BMC Nephrology (BMC Nephrol)

Publisher: BioMed Central

Journal description

BMC Nephrology publishes original research articles in all aspects of the prevention, diagnosis and management of kidney and associated disorders, as well as related molecular genetics, pathophysiology, and epidemiology.

Current impact factor: 1.52

Impact Factor Rankings

2015 Impact Factor Available summer 2015
2013 / 2014 Impact Factor 1.52
2012 Impact Factor 1.644
2011 Impact Factor 2.176
2010 Impact Factor 2.136

Impact factor over time

Impact factor
Year

Additional details

5-year impact 0.00
Cited half-life 3.60
Immediacy index 0.10
Eigenfactor 0.00
Article influence 0.00
Website BMC Nephrology website
Other titles BioMed Central nephrology, Nephrology
ISSN 1471-2369
OCLC 45259909
Material type Document, Periodical, Internet resource
Document type Internet Resource, Computer File, Journal / Magazine / Newspaper

Publisher details

BioMed Central

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    • All titles are open access journals
    • 'BioMed Central' is an imprint of 'Springer Verlag (Germany)'
  • Classification
    ​ green

Publications in this journal

  • [Show abstract] [Hide abstract]
    ABSTRACT: Background Kidney injury molecule-1 (KIM-1) is expressed in tubular epithelial cells after injury and may have a role in the development of renal graft fibrosis. In this study we evaluated the molecular and protein expressions of KIM-1 in dysfunctional allografts and also mRNA KIM-1 expression in urine as potential biomarkers of graft fibrosis. Methods Protein and mRNA levels in renal tissue and urinary sediment cells of 69 kidney transplant recipients that undertook for-cause graft biopsies were evaluated by immunohistochemistry and real-time polymerase chain reaction. The histopathology was classified according to the 2007 Banff schema. Results KIM-1 protein expression was increased in biopsies with interstitial fibrosis and tubular atrophy (IF/TA) compared with biopsies showing acute calcineurin inhibitor nephrotoxicity (CIN) (P <0.05). Kidney tissue KIM-1 mRNA signaling (in) was increased in biopsies with IF/TA compared with all other groups (P <0.05). In the urine cells KIM-1 mRNA was also increased in patients with IF/TA compared with patients with acute CIN (P <0.05). Significant correlations were found between KIM-1 protein and mRNA levels in tissue, between mRNA expressions in tissue and urine and between protein tissue expression and gene expression in the urine. Conclusions KIM-1 seems to be a marker of kidney graft fibrosis. Urinary KIM-1 mRNA may become a useful non-invasive biomarker of the injuries that can trigger intra-graft fibrotic processes, such as interstitial fibrosis and tubular atrophy.
    BMC Nephrology 12/2015; 16(1). DOI:10.1186/s12882-015-0011-y
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    ABSTRACT: Disparities in access to kidney transplantation (KT) remain inadequately understood and addressed. Detailed descriptions of patient attitudes may provide insight into mechanisms of disparity. The aims of this study were to explore perceptions of dialysis and KT among African American adults undergoing hemodialysis, with particular attention to age- and sex-specific concerns. Qualitative data on experiences with hemodialysis and views about KT were collected through four age- and sex-stratified (males <65, males ≥65, females <65, and females ≥65 years) focus group discussions with 36 African American adults recruited from seven urban dialysis centers in Baltimore, Maryland. Four themes emerged from thematic content analysis: 1) current health and perceptions of dialysis, 2) support while undergoing dialysis, 3) interactions with medical professionals, and 4) concerns about KT. Females and older males tended to be more positive about dialysis experiences. Younger males expressed a lack of support from friends and family. All participants shared feelings of being treated poorly by medical professionals and lacking information about renal disease and treatment options. Common concerns about pursuing KT were increased medication burden, fear of surgery, fear of organ rejection, and older age (among older participants). These perceptions may contribute to disparities in access to KT, motivating granular studies based on the themes identified.
    BMC Nephrology 12/2015; 16(1):49. DOI:10.1186/s12882-015-0045-1
  • Rulan S Parekh, Lucy A Meoni, Bernard G Jaar, Stephen M Sozio, Tariq Shafi, Gordon F Tomaselli, Joao A Lima, Larisa G Tereshchenko, Michelle M Estrella, W H Linda Kao
