BMC Nephrology

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NSD2 is poorly expressed in patients with DN. A serum levels of FBG, SCr, S-Cys-C, 24-h U-protein, and U-Cys-C in patients with DN and in healthy individuals determined using an automatic biochemical analyzer; B serum level of NSD2 in patients with DN and in healthy controls determined by RT-qPCR; C correlations between NSD2 and the levels of FBG, SCr, S-Cys-C, 24-h U-protein, and U-Cys-C in patients with DN. There were 25 healthy individuals and 34 patients. Data were collected from three independent experiments and expressed as the mean ± SD. Differences were analyzed by the unpaired t test (A-B). In panel C, the correlations were analyzed by Pearson's correlation analysis. *p < 0.05
METTL3 upregulates NSD2 to reduce HG-induced mesangial cell activation and interstitial fibrosis. A Transfection efficacy of sh-NSD2 in SV40-MES-13 cells after vector-METTL3 transfection determined by RT-qPCR; B DNA replication ability of cells examined by EdU labeling; C-E, MFI of COL1A1 (C), Fibronectin (D) and E-cadherin (E) in cells examined by immunofluorescence staining. Data were expressed as the mean ± SD from three independent experiments. Differences were analyzed by unpaired t test (A) or one-way (B-E). *p < 0.05
Article
Background Nuclear receptor-binding SET domain protein 2 (NSD2) is a histone methyltransferase that has been demonstrated to regulate insulin secretion and glucose concentration. This study focused on the role of NSD2 in the renal impairment during diabetic nephropathy (DN). Methods Serum NSD2 level in patients with DN was examined, and its correlations with the renal impairment-related indicators were examined. A murine model of DN was established, and mouse mesangial cells (SV40-MES-13) were treated with high-glucose (HG) to mimic a DN-like condition in vitro . Overexpression of NSD2 was introduced into mice or cells for in vivo and in vitro studies. The m6A level in HG-treated SV40-MES-13 cells was analyzed. METTL3 expression and its correlation with NSD2 were determined. Results NSD2 was poorly expressed in the serum of patients with DN and was negatively correlated with the levels of fasting blood sugar (FBG), serum creatinine (SCr), serum cystatin C (S-Cys-C), the 24-h urine protein (24-h U-protein) and the urine cystatin C (U-Cys-C). NSD2 overexpression reduced the kidney weight and reduced renal impairment in mice. It also suppressed interstitial fibrosis in mouse kidney tissues and reduced fibrosis-related markers in HG-treated SV40-MES-13 cells. HG treatment reduced the m6A level in the cells. METTL3 promoted m6A modification of NDS2 mRNA and enhanced its stability by YTHDF1. METTL3 overexpression alleviated renal impairment and fibrosis in vivo and in vitro . But the protective role was blocked upon NSD2 silencing. Conclusion This study demonstrates that METTL3 promotes NSD2 mRNA stability by YTHDF1 to alleviate progression of DN.
 
Patient chart selection flow diagram
Article
  • Karen CourvilleKaren Courville
  • Norman BustamanteNorman Bustamante
  • Bárbara HurtadoBárbara Hurtado
  • [...]
  • Iván LandiresIván Landires
Background Over the last three decades, the mesoamerican region has seen an increase in the frequency of patients diagnosed with Chronic Kidney Disease of nontraditional causes (CKDnt) also known as Meso-American Nephropathy (MeN). A region with an increased frequency of patients with Chronic Kidney Disease (CKD) has been identified in central Panama. The present study aims to characterize the clinical presentation of patients with CKDnt in an understudied population of the central region of Panama and to compare them with patients with traditional chronic kidney disease (CKDt). Methods A retrospective descriptive study was conducted in a nephrology reference hospital in the central provinces of Herrera and Los Santos, comparing a group of 15 patients with CKDnt to 91 patients with CKDt. Sociodemographic variables, personal history, laboratory parameters, and of renal ultrasound were compared. Results Patients with CKDnt had a median age of 58 years (IQR: 52–61), significantly lower ( P < 0.001) than patients with CKDt with a median age of 71 years (IQR: 64–78). Patients with CKDnt had a history of being agricultural (60%) and transportation (20%) workers, significantly higher than patients with CKDt (15%, P < 0.001 and 0%, P < 0.01 respectively). Renal atrophy and hyperuricemia are significant clinical markers of CKDnt ( P < 0.001 and P < 0.05 respectively). Conclusion To our knowledge, this is the first study in Panama to investigate the clinical presentation of patients with CKDnt and one of the few in Central America and the world that compares them with patients with CKDt. In central Panama the typical CKDnt patient is a male in his 50 s who is primarily engaged in agriculture or as a public transport driver. Renal atrophy and hyperuricemia are significant clinical markers of CKDnt. Further studies are needed to help understand the common determinants and risk factors for CKDnt development in Panama and Mesoamerica.
 
Flow chart to dialysis selection. Three healthcare stages are shown. Similar arrowheads and lines reflect similar trajectories. STOP signs indicate endpoints in participants’ journeys
Study findings embedded in the Social Ecological Framework. The figure depicts how the findings are interrelated within a social-ecological system. *Note: “Unknown CKD status” under Policy/National-level factors refers to unknown CKD status due to lack of screening criteria for patients with common CKD comorbidities
Article
  • Miriam Vélez-BermúdezMiriam Vélez-Bermúdez
  • Jenna L. AdamowiczJenna L. Adamowicz
  • Natoshia M. AskelsonNatoshia M. Askelson
  • [...]
  • Alan J. ChristensenAlan J. Christensen
Background Patients with end-stage kidney disease (ESKD) may choose to undergo dialysis in-center or at home, but uptake of home dialysis in the US has been minimal despite its benefits over in-center dialysis. Factors that may have led patients to select home dialysis over in-center dialysis are poorly understood in the literature, and interventions to improve selection of home dialysis have focused on patient knowledge and shared decision-making processes between patients and providers. The purpose of this study was to explore micro- and macro-level factors surrounding dialysis modality decision-making among patients undergoing in-center and home dialysis, and explore what leads patients to select home dialysis over in-center dialysis. Methods Semi-structured qualitative interviews were conducted in a dialysis clinic at a large Midwestern research hospital, from September 2019 to December 2020. Participants were 18 years or older, undergoing dialysis for ESKD, and had the cognitive ability to provide consent. Surveys assessing demographic and clinical information were administered to participants following their interviews. Results Forty patients completed interviews and surveys (20 [50%] in-center dialysis, 17 [43%] female, mean [SD] age, 59 [15.99] years). Qualitative findings suggested that healthcare access and engagement before entering nephrology care, after entering nephrology care, and following dialysis initiation influenced patients’ awareness regarding their kidney disease status, progression toward ESKD, and dialysis options. Potential modifiers of these outcomes include race, ethnicity, and language barriers. Most participants adopted a passive-approach during decision-making. Finally, fatigue, concerns regarding one’s dialyzing schedule, and problems with fistula/catheter access sites contributed to overall satisfaction with one’s dialysis modality. Conclusions Findings point to broader factors affecting dialysis selection, including healthcare access and racial/ethnic inequities. Providing dialysis information before entering nephrology and after dialysis initiation may improve patient agency in decision-making. Additional resources should be prioritized for patients of underrepresented backgrounds. Dialysis decision-making may be appropriately modeled under the social-ecological framework to inform future interventions.
 
Correlation matrix between Waterlow score and modified Charlson score
Kaplan-Meir survival for study cohort stratified by pre-op Waterlow category (multiple imputation model)
Article
Background Waterlow scoring was introduced in the 1980s as a nursing tool to risk stratify for development of decubitus ulcers (pressure sores) and is commonly used in UK hospitals. Recent interest has focussed on its value as a pre-op surrogate marker for adverse surgical outcomes, but utility after kidney transplantation has never been explored. Methods In this single-centre observational study, data was extracted from hospital informatics systems for all kidney allograft recipients transplanted between 1st January 2007 and 30th June 2020. Waterlow scores were categorised as per national standards; 0–9 (low risk), 10–14 (at risk), 15–19 (high risk) and ≥ 20 (very high risk). Multiple imputation was used to replace missing data with substituted values. Primary outcomes of interest were post-operative length of stay, emergency re-admission within 90-days and mortality analysed by linear, logistic or Cox regression models respectively. Results Data was available for 2,041 kidney transplant patients, with baseline demographics significantly different across Waterlow categories. As a continuous variable, the median Waterlow score across the study cohort was 10 (interquartile range 8–13). As a categorical variable, Waterlow scores pre-operatively were classified as low risk (n = 557), at risk (n = 543), high risk (n = 120), very high risk (n = 27) and a large proportion of missing data (n = 794). Median length of stay in days varied significantly with pre-op Waterlow category scores, progressively getting longer with increasing severity of Waterlow category. However, no difference was observed in risk for emergency readmission within 90-days of surgery with severity of Waterlow category. Patients with ‘very high risk’ Waterlow scores had increased risk for mortality at 41.9% versus high risk (23.7%), at risk (17.4%) and low risk (13.4%). In adjusted analyses, ‘very high risk’ Waterlow group (as a categorical variable) or Waterlow score (as a continuous variable) had an independent association with increase length of stay after transplant surgery only. No association was observed between any Waterlow risk group/score with emergency 90-day readmission rates or post-transplant mortality after adjustment. Conclusions Pre-operative Waterlow scoring is a poor surrogate marker to identify kidney transplant patients at risk of emergency readmission or death and should not be utilised outside its intended use.
 
Article
Background Haemostatic derangements are thought to be due to an imbalance between hepatic synthesis of pro-coagulants and urinary losses of anticoagulants. Objectives This study evaluated the coagulation profile of Nigerian children with nephrotic syndrome and examined the relationship between coagulation variables, disease state and steroid responsiveness. Methods A cross- sectional hospital based study on evaluation of coagulation profile of children with nephrotic syndrome compared with their age- and gender- matched controls. Results The median fibrinogen level in subjects and controls was the same (2.9 g/L). Sixteen of 46 (35%) children with nephrotic syndrome had hyperfibrinogenaemia. The median fibrinogen level of children in remission was 2.3 g/L and differed significantly when compared with those of children in relapse (p = 0.001). The median APTT of children with nephrotic syndrome was 45.0 s and differed significantly compared with those of controls (42.0 s) (p value = 0.02). The median prothrombin time in children with and without nephrotic syndrome were 12.0 and 13.0 s respectively, (p = 0.004). About 90% of children with nephrotic syndrome had INR within reference range. Thrombocytosis was found in 15% of children with nephrotic syndrome. The median platelet count in children with new disease was 432 × 10³cells/mm³ and differed significantly when compared with those of controls (p = 0.01). INR was significantly shorter in children with steroid resistant nephrotic syndrome (SRNS) (median 0.8 s; IQR 0.8 -0.9 s) compared with controls (median 1.0 s; IQR 1.0 -1.1 s) (p = 0.01). Steroid sensitivity was the strongest predictor of remission in children with nephrotic syndrome; steroid sensitive patients were 30 times more likely to be in remission than in relapse (OR 30.03; CI 2.01 – 448.04). Conclusion This study shows that the haemostatic derangements in childhood nephrotic involve mostly fibrinogen, APTT, PT, INR and platelet counts. Antithrombin levels are largely unaffected. Variations in fibrinogen, APTT, PT and INR values may be due to the heterogeneous nature of the disease.
 
