and humans worldwide. Multiple organ involvement
may be encountered in leptospirosis, and early renal involvement is very common, characterized by tubulo‐interstitial nephritis
and tubular dysfunction. All 12 patients diagnosed in Chang Gung Memorial Hospital (Taiwan) between 1997 and 1999 had acute
renal failure, with five patients requiring dialysis. Leptospira shermani is the main serovar encountered in Taiwan, and penicillin may dramatically rescue patients from multiple organ failure provided
it is given early. To understand the mechanism behind tubular injuries by leptospira infection, outer membrane proteins (OMPs)
extracted from pathogenic leptospira were given to tubular cells in culture. Our in vitro experiment showed that OMPs of pathogenic leptospira activate nuclear NFκB binding and stimulate downstream inducible nitric oxide (iNOS), monocyte chemoattractant protein‐1 (MCP‐1) and tumor necrosis
factor‐α (TNF‐α) expression. These results indicate that leptospiral infection may induce tubulo‐interstitial nephritis through a toxic component
in the outer membrane followed by expression of inflammatory genes.
Aristolochic acid nephropathy (AAN), a progressive renal interstitial fibrosis frequently associated with urothelial malignancies, was initially reported in a Belgian cohort of more than 100 patients after the intake of slimming pills containing a Chinese herb, Aristolochia fangchi. Although botanicals known or suspected to contain aristolochic acid (AA) were no longer permitted in many countries, several AAN cases were regularly observed all around the world. The incidence of AAN is probably much higher than initially thought, especially in Asia and the Balkans. In Asian countries, where traditional medicines are very popular, the complexity of the pharmacopoeia represents a high risk for AAN because of the frequent substitution of the botanical products by AA-containing herbs. In the Balkan regions, the exposure to AA found in flour obtained from wheat contaminated with seeds of Aristolochia clematitis could be responsible for the so-called Balkan-endemic nephropathy. Finally, despite the Food and Drug Administration's warnings concerning the safety of botanical remedies containing AA, these herbs are still sold via the Internet.
Objective. —To examine the association between silica exposure and end-stage renal disease (ESRD). Design. —Retrospective cohort study. Participants. —A cohort of 2412 white male gold miners was studied. Eligible gold miners worked underground for at least 1 year between 1940 and 1965 in a South Dakota gold mine and were alive on January 1,1977. Of primary interest was exposure to silica. Methods. —The ESRD Program Management and Medical Information System (PMMIS) was used to identify members of the gold mine cohort who had treated ESRD and to create a US rate file for treated ESRD. The ESRD incidence among the gold miners was compared with that in the US population. Results. —Based on the 11 cohort members identified with treated ESRD, the risk for ESRD in the cohort was elevated (standardized incidence ratio [SIR], 1.37; 95% confidence interval [CI], 0.68-2.46). The risk was greatest for nonsystemic ESRD (ESRD caused by glomerulonephritis or interstitial nephritis) for which the SIR was 4.22 (95% CI, 1.54-9.19), increasing to 7.70 (95% CI, 1.59-22.48) among workers with 10 or more years of employment underground. Conclusions. —To our knowledge this is the first epidemiologic study to examine ESRD incidence in an occupational cohort. This study provides evidence that silica exposure is associated with an increased risk for ESRD, especially ESRD caused by glomerulonephritis. This study also demonstrates the usefulness of the ESRD PMMIS to assess ESRD risk among cohorts exposed to potential nephrotoxins.
• Nephrotoxic reaction occurred after inhalation exposure to methylene chloride. This exposure is associated with acute renal failure, myoglobinuria, hypocomplementemia, and liver enzyme elevations. Pathologic specimens, both light and electron microscopic, demonstrate renal tubular damage. We conclude that methylene chloride may have potential as both a hepatotoxic and nephrotoxic agent when inhaled at high concentrations over an extended period of time.