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    ABSTRACT: Sudden cardiac death occurs commonly in the end-stage renal disease population receiving dialysis, with 25% dying of sudden cardiac death over 5 years. Despite this high risk, surprisingly few prospective studies have studied clinical- and dialysis-related risk factors for sudden cardiac death and arrhythmic precursors of sudden cardiac death in end-stage renal disease. We present a brief summary of the risk factors for arrhythmias and sudden cardiac death in persons with end-stage renal disease as the rationale for the Predictors of Arrhythmic and Cardiovascular Risk in End Stage Renal Disease (PACE), a prospective cohort study of patients recently initiated on chronic hemodialysis, with the overall goal to understand arrhythmic and sudden cardiac death risk. Participants were screened for eligibility and excluded if they already had a pacemaker or an automatic implantable cardioverter defibrillator. We describe the study aims, design and data collection of 574 incident hemodialysis participants from the Baltimore region in Maryland, U.S.A.. Participants were recruited from 27 hemodialysis units and underwent detailed clinical, dialysis and cardiovascular evaluation at baseline and follow-up. Cardiovascular phenotyping was conducted on nondialysis days with signal averaged electrocardiogram, echocardiogram, pulse wave velocity, ankle brachial index and cardiac computed tomography and angiography conducted at baseline. Participants were followed annually with study visits including electrocardiogram, pulse wave velocity and ankle brachial index up to 4 years. A biorepository of serum, plasma, DNA, RNA and nails were collected to study genetic and serologic factors associated with disease. Studies of modifiable risk factors for sudden cardiac death will help set the stage for clinical trials to test therapies to prevent sudden cardiac death in this high-risk population.
    BMC Nephrology 04/2015; 16(1):63. DOI:10.1186/s12882-015-0050-4
  • Igor Salvadé, Sibylle Schätti-Stählin, Eleonora Violetti, Carlo Schönholzer, Claudio Cereghetti, Hugo Zwahlen, Lorenzo Berwert, Michel Burnier, Luca Gabutti
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    ABSTRACT: Chronic kidney disease (CKD) accelerates vascular stiffening related to age. Arterial stiffness may be evaluated measuring the carotid-femoral pulse wave velocity (PWV) or more simply, as recommended by KDOQI, monitoring pulse pressure (PP). Both correlate to survival and incidence of cardiovascular disease. PWV can also be estimated on the brachial artery using a Mobil-O-Graph; a non-operator dependent automatic device. The aim was to analyse whether, in a dialysis population, PWV obtained by Mobil-O-Graph (MogPWV) is more sensitive for vascular aging than PP. A cohort of 143 patients from 4 dialysis units has been followed measuring MogPWV and PP every 3 to 6 months and compared to a control group with the same risk factors but an eGFR > 30 ml/min. MogPWV contrarily to PP did discriminate the dialysis population from the control group. The mean difference translated in age between the two populations was 8.4 years. The increase in MogPWV, as a function of age, was more rapid in the dialysis group. 13.3% of the dialysis patients but only 3.0% of the control group were outliers for MogPWV. The mortality rate (16 out of 143) was similar in outliers and inliers (7.4 and 8.0%/year). Stratifying patients according to MogPWV, a significant difference in survival was seen. A high parathormone (PTH) and to be dialysed for a hypertensive nephropathy were associated to a higher baseline MogPWV. Assessing PWV on the brachial artery using a Mobil-O-Graph is a valid and simple alternative, which, in the dialysis population, is more sensitive for vascular aging than PP. As demonstrated in previous studies PWV correlates to mortality. Among specific CKD risk factors only PTH is associated with a higher baseline PWV. ClinicalTrials.gov Identifier: NCT02327962 .
    BMC Nephrology 04/2015; 16(1):62. DOI:10.1186/s12882-015-0058-9
  • Aiqing Zhang, Bin Wang, Min Yang, Huimin Shi, Weihua Gan
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    ABSTRACT: The objective of this study was to investigate the influence of β2-microglobulin (β2-M) on the epithelial-mesenchymal transition (EMT) in renal tubular epithelial cells. A human kidney proximal tubular cell line (HK-2) was used as the proximal tubular cell model. HK-2 cells were exposed to different concentrations of β2-M (5, 10, 25, and 50 μM) for up to 24, 48 and 72 h. The effects of β2-M on cell morphology were observed by phase contrast microscopy, and the possible associated mechanisms were assessed by immunofluorescence staining, western blot, RNA interference, immunoprecipitation, and induced coupled plasma mass spectroscopy. β2-M induced marked morphological alterations in the HK-2 cells, accompanied by the increased expression of extracellular matrix components and α-smooth muscle actin (α-SMA), vimentin and fibronectin and the reduced expression of E-cadherin. Our results also revealed that β2-M could induce the EMT in the HK-2 cells without significant affecting cell viability. Excess β2-M in the HK-2 cells led to a decrease in iron and an increase in hypoxia inducible factor-1α (HIF-1α), which induced EMT in the HK-2 cells. Additionally, disrupting the function of the β2-M/hemochromatosis (HFE) complex by HFE knockdown was sufficient to reverse β2-M-mediated EMT in the HK-2 cells. These findings demonstrate that the activity of β2-M is mediated by the β2-M/HFE complex, which regulates intracellular iron homeostasis and HIF-1α and ultimately induces EMT in HK2 cells.