Article
Background Chronic kidney disease (CKD) is responsible for large personal health and societal burdens. Screening populations at higher risk for CKD is effective to initiate earlier treatment and decelerate disease progress. We externally validated clinical prediction models for unknown CKD that might be used in population screening. Methods We validated six risk models for prediction of CKD using only non-invasive parameters. Validation data came from 4,185 participants of the German Heinz-Nixdorf-Recall study (HNR), drawn in 2000 from a general population aged 45–75 years. We estimated discrimination and calibration using the full model information, and calculated the diagnostic properties applying the published scoring algorithms of the models using various thresholds for the sum of scores. Results The risk models used four to nine parameters. Age and hypertension were included in all models. Five out of six c-values ranged from 0.71 to 0.73, indicating fair discrimination. Positive predictive values ranged from 15 to 19%, negative predictive values were > 93% using score thresholds that resulted in values for sensitivity and specificity above 60%. Conclusions Most of the selected CKD prediction models show fair discrimination in a German general population. The estimated diagnostic properties indicate that the models are suitable for identifying persons at higher risk for unknown CKD without invasive procedures.
 
Simplified diagram of the haemodialysis access in the present case (A). Photograph of the left upper limb (B and C). Simplified diagram of the thrombosed arteriovenous fistula (D). The thrombus was identified in the vein from the anastomotic site to the elbow using colour ultrasound (E)
Simplified diagram of the incisions made during the operation (A). Photograph of the reverse ‘Z’-shaped thrombus in the elbow perforating vein and the thrombus in the aneurysm (B and C). Simplified diagram and photograph of anastomotic reconstruction (D and E). Simplified diagram and photograph of the forearm median vein transposition (F and G). Photograph at the end of the operation (H)
Vascular ultrasound after the operation in 2D and colour mode (A and B). Colour ultrasound image of the transposed median vein of the forearm (C). Photograph of postoperative haemodialysis (D)
Article
Background We report a case of a patient who suffered thrombosis of a radial artery-cephalic vein fistula accompanied by aneurysm and a single outflow path of the elbow perforating vein. We performed open surgery combined with Fogarty balloon catheter embolectomy, anastomotic reconstruction and forearm median vein transposition. Case presentation The patient presented with an arteriovenous fistula (AVF) after haemodialysis 5 years ago. In the process of dialysis, the fistula vein was punctured, resulting in aneurysm, high pressure and difficult haemostasis after needle extraction. AVF occlusion was observed on April 12, 2022. We performed a combined open surgery. First, a Fogarty balloon catheter was used to remove the thrombus, and the anastomosis was then reconstructed to restore AVF fistula patency. Finally, forearm median vein transposition was used to establish dual outflow. Postoperative haemodialysis was possible. There are various methods for removing the thrombus in AVF. Here, we report a case in which we performed open surgery combined with Fogarty balloon catheter embolectomy, anastomotic reconstruction and forearm median vein transposition to ensure fistula patency. Conclusion We removed a complete reverse ‘Z’-shaped thrombus of the elbow perforating vein in a haemodialysis fistula. This report provides an effective strategy to manage a high-pressure fistula with single outflow of the elbow perforating vein.
 
Article
Background There are few studies on immunoglobulin A nephropathy (IgAN) at high altitude. This study aimed to analyze the clinical and pathological characteristics of IgAN between Tibet and Beijing, which provided a basis for improving diagnosis and treatment in Tibet. Method The clinical and pathological data of 80 patients from the People’s Hospital of Tibet Autonomous Region (Tibetan group) and 991 patients from Peking University First Hospital (Beijing group) with IgAN proven by renal biopsy were compared retrospectively between January 2016 and July 2020. The kidney biopsy tissue was sent to the Department of Nephrology, Peking University First Hospital for pathological evaluation. Results The proteinuria (2.9 [2.0, 4.9] vs. 1.1 [0.5, 2.4] g/day, P < 0.001) in the Tibetan group was significantly higher than that in the Beijing group. The serum albumin (30.4 ± 7.7 vs. 38.2 ± 5.5 g/L, P < 0.001) was significantly lower in the Tibetan group. The eGFR (77.7 ± 37.8 vs. 62.1 ± 33.6 ml/min/1.73 m², P = 0.001) was higher in the Tibetan group. The percentage of patients with nephrotic syndrome in the Tibetan group was significantly higher than that in the Beijing group (33.8% vs. 4.7%, P < 0.001). Conclusion There are differences in the clinical and pathological characteristics of IgAN between plateau and plain regions.
 
Article
Background Currently, there is a lack of clinical indicators that can accurately distinguish diabetic kidney disease (DKD) from non-diabetic kidney disease (NDKD) in type 2 diabetes. The purpose of this study was to investigate the diagnostic value of triglyceride and cystatin C (TG/ Cys-C) ratio in DKD. Nowadays, there are few studies on the differential diagnosis of TG/ Cys-C ratio between DKD and NDKD. Methods The clinical data of patients with type 2 diabetes complicated with proteinuria who underwent renal biopsy from January 2013 to September 2019 in 2 hospitals in Xuzhou were retrospectively collected. According to the pathological classification of kidney, 25 patients in group DKD and 34 patients in non-diabetic kidney disease (NDKD) group were divided into two groups. The admission information and blood biochemical indexes of all patients with renal biopsy were collected, and the TG / Cys-C ratio was calculated. Logistic regression analysis was used to analyze the related factors of DKD in patients with type 2 diabetes and proteinuria. Receiver operating characteristic (ROC) curve was used to evaluate the diagnostic value of TG/Cys-C ratio for DKD in patients with type 2 diabetes and proteinuria. Another 37 patients with type 2 diabetes complicated by proteinuria who were treated in the Department of Nephrology, four hospitals in Xuzhou from October 2019 to October 2021 were selected as the research objects. The TG/Cys-C value cut-off value selected in the retrospective study was selected as the boundary point and divided into two groups according to the values of greater than or equal to the tangent point and less than the tangential point. Serum triglyceride and cystatin C levels were measured and TG / Cys-C ratio was calculated. All patients underwent ultrasound-guided fine-needle renal biopsy. The positive rates of DKD diagnosis in the two groups were compared to verify the predictive value of TG / Cys-C ratio in the diagnosis of DKD. Results Retrospective study showed that compared with group NDKD, the DKD group had higher systolic blood pressure, higher cystatin C and creatinine, more diabetic retinopathy, longer duration of diabetes, lower hemoglobin concentration, lower glomerular filtration rate, lower cholesterol, lower triglyceride and lower TG/ Cys-C ratio (P < 0.05).Multivariate Logistic regression analysis showed that TG/Cys-C ratio (OR = 0.429, P = 0.009) was a protective factor for DKD in patients with type 2 diabetes and proteinuria. Diabetic retinopathy (OR = 7.054, P = 0.021) and systolic blood pressure (OR = 1.041, P = 0.047) were independent risk factors for DKD in patients with type 2 diabetes complicated with proteinuria. ROC curve showed that the area under the curve predicted by TG/Cys-C ratio for the diagnosis of DKD was 0.816, the sensitivity was 84%, and the specificity was 67.6%. The tangent value of TG / Cys-C ratio is 2.43. Prospective studies showed that in 37 patients with type 2 diabetes and proteinuria, 29 patients had a TG/Cys-C ratio of less than 2.43. The TG/Cys-C ratio of 8 patients was more than 2.43. Ultrasound guided fine needle aspiration biopsy revealed that 22 of the 29 patients had pathological diagnosis of DKD, sensitivity 91.67%, specificity 46.15%, positive predictive value 75.80%, and negative predictive value 75%. Conclusion In type 2 diabetic patients with proteinuria, the ratio of TG/Cys-C has certain predictive value for the diagnosis of DKD.
 
Trial Flowchart
The Iron and Muscle Study design
Article
Background Many people living with chronic kidney disease (CKD) are iron deficient, even though they may not be anaemic. The Iron and Muscle study aims to evaluate whether iron supplementation reduces symptoms of fatigue, improves muscle metabolism, and leads to enhanced exercise capacity and physical function. We report here the trial design and baseline characteristics. Methods This is a prospective, double-blind multicentre randomised controlled trial (RCT) including 75 non-dialysis stage 3–4 CKD patients with iron deficiency but without anaemia. Patients were randomly (1:1) assigned to either: i) intravenous iron therapy, or ii) placebo, with concurrent recruitment of eight CKD non-iron deficient participants and six healthy volunteers. The primary outcome of the study is the six-minute walk test (6MWT) distance between baseline and four-weeks. An additional exercise training programme for patients in both groups was initiated and completed between 4 and 12 weeks, to determine the effect of iron repletion compared to placebo treatment in the context of patients undertaking an exercise programme. Additional secondary outcomes include fatigue, physical function, muscle strength, muscle metabolism, quality of life, resting blood pressure, clinical chemistry, safety and harms associated with the iron therapy intervention and the exercise training intervention, and hospitalisations. All outcomes were conducted at baseline, 4, and 12 weeks, with a nested qualitative study, to investigate the experience of living with iron deficiency and intervention acceptability. The cohort have been recruited and baseline assessments undertaken. Results Seventy-five individuals were recruited. 44% of the randomised cohort were male, the mean (SD) age was 58 (14) years, and 56% were White. Body mass index was 31 (7) kg/m ² ; serum ferritin was 59 (45) μg/L, transferrin saturation was 22 (10) %, and haemoglobin was 125 (12) g/L at randomisation for the whole group. Estimated glomerular filtration rate was 35 (12) mL/min/1.73 m ² and the baseline 6MWT distance was 429 (174) m. Conclusion The results from this study will address a substantial knowledge gap in the effects of intravenous iron therapy, and offer potential clinical treatment options, to improve exercise capacity, physical function, fatigue, and muscle metabolism, for non-dialysis patients with CKD who are iron-deficient but not anaemic. It will also offer insight into the potential novel effects of an 8-week exercise training programme. Trial registration EudraCT: 2018–000,144-25 Registered 28/01/2019.
 
ROC curve of CKD knowledge scale
Article
Introduction: Good knowledge and early identification of chronic kidney disease (CKD) can help in preventing disease progression in its early stages and reducing undesired outcomes. The aim of the current study was to assess the level of public knowledge about CKD, determine predictors of better knowledge, and to construct and validate a CKD knowledge scale for public health assessment and research use. Methods: A community-based cross-sectional study was conducted using an electronic self-administered questionnaire. All people living in Lebanon and being 18 years of age and above were considered eligible for recruitment. CKD knowledge was assessed by a 37-item scale that was constructed by principal component analysis and then validated. The score of the CKD knowledge scale was computed from the extracted factors. A multivariable binomial logistic regression model evaluated the sociodemographic and clinical predictors of the knowledge score. Results: A total of 1308 participants were included. The scale items converged over 9 factors with Eigenvalue greater than 1 and explaining 53.26% of the total variance, and the total scale had a high Cronbach's alpha of 0.804. All items of the scale significantly correlated with the full scale with correlation coefficients ranging from 0.082 to 0.558. The ROC curve analysis determined an optimal cutoff point of better knowledge at 47.5 with 70.6% sensitivity and 44.2% specificity. The CKD knowledge score had a median of 51.00 (IQR 47.00-55.00). Higher knowledge score was significantly associated with old age (ORa = 1.018, 95% CI 1.006-1.030, P = 0.003),, occupation (ORa = 3.919, 95% CI 2.107-7.288, P < 0.001), and recent renal function assessment (ORa = 2.314, 95% CI 1.532-3.495, P < 0.001). However, a lower knowledge score was significantly associated with lower level of education (ORa = 0.462, 95% CI 0.327-0.653, P < 0.001). Conclusion: A reliable tool to assess public knowledge and awareness about CKD was developed and validated. The overall knowledge was good, however, important gaps in CKD awareness were detected in some areas and subpopulations. Therefore, public health stakeholders need to implement targeted CKD educational activities to minimize the disease burden.
 