(Arch Intern Med 1985;145:145-146)
Dibromochloropropane (DBCP) was developed in the early 1950s as a highly efficient anti-helminth that penetrates the soil and kills microscopic worms that attack the root systems of plants. The first indication of a problem with DBCP was when exposure to laboratory rats resulted in testicular atrophy. Prolonged exposure resulted in liver and kidney function failure. Though no longer produced in North America, the product is currently produced in several Central and South American countries. Many agricultural workers have succumbed to kidney disorders after prolonged exposure to this pesticide. This case study focuses on one specific village (village ‘X’) in an underdeveloped Latin American country where the only employment is in the agricultural industry. Of the 134 family units living in village ‘X’, 65 workers have been diagnosed with chronic kidney disease. When the creatinine level reaches 1.7 mg/dl, the workers are released and placed on terminal disability. Eight of these workers have died from complications of chronic renal insufficiency, within the past five years. In March 2005, 26 diagnosed workers were interviewed and the following demographic statistics were obtained: mean age was 42.7 years (δ=2.73 years), age released from work for high creatinine levels was 38.7 years (δ=2.59 years), and years worked before being released was 16.9 years (δ=2.60 years). In January 2006, blood samples from 72 subjects from each of the following four groups were taken: not employed by the plantation (male), not employed by the plantation (female), workers currently employed (male) whose creatinine levels were within the plantations criteria, and former workers (male) medically released for creatinine levels equal to or above 1.7 mg/dl. The medically released men had creatinine levels significantly higher than the other three groups. Forty-five current workers and medically released workers volunteered to participate in follow-on blood samples and sonograms. Again creatinine levels for the medically released workers were significantly higher than those who had not been released. Sonograms showed statistically significant smaller kidney volumes for those who had been medically released than for those who had not been medically released. Sonograms and analysis also determined that the medically released workers do have significant kidney damage. It can be inferred from this case study that high creatinine levels in the workers in village ‘X’ are likely directly attributed to the agricultural company's continued use of the chemical DBCP. It is the intention of the researchers that a longitudinal study be conducted on medically released workers whom have been exposed to this specific chemical. This study should include kidney tissue biopsy. It is also recommended that international health and safety institutions take appropriate action to ban the production and use of DBCP.
End-stage kidney disease overwhelms health services in Central America. We determined prevalences of decreased kidney function in distinct populations in the most affected region of Nicaragua.
Cross-sectional survey.
Total populations aged 20-60 years of 5 villages in Northwest Nicaragua: mining/subsistence farming (elevation, 100-300 m above sea level), banana/sugarcane (100-300 m), fishing (0-100 m), services (0-100 m), and coffee (200-675 m); 479 men and 617 women (83% response).
Village; participant sex, age, and occupation; conventional chronic kidney disease risk factors.
Serum creatinine (SCr) values greater than laboratory reference range for sex, estimated glomerular filtration rate <60 mL/min/1.73 m(2), proteinuria stratified in the low (dipstick protein excretion, 30-300 mg/dL) and high (>300 mg/dL) range.
Prevalences of abnormal SCr levels: 18% (of all men) and 5% (of all women); in the mining/subsistence farming village, 26% and 7%; banana/sugarcane, 22% and 6%; fishing, 13% and 4%; services, 0% and 1%; and coffee, 7% and 0%. Prevalences of estimated glomerular filtration rate <60 mL/min/1.73 m(2): 14% (of all men) and 3% (of all women); in the listed villages, 19% and 5%, 17% and 4%, 10% and 2%, 0% and 0%, and 7% and 0%, respectively. Proteinuria, predominantly in the low range, affected 14% and 11% of all men and women without marked differences between villages. By occupation, abnormal SCr levels occurred in 31% and 24% of male and female agricultural workers at 100-300 m above sea level, but not at higher altitudes, and also was high in male artisans (43%), construction workers (15%), and miners (14%). In logistic regression models, for the banana/sugarcane and mining/subsistence farming villages, high blood pressure and age were significant predictors of abnormal SCr levels in men, and for mining/subsistence farming, age in women.
Causality is not addressed.
In some Nicaraguan villages and population segments, men in particular show a high prevalence of decreased kidney function of unknown origin, possibly environmental or occupational.
Inorganic arsenic has been linked to decreased kidney function through oxidative damage. Arsenic methylation is believed to be a pathway for arsenic metabolism. Lycopene is an antioxidant that reduces oxidative stress; however, the association between urinary arsenic species, plasma lycopene level, and chronic kidney disease (CKD) has seldom been evaluated.
Case-control study.
125 patients with CKD and 229 controls were recruited from a hospital-based pool.
Urinary arsenic species and plasma lycopene level.
CKD was defined as estimated glomerular filtration rate (eGFR) less than 60 mL/min/1.73 m(2), calculated by using the Modification of Diet in Renal Disease Study equation. Plasma lycopene was measured by means of high-performance liquid chromatography. Urinary arsenic species, including arsenite, arsenate, monomethylarsonic acid, and dimethylarsinic acid, were determined by means of high-performance liquid chromatography and hydride generator-atomic absorption spectrometry.
Lycopene level was associated positively with eGFR, and participants with a high serum lycopene level had a significant, inverse association with CKD (odds ratio, 0.41; 95% confidence interval, 0.21 to 0.81). Total arsenic level was associated significantly with CKD in a dose-response relationship, especially in participants with a total arsenic level greater than 20.74 compared with 11.78 microg/g creatinine or less (odds ratio, 4.34; 95% confidence interval, 1.94 to 9.69). Furthermore, participants with a high urinary total arsenic level or participants with a low percentage of dimethylarsinic acid had a positive association with CKD when their plasma lycopene level was low.