    BMC Nephrology 04/2015; 16(1):60. DOI:10.1186/s12882-015-0057-x
  • Thomas Clark Powell, John P Donnelly, Orlando M Gutiérrez, Russell L Griffin, Monika M Safford, Henry E Wang
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    ABSTRACT: Chronic kidney disease (CKD) and systemic inflammation are risk factors for sepsis. While often viewed as a marker of chronic kidney disease, Cystatin C (Cyst-C) may also reflect systemic inflammation. We sought to determine the association between elevated baseline Cyst-C and long-term rates of community-acquired sepsis, and to determine if this relationship is influenced by traditional markers of CKD (estimated glomerular filtration rate [eGFR], albumin-to-creatinine ratio [ACR]) and inflammation (high sensitivity C-reactive protein [hsCRP]). We studied 30,239 adults ≥45 years old from the REasons for Geographic and Racial Differences in Stroke (REGARDS) cohort. The primary exposure was elevated Cyst-C (>1.12 mg/dL) measured at study baseline. The primary outcome was the first sepsis hospitalization during a 10-year observation period. Using Cox regression, we evaluated the association between elevated Cyst-C and first sepsis event, adjusted for sociodemographics, health behaviors, chronic medical conditions, eGFR, ACR and hsCRP. Among participants, 1,532 experienced a sepsis event. Median Cyst-C levels were: sepsis 1.08 (IQR 0.91-1.33) mg/dL (43.8% >1.12 mg/dL), non-sepsis 0.94 (IQR 0.82-1.10) mg/dL (23.4% >1.12 mg/dL). Cyst-C > 1.12 mg/dL was independently associated with increased rates of sepsis, adjusted for participant demographics, health behaviors and chronic medical conditions (HR 1.75; 95% CI: 1.55-1.96). The addition of eGFR < 60 mg/min/1.73 m(2,) ACR ≥ 30 mg/g and hsCRP > 3.0 mg/dL only partially attenuated the association between Cyst-C > 1.12 mg/dL and rates of sepsis (adjusted HR 1.51; 1.32-1.72). Elevated Cyst-C is associated with increased long-term rates of community-acquired sepsis, independent of abnormal eGFR, ACR or hsCRP. Cyst-C may play a role in long-term sepsis risk prediction and prevention.
    BMC Nephrology 04/2015; 16(1):61. DOI:10.1186/s12882-015-0055-z
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    ABSTRACT: Data regarding the epidemiology of end-stage renal disease (ESRD) and dialysis in sub-Saharan Africa are scarce and knowledge about the spectrum renal disease is very limited. This study is on the profile of patients with ESRD in a referral hospital in Cameroon. Medical records of patients with ESRD covering a 10-year period of activities of the Douala General Hospital were reviewed. Data were retrieved on socio demographic, and clinical data such as major comorbidities, the presumed aetiology of ESRD, blood pressure, biological variables and renal replacement therapy. In all 863 patients were included with 66% being men. Mean age was 47.4 years overall, 48.9 in men and 44.5 in women (p < 0.001). The main background aetiologies of ESRD were hypertension (30.9%), glomerulonephritis (15.8%), diabetes (15.9%), HIV (6.6%) and unknown (14.7%). Participants with HIV, glomerulonephritis or unknown background nephropathy were younger, more likely to be women, to be single and unemployed, while those with hypertension and/or diabetes were older, more likely to be men, to be either married or widow, and to be retired or working in the public sector. A total of 677 patients started haemodialysis with decreasing trend across age quartiles (p = 009), and variation across background nephropathies (p < 0.001). Emergency dialysis unplanned on a temporary catheter occurs in 88.3% of patients. This study has revealed substantial gender and age differentials in the socio-demographic features and background nephropathy in patients with ESRD in this setting. The likelihood of starting maintenance dialysis varied across background nephropathies, driven at least in part by age differences across background nephropathies.
    BMC Nephrology 04/2015; 16(1):59. DOI:10.1186/s12882-015-0044-2