Gene analysis results. A, C. The patient and his father carry a c.536T>A, p.V179D (arrow) heterozygous mutation in SLC12A3 gene, respectively and his mother has no mutation in SLC12A3 gene at this site. B, D. The patient and his mother carry a c.1456G>A, p.D486N (arrow) heterozygous mutation in SLC12A3 gene, respectively and his father had no mutation in SLC12A3 gene at this site
Renal pathology. A, B, C and D: PLA2R、IgG、IgG1、IgG4 were granular deposition along capillaries (Immunofluorescence×200, fluorescence microscope is OLYMPUSmicroscope), respectively; E: spike like structure (red arrow), and subepithelial deposition of erythrophilic proteins (PASM×400, light microscope is OLYMPUSmicroscope); F: Electron microscope showed subepithelial deposition of electron dense substance (red arrow), diffuse foot process effacement (Electron microscope×5000, electron microscope is JEOL)
Article
Background Gitelman syndrome (GS) is a rare autosomal recessive inherited salt-losing tubulopathy (SLT). Here, we report, for the first time, a case of GS overlapping nephrotic syndrome (NS) related to PLA2R-associated membranous nephropathy (MN). Case presentation We described a male patient had a 4-year history of recurrent fatigue. Serum biochemistry revealed hypokalemia with renal potassium wasting, hypomagnesemia, metabolic alkalosis, hyperreninemia, hypocalciuria, as well as nephrotic-range proteinuria, hypoalbuminemia, and elevated serum anti-phospholipase A2 receptor (PLA2R) antibody. Gene sequencing identified compound heterozygous mutations in SLC12A3 [c.536T > A(p.V179D) and c.1456G > A(p.D486N)]. The unusual association of SLTs and nephrotic-range glomerular proteinuria prompted us to perform a renal biopsy. Renal biopsy showed idiopathic MN. Due to the potential to activate the sodium-chloride co-transporter (NCC) and cause hyperkalemia, tacrolimus was selected to treat NS. Following treatment with potassium chloride, magnesium oxide, low-dose glucocorticoid combined with tacrolimus, the fatigue significantly improved, and concurrently hypokalemia, hypomagnesemia were corrected and NS was remitted. Conclusions Renal biopsy should be warranted for GS patients with moderate to nephrotic-range proteinuria. Tacrolimus was preferred to the management of GS patients with NS.
 
Article
Background Percutaneous kidney biopsies are important tools for the diagnosis of kidney diseases. Nephrologists must be familiar with the expected complications of the procedure to provide an adequate informed consent. Here, we present a quality improvement analysis that reviews the complication rate of percutaneous kidney biopsies performed over a 2-year period by nephrologists at a single center, and that tabulates the nature and timing of these events. Methods From a single center cohort, pre- and post-biopsy anthropomorphic and clinical measurements were collected. Post-biopsy complications were tracked and sorted into either major or minor complications. Statistical tests were used to analyze complication incidence across the pre- and post-biopsy measurements obtained. Results Of the 154 nephrologist-performed percutaneous native kidney biopsies, 2 biopsies (1.3%) were found to result in a major complication. Both major complications were detected within 4 hours of the biopsy. Analysis of the pre-biopsy and post-biopsy measurements found that the proportion of complications was higher in patients with hematuria prior to biopsy. It was also found that patients with complications were statistically younger and had fewer comorbidities. Under univariable analysis, older age was associated with a lower incidence rate ratio for complications. However, no pre-or-post biopsy measurement or characteristic had a statistically significant change in incidence rate ratio under multivariable analysis. Conclusions Percutaneous kidney biopsies were found to be low risk when performed by nephrologists in this single center cohort. Consistent with past literature, life threatening major complications rarely occurred and were reliably identified within 4 hours of biopsy, suggesting that centers can consider reduced observation times without compromising patient safety. Minor complications, such as pain, were more likely to occur in younger, healthier patients, and in those with hematuria prior to biopsy. This extensive tabulation of all biopsy adverse events is the first of its kind and will be beneficial for nephrologists to inform discussions with patients about expectations and risk-benefit of this procedure.
 
A-C Light microscopy of renal biopsy: Jones Silver (A and B) and Periodic Acid-Schiff (C) staining shows prominence of glomerular peripheral capillary loop cells (arrowheads), predominantly representing swollen endothelial cells. There are segmental areas suggestive for mesangiolysis (B and C: arrows). There is a background of a mild nodular increase in mesangial matrix (A: white asterisk). Peripheral capillary loop glomerular basement membrane double contours are not a prominent finding. There are no peripheral capillary loop thrombi or hyaline pseudothrombi. Focal acute tubular injury is seen (C: black asterisk) (400X magnification). Equipment used: Microscope-Olympus BX53; objective lenses – Olympus U PlanFL N; camera – Olympus DP73; Acquisition software- Olympus cellSens Standard. D Electron microscopy of renal biopsy: glomerular peripheral capillary loops show swollen reactive endothelial cells (arrows) and associated narrowing of capillary lumens. Overlying podocytes show effacement of foot process (arrows). Glomerular basement reduplication and cellular interposition is not seen, and there are no specific granular glomerular electron dense deposits (800X magnification)
Article
Background Glomerular endotheliosis is the pathognomonic glomerular lesion in pre-eclampsia that has also been described in those taking tyrosine kinase inhibitors for cancer treatment. Ibrutinib is a Bruton’s tyrosine kinase inhibitor used to treat chronic lymphocytic leukemia (CLL). We report the first known case of glomerular endotheliosis on kidney biopsy in a patient on ibrutinib monotherapy. Case presentation The patient presented with acute on chronic kidney disease, proteinuria, low C3 and C4 and a high rheumatoid factor titer. A kidney biopsy was performed to confirm a preliminary diagnosis of membranoproliferative glomerulonephritis (MPGN), the most common glomerular disease in patients with CLL. Unexpectedly, the kidney biopsy showed pre-eclampsia-like lesions on light and electron microscopy: occlusion of glomerular peripheral capillary lumens by swollen reactive endothelial cells. Findings of glomerulonephritis were not seen, and there were no specific glomerular immune deposits by immunofluorescence or electron microscopy. Conclusions CLL is known to cause glomerular lesions, mainly MPGN. There is increasing evidence that ibrutinib, a major treatment for CLL, can cause kidney disease, but the precise pathology is not characterized. We present a patient with CLL on ibrutinib with signs of glomerular endotheliosis. Based on the absence of CLL-induced kidney pathologies typically seen on the kidney biopsy and the non-selectivity of ibrutinib, we attributed the glomerular endotheliosis to ibrutinib. In pre-eclampsia, increased soluble fms-like tyrosine kinase 1 (sFlt1) levels induce endothelial dysfunction by decreasing vascular endothelial growth factor (VEGF). Ibrutinib has been demonstrated to have non-selective tyrosine kinase inhibition, including inhibition of VEGF receptor (VEGFR) and epidermal growth factor receptor (EGFR). VEGFR and EGFR inhibitors have recently been described in the literature to cause hypertension, proteinuria, and glomerular endotheliosis. Kidney biopsy should be performed in CLL patients on ibrutinib that present with acute kidney injury (AKI) or proteinuria to determine whether the clinical picture is attributable to the disease itself or a complication of the therapy.
 
Histogram showing distribution of interdialytic (44-hour) urine output (ml) in patients with Residual Kidney Function who had Urine Output ≥100 ml / day (n: 29)
MoCA domains according to RKF status
Article
Background Residual kidney function (RKF) may provide many benefits to patients on permanent renal replacement therapy that are reflected in better control of biochemical parameters. In hemodialysis patients, quality of life (QOL) and cognitive function are often impaired. This study aimed to assess the predictors of RKF and its impact on QOL and cognitive function in chronic hemodialysis patients. Patients and methods The study involved seventy-eight patients suffering from end-stage renal disease on regular hemodialysis. The patients were divided into two groups according to the presence or absence of RKF (24-hour urine volume ≥ 100 ml). Beside basic laboratory investigations, all patients were subjected to Kidney Disease Quality of Life-Short Form (KDQOL-SF) version 1.3 for assessing the quality of life and Montreal cognitive assessment (MoCA) score for assessing cognitive function. Results There was a significantly higher score for KDQOL domains and MoCA score in patients with RKF compared to patients without RKF. There was a significant positive correlation between RKF and both of MoCA score and the physical composite score (PCS) of QOL. Moreover, there were statistically significant positive correlations between the MoCA score and both PCS and mental composite score (MCS). On multivariate analysis, hemodialysis duration was the only predictor for RKF; whereas age was a significant predictor for PCS; and MoCA score could be significantly predicted by the measured RKF and patients’ age. Conclusion HD patients with maintained RKF had better QOL and cognitive function. The duration of HD and the age of the patients were found to be related to RKF and PCS in this study. RKF was associated with the cognitive performance of hemodialysis patients.
 