Because of the single spot evaluation of plasma antioxidants and urinary arsenic species and the small sample size, statistical significance should be interpreted with caution.
This study shows that high urinary total arsenic or low plasma lycopene level is associated positively with CKD. Results suggest that the capacity for arsenic methylation may be associated with CKD in individuals who ingest low arsenic levels in drinking water and also have a low plasma lycopene level.
Acute kidney injury (AKI) is common in hospitalized patients. The impact of AKI on long-term outcomes is controversial.
Systematic review and meta-analysis.
Persons with AKI.
MEDLINE and EMBASE databases were searched from 1985 through October 2007. Original studies describing outcomes of AKI for patients who survived hospital discharge were included. Studies were excluded from review when participants were followed up for less than 6 months.
AKI, defined as acute changes in serum creatinine level or acute need for renal replacement therapy.
Chronic kidney disease (CKD), cardiovascular disease, and mortality.
48 studies that contained a total of 47,017 participants were reviewed; 15 studies reported long-term data for patients without AKI. The incidence rate of mortality was 8.9 deaths/100 person-years in survivors of AKI and 4.3 deaths/100 patient-years in survivors without AKI (rate ratio [RR], 2.59; 95% confidence interval, 1.97 to 3.42). AKI was associated independently with mortality risk in 6 of 6 studies that performed multivariate adjustment (adjusted RR, 1.6 to 3.9) and with myocardial infarction in 2 of 2 studies (RR, 2.05; 95% confidence interval, 1.61 to 2.61). The incidence rate of CKD after an episode of AKI was 7.8 events/100 patient-years, and the rate of end-stage renal disease was 4.9 events/100 patient-years.
The relative risk for CKD and end-stage renal disease after AKI was unattainable because of lack of follow-up of appropriate controls without AKI.
The development of AKI, defined as acute changes in serum creatinine level, characterizes hospitalized patients at increased risk of long-term adverse outcomes.
Chronic kidney disease (CKD) is a public health threat in the United States, with increasing prevalence, high costs, and poor outcomes. More widespread effort at the prevention, early detection, evaluation, and management of CKD and antecedent conditions could prevent complications of decreased kidney function, slow the progression of kidney disease to kidney failure, and reduce cardiovascular disease risk. In 2006, the Centers for Disease Control and Prevention (CDC) launched an initiative on CKD. As part of this initiative, the CDC convened an expert panel to outline recommendations for a comprehensive public health strategy to prevent the development, progression, and complications of CKD in the United States. The panel adapted strategies for primary, secondary, and tertiary prevention for chronic diseases to the conceptual model for the development, progression, and complications of CKD; reviewed epidemiological data from US federal agencies; and discussed ways of integrating public health efforts from various agencies and organizations. The panel recommended a 10-point plan to the CDC to improve surveillance, screening, education, and awareness directed at 3 target populations: people with CKD or at increased risk of developing CKD; providers, hospitals, and clinical laboratories; and the general public. Cooperation among federal, state, and local governmental and private organizations will be necessary to carry out these recommendations.
The aim of this study was to clarify whether consumption of cadmium (Cd)-polluted rice or Jinzu River water exerted any influence on the occurrence of renal tubular dysfunction and/or Itai-itai disease. From the participants of health examinations conducted in 1967 and 1968, 3,078 subjects who had resided for >30 years in the present hamlet and were aged >50 years were selected as the target population and were divided according to their residence in 55 hamlets. In a multiple regression analysis, the regression coefficients between rice-Cd concentration and prevalence of abnormal urinary findings (proteinuria, glucosuria, or proteinuria with glucosuria) or patients with Itai-itai disease were statistically significant between both sexes. The correlation between the prevalence of users of Jinzu River water and the occurrence of glucosuria in men as well as abnormal urinary findings in women was not statistically significant. We surmise that eating Cd-polluted rice and drinking and/or cooking with Jinzu River water influenced the occurrence of Itai-itai disease. The occurrence of renal tubular dysfunction is likely to have also been influenced by both factors, with eating Cd-polluted rice having a greater impact on the occurrence of renal tubular dysfunction as compared to drinking and/or cooking with Jinzu River water.