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    ABSTRACT: Multipass hemodialysis (MPHD) is a recently described dialysis modality, involving the use of small volumes of dialysate which are repetitively recycled. Dialysis regimes of 8 hours for six days a week using this device result in an increased removal of small water soluble solutes and middle molecules compared to standard hemodialysis (SHD). Since protein-bound solutes (PBS) exert important pathophysiological effects, we investigated whether MPHD results in improved removal of PBS as well. A cross-over study (Clinical Trial NCT01267760) was performed in nine stable HD patients. At midweek a single dialysis session was performed with either 4 hours SHD using a dialysate flow of 500 mL/min or 8 hours MPHD with a dialysate volume of 50% of estimated body water volume. Blood and dialysate samples were taken every hour to determine concentrations of p-cresylglucuronide (PCG), hippuric acid (HA), indole acetic acid (IAA), indoxyl sulfate (IS), and p-cresylsulfate (PCS). Dialyser extraction ratio, reduction ratio, and solute removal were calculated for these solutes. Already at 60 min after dialysis start, the extraction ratio in the hemodialyser was a factor 1.4-4 lower with MPHD versus SHD, resulting in significantly smaller reduction ratios and lower solute removal within a single session. Even when extrapolating our findings to 3 times 4 h SHD and 6 times 8 h MPHD per week, the latter modality was at best similar in terms of total solute removal for most protein-bound solutes, and worse for the highly protein-bound solutes IS and PCS. When efficiency was calculated as solute removal/litre of dialysate used, MPHD was found superior to SHD. When high water consumption is a concern, a treatment regimen of 6 times/week 8 h MPHD might be an alternative for 3 times/week 4 h SHD, but at the expense of a lower total solute removal of highly protein-bound solutes.
    BMC Nephrology 04/2015; 16(1):57. DOI:10.1186/s12882-015-0056-y
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    ABSTRACT: Primary care providers do not routinely follow guidelines for the care of patients with chronic kidney disease (CKD). Multidisciplinary efforts may improve care for patients with chronic disease. Pharmacist based interventions have effectively improved management of hypertension. We performed a pragmatic, randomized, controlled trial to evaluate the effect of a pharmacist based quality improvement program on 1) outcomes for patients with CKD and 2) adherence to CKD guidelines in the primary care setting. Patients with moderate to severe CKD receiving primary care services at one of thirteen community-based Veterans Affairs outpatient clinics were randomized to a multifactorial intervention that included a phone-based pharmacist intervention, pharmacist-physician collaboration, patient education, and a CKD registry (n = 1070) or usual care (n = 1129). The primary process outcome was measurement of parathyroid hormone (PTH) during the one year study period. The primary clinical outcome was blood pressure (BP) control in subjects with poorly controlled hypertension at baseline. Among those with poorly controlled baseline BP, there was no difference in the last recorded BP or the percent at goal BP during the study period (42.0% vs. 41.2% in the control arm). Subjects in the intervention arm were more likely to have a PTH measured during the study period (46.9% vs. 16.1% in the control arm, P <0.001) and were on more classes of antihypertensive medications at the end of the study (P = 0.02). A one-time pharmacist based intervention proved feasible in patients with CKD. While the intervention did not improve BP control, it did improve guideline adherence and increased the number of antihypertensive medications prescribed to subjects with poorly controlled BP. These findings can inform the design of quality improvement programs and future studies which are needed to improve care of patients with CKD. ClinicalTrials.gov: NCT01290614 .
    BMC Nephrology 04/2015; 16(1):56. DOI:10.1186/s12882-015-0052-2
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    ABSTRACT: In western Nicaragua and El Salvador, chronic kidney disease (CKD) is highly prevalent and generally affects young, male, agricultural (usually sugar cane) workers without the established CKD risk factors. It is yet unknown if the prevalence of this CKD of Non-Traditional causes (CKDnT) extends to the northernmost Central American country, Guatemala. Therefore, we sought to compare dialysis enrollment rates by region, municipality, sex, daily temperature, and agricultural production in Guatemala and assess if there is a similar CKDnT distribution pattern as in Nicaragua and El Salvador. The National Center for Chronic Kidney Disease Treatment (Unidad Nacional de Atención al Enfermo Renal