Percentage of distribution of gastrointestinal system complaints and signs in patients with chronic kidney disease
Percentage of distribution of gastrointestinal system diseases in patients with chronic kidney disease
% Distribution of patients with CKD by the total number of gastrointestinal system symptoms. * SP means SYMPTOM (count of gastrointestinal symptoms)
Article
Objective Chronic kidney disease (CKD) affects gastrointestinal system (GIS) and causes histological, functional and mucosal changes. There are scarce data investigating GIS symptoms and findings in patients with CKD stage III-V, receiving hemodialysis (HD) and peritoneal dialysis (PD). In this study, we aimed to evaluate the frequency of gastrointestinal symptoms and findings and compare between renal replacement therapies. Method A total of 290 patients (97 in CKD stage III-V, 92 PD, 101 HD) were included in this study. Gastrointestinal complaints, diseases, background characteristics of patients and drugs they used were questioned by interviews, forms were filled and examinations of patients were performed. Results of upper GIS endoscopy, colonoscopy, abdominal ultrasonography and tomography of patients were evaluated. Results The most common signs were dyspepsia (50%), nausea (45%) and epigastric pain (44%) among all patients, generally. Gastrointestinal disorders like gastritis (62%) and gastroesophageal reflux (39%) were frequent in patients. Prevalence of patients with weight loss was 20% in predialysis and 8% in PD and the ratio was higher in predialysis group statistically significantly ( p = 0,016). The prevalence of gastritis was 70% in PD, 55% in HD and the prevalence of hemorrhoids was 24% in PD and 12% in HD. The prevalence of gastritis and hemorrhoids was higher in the PD group than in the HD group statistically significantly ( p = 0.043, p = 0.028), otherwise, there wasn’t a difference between the PD and predialysis groups, statistically significantly. Conclusion This study showed that; gastrointestinal symptoms and disorders were very common in CKD, besides this; while gastritis and hemorrhoids were more frequent in the PD, esophagitis and hiatal hernia were more frequent in the HD.
 
a Lymphatic tissue with preserved follicular structure and enlarged interfollicular spaces (hematoxylin and eosin staining, × 100). b Prominent plasmacytoid cells between follicles in lymph nodes. The vitrified blood vessels between the follicles are inconspicuous (hematoxylin and eosin staining, × 400)
Bone marrow showing extensive mild fibrosis (silver staining, × 400)
a-c Light microscopy showing diffuse global endocapillary proliferative changes with endothelial swelling and expansion of the subendothelial space in the glomerulus (periodic acid–Schiff staining, × 400). c Light microscopy showing no evidence of double contours in capillary walls or spike (periodic acid-methenamine silver staining, × 400). d Immunofluorescence studies revealing mesangial deposits of only IgM in the glomerulus
Electron microscopy showing endothelial cell swelling with expansion of the subendothelial space (arrows)
The patient’s clinical course. Abbreviations: CRP: C-reactive protein; PLT: Platelet; Cr: Creatinine; UTP: Urinary Total protein; PSL: Prednisolone
Article
Background TAFRO syndrome is an acute or subacute systemic inflammatory disease with no apparent cause, presenting with fever, generalized edema, thrombocytopenia, renal damage, anemia, and organ enlargement. Interleukin-6, vascular endothelial growth factor, and other cytokines are thought to be the etiologic agents that increase vascular permeability and cause the resulting organ damage. Only few reports of renal biopsy performed in patients with TAFRO syndrome exist. Case presentation A 61-year-old woman, with a history of Sjogren’s syndrome, was admitted to our hospital with anasarca and abdominal distension. Based on the clinical course and various laboratory findings, we diagnosed TAFRO syndrome. Renal biopsy revealed thrombotic microangiopathy, including endothelial cell swelling, subendothelial space expansion, and mesangiolysis. She was treated with oral prednisolone and cyclosporine, with consequent resolution of anasarca, pleural effusion, and ascites, and improvement in renal function and urinary findings. The patient’s platelet count also normalized after 2 months of treatment. Conclusions Given that only few reports of improvement in the systemic symptoms of TAFRO syndrome using steroids and cyclosporine exist, our study investigating the relationship between the pathogenesis of TAFRO syndrome and renal disorders, as well as treatment methods, provides valuable insights.
 
Research algorithm according to Consolidated Standards of Reporting Trials (CONSORT)
Article
Background Gut microbiota dysbiosis in patients with chronic kidney disease on haemodialysis (CKD-HD) creates an increase in proteolytic bacteria activity, leading to an increase in the production of uraemic toxins, such as indoxyl sulphate, worsening of constipation symptoms and reducing patients’ quality of life. Improving gut microbiota dysbiosis is expected to improve this condition. This study aimed to evaluate the effect of synbiotics on indoxyl sulphate levels, constipation symptoms, and constipation-related quality of life in haemodialysis patients. Methods This was a double-blinded randomized controlled clinical trial with a parallel design involving haemodialysis patients. We included chronic haemodialysis patients with gastrointestinal complaints, difficulty defecating, faeces with hard consistency, or a bowel movement frequency of fewer than three times per week. Patients were randomly divided into two groups (synbiotics (Lactobacillus acidophilus and Bifidobacterium longum 5x10⁹ CFU) and placebo) for 60 days of oral intervention. All participants, caregivers, and outcome assessors were blinded to group assignment. The primary outcome was a decrease in indoxyl sulphate toxin levels. Meanwhile, improvement in constipation symptoms (measured using the Patient Assessment of Constipation: Symptoms (PAC-SYM) questionnaire) and improvement in constipation-related quality of life (measured using the Patient Assessment of Constipation Quality of Life (PAC-QOL) questionnaire) were assessed as secondary outcomes. Results We included 60 patients (30 intervention; median age of 51.23 (13.57) years, 33.3% male; 30 control; median age of 52.33 (11.29) years, 36.7% male). There was no significant difference in terms of pre- and postintervention indoxyl sulphate toxin levels in the synbiotics group compared to the placebo group (p=0.438). This study found an improvement in constipation symptoms (p = 0.006) and constipation-related quality of life (p=0.001) after synbiotic administration. Conclusion Two months of synbiotic supplementation did not lower indoxyl sulphate toxin levels. Nevertheless, it had a major effect in improving constipation and quality of life affected by constipation in patients undergoing chronic haemodialysis. Trial registration NCT04527640 (date of first registration: 26/08/2020)
 
A socioecological model of living with frailty and receiving HD, with examples of key themes at each level
Article
Background Frailty is highly prevalent in people receiving haemodialysis (HD) and is associated with poor outcomes. Understanding the lived experiences of this group is essential to inform holistic care delivery. Methods Semi-structured interviews with N = 25 prevalent adults receiving HD from 3 HD units in the UK. Eligibility criteria included a Clinical Frailty Scale (CFS) score of 4–7 and a history of at least one fall in the last 6 months. Sampling began guided by maximum variation sampling to ensure diversity in frailty status; subsequently theoretical sampling enabled exploration of preliminary themes. Analysis was informed by constructivist grounded theory; later we drew upon the socioecological model. Results Participants had a mean age of 69 ± 10 years, 13 were female, and 13 were White British. 14 participants were vulnerable or mildly frail (CFS 4–5), and 11 moderately or severely frail (CFS 6–7). Participants characterised frailty as weight loss, weakness, exhaustion, pain and sleep disturbance arising from multiple long-term conditions. Participants’ accounts revealed: the consequences of frailty (variable function and psychological ill-health at the individual level; increasing reliance upon family at the interpersonal level; burdensome health and social care interactions at the organisational level; reduced participation at the community level; challenges with financial support at the societal level); coping strategies (avoidance, vigilance, and resignation); and unmet needs (overprotection from family and healthcare professionals, transactional health and social care exchanges). Conclusions The implementation of a holistic needs assessment, person-centred health and social care systems, greater family support and enhancing opportunities for community participation may all improve outcomes and experience. An approach which encompasses all these strategies, together with wider public health interventions, may have a greater sustained impact. Trial registration ISRCTN12840463.
 
Article
Background Given the complexity and variety in treatment options for advanced chronic kidney disease (CKD), shared decision-making (SDM) can be a challenge. SDM is needed for making decisions that best suit patients’ needs and their medical and living situations. SDM might be experienced differently by different stakeholders. This study aimed to explore clinical practice and perspectives on SDM in nephrology from three angles: observers, patients and healthcare professionals (HCPs). Methods An explanatory sequential mixed methods design was used. First, in the quantitative part of the study, outpatient consultations with patients with advanced chronic kidney disease (eGFR < 20 ml/min) were video recorded and SDM was assessed using the OPTION⁵ instrument. Subsequently, in the qualitative part, patients and HCPs reflected on their own SDM behaviour during individual stimulated recall interviews which were analysed using deductive thematic content analysis. Results Twenty nine consultations were recorded and observed in seven hospitals. The mean SDM score was 51 (range 25–80), indicating that SDM was applied to a moderate extent. The stimulated recall interviews with patients showed that they rely on the information provision and opinion of HCPs, expect consistency and support, and desire a proactive role. They also expect to be questioned by the HCP about their SDM preferences. HCPs said they were willing to incorporate patients’ preferences in SDM, as long as there are no medical contraindications. They also prefer patients to take a prominent role in SDM. HCPs ascribe various roles to themselves in supporting patients’ decision-making. Conclusions Although SDM was applied by HCPs to a moderate extent, improvement is needed, especially in helping patients get the information they need and in making sure that every patient is involved in SDM. This is even more important given the complex nature of the disease and the relatively high prevalence of limited health literacy among patients with chronic kidney disease.
 
Distribution of the 10-year Framingham risk by gender and tercile of low-grade albuminuria. The 10-year risk of coronary heart disease according to the Framingham score: > 20% = high-risk; 10–20% = intermediate-risk, and < 10% = low-risk instances
Article
Objective To evaluate the presence of LGA and the relationship with the 10-year risk of a cardiovascular event in hypertensive and diabetic patients in Primary Health Care. Study design The study design used is cross-sectional. Methods This study was based on the application of questionnaires, anthropometric measurements, and laboratory tests carried out from August 2017 to April 2018. Logistic regression was used to evaluate the odds ratio of the explanatory variables in relation to the highest tercile of LGA. The Framingham risk score was used to assess the 10-year risk of cardiovascular event. The comparison of this score with the LGA terciles was analyzed using ANOVA. Results An increase in the 10-year risk of cardiovascular event score was observed with an increasing LGA tercile, and this pattern prevailed after adjusting for confounding variables. Conclusion An association between LGA and the 10-year risk of cardiovascular event was observed in a representative sample of hypertensive and diabetic patients.
 
Study flow diagram that showed the process of enrollment and exclusion
Pathologic features of IgA nephropathy associated with Crohn’s disease. A Glomeruli with mild segmental mesangial matrix expansion and mesangial hypercellularity (Periodic acid-Schiff, original magnification × 400). B Glomeruli with segmental mesangial matrix expansion, mesangial hypercellularity, and the not thickened basement membrane (Masson, original magnification × 400). C Glomeruli with massive IgA deposits in the mesangial region (Immunofluorescence, original magnification × 400). D Electron-dense deposits in the mesangial region (Arrow) (Electron microscopy, original magnification × 3000)
Pathologic features of minimal change disease, thin-basement-membrane nephropathy, and interstitial nephritis associated with Crohn’s disease. A Minimal change disease with the diffuse fusion of foot processes (Arrow) (Electron microscopy, original magnification × 4000). B Thin-basement-membrane nephropathy with the basement membrane less than 250 nm and segmentally shriveled (Arrow) (Electron microscopy, original magnification × 800). C Acute interstitial nephritis with predominantly lymphocytes and the irregular oxalate crystals deposited in the lumen of the renal tubules under polarized light (Arrows) (Hematoxylin and eosin, original magnification × 200). D Granulomatous interstitial nephritis with several noncaseating granulomas in the renal interstitium (Arrow) (Hematoxylin and eosin, original magnification × 400)
Article
Background The inflammatory bowel disease, containing Crohn’s disease and ulcerative colitis, was rare in the population, especially in the complication of kidney disease. A few studies had found proteinuria played a potential indicator of inflammatory bowel disease occurrence and activity. This study aimed to better define the histopathologic spectrum and study the outcome of renal disease in Crohn’s disease. Methods A retrospective study of 3557 Crohn's disease from January 1 st , 2016 to July 1 st , 2021 in the Sixth Affiliated Hospital of Sun Yat-sen University identified 20 (0.56% [20/3557]) patients who underwent kidney biopsy. All biopsy specimens were examined by standard procedures containing light microscopy, immunofluorescence, and electron microscopy. Results Twenty cases were shown in this review study. Subnephrotic proteinuria (30% [6 of 20]), persistent hematuria and proteinuria (25% [5 of 20]), and isolated hematuria with acanthocytes (25% [5 of 20]) were the main indications for kidney biopsy. The most common diagnosis was IgA nephropathy (70% [14/20]), followed by minimal change disease (10% [2/20]), acute interstitial nephritis (5% [1/20]), granulomatous interstitial nephritis (5% [1/20]), non-IgA mesangial proliferative nephritis (5% [1/20]) and thin basement membrane nephropathy (5% [1/20]). The Lee classification of IgA nephropathy was mostly II or III level. Glomerular mesangial hyperplasia was the most common pathologic manifestation according to the MEST-C Sore. After twelve-month treatment, the majority of patients turned to complete remission of renal disease by measuring proteinuria, while 3 patients still stayed in the relapse stage and 6 patients turned to partial remission by measuring hematuria. Conclusions IgA nephropathy is the most common kidney biopsy diagnosis in Crohn's disease. Renal damage in Crohn's disease mainly involves the glomerulus, especially the mesangial matrix. After the treatment, proteinuria might be in remission, but hematuria remains.
 