Balkan endemic nephropathy (BEN), originally described in the late 1950s as a chronic tubulointerstitial kidney disease, is identified by its unique epidemiological features. The most remarkable characteristic of BEN is the focal topographical nature that characterizes its occurrence at the global, national, and even household level. BEN affects only certain endemic rural foci along tributaries of the Danube River in the Balkan countries of Bosnia, Bulgaria, Croatia, Romania, and Serbia. The spatial distribution has remained astonishingly unchanged with time because the disease affects the same endemic clusters as 50 years ago. The natural course of the disease is characterized by universal development of end-stage renal disease and the frequent development of upper urinary tract tumors, posing a substantial disease burden to the afflicted areas. The greatest challenge in the study of BEN has been the elucidation of its cause. The unique features of the disease, in particular its endemic nature and the long incubation period required for the disease to develop, have led to the proposal that BEN represents a unique environmental disease. The quest for the responsible environmental factor has been long and diverse, and although no definitive answer has been provided to date, converging lines of evidence support the theory that long-term consumption of food contaminated with aristolochic acid underlies the pathogenesis of BEN. The present review describes the evolution of our knowledge of BEN in relation to the development of the main theories for its pathogenesis.
"Minamata disease" was found among the residents along Minamata bay contaminated with the effluent from an industrial plant using mercury. The patients were suffering from various neurologic disorders primarily due to organic mercury poisoning. Evidence is described of renal tubular dysfunction associated with this disease by the immunochemical demonstration or renal tubular epithelial antigen and beta-2-microglobulin in the urine. Nineteen patients with Minamata disease and 35 diseased and healthy control subjects were examined. The contents of urinary renal tubular epithelial antigen and beta-2-microglobulin, and the ratios of these proteins to albumin in individuals with Minamata disease were significantly different from the levels in healthy control subjects (P less than 0.05) were identical to those found in patients with tubular and the values, proteinuria. These results indicate that Minamata disease is associated with renal tubular dysfunction, and also suggest that these procedures would be useful for screening the nephrotoxicity in the environmental exposure of heavy metals.
Eight sailors on board the Asiafreighter were exposed to arsine that had escaped from a cylinder in the cargo hold. Four suffered severe toxicity and within a few hours had developed fever, weakness, nausea, vomiting, diarrhoea, abdominal pain, and haemoglobinuria. These patients had pronounced intravascular haemolysis, which in one patient was complete. This patient was also stuporose and anoxic, a condition attributed to failure of oxygen transport and sludging of red cell debris in the cerebral and pulmonary circulations, but he regained a normal level of consciousness after exchange transfusion. Evidence of marrow depression was present: the reticulocyte response to the haemolysis was poor and there was a thrombocytopenia. All four patients developed renal failure, one being totally anuric for five weeks. Two patients developed peripheral neuropathy, and one was still severely disabled six months after the incident. The other four patients had a similar, though less severe, illness.
Fourteen workers in an isopropyl alcohol packaging plant became ill after accidental exposure to carbon tetrachloride. In four, renal failure or hepatitis developed. Isopropyl alcohol potentiation of carbon tetrachloride toxicity has been shown previously only in rats. Acetone, a product of isopropyl alcohol metabolism, is a major potentiator of carbon tetrachloride toxicity. Workers had elevated levels of acetone in samples of expired alveolar gas and thus were metabolically predisposed to carbon tetrachloride injury. Stricter limits for industrial carbon tetrachloride exposure should be established where concomitant isopropyl alcohol use occurs.
(JAMA 236:1853-1856, 1976)
This report deals with severe myoglobinuria and acute renal failure necessitating haemodialysis after acute exposure to toluene in a 45 yr old labourer in a paint factory. A low BUN/creatinine ratio was noted, initially about 5. This ratio increased rather rapidly and was already about 13 just before his first haemodialysis on the fifth hospital day. This increase to the usual levels of over 10 seems to indicate that the muscle damage was acute and transitory followed by acute tubular necrosis without further disproportionate creatininaemia. It seems that the myoglobinuria was the direct cause of the renal failure which was rapidly transformed into a nonoliguric form by the early administration of intravenous fluids, osmotic diuretics, and frusemide. Recovery was complete.
Lead may exert toxic effects on several organ systems, but those in the kidney are the most insidious. Acute lead nephropathy is characterized by proximal tubular dysfunction with the development of a Fanconi-type syndrome, alterations in mitochondrial structure and the development of cytosolic and nuclear inclusion bodies. Intracellular lead is associated with specific high affinity proteins and can also bind to metallothionein. Chronic lead nephropathy is irreversible and is typically accompanied by interstitial fibrosis, both hyperplasia and atrophy of the tubules, glomerulonephritis and, ultimately, renal failure. In addition, lead produces renal neoplasms in experimental animals. Chronic lead exposure is also implicated in the development of saturnine gout and hypertension. The metal interacts with renal membranes and enzymes and disrupts energy production, calcium metabolism, glucose homeostasis, ion transport processes and the renin-angiotensin system. This review summarizes the biochemical effects of lead on the kidney to understand the mechanisms of lead-induced nephropathy and other associated disorders.