Crónico) is the largest provider of dialysis in Guatemala. We used population, Human Development Index, literacy, and agricultural databases to assess the geographic, economic, and educational correlations with the National Center for Chronic Kidney Disease Treatment's hemodialysis and peritoneal dialysis enrollment database. Enrollment rates (per 100 000) inhabitants were compared by region and mapped for comparison to regional agricultural and daytime temperature data. The distribution of men and women enrolled in dialysis were compared by region using Fisher's exact tests. Spearman's rank correlation coefficients were calculated. Dialysis enrollment is higher in the Southwest compared to the rest of the country where enrollees are more likely (p < 0.01) to be male (57.8%) compared to the rest of the country (49.3%). Dialysis enrollment positively correlates with Human Development Index and literacy rates. These correlations are weaker in the agricultural regions (predominantly sugar cane) of Southwest Guatemala. In Guatemala, CKDnT incidence may have a similar geographic distribution as Nicaragua and El Salvador (higher in the high temperature and sugar cane growing regions). Therefore, it is likely that the CKNnT epidemic extends throughout the Mesoamerican region.
    BMC Nephrology 04/2015; 16(1):54. DOI:10.1186/s12882-015-0049-x
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    ABSTRACT: Small non-coding RNA molecules (miRNAs) play a pivotal role in regulating gene expression in development. miRNAs regulate key processes at the cellular level and thereby influence organismal and tissue development including kidney morphogenesis. A miRNA molecule is initially synthesized as a longer hairneedle-shaped RNA transcript and then processed through an enzymatic complex that contains the RNA-processing enzyme Drosha and its essential interactor Dgcr8. Resulting pre-miRNAs are then cleaved by Dicer. Recent data showed that loss of Dicer resulted in severe developmental kidney phenotypes. However, as Dicer has multiple miRNA-independent functions, it was not entirely clear whether the observed renal phenotypes could be exclusively attributed to a lack of miRNA expression. We analyzed the role of miRNAs in kidney development by conditional gene deletion of Dgcr8 in the developing kidney using a transgenic mouse line that expresses Cre recombinase in the distal nephron and derivatives of the ureteric bud in kidney development. Animals with a gene deletion of Dgcr8 in these tissues developed severe hydronephrosis, kidney cysts, progressive renal failure and premature death within the first two months after birth, a phenotype strongly resembling Dicer deletion. Here we show that conditional gene deletion of the essential miRNA-processing enzyme Dgcr8 in the developing renal tubular system results in severe developmental defects and kidney failure. These data confirm earlier findings obtained in Dicer knock-out animals and clearly illustrate the essential role of miRNAs in kidney development. The data suggests that miRNA dysregulation may play an important, yet ill-defined role in the pathogenesis of inborn defects of the genitourinary system and indicate that miRNA defects may be causative in the development of human disease.
    BMC Nephrology 04/2015; 16(1):55. DOI:10.1186/s12882-015-0053-1
  • Gianluigi Zaza, Carlo Rugiu, Alessandra Trubian, Simona Granata, Albino Poli, Antonio Lupo
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    ABSTRACT: Background The last decade has witnessed considerable improvement in dialysis technology and changes in clinical management of patients in peritoneal dialysis (PD) with a significant impact on long term clinical outcomes. However, the identification of factors involved in this process is still not complete. Methods Therefore, to assess this objective, we retrospectively analyzed clinical records of 260 adult patients who started PD treatment from 1983 to 2012 in our renal unit. For the analysis, we divided them into three groups according to the time of starting dialysis: GROUP A (n: 62, 1983–1992), GROUP B (n: 66, 1993–2002) and GROUP C (n: 132, 2003 to 2012). Results Statistical analysis revealed that patients included in the GROUP C showed a reduction in mean patients’ age (p = 0.03), smoking habit (p = 0.001), mean systolic blood pressure (p < 0.0001) and an increment in hemoglobin levels (p < 0.0001) and residual diuresis (p = 0.016) compared to the other two study groups. Additionally, patients included in GROUP C, mainly treated with automated peritoneal dialysis, showed a reduced risk of all-causes mortality and a decreased risk to develop acute myocardial infarction and cerebrovascular disease. Patients’ age, diabetes mellitus and smoking habit were all positively