Article
Background To investigate the relationship between serum uric acid levels and glomerular ischemic lesions in patients with immunoglobulin A nephropathy (IgAN) and the relevant risk factors. Methods A total of 86 patients with IgAN and normal renal functions were divided into a hyperuricemia group and a normal serum uric acid group (control group). These patients were further divided into a glomerular ischemic lesions group and a non-glomerular ischemic lesions group (control group) based on the renal biopsy results. The relationship between serum uric acid levels and glomerular ischemic lesions was analysed. Results In patients with IgAN, the prevalence or occurrence of glomerular ischemic lesions was significantly higher in the hyperuricemia group compared with the normal serum uric acid group. Elevated serum uric acid levels are independently associated with glomerular ischemic disease. Conclusion Hyperuricemia in patients with IgAN may lead to glomerular ischemic lesions, and lowering serum uric acid levels may delay the progression of IgAN.
 
Target network comprising of HAVCR1 and its neighbors
HAVCR1 and its neighboring genes
Major deregulated pathways and genes involved
Article
Background Human Kidney Injury Molecule-1, also known as HAVCR-1 (Hepatitis A virus cellular receptor 1), belongs to the cell-surface protein of immunoglobulin superfamily involved in the phagocytosis by acting as scavenger receptor epithelial cells. The study focused on pinpointing the mechanisms and genes that interact with KIM-1. Methods This in-silico study was done from March 2019 to December 2019. The Enrichment and protein-protein interaction (PPI) network carefully choose proteins. In addition, the diagramed gene data sets were accomplished using FunRich version 3.1.3. It was done to unveil the proteins that may affect the regulation of HAVCR1 or may be regulated by this protein. These genes were then further considered in pathway analysis to discover the dysregulated pathways in diabetic nephropathy. The long list of differentially expressed genes is meaningless without pathway analysis. Results Critical pathways that are dysregulated in diabetic nephropathy patients have been identified. These include Immune System (Total = 237, P < 0.05), Innate Immune System (Total = 140, P < 0.05), Cytokine Signaling Immune system (Total = 116, P < 0.05), Adaptive Immune System (Total = 85) and Neutrophil degranulation (Total = 78). Conclusion The top 5 genes that are interacting directly with HIVCR1 include CASP3, CCL2, SPP1, B2M, and TIMP1 with degrees 161, 144, 108, 107, and 105 respectively for Immune system pathways (Innate Immune System, Cytokine Signaling Immune system, Adaptive Immune System and Neutrophil degranulation).
 
Article
Background Alport syndrome is a hereditary kidney disease characterized by hematuria and proteinuria. Although there have been reports of autosomal dominant COL4A4 variants, this is likely an underdiagnosed condition. Improved access to affordable genetic testing has increased the diagnosis of Alport syndrome. As genetic testing becomes ubiquitous, it is imperative that clinical nephrologists understand the benefits and challenges associated with clinical genetic testing. Case Presentation We present a family of Mexican descent with a heterozygous COL4A4 variant (c.5007delC, ClinVar accession numbers: SCV001580980.2, SCV001993731.1) not previously discussed in detail in the literature. The proband received a biopsy diagnosis suggestive of Fabry disease 18 years after she first developed hematuria and progressed to chronic kidney disease stage III. One year later, the proband was provisionally diagnosed with Alport syndrome after a variant of uncertain significance in the COL4A4 gene was identified following targeted family variant testing of her daughter. Upon review of the medical histories of the proband’s children and niece, all but one had the same variant. Of the four with the variant, three display clinical symptoms of hematuria, and/or proteinuria. The youngest of the four, only months old, has yet to exhibit clinical symptoms. Despite these findings there was a considerable delay in synthesizing this data, as patients were tested in different commercial genetic testing laboratories. Subsequently, understanding this family’s inheritance pattern, family history, and clinical symptoms, as well as the location of the COL4A4 variant resulted in the upgrade of the variant’s classification. Although the classification of this variant varied among different clinical genetic testing laboratories, the consensus was that this variant is likely pathogenic. Conclusions This COL4A4 variant (c.5007delC) not yet discussed in detail in the literature is associated with Alport syndrome. The inheritance pattern is suggestive of autosomal dominant inheritance. This report highlights the intricacies of variant interpretation and classification, the siloed nature of commercial genetic testing laboratories, and the importance of a thorough family history for proper variant interpretation. Additionally, the cases demonstrate the varied clinical presentations of Alport syndrome and suggest the utility of early screening, diagnosis, monitoring, and treatment.
 
Demographic Characteristics of Patients at Transplant Referral. A Patient Age (Years) at Transplant Referral. B Patient Sex at Transplant Referral
Transplant Outcomes of Spanish-Speaking Patients at the University of Colorado Hospital between 2015–2017 and 2018–2020
Differences in transplant outcomes between 2015-2017 and 2018-2020
Article
Introduction Hispanic Americans receive disproportionately fewer organ transplants than non-Hispanic whites. In 2018, the Hispanic Kidney Transplant Program (HKTP) was established as at the University of Colorado Hospital (UCH). The purpose of this quality improvement study was to examine the effect of this culturally sensitive program in reducing disparities in kidney transplantation. Methods We performed a mixed-methods analysis of data from 436 Spanish-speaking patients referred for transplant to UCH between 2015 and 2020. We compared outcomes for patients referred between 2015–2017 ( n = 156) to those referred between 2018–2020 ( n = 280). Semi-structured phone interviews were conducted with 6 patients per time period and with 6 nephrology providers in the Denver Metro Area. Patients and providers were asked to evaluate communication, transplant education, and overall experience. Results When comparing the two time periods, there was a significant increase in the percentage of patients being referred (79.5% increase, p-0.008) and evaluated for transplant (82.4% increase, p = 0.02) during 2018–2020. While the number of committee reviews and number waitlisted increased during 2018–2020, it did not reach statistical significance (82.9% increase, p = 0.37 and 79.5% increase, p = 0.75, respectively. During patient and provider interviews, we identified 4 themes reflecting participation in the HKTP: improved communication, enhanced patient education, improved experience and areas for advancement. Overall, patients and providers reported a positive experience with the HKTP and noted improved patient understanding of the transplantation process. Conclusions The establishment of the HKTP is associated with a significant increase in Spanish-speaking Hispanic patients being referred and evaluated for kidney transplantation.
 
Pathological results of renal biopsy. A HE staining; B PAS staining; C PASM staining; D Masson staining. (Scale bars: A-D:10×400)
Electron microscope pathological results. (Scale bars: A 0.5μm; B 1μm)
Sequencing results
Genogram
Article
Background Glomerulopathy with fibronectin deposits (GFND) is a rare autosomal dominant genetic disorder, and proteinuria and hematuria are the most common clinical manifestations. The pathogenesis of this disease is primarily related to mutation of the fibronectin 1 gene. Unfortunately, without specific treatment, the prognosis remains poor. Here we present a case report that investigates the clinical characteristics, renal pathology, and gene testing of childhood GFND. Case presentation A two-year-old child was brought to our hospital for “persistent hematuria for 1 year and 10 months.” The disease onset was at the age of 4 months, with persistent microscopic hematuria accompanied by intermittent gross hematuria, occasionally with proteinuria, and without hypertension or renal failure. The chief complaint was intermittent gross hematuria, without massive proteinuria, hypertension, or renal failure. Family history: The child’s mother had microscopic hematuria, his maternal aunt had nephrotic syndrome due to focal segmental glomerulosclerosis, and his maternal grandmother had end-stage renal disease. No significant pathological changes were found in the renal pathological biopsy of the child under a light microscope. Under the electron microscope, the basement membrane was found to be of uneven thickness, ranging from 150 to 400 nm. The stratum compactum of the basement membrane was thickened, with a small part showing tear-like and cobweb-like morphology. No electron-dense deposits were found. The renal tubular epithelial cells were vacuolated, and there were no unique pathological changes in the renal interstitium. Immunofluorescence showed that IgG, IgM, IgA, C3, and C1q were all negative. Alport syndrome was preliminarily considered. However, exome sequencing revealed a mutated site in the fibronectin 1 gene. The child’s mother was the carrier of the pathogenic gene and the final diagnosis was GFND. Conclusions Fibronectin deposition is a typical pathological change in GFND, and the disease progresses slowly to end-stage renal disease. There is no specific treatment so far, and the prognosis is poor. The early onset of childhood patients may not show typical renal pathological changes, but only changes in the thickness of basement membrane, etc. Genome sequencing technology may helpful for the early diagnosis of GFND.
 
Pathological findings of three cases. a Case 1: mesangiolysis, and fragmented red blood cells (arrow) in the glomeruli (HE × 400). b Case 1: glomerular endothelial cell swelling and inflammatory cell (arrow) infiltration (PAS × 400). c Case 2: thickening of walls and narrowing of the lumen of arteriole (black arrow) with fragmented red blood cells (red arrow) (PASM × 200). d Case 3: the first allograft biopsy showed glomerular inflammatory cell (arrow) infiltration (PAS × 200). e Case 3: the second graft biopsy appeared an "Onion skin" pattern lesion (arrow) in the arteriole (PAS × 200)
Hypothesis based on our case series: both recipients and donors carried the complement genetic abnormality, contributing to the continuous injury of endothelial cells and leading to early graft loss after activation of TMA by triggers in our case series. Advice for these patients: (1) before transplantation, recipients with kidney disease of unknown etiology may consider complement genetic testing. A deceased donor kidney transplant should be recommended if testing reveals complement genetic variant in both donor and recipient; (2) after transplantation, intensive monitoring and timely treatment of triggers are critical. Besides, surveillance allograft biopsy, more testing, and exome sequence may help to diagnosis; (3) since diagnosis of post-transplant TMA, early anti-complement treatment is necessary. LKT, living-relative kidney disease; DD, deceased donor; ABMR, antibody-mediated rejection; CNIs, calcineurin inhibitors; TMA, thrombotic microangiopathy; LDH, lactic dehydrogenase; PE, plasma exchange
Article
Background Recently, early graft loss has become very rare in living-related kidney transplantation (LKT) as a result of decreased risk of hyperacute rejection and improvements in immunosuppressive regimens. Post-transplant acute thrombotic microangiopathy (TMA) is a rare, multi-factorial disease that often occurs shortly after kidney transplantation and is usually resistant to treatment with dismal renal outcomes. The complement genetic variants may accelerate the development of TMA. However, the complement genetic test was seldom performed in unknown native kidney disease recipients scheduled for LKT. Case presentation We reported three cases of unknown native kidney diseases who had fulminant TMA in the allograft shortly after LKT. Both the donors and the recipients were noted to carry complement genetic variants, which were identified by genetic testing after transplantation. However, all recipients were refractory to treatment and had allograft loss within 3 months after LKT. Conclusion This case series highlights the suggestion to screen complement gene variants in both the donors and the recipients with unknown native kidney diseases scheduled for LKT.
 