In this unusual case of trichloroethylene (TCE) poisoning the patient developed acute renal failure with few of the other features of TCE toxicity. Nephrotoxicity is thought to be a rare complication of TCE toxicity and only one report of proved acute tubular necrosis is available.
Kidney International aims to inform the renal researcher and practicing nephrologists on all aspects of renal research. Clinical and basic renal research, commentaries, The Renal Consult, Nephrology sans Frontieres, minireviews, reviews, Nephrology Images, Journal Club. Published weekly online and twice a month in print.
Nephrotoxic reaction occurred after inhalation exposure to methylene chloride. This exposure is associated with acute renal failure, myoglobinuria, hypocomplementemia, and liver enzyme elevations. Pathologic specimens, both light and electron microscopic, demonstrate renal tubular damage. We conclude that methylene chloride may have potential as both a hepatotoxic and nephrotoxic agent when inhaled at high concentrations over an extended period of time.
Twenty one marine recruits in three training programs at the Marine Corps Recruit Depot, Parris Island, South Carolina, were prospectively studied for one week for the presence of myoglobinemia and development of clinical rhabdomyolysis. Myoglobinemia was found in two thirds of the recruits at least once during the study period despite the absence of clinical symptoms. Serum myoglobin value ranged from 0.30 to 3.60 μg/ml and correlated poorly with serum levels of creatine phosphokinase, glutamic oxaloacetic transaminase, and lactic dehydrogenase. With the exception of one recruit believed to have subclinical exertional rhabdomyolysis, those recruits in apparently poorer physical condition had higher average daily serum myoglobin and enzyme levels. Eleven marine recruits who were hospitalized for exertional rhabdomyolysis are compared to the asymptomatic recruits. Serum myoglobin and enzyme concentrations were 10 to 100 times greater in the hospitalized men than in asymptomatic recruits.
Barry, P. S. L., and Mossman, D. B. (1970).Brit. J. industr. Med.,27, 339-351. Lead concentrations in human tissues. A study of 69 subjects at post-mortem, four of whom had histories of occupational exposure to lead, demonstrated a marked difference in the lead concentrations between bones and soft tissues.The soft tissues of infants and young children contained low concentrations of lead, varying from 0·01 ppm in muscle to 0·46 ppm in liver. By the end of the second decade of life the concentrations of lead in most of the soft tissues showed values varying between 0·06 ppm in muscle and 1·35 ppm in liver and thereafter did not increase with advancing age.The concentrations of lead in bone were considerably greater than those in soft tissues, being about 1 ppm in infants and young children and increasing to more than 40 ppm in persons over the age of 50 years. Adult male bones contained more lead than adult females by a ratio of 3 to 2, and in both sexes the long bone contained concentrations of lead two and a half times that observed in the flat bone. No marked difference was noted in lead concentrations between the corresponding soft tissues of the two sexes.From the findings it appeared that in adults the total body burden varied widely from subject to subject. Nearly 95% was represented by the lead content in bone, of which more than 70% was in dense bone. A far lower concentration of lead was found in the bones of children than in those of adults, but there was less divergence in the lead concentrations in the soft tissues.The total lead content in the soft tissues of the majority of the subjects investigated appeared to be relatively stable and did not correlate with levels in bone.The four male subjects with known occupational exposure to lead had greater concentrations of lead in bone than those with no known occupational exposure, but no difference was noted in the soft tissues between the two groups, with the exception of the most heavily exposed subject in whom concentrations of lead in the brain were over 4 ppm and in the aorta 28 ppm.Hair and nails were found to contain relatively high concentrations of lead, approximately 20 ppm; some significance may be attached to this finding in a medico-legal context.The findings of this study would suggest that the present intake of lead among the general population is no greater than in the past.
This paper is concerned with quantifying the major sources of cadmium in the European Community and assessing the relative significance of such inputs to the environmental compartments, air, land, and water. The methodology involved identification of potential sources of cadmium, including natural processes, as well as those associated with human activities. This was followed by a review of any emission studies of these processes and subsequent estimation of an emission factor for each source. The emission factor was applied to the most recent production or consumption data for the process in question to obtain an estimate of the annual discharge. The steel industry and waste incineration, followed by volcanic action and zinc production, are estimated to account for the largest emissions of atmospheric cadmium in the region. Waste disposal results in the single largest input of cadmium to land; the quantity of cadmium associated with this source is greater than the total from the four other major sources--coal combustion, iron and steel production, phosphate fertilizer manufacture and use, and zinc production. The characterization of cadmium inputs to aquatic systems is incomplete but of the sources considered, the manufacture of cadmium-containing articles accounts for the largest discharge, followed by phosphate fertilizer manufacture and zinc production.