associated with a significant increased risk of mortality in our PD patients, while serum albumin levels and residual diuresis were negatively correlated. Conclusions Therefore, the present study, revealed that in the last decade there has been a growth of our PD program with a concomitant modification of our patients’ characteristics. These changes, together with the evident technical advances, have caused a significant improvement of patients’ survival and a decrement of the rate of hospitalization. Moreover, it reveals that our pre-dialysis care, modifying the above-mentioned factors, has been a major cause of these clinical improvements. Electronic supplementary material The online version of this article (doi:10.1186/s12882-015-0051-3) contains supplementary material, which is available to authorized users.
    BMC Nephrology 04/2015; 16. DOI:10.1186/s12882-015-0051-3
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    ABSTRACT: Background In view of the prevalence of oxidative stress in chronic kidney disease (CKD) patients, the loss of low-molecular-weight biomolecules by hemodialysis and the antioxidant potential of some uremic solutes that accumulate in CKD, we used in vitro model systems to test the antioxidant potential of the following uremic solutes: uric acid, hippuric acid, p-cresol, phenol, methylguanidine, L-arginine, L-tyrosine, creatinine and urea. Methods The in vitro antioxidant efficiencies of the uremic solutes, isolated or in mixtures, were tested with the following assays: i) ABTS radical cation decolorization assay; ii) hypochlorous acid (HOCl/OCl−) scavenging activity; iii) superoxide anion radical (O2•-) scavenging activity; iv) crocin bleaching assay (capture of peroxyl radical, ROO•); v) hydrogen peroxide (H2O2) scavenging activity. Results Four of the tested uremic solutes (p-cresol, phenol, L-tyrosine, uric acid) were effective antioxidants and their IC50 were found in three model systems: ABTS•+, HOCl/OCl− and crocin bleaching assay. In the 4-solutes mixtures, each one of the solute captured 12.5% for the IC50 of the mixture to ABTS•+ or HOCl/OCl−, exhibiting a virtually exact additive effect. In the 2-solutes mixtures, for ROO• capture, it was observed the need of more mass of uremic solutes to reach an IC50 value that was higher than the projected IC50, obtained from the IC50 of single solutes (25% of each, in the binary mixtures) in the same assay. In model systems for O2•- and H2O2, none of the uremic solutes showed scavenging activity. Conclusions The use of the IC50 as an analytical tool to prepare and analyze mixtures allows the determination of their scavenging capacities and may be useful for the assessment of the antioxidant status of biological samples under conditions of altered levels of the endogenous antioxidant network and/or in the employment and monitoring of exogenous antioxidant therapy.
    BMC Nephrology 04/2015; 16(1). DOI:10.1186/s12882-015-0029-1
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    ABSTRACT: Hyperlipidemia is thought to be a major risk factor for the progression of renal diseases in diabetes. Recent studies have shown that lipid profiles are commonly abnormal early on type 2 diabetes mellitus (T2DM) with diabetic nephropathy. However, the early effects of triglyceride and cholesterol abnormalities on renal injury in type 1 diabetes mellitus (T1DM) are not fully understood and require reliable animal models for exploration of the underlying mechanisms. Hamster models are important tools for studying lipid metabolism because of their similarity to humans in terms of lipid utilization and high susceptibility to dietary cholesterol and fat. Twenty-four male Golden Syrian hamsters (100-110 g) were rendered diabetes by intraperitoneal injections of streptozotocin (STZ) on consecutive 3 days at dose of 30 mg/kg, Ten days after STZ injections, hamsters with a plasma Glu concentration more than 12 mmol/L were selected as insulin deficient ones and divided into four groups (D-C, D-HF, D-HC, and D-HFHC), and fed with commercially available standard rodent chow, high-fat diet, high-cholesterol diet, high-fat and cholesterol diet respectively, for a period of four weeks. After an induction phase, a stable model of renal injury was established with the aspects of early T1DM kidney disease, These aspects were severe hypertriglyceridemia, hypercholesterolemia, proteinuria with mesangial matrix accumulation, upgraded creatinine clearance, significant cholesterol and triglyceride deposition, and increasing glomerular surface area, thickness of basement membrane and mesangial expansion. The mRNA levels of sterol regulatory element binding protein-1c, transforming growth factors-β, plasminogen activator inhibitor-1, tumor necrosis factor-α and interleukin-6 in the D-HFHC group were significantly up-regulated compared with control groups. This study presents a novel, non-transgenic, non-surgical method for induction of renal injury in hamsters, which is an important complement to existing diabetic models for pathophysiological studies in early acute and chronic kidney disease, especially hyperlipidemia. These data suggest that both severe hypertriglyceridemia and hypercholesterolemia can accelerate renal injury in the early development of T1DM.