Sagittal T2-weighted whole spine magnetic resonance imagings (MRIs) of the patient indicating syringomyelia at T2–T7 level (arrow)
Article
Background Distal renal tubular acidosis (dRTA) is the most common type of renal tubular acidosis (RTA) in children. Pediatric dRTA is usually genetic and rarely occurs due to acquired issues such as obstructive uropathies, recurrent urinary tract infections (UTIs), and chronic kidney disease (CKD). Although persistent hypokalemia frequently occurs with dRTA, acute hypokalemic paralysis is not frequently reported, especially in older children. Case presentation An eight-year-old girl presented with an acute first episode of paralysis. A physical examination revealed normal vital signs, short stature consistent with her genetic potential, and decreased muscle strength of her upper and lower extremities. Preexisting conditions included stage 4 CKD due to recurrent UTIs, severe vesicoureteral reflux and bilateral hydronephrosis, neurogenic bladder, and multisegment thoracic syringomyelia. Her laboratory work-up revealed hypokalemic, hyperchloremic metabolic acidosis with a normal anion gap. She also had a urine osmolal gap of 1.9 mOsmol/kg with a high urine pH. Intravenous potassium replacement resulted in a complete resolution of her paralysis. She was diagnosed with dRTA and discharged with oral bicarbonate and slow-release potassium supplementation. Conclusions This case report highlights the importance of considering dRTA in the differential diagnosis of hypokalemic acute paralysis in children. Additionally, in children with neurogenic lower urinary tract dysfunction and recurrent UTIs, early diagnosis of spinal cord etiology is crucial to treat promptly, slow the progression of CKD, and prevent long-term complications such as RTA.
 
Feature selection by the least absolute shrinkage and selection operator (LASSO) model. A LASSO coefficient profiles of 25 clinical and pathological features. B The deviance profiles of LASSO Cross-Validation
Nomogram of prediction model based on derivation. Sex: 1. male, 2. female; age:1. < 55 yr, 2. > 55 yr; GBM: 1. stage I, 2. stage II; hypertensive nephropathy: 1. patients with comorbidity of hypertensive nephropathy, 0. without hypertensive nephropathy; Diuretics: 1. patients with diuretic use, 0. without diuretic use
The calibration curves of the nomogram Model in derivation cohort. A predictive recovery probability and observational recovery probability during 12 months; B predictive recovery probability and observational recovery probability during 3 months
The calibration curves of the nomogram Model in validation cohort. A, predictive recovery probability and observational recovery probability during 12 months; B, predictive recovery probability and observational recovery probability during 3 months
Five determinants for predicting recovery base on Cox regression
Article
Background and objectives The clinical and pathological impact factors for renal function recovery in acute kidney injury (AKI) on the progression of renal function in primary membranous nephropathy (PMN) with AKI patients have not yet been reported, we sought to investigate the factors that may influence renal function recovery and develop a nomogram model for predicting renal function recovery in PMN with AKI patients. Methods Two PMN with AKI cohorts from the Nephrology Department, the First Affiliated Hospital of Wenzhou Medical University during 2012–2018 and 2019–2020 were included, i.e., a derivation cohort during 2012–2018 and a validation cohort during 2019–2020. Clinical characteristics and renal pathological features were obtained. The outcome measurement was the recovery of renal function within 12 months. Lasso regression was used for clinical and pathological features selection. Prediction model was built and nomogram was plotted. Model evaluations including calibration curves were performed. Result Renal function recovery was found in 72 of 124 (58.1%) patients and 41 of 72 (56.9%) patients in the derivation and validation cohorts, respectively. The prognostic nomogram model included determinants of sex, age, the comorbidity of hypertensive nephropathy, the stage of glomerular basement membrane and diuretic treatment with a reasonable concordance index of 0.773 (95%CI,0.716–0.830) in the derivation cohort and 0.773 (95%CI, 0.693–0.853) in the validation cohort. Diuretic use was a significant impact factor with decrease of renal function recovery in PMN with AKI patients. Conclusion The predictive nomogram model provides useful prognostic tool for renal function recovery in PMN patients with AKI.
 
Article
Introduction Over half of the patients with hepatitis B virus associated membranous nephropathy (HBV-MN) were found to be phospholipase A2 receptor (PLA2R) positive. Whether MN is really secondary to hepatitis B or just coincidence of hepatitis and PLA2R positive idiopathic MN (IMN) remains controversial. Methods We retrospectively studied seven PLA2R positive HBV-MN patients with complete data in Huashan Hospital from 2009 to 2016 and compared them with PLA2R positive idiopathic MN patients. Results Proteinuria and renal function of these 7 HBV-MN patients were similar to that of IMN patients. However, 5 of them were female and half showed hypocomplementemia, while in IMN group only 32.4% were female and 20% had hypocomplementemia, and the level of hematuria was 94.5/μL in HBV-MN patients and 64.9 /μL in IMN patients, though there was no statistically significant difference. Renal biopsies revealed significantly increased mesangial eletron-deposits in HBV-MN patients. All 7 patients received antiviral therapy, and one patient received immunosuppresants due to severe nephrotic syndrome with acute myocardial infarction and elevated serum creatinine. Compared with IMN group, the prevalence of remission without immunosuppressive therapy of HBV-MN patients was higher (85.7% vs. 43.7%), while the percentage of patients receiving immunosuppresants was lower (14.3% vs. 47.9%) (P=0.048). Conclusion Compared with IMN patients, PLA2R positive HBV-MN patients had a more favorable prognosis after antiviral therapy, indicating a secondary form of MN. For these patients, antiviral treatment is recommended and long observation time should be provided before use of immunosuppressive treatment.
 
Changes in Study Clinical Values. A Change in Serum Phosphorus. B Change in Serum Albumin. C Change in Phosphorus Attuned Albumin. BL, baseline visit; M3, month-3 visit; M6, month-6 visit. * P value < 0.05
Article
Background Hyperphosphatemia is common in patients on peritoneal dialysis (PD). Restricting dietary phosphorus often leads to a decrease in protein intake, which may result in hypoalbuminemia. The high pill burden of phosphate binders may also contribute to compromised appetite and dietary intake. Hypoalbuminemia is associated with an increased risk of morbidity and mortality in PD patients. The goal of this study was to determine if sucroferric oxyhydroxide improves albumin and self-reported measures of appetite in PD patients. Methods We performed a prospective, open-label, 6-month, pilot study of 17 adult PD patients from the Denver Metro Area. Patients had to use automated peritoneal dialysis for ≥ 3 months, have a serum albumin ≤ 3.8 g/dL, and have serum phosphate ≥ 5.5 mg/dL or ≤ 5.5 mg/dL on a binder other than SO. SO was titrated to a goal serum phosphate of < 5.5 mg/dL. The primary outcome was change in serum phosphate, albumin, and phosphorus-attuned albumin (defined as albumin divided by phosphorus) over 6 months. Results The mean (SD) age and dialysis vintage was 55 ± 13 years and 3.8 ± 2.7 years, respectively. Participants’ serum phosphate significantly decreased with fewer phosphate binder pills/day after switching to SO. There was no change in serum albumin, appetite, or dietary intake. However, participants had significant improvements in phosphorus-attuned albumin. Conclusion The transition to SO improved phosphorus control, phosphorus-attuned albumin, and pill burden. There were no significant changes in self-reported appetite or dietary intake during the study. These findings suggest that PD patients maintained nutritional status with SO therapy. Trial registration First registered at ClinicalTrials.gov ( NCT04046263 ) on 06/08/2019.
 
Participant Goal Categories. * Types of physical discomfort included worry about eyes, sleep, teeth, pain, and dressings. * Ceremony refers to gatherings that reflect the diversity of cultural and spiritual practices within communities and that help pass down this rich cultural knowledge.* Sorry business refers to cultural practices and protocols associated with death
Three broad themes within participant goal setting
Article
Background The high burden of chronic kidney disease in First Nations peoples requires urgent attention. Empowering people to self-manage their own condition is key, along with promotion of traditional knowledge and empowerment of First Nations communities. This study explores the potential of a culturally responsive tool, already found to have high acceptability and feasibility among First Nations people, to support self-management for First Nations people with kidney failure. The Stay Strong app is a holistic wellbeing intervention. This study explores the suitability of the Stay Strong app to support self-management as shown by the readiness of participants to engage in goal setting. Data were collected during a clinical trial which followed adaption of research tools and procedures through collaboration between content and language experts, and community members with lived experience of kidney failure. Methods First Nations (i.e., Aboriginal and Torres Strait Islander) participants receiving haemodialysis in the Northern Territory ( n = 156) entered a three-arm, waitlist, single-blind randomised controlled trial which provided collaborative goal setting using the Stay Strong app at baseline or at 3 months. Qualitative data gathered during delivery of the intervention were examined using both content and thematic analysis. Results Almost all participants (147, 94%) received a Stay Strong session: of these, 135 (92%) attended at least two sessions, and 83 (56%) set more than one wellbeing goal. Using a deductive approach to manifest content, 13 categories of goals were identified. The three most common were to: ‘connect with family or other people’, ‘go bush/be outdoors’ and ‘go home/be on country’. Analysis of latent content identified three themes throughout the goals: ‘social and emotional wellbeing’, ‘physical health’ and ‘cultural connection’. Conclusion This study provides evidence of the suitability of the Stay Strong app for use as a chronic condition self-management tool. Participants set goals that addressed physical as well as social and emotional wellbeing needs, prioritising family, country, and cultural identity. The intervention aligns directly with self-management approaches that are holistic and prioritise individual empowerment. Implementation of self-management strategies into routine care remains a key challenge and further research is needed to establish drivers of success.
 