The biological half-time of cadmium in the blood of previously exposed workers was estimated after the cessation of exposure. Five men were followed for a period of 10 to 13 years. One-compartment and two-compartment exponential elimination models were used to describe the decrease in blood cadmium levels over time. The best fit to the observed data was obtained with a two-compartment model. The half-times estimated from this model ranged from 75 to 128 d for the fast component and from 7.4 to 16.0 years for the slow component. The results confirm that there is a very long whole-body biological half-time for cadmium, and the estimated half-times are similar to those obtained with different methods.
Summary— The non-essential trace metal cadmium may cause major pathological effects on the kidneys. A group of coppersmiths who have been chronically exposed to cadmium poisoning was systematically studied over a 6-year period.
The stone prevalence in the group is now just under 40% as compared with 3.5% in a general population. The blood cadmium levels have remained persistently elevated despite removal of the cadmium source.
The measurement of cadmium as a means of monitoring chronic poisoning has been undertaken in terms of the prospective study in the coppersmiths and also in its relationship to other trace metals, namely serum zinc and copper. Urologists should be aware of the possibility of cadmium poisoning.
Kidneys of six wild-trapped, adult Norway rats with high agglutinating titers to Leptospira icterohaemmorhagiae were examined ultrastructurally. Although many leptospires were seen in the lumen of proximal kidney tubules, few changes in epithelial cells of this region were found. The predominant lesion in chronic rat leptospirosis was diffuse interstitial nephritis. Principal kidney lesions were proximal tubule cell basement membrane thickening with or without the presence of granular particles, and an interstitial response that varied from mixed hypercellular to chiefly plasmacytic. The association of leptospires with membrane-bound protein droplets of the proximal kidney tubules may be important in the maintenance of the chronic carrier state in rat leptospirosis.
Two similar cases of rapidly progressive fibrosing interstitial nephritis in young women who followed the same slimming regimen prompted us to conduct an epidemiological survey of the nephrology centres of Brussels and to further investigate the exact nature of this slimming treatment. Seven other women under the age of 50 in terminal or preterminal renal failure were admitted for dialysis in 1991 and 1992. They had all followed a slimming regimen in the same medical clinic. Renal biopsy samples in eight of the nine cases showed extensive interstitial fibrosis without glomerular lesions. Two of the patients were seen for the first time in terminal renal failure and were started immediately on dialysis. For the seven other women, the nephropathy was characterised by a rapid deterioration in renal function, with initial serum creatinine doubling within about 3 months. The clinic had specialised in slimming treatments for the previous 15 years without any problems. In May, 1990, therapy was changed, with the introduction of two Chinese herbs (Stephania tetrandra and Magnolia officinalis). In June, 1992, three of twenty-five randomly selected women who had followed the same regimen during at least 3 months from 1990 had impaired renal function. Chemical analysis of some brands of these Chinese herbs did not show nephrotoxic contaminants of fungal or plant origin (ochratoxin or aristolochic acid) or adulteration by diuretics or antiinflammatory drugs. However, the medicinal preparation of the capsules taken by patients had different alkaloid profiles from those expected in Chinese plants. The striking relation between a specific type of fibrosing interstitial nephritis in young women and a slimming treatment involving Chinese herbs adds support to the arguments against uncontrolled therapy with herbal preparations.
Kidney International aims to inform the renal researcher and practicing nephrologists on all aspects of renal research. Clinical and basic renal research, commentaries, The Renal Consult, Nephrology sans Frontieres, minireviews, reviews, Nephrology Images, Journal Club. Published weekly online and twice a month in print.
This study is the first cytogenetic investigation of healthy relatives of patients with Balkan endemic nephropathy (BEN) who were born in nonendemic areas. Characteristics of BEN No. 3 chromosomal anomalies (extremely high frequencies of 3q25 homologue discordance - 68.5 +/- (SD) 5.03% vs. 6.65 +/- 0.95% in controls, p < 0.001; chromosome breaks at 3q25 band - 0.79 +/- 0.25% vs. 0.01% in controls, p < 0.001; structural aberrations affecting 3q25 band), very high frequency of acquired chromosomal aberrations (5.74 +/- 0.64% vs. 1.72 +/- 0.3% in controls) and a family history with 1 or 2 BEN parents were identified in 5 relatives. It is proposed that they are at high risk for developing the disease and that a genetic mechanism might be involved in the etiology of BEN.
To examine the association between silica exposure and end-stage renal disease (ESRD).
Retrospective cohort study.
A cohort of 2412 white male gold miners was studied. Eligible gold miners worked underground for at least 1 year between 1940 and 1965 in a South Dakota gold mine and were alive on January 1,1977. Of primary interest was exposure to silica.