    BMC Nephrology 04/2015; 16(1):51. DOI:10.1186/s12882-015-0041-5
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    ABSTRACT: People with kidney failure are often deficient in zinc and selenium, but little is known about the optimal way to correct such deficiency. We did a double-blind randomized trial evaluating the effects of zinc (Zn), selenium (Se) and vitamin E added to the standard oral renal vitamin supplement (B and C vitamins) among hemodialysis patients in Alberta, Canada. We evaluated the effect of two daily doses of the new supplement (medium dose: 50 mg Zn, 75 mcg Se, 250 IU vitamin E; low dose: 25 mg Zn, 50 mcg Se, 250 IU vitamin E) compared to the standard supplement on blood concentrations of Se and Zn at 90 days (primary outcome) and 180 days (secondary outcome) as well as safety outcomes. We enrolled 150 participants. The proportion of participants with low zinc status (blood level <815 ug/L) did not differ between the control group and the two intervention groups at 90 days (control 23.9% vs combined intervention groups 23.9%, P > 0.99) or 180 days (18.6% vs 28.2%, P = 0.24). The proportion with low selenium status (blood level <121 ug/L) was similar for controls and the combined intervention groups at 90 days (32.6 vs 19.6%, P = 0.09) and 180 days (34.9% vs 23.5%, P = 0.17). There were no significant differences in the risk of adverse events between the groups. Supplementation with low or medium doses of zinc and selenium did not correct low zinc or selenium status in hemodialysis patients. Future studies should consider higher doses of zinc (≥75 mg/d) and selenium (≥100 mcg/d) with the standard supplement. Registered with ClinicalTrials.gov ( NCT01473914 ).
    BMC Nephrology 04/2015; 16(1):52. DOI:10.1186/s12882-015-0042-4
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    ABSTRACT: Peritoneal fibrosis is a common complication in patients treated with long-term peritoneal dialysis. The aim of this study was to identify the microRNAs (miRNAs) involved in regulation of peritoneal fibrosis in a rat model of peritoneal dialysis. Twenty-four Sprague-Dawley (SD) rats were randomly allocated into three groups: (i) Control group (Cg, n = 8); (ii) Saline group (Sg, n = 8): daily intraperitoneal injection with 0.9% normal saline; (iii) Hypertonic dialysate group (HDg, n = 8): daily intraperitoneal injection with 4.25% peritoneal dialysis solution. Rats were sacrificed after four weeks for histological evaluation of peritoneal membrane and the expression of α-SMA and COL-1. A miRNA screen was performed using microarray analysis to identify differentially expressed miRNAs, which were then validated by real-time PCR. Compared with the control and the saline groups, hypertonic dialysate group showed impaired peritoneal function accompanied by a spectrum of morphological changes including thicker peritoneal membrane, higher collagen deposition, infiltration of mononuclear cells and neovascularization in the peritoneum. Increased mRNA and protein levels of α-SMA and COL-1 were observed in hypertonic dialysate group, indicating the progression of peritoneal fibrosis. The miRNA screen identified 8 significantly down-regulated miRNAs (miR-31, miR-93, miR-100, miR-152, miR-497, miR-192, miR-194 and miR-200b) and one highly up-regulated miRNA (miR-122) in the hypertonic dialysate group. The results were confirmed by real-time PCR. Altered miRNA expression in peritoneum was found in the rat model of peritoneal fibrosis, indicating that these miRNAs may be associated with pathogenesis of peritoneal fibrosis.
    BMC Nephrology 04/2015; 16(1):48. DOI:10.1186/s12882-015-0039-z