Article
Background: Lupus nephritis (LN) is a common and serious complication of systemic lupus erythematosus (SLE). However, the aetiology and pathogenesis of LN remain unknown. 1,25-dihydroxyvitamin D3 [1,25-(OH)2-VitD3] is the active form of vitamin D, and it has been shown to perform important functions in inflammatory and immune-related diseases. In this study, we investigated the time-dependent effects of 1,25-dihydroxyvitamin D3 and explored the underlying mechanism in MRL/lpr mice, a well-studied animal model of LN. Methods: Beginning at 8 weeks of age, 24-h urine samples were collected weekly to measure the levels of protein in the urine. We treated female MRL/lpr mice with 1,25-dihydroxyvitamin D3 (4 μg/kg) or 1% DMSO by intraperitoneal injection twice weekly for 3 weeks beginning at the age of 11 weeks. The mice were separately sacrificed, and serum and kidney samples were collected at the ages of 14, 16, 18, and 20 weeks to measure creatinine (Cr) levels, blood urea nitrogen (BUN) levels, histological damage, immunological marker (A-ds DNA, C1q, C3, IgG, IgM) levels, and inflammatory factor (TNF-α, IL-17, MCP-1) levels. Furthermore, the nuclear factor kappa B (NF-κB) and the mitogen-activated protein kinase (MAPK) signalling pathways were also assessed to elucidate the underlying mechanism. Results: We found that MRL/lpr mice treated with 1,25-dihydroxyvitamin D3 displayed significantly attenuated LN. VitD3-treated mice exhibited significantly improved renal pathological damage and reduced proteinuria, BUN, SCr, A-ds DNA antibody and immune complex deposition levels (P < 0.05) compared with untreated MRL/lpr mice. Moreover, 1,25-dihydroxyvitamin D3 inhibited the complement cascade, inhibited the release of proinflammatory cytokines, such as TNF-α, IL-17, and MCP-1, and inhibited NF-κB and MAPK activation (P < 0.05). Conclusion: 1,25-dihydroxyvitamin D3 exerts a protective effect against LN by inhibiting the NF-κB and MAPK signalling pathways, providing a potential treatment strategy for LN. Interestingly, the NF-κB and MAPK signalling pathways are time-dependent mediators of LN and may be associated with lupus activity.
 
First Kidney Biopsy. a Hematoxylin and eosin (H&E) stain shows glomeruli with rigid and mildly thickened capillary walls. b PAS reveals glomerulus with rigid and mildly thickened capillary walls. c, d Immunofluorescence demonstrates 3 + IgG and 2 + C3 granular staining with capillary loop predominance. e Electron microscopy shows numerous electron dense subepithelial deposits with diffuse overlying effacement of the podocyte foot processes
Second Kidney Biopsy. a Hematoxylin and eosin (H&E) stain shows glomeruli with endocapillary hypercellularity including neutrophils and eosinophils. A few glomeruli showed cellular crescents (black arrow). b Spike lesions were noted on the silver stain (yellow arrow). c, d Granular and global staining of IgG and C3, predominantly on the capillary loops on immunofluorescence. e Electron microscopy shows numerous electron dense subepithelial deposits with diffuse overlying effacement of the podocyte foot processes. Several “hump” lesions were identified (red arrow)
Article
Background The clinical trajectory for patients with primary membranous nephropathy ranges widely from spontaneous remission to a rapid decline in kidney function. Etiologies for rapid progression with membranous nephropathy include concurrent bilateral renal vein thrombosis, malignant hypertension, and crescentic membranous nephropathy. Given the wide heterogeneity in prognosis, timing of immunosuppressive therapy is often challenging and centers around an individual patient’s perceived risk for rapidly progressive disease. Case presentation Herein, we describe the clinical course of a young patient who initially developed a typical presentation of membranous nephropathy with consistent kidney biopsy findings. Given clinical stability, a six month observation period was undertaken prior to initiating immunosuppression. Within this observation window, the patient developed community acquired pneumonia followed several weeks later by a sudden, rapid decline in kidney function requiring dialysis. Repeat kidney biopsy revealed post-infectious glomerulonephritis superimposed upon a background of membranous nephropathy. Immunosuppressive therapy resulted in a favorable long-term outcome with normalization of kidney function and remission of nephrotic syndrome. To our knowledge, this is the first report of the simultaneous occurrence of these two glomerular disease processes. Conclusion This case illustrates the value of repeat kidney biopsy during an atypical course of membranous nephropathy. Superimposed glomerular disease processes should be considered during a course of rapidly progressive membranous nephropathy.
 
Covid-19 KTR (n-218)
Article
Background COVID-19 infection is considered to cause high mortality in kidney transplant recipients (KTR). Old age, comorbidities and acute kidney injury are known risk factors for increased mortality in KTR. Nevertheless, mortality rates have varied across different regions. Differences in age, comorbidities and varying standards of care across geographies may explain some variations. However, it is still unclear whether post-transplant duration, induction therapy, antirejection therapy and co-infections contribute to increased mortality in KTR with COVID-19. The present study assessed risk factors in a large cohort from India. Methods A matched case–control study was performed to analyze risk factors for death in KTR (N = 218) diagnosed with COVID-19 between April 2020 to July 2021 at the study centre. Cases were KTR who died (non-survivors, N = 30), whereas those who survived were taken as controls (survivors, N = 188). Results A high death-to-case ratio of 13.8% was observed amongst study group KTR infected with COVID-19. There was a high incidence (12.4%) of co-infections, with cytomegalovirus being the most common co-infection among non-survivors. Diarrhea, co-infection, high oxygen requirement, and need for mechanical ventilation were significantly associated with mortality on regression analyses. Antirejection therapy, lymphopenia and requirement for renal replacement therapy were associated with worse outcomes. Conclusions The mortality was much higher in KTR who required mechanical ventilation and had co-infections. Mortality did not vary with the type of transplant, post-transplant duration and usage of depletion induction therapy. An aggressive approach has to be taken for an early diagnosis and therapeutic intervention of associated infections.
 
The change of urine output (solid line) and serum creatinine (dashed line) after transplantation. *Hemodialysis was done second and fourth day after transplantation
Doppler USG showing 28 mm in depth hematoma (A) and diastolic flow reversal (resistive index = 0.9–1) (B)
Subcapsular hematoma covering about 75% of the entire kidney surface area
Article
Background Page kidney (PK) is the occurrence of kidney hypoperfusion and ischemia due to pressure on the kidney by a subcapsular hematoma (SH), a mass, or fluid collection. SH after renal transplantation may result in kidney ischemia and graft loss. Case presentation We present a rare case of early spontaneous SH in an allograft kidney that led to a decrease in renal function. A 56-year-old male patient underwent deceased donor kidney transplantation. After declamping, appropriate renal perfusion and immediate diuresis were observed, with no evidence of SH. However, his urinary output abruptly decreased 6 h postoperatively. Abdominal ultrasonography showed 28 mm deep SH on transplant and the resistive index (RI) increased to 0.98–1 and diastolic flow reversal was observed. Surgical interventions were performed 2 days after transplantation, following a further decrease in urinary output. Serum creatinine decreased to 2.2 mg/dL, urinary output increased to an average of 200 cc per hour and the RI value was decreased to 0.7 on POD 7. Conclusion In patients with abrupt decreased renal function after transplantation, SH should be suspected and the presence of PK should be determined using Doppler USG. In these cases, surgical intervention may avoid allograft dysfunction.
 
Patient flow chart from enrollment to end of the study: Flow chart shows that 717 patients were screen, 360 excluded basing on exclusion criteria
Comparison of prevalence of kidney disease basing on proteinuria ≥  + 1 and or KDIGO eGFR criteria of < 60 ml/min/1.73m² calculated by various eGFR creatinine-based equations. Bar chart shows that among the 357 patients enrolled in the study, both FAS and CKD EPI 2009 without race factor equations and or proteinuria of ≥  + 1 revealed the highest overall prevalence of kidney disease at 27.2% while CKD EPI 2009 with race factor and or proteinuria of ≥  + 1 showed the lowest overall prevalence of kidney disease at 23%. N = Number of patients enrolled in the study
Comparison of prevalence of kidney disease using KDIGO eGFR criteria (< 60 ml/min/1.73m²) for defining CKD vs age adapted eGFR thresholds for CKD definition. Bar chart shows that KDIGO eGFR criteria of < 60 ml/min/1.73m² for defining CKD identifies 0.3–3% slightly more patients with kidney disease than age adapted eGFR thresholds for CKD definition while using all eGFR serum creatinine-based equations. N = Number of patients enrolled in the study
Comparison of prevalence of CKD at ≥ 90 days determined by of proteinuria ≥ 1 + and or KDIGO eGFR criteria of < 60 ml/min/1.73m² using various eGFR serum creatinine-based equations. Bar chart shows that CKD confirmed by proteinuria ≥  + 1 and/or KDIGO eGFR criteria of < 60 ml/min/1.73m² determined by CKD EPI 2009 without race factor identified the highest number of patients with CKD at 15.1% while CKD EPI 2009 with race factor identified the least number of patients at 12.8%
Comparison of prevalence of CKD after 90 days using KDIGO eGFR criteria of < 60mls/minute Vs age adapted eGFR thresholds to define CKD. Bar chart shows that KDIGO definition of CKD by eGFR < 60mls/minute/1.73m² identifies slightly more patients with CKD than age adapted eGFR thresholds for CKD across most eGFR serum creatinine-based equations: FAS 13.5% vs 12.3%, CKD EPI 2021 14.1% vs 13.4%, CKD EPI 2009 without race 14.9% vs 13% respectively
Article
Background Despite estimated glomerular filtration rate (eGFR) being the best marker for kidney function, there are no studies in sub-Saharan Africa comparing the performance of various equations used to determine eGFR. We compared prevalence of kidney disease determined by proteinuria of ≥ + 1 and or kidney disease improving global outcomes (KDIGO) eGFR criteria of < 60 ml/minute/1.73m² determined using three creatinine-based equations among patients admitted on medical ward of Masaka Regional Referral Hospital. Methods This was a prospective study conducted among adult patients admitted on medical wards between September 2020 to March 2021. Spot urine samples were collected to assess for proteinuria and blood samples were collected to assess serum creatinine levels. Kidney disease was defined as proteinuria of ≥ 1 + on spot urine dipstick and or KDIGO eGFR criteria of < 60 ml/minute/1.73m². Estimated glomerular filtration rate was calculated using three creatinine-based equations: a) Full Age Spectrum equation (FAS), b) chronic kidney disease-Epidemiology collaboration (CKD-EPI) 2021 equation, c) CKD EPI 2009 (without and with race factor) equation. CKD was determined after followed up at 90 days post enrollment to determine the chronicity of proteinuria of ≥ + 1 and or KDIGO eGFR criteria of < 60mls /minute/1.73m². We also compared prevalence of CKD determined by KDIGO eGFR criteria of < 60mls /minute/1.73m² vs age adapted eGFR threshold criteria for defining CKD. Results Among the 357 patients enrolled in the study, KDIGO eGFR criteria of < 60mls / minute determined using FAS and CKD-EPI 2009 without race factor equations and or proteinuria of ≥ + 1 showed the highest overall prevalence of kidney disease at 27.2%. Prevalence of confirmed CKD at 90 days was highest with proteinuria ≥ + 1 and or KDIGO eGFR criteria of < 60mls/min determined using CKD EPI 2009 without race factor Equation (15.1%). Conclusions Use of KDIGO eGFR criteria of < 60mls / minute /1.73m² using FAS and CKD-EPI 2009 without race equations identifies the largest number of patients with CKD. Health care systems in sub-Saharan Africa should calculate eGFR using FAS equations or CKD-EPI 2009 without race equations during basic screening and management protocols.
 