The ESRD Program Management and Medical Information System (PMMIS) was used to identify members of the gold mine cohort who had treated ESRD and to create a US rate file for treated ESRD. The ESRD incidence among the gold miners was compared with that in the US population.
Based on the 11 cohort members identified with treated ESRD, the risk for ESRD in the cohort was elevated (standardized incidence ratio [SIR], 1.37; 95% confidence interval [CI], 0.68-2.46). The risk was greatest for nonsystemic ESRD (ESRD caused by glomerulonephritis or interstitial nephritis) for which the SIR was 4.22 (95% CI, 1.54-9.19), increasing to 7.70 (95% CI, 1.59-22.48) among workers with 10 or more years of employment underground.
To our knowledge this is the first epidemiologic study to examine ESRD incidence in an occupational cohort. This study provides evidence that silica exposure is associated with an increased risk for ESRD, especially ESRD caused by glomerulonephritis. This study also demonstrates the usefulness of the ESRD PMMIS to assess ESRD risk among cohorts exposed to potential nephrotoxins.
Renal diseases are conventionally classified into acute and chronic disorders. We questioned whether acute, reversible, renal insults may be induced to incite a chronic scarring process, employing as an acute insult the glycerol model of heme protein-induced renal injury.
Rats were subjected to weekly injections of hypertonic glycerol for up to six months. Renal function was serially determined, and the effect of such insults on renal histology and renal expression of collagen and fibrogenic cytokines was assessed.
After the first injection of glycerol, which, expectedly, induced a prompt fall in the glomerular filtration rate (GFR), subsequent injections encountered a remarkable renal resistance in that the fall in GFR was markedly blunted. This resistance to acute decline in renal function in rats subjected to repetitive injections of glycerol was accompanied by less necrosis and apoptosis of renal tubular epithelial cells after such injections. The attenuation in the fall in GFR in response to repetitive exposure to glycerol-induced heme protein injury was maintained for up to six months. A progressive decline in GFR appeared after three months and was accompanied by histologic tubulointerstitial injury, the latter assessed at six months. These kidneys demonstrated up-regulation of collagen I, III, and IV in conjunction with increased expression of the oxidant-inducible, chemotactic cytokine, monocyte chemoattractant protein-1 (MCP-1), and the oxidant-inducible, fibrogenic cytokine, transforming growth factor-beta1 (TGF-beta1). The exposure of the kidney to a single injection of hypertonic glycerol increased the expression of both cytokines some three to five days following this exposure, while the exposure of NRK 49F cells in culture to an iron-dependent model of oxidative stress also increased expression of TGF-beta1 and collagen mRNAs.
We conclude that this nephrotoxic insult, repetitively administered, encounters a resistance in the kidney such that the expected fall in GFR does not occur. However, with time, such resistance is accompanied by a decrease in GFR, the latter associated with chronic tubulointerstitial disease. Thus, a long-term cost is exacted, either along with, or as a consequence of, such resistance. We suggest that chronic up-regulation of such oxidant-inducible genes such as TGF-beta1 and MCP-1 contributes to tubulointerstitial disease, and iron-mediated oxidative stress may directly induce TGF-beta1.
Chinese herbs nephropathy (CHN), a unique type of nephropathy has been associated with the intake of weight-reducing pills containing the Chinese herb Aristolochia fangchi. Moreover, an association between the use of A. fangchi and urothelial cancer in CHN patients has been reported indicating that aristolochic acid (AA) the major alkaloid of A. fangchi might be the causal agent. Similarities of CHN to the Balkan endemic nephropathy (BEN) have led to the hypothesis of a common etiological agent for both diseases. Evidence has accumulated that BEN is an environmentally-induced disease strongly associated with the fungal mycotoxin ochratoxin A (OTA). Both, AA and OTA are nephrotoxic and carcinogenic and induce the formation of DNA adducts. As OTA has been suspected as fungal contaminant in the herbal batches used for the preparation of the weight-reducing pills we analysed tissues from CHN patients by the 32P-postlabeling procedure for the presence of DNA adducts related to both OTA and AA exposure. Whereas, AA-specific DNA adducts were detected in all five urinary tract tissues from five patients (total RAL: 32-251 adducts per 10(9) nucleotides), OTA-related DNA adducts were detectable in two kidneys and one ureter only (total RAL: 1.5-3.7 adducts per 10(9) nucleotides). Thus, OTA-related DNA adduct levels were about 50 times lower than AA-DNA adduct levels. In female and male rats that were treated with the slimming regimen in the same way like the CHN patients except that the amount of Chinese herbs was 10 times higher, AA-DNA adducts were found in kidney tissues (total RAL ranging from 51 to 83 adducts per 10(9) nucleotides) but adducts derived from OTA were not observed. These results demonstrate that OTA-related DNA adducts do not play a key role in CHN or CHN-associated urothelial cancer.