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    ABSTRACT: Background We examined whether renal resistive index (RI), a simple index of renal vascular resistance, is associated with the presence and severity of anemia, and can predict the future development of anemia in patients with hypertension. Methods We retrospectively examined 175 patients with hypertension (mean age 67 ± 11 years, 32-85 years, 134 males) who underwent renal ultrasonography. Anemia was defined as a reduction in the concentration of hemoglobin <13.0 g/dL for men and <12.0 g/dL for women. Renal RI was measured in the interlobar arteries. Results Anemia was present in 37% of men and 34% of women. The mean estimated glomerular filtration rate (eGFR) was 58 ± 23 ml/min/1.73 m2 (median: 56 ml/min/1.73 m2, range: 16-168 ml/min/1.73 m2) and the mean renal RI was 0.70 ± 0.09 (median: 0.70, range: 0.45-0.92). Proteinuria was present in 29% of patients. Both eGFR and renal RI correlated significantly with hemoglobin levels. In the stepwise multivariate linear regression analysis, renal RI was associated with hemoglobin levels independently of potential confounders including eGFR. During the follow-up period (median: 959 days, range: 7-3595 days), Kaplan–Meier curves demonstrated that patients with renal RI above the median value had a higher incidence of the future development of anemia than other patients. Cox regression analysis showed that renal RI (hazard ratio 1.18, 95% CI 1.02-1.37 per 0.05 rises in renal RI, p =0.03) and the presence of proteinuria were (hazard ratio 1.80, 95% CI 1.08-3.01, p =0.03) were independently associated with the future development of anemia after correcting for confounding factors. Conclusions Measurement of renal RI can be useful for elucidating the pathogenesis of anemia and for inferring its potential risk in patients with hypertension.
    BMC Nephrology 04/2015; 16(1). DOI:10.1186/s12882-015-0040-6
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    ABSTRACT: Urinary density (UD) has been routinely used for decades as a surrogate marker for urine osmolality (Uosm). We asked if UD can accurately estimate Uosm both in healthy subjects and in different clinical scenarios of kidney disease. UD was assessed by refractometry. Uosm was measured by freezing point depression in spot urines obtained from healthy volunteers (N = 97) and in 319 inpatients with acute kidney injury (N = 95), primary glomerulophaties (N = 118) or chronic kidney disease (N = 106). UD and Uosm correlated in all groups (p < 0.05). However, a wide range of Uosm values was associated with each UD value. When UD was ≤ 1.010, 28.4% of samples had Uosm above 350 mOsm/kg. Conversely, in 61.6% of samples with UD above 1.020, Uosm was below 600 mOsm/kg. As expected, Uosm exhibited a strong relationship with serum creatinine (Screat), whereas a much weaker correlation was found between UD and Screat. We found that UD is not a substitute for Uosm. Although UD was significantly correlated with Uosm, the wide dispersion makes it impossible to use UD as a dependable clinical estimate of Uosm. Evaluation of the renal concentrating ability should be based on direct determination of Uosm.
    BMC Nephrology 04/2015; 16(1):46. DOI:10.1186/s12882-015-0038-0
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    ABSTRACT: Background Uremic pruritus is a common and deleterious condition among hemodialysis (HD) patients. Central gating of μ/κ opiate circuitry plays an important role in mediating and countering pruritogenic sensation. The objective of this study was to assess the safety and pharmacokinetics (PK) of the mixed μ-antagonist/κ-agonist nalbuphine, administered orally as nalbuphine HCl extended release (ER) tablets in HD patients, and explore its effect on pruritus. Methods In this open-label multiple escalating dose study, 15 HD patients with pruritus and 9 matched healthy subjects were enrolled. Nalbuphine HCl ER dose was escalated from 30 mg QD to 240 mg BID over 15 days. A full PK profile was obtained under dialysis and non-dialysis conditions as a function of dose. Clearance during dialysis was determined by sampling dialysate and arterial/venous blood during dialysis. Pruritus severity was assessed twice daily using a Visual Analog Scale (VAS). Safety monitoring included extensive monitoring of EKG, blood pressure, and pulse oximetry. Results In HD patients, nalbuphine concentration peaked within 4–9 hours and attained steady state within 2–3 days, with no significant accumulation. Mean half-life was 14.2 hours, mean Cmax and AUCtau ranged between 13 and 83 ng/mL and 118 and 761 ng∙h/mL, respectively, with exposure increasing in a nearly dose-proportional fashion. Exposure in HD patients was about 2-fold higher than in healthy subjects. There was no meaningful difference between exposure on dialysis and non-dialysis days with 1% or less of the dose removed by dialysis. Nalbuphine suppressed itch in a dose-dependent manner, reducing mean VAS score from 4.0 to 1.2 at 180 mg and 0.4 at 240 mg. Conclusions Nalbuphine HCl ER tablets can be safely administered to HD patients without dose adjustment up to 240 mg BID and may hold promise in treating uremic pruritus. Electronic supplementary material The online version of this article (doi:10.1186/s12882-015-0043-3) contains supplementary material, which is available to authorized users.
    BMC Nephrology 04/2015; 16(1). DOI:10.1186/s12882-015-0043-3