In the present work, 199 patients with leprosy who underwent autopsy between 1970 and 1986 were retrospectively studied to determine the prevalence, types, clinical characteristics, and etiologic factors of renal lesions (RLs) in leprosy. Patients were divided into two groups: 144 patients with RLs (RL+) and 55 patients without RLs (RL-). RLs observed in 72% of the autopsied patients were amyloidosis (AMY) in 61 patients (31%), glomerulonephritis (GN) in 29 patients (14%), nephrosclerosis (NPS) in 22 patients (11%), tubulointerstitial nephritis (TIN) in 18 patients (9%), granuloma in 2 patients (1%), and other lesions in 12 patients (6%). AMY occurred most frequently in patients with lepromatous leprosy (36%; nonlepromatous leprosy, 5%; P < 0.01), recurrent erythema nodosum leprosum (33%; P < 0.02), and trophic ulcers (27%; 0.05 < P < 0.10). Ninety-seven percent of AMY was found in patients with lepromatous leprosy, 88% showed recurrent trophic ulcers, and 76% presented with erythema nodosum leprosum. NPS was found in older patients with arterial hypertension, neoplastic diseases, infectious diseases, and vasculitis associated with GN. Most patients with AMY presented with proteinuria (95%) and renal failure (88%). The most frequent causes of death were renal failure in patients with AMY (57%), infectious diseases in patients with GN (41%) and TIN (45%), and cardiovascular diseases in patients with NPS (41%). No difference in survival rates was observed among RL- patients and those with AMY, GN, NPS, or TIN.
Environmental exposure to cadmium may cause kidney damage and tubular proteinuria. We investigated the relationship between low-level cadmium exposure and end-stage renal disease (ESRD), indicated by renal replacement therapy (RRT), in a Swedish population environmentally or occupationally exposed to cadmium. Based on records of all persons in the population previously or presently employed in cadmium-battery production or residing in cadmium-polluted areas near the battery plants, we defined exposure as high (occupational), moderate (domicile < 2 km from a plant), low (domicile 2 to 10 km from a plant), or no exposure (domicile > 10 km from a plant). Comprehensive data were available for all individuals undergoing RRT since 1978. The annual incidence of RRT increased from 41 per million in the age group 20 to 29 years to 243 per million in the age group 70 to 79 years and was greater in a priori-defined populations with cadmium exposure. Adjusting for age and sex gave an increased Mantel-Haenszel rate ratio (MH-RR) of 1.8 (95% confidence interval [CI], 1.3 to 2.3) for RRT in the cadmium-exposed population compared with the unexposed group; the MH-RR was even higher for women (MH-RR, 2.3; 95% CI, 1.5 to 3.5). Directly age-standardized rate ratios for RRT and cadmium exposure increased from 1.4 (95% CI, 0.8 to 2.0) in the low-exposure group to 1.9 (95% CI, 1.3 to 2.5) and 2.3 (95% CI, 0.6 to 6.0) in the moderate- and high-exposure groups, respectively. We conclude that exposure to occupational or relatively low environmental levels of cadmium appears to be a determinant for the development of ESRD.
Concern has been voiced about exposure to mercury (Hg) from dental amalgam fillings, and there is a need to assess whether this leads to signs of nephrotoxicity.
A total of 101 healthy adults (80 males and 21 females) were included in this study. The population as grouped into those having amalgam fillings (39 males and 10 females) and those without (41 males and 11 females). Hg was determined in blood, urine, hair and nails to assess exposure. Urinary excretion of beta2-microglobulin (beta2M), N-acetyl-beta-D-glucosaminidase (NAG), gamma-glutamyltransferase (gammaGT) and alkaline phosphatase (ALP) were determined as markers of tubular damage. Albuminuria was assayed as an early indicator of glomerular dysfunction. Serum creatinine, beta2M and blood urea nitrogen (BUN) were determined to assess glomerular filtration.
Hg levels in blood and urine were significantly higher in persons with dental amalgam than those without; in the dental amalgam group, blood and urine levels of Hg significantly correlated with the number of amalgams. Urinary excretion of NAG, gammaGT and albumin was significantly higher in persons with dental amalgam than those without. In the amalgam group, urinary excretion of NAG and albumin significantly correlated with the number of fillings. Albuminuria significantly correlated with blood and urine Hg.
From the nephrotoxicity point of view, dental amalgam is an unsuitable filling material, as it may give rise to Hg toxicity. Hg levels in blood and urine are good markers of such toxicity. In these exposure conditions, renal damage is possible and may be assessed by urinary excretions of albumin, NAG, and gamma-GT.