Infographics of MANOS Round 1 data collection process which were shared with workers.
Round 1 data collection process at the work site.
Cohort derivation.
Article
Background Mortality from chronic kidney disease of unknown etiology (CKDu) is extremely high along the Pacific coast of Central America, particularly among sugarcane workers. The Mesoamerican Nephropathy Occupational Study (MANOS) is a prospective cohort study of CKDu among agricultural and non-agricultural workers in El Salvador and Nicaragua. The objective of this manuscript is to describe the MANOS cohort recruitment, baseline data collection, and CKDu prevalence after two rounds. Methods Workers with no known diabetes, hypertension, or CKD were recruited from sugarcane, corn, plantain, brickmaking, and road construction industries (n = 569). Investigators administered questionnaires, collected biological samples, and observed workers for three consecutive workdays at the worksite. Serum specimens were analyzed for kidney function parameters, and used to calculate estimated glomerular filtration rate (eGFR). At six months, serum was collected again prior to the work shift. CKD at baseline is defined as eGFR ≤ 60 ml/min/1.73m² at both timepoints. Age-standardized prevalence was calculated by industry, country, and demographic measures. Kidney function parameters were compared by CKD status. Results Prevalence of CKD at baseline was 7.4% (n = 42). Age-standardized prevalence was highest in Salvadoran sugarcane (14.1%), followed by Salvadoran corn (11.6%), and Nicaraguan brickmaking (8.1%). Nicaraguan sugarcane had the lowest prevalence, likely due to kidney function screenings prior to employment. Conclusion Despite efforts to enroll participants without CKD, our identification of prevalent CKD among agricultural and non-agricultural workers in the MANOS cohort indicates notable kidney disease in the region, particularly among sugarcane workers.
 
Overview of PtDA development. PtDA = Patient decision aid
Overview of PtDA integration in Dutch advanced CKD care pathway. PtDA = Patient decision aid, LDKT = Living donation kidney transplantation, DDKT = Deceased donation kidney transplantation, PD = Peritoneal dialysis, HD = Haemodialysis, CCM  = Conservative care management
Survival probabilities in the ‘Kidney Failure Decision Aid’. LDKT  Living donation kidney transplantation, DDKT  Deceased donation kidney transplantation, CCM  Conservative care management. *Note: this is a translation from Dutch to English
The three components of the ‘Kidney Failure Decision Aid’. SDM = shared decision-making. *Note: this is a translation from Dutch to English
Article
Background Patient decision aids (PtDAs) support patients and clinicians in shared decision-making (SDM). Real-world outcome information may improve patients’ risk perception, and help patients make decisions congruent with their expectations and values. Our aim was to develop an online PtDA to support kidney failure treatment modality decision-making, that: 1) provides patients with real-world outcome information, and 2) facilitates SDM in clinical practice. Methods The International Patient Decision Aids Standards (IPDAS) development process model was complemented with a user-centred and convergent mixed-methods approach. Rapid prototyping was used to develop the PtDA with a multidisciplinary steering group in an iterative process of co-creation. The results of an exploratory evidence review and a needs-assessment among patients, caregivers, and clinicians were used to develop the PtDA. Seven Dutch teaching hospitals and two national Dutch outcome registries provided real-world data on selected outcomes for all kidney failure treatment modalities. Alpha and beta testing were performed to assess the prototype and finalise development. An implementation strategy was developed to guide implementation of the PtDA in clinical practice. Results The ‘Kidney Failure Decision Aid’ consists of three components designed to help patients and clinicians engage in SDM: 1) a paper hand-out sheet, 2) an interactive website, and 3) a personal summary sheet. A ‘patients-like-me’ infographic was developed to visualise survival probabilities for each treatment modality on the website. Other treatment outcomes were incorporated as event rates (e.g. hospitalisation rates) or explained in text (e.g. the flexibility of each treatment modality). No major revisions were needed after alpha and beta testing. During beta testing, some patients ignored the survival probabilities because they considered these too confronting. Nonetheless, patients agreed that every patient has the right to choose whether they want to view this information. Patients and clinicians believed that the PtDA would help patients make informed decisions, and that it would support values- and preferences-based decision-making. Implementation of the PtDA has started in October 2020. Conclusions The ‘Kidney Failure Decision Aid’ was designed to facilitate SDM in clinical practice and contains real-world outcome information on all kidney failure treatment modalities. It is currently being investigated for its effects on SDM in a clinical trial.
 
Kaplan–Meier analysis of composite adverse renal outcome in patients received Mycophenolate
Aetiology of infections organ system (Top) and organisms (Bottom)
Article
Background: Lupus nephritis is a common manifestation of Systemic Lupus Erythematosus. Mycophenolate is recommended by guidelines for induction therapy in patients with proliferative lupus nephritis and nephrotic range proteinuria Class V lupus nephritis. Indigenous Australians suffer disproportionally from systemic lupus erythematosus compared to non-Indigenous Australians (Anstey et al., Aust N Z J Med 23:646-651, 1993; Segasothy et al., Lupus 10:439-444, 2001; Bossingham, Lupus 12:327-331, 2003; Grennan et al., Aust N Z J Med 25:182-183, 1995). Methods: We retrospectively identified patients with newly diagnosed biopsy-proven class III lupus nephritis, class IV lupus nephritis and class V lupus nephritis with nephrotic range proteinuria from 1st Jan 2010 to 31st Dec 2019 in our institution and examined for the patterns of prescribed induction therapy and clinical outcome. The primary efficacy outcome of interest was the incidence of complete response (CR) and partial response (PR) at one-year post diagnosis as defined by the Kidney Disease: Improving Global Outcome (KDIGO) guideline. Secondary efficacy outcome was a composite of renal adverse outcome in the follow-up period. Adverse effect outcome of interest was any hospitalisations secondary to infections in the follow-up period. Continuous variables were compared using Student's t-test or Mann-Whitney U-test. Categorical variables were summarised using frequencies and percentages and assessed by Fisher's exact test. Time-to-event data was compared using the Kaplan-Meier method and Log-rank test. Count data were assessed using the Poisson's regression method and expressed as incident rate ratio. Results: Twenty of the 23 patients included in the analysis were managed with mycophenolate induction upfront. Indigenous Australian patients (N = 15), compared to non-Indigenous patients (N = 5) received lower cumulative dose of mycophenolate mofetil over the 24 weeks (375 g vs. 256 g, p < 0.05), had a non-significant lower incidence of complete remission at 12 months (60% vs. 40%, p = 0.617), higher incidence of composite renal adverse outcome (0/5 patients vs. 5/15 patients, p = 0.20) and higher incidence of infection related hospitalisations, (incident rate ratio 3.66, 95% confidence interval 0.89-15.09, p = 0.073). Conclusion: Mycophenolate as upfront induction in Indigenous Australian patients were associated with lower incidence of remission and higher incidence of adverse outcomes. These observations bring the safety and efficacy profile of mycophenolate in Indigenous Australians into question.
 
Details of accidental falls in patients undergoing hemodialysis (HD). Frequency of accidental falls in a year, b season, c timing, d location, and e action are shown
Correlation between the frequency of falls and balance functions. Correlation of frequency of accidental falls with timed-up-and-go test (TUG) at pre-a and post-b hemodialysis (HD) treatment, and length of center of pressure (CoP) at pre-c and post-d HD treatment are shown
Article
Background: Patients with chronic kidney disease undergoing hemodialysis (HD) have a high incidence of falls. Impairment of balance function is a risk factor for falls in the general elderly, and no report examining the association between balance dysfunction and fall incidence in HD patients exists. Methods: This prospective cohort study was conducted at a single center. The timed-up-and-go test (TUG) as a dynamic balance function was performed and length of the center of pressure (CoP) as a static balance function was measured before and after the HD session at baseline. Data of the number and detailed information of accidental falls for 1 year were collected. Multiple regression analyses were performed to assess the relationships between the number of falls and balance function. Results: Forty-three patients undergoing HD were enrolled in the study. During 1 year of observation, 24 (55.8%) patients experienced accidental falls. TUG time was longer, and CoP was shorter in the post-HD session than in the pre-HD session. Adjusted multiple regression analyses showed that the number of accidental falls was independently associated with TUG time in the pre-HD session (B 0.267, p < 0.001, R2 0.413) and that in the post-HD session (B 0.257, p < 0.001, R2 0.530), but not with CoP. Conclusions: Dynamic balance was associated with fall incidence in maintenance HD patients. The evaluation and intervention of dynamic balance function might reduce the risk of falls in HD patients. Trial registration: This study was carried out with the approval of the Niigata Rinko Hospital Ethics Committee (approval number 2005-92) (Registered on December 11, 2019) and registered in The University Hospital Medical Information Network (registration number 000040618 ).
 
Article
Background The all-cause mortality of patients undergoing hemodialysis (HD) is higher than in the general population. The first 6 months after dialysis are important for new patients. The aim of this study was to develop and validate a nomogram for predicting the 6-month survival rate of HD patients. Methods A prediction model was constructed using a training cohort of 679 HD patients. Multivariate Cox regression analyses were performed to identify predictive factors. The identified factors were used to establish a nomogram. The performance of the nomogram was assessed using the C-index and calibration plots. The nomogram was validated by performing discrimination and calibration tests on an additional cohort of 173 HD patients. Results During a follow-up period of six months, 47 and 16 deaths occurred in the training cohort and validation cohort, respectively, representing a mortality rate of 7.3% and 9.2%, respectively. The nomogram comprised five commonly available predictors: age, temporary dialysis catheter, intradialytic hypotension, use of ACEi or ARB, and use of loop diuretics. The nomogram showed good discrimination in the training cohort [C-index 0.775(0.693–0.857)] and validation cohort [C-index 0.758(0.677–0.836)], as well as good calibration, indicating that the performance of the nomogram was good. The total score point was then divided into two risk classifications: low risk (0–90 points) and high risk (≥ 91 points). Further analysis showed that all-cause mortality was significantly different between the high-risk group and the low-risk group. Conclusions The constructed nomogram accurately predicted the 6-month survival rate of HD patients, and thus it can be used in clinical decision-making.
 
Flow chart of study
Prevalence of metabolic syndrome components by phenotype obesity
Article
Background Investigating the effect of metabolic disorders on chronic kidney disease (CKD) in the presence or the absence of obesity is of great importance. This study aimed to examine the independent and joint relationships of obesity and metabolic syndrome (MetS) with CKD. Methods The present study was performed on 9,762 participants from the baseline phase of the Ravansar non- communicable diseases (RaNCD) study. Thereafter, the CKD was estimated by glomerular filtration rate (eGFR) using the Modification of Diet in Renal Disease (MDRD) equation. All the included participants were categorized into the following four phenotypes: metabolically healthy non-overweight/obesity (MHNO), metabolically unhealthy non-overweight/obesity (MUNO), metabolically healthy overweight/obesity (MHO), and metabolically unhealthy overweight/obesity (MUO). Finally, Logistic regression analysis was used to estimate the odds ratio (ORs). Results The mean age of the included participants was 47.33 ± 8.27 years old, %48.16 (4,701) of whom were men. As well, 1,058(10.84%) participants had CKD (eGFR less than 60 ml/min/1.73m ² ). The overweight/obesity was not significantly associated with odds of CKD. The odds of CKD in male subjects with MetS was 1.48 times higher than non-MetS ones (95% CI: 1.10, 2.01). After adjusting the confounders, the odds of CKD were 1.54 times (95% CI: 1.12, 2.11) higher in the MUNO and 2.22 times (95% CI: 1.44, 3.41) higher in the MUO compared to MHNO phenotype in male subjects. The odds of CKD in the MUNO and MUO was 1.31 times (95% CI: 1.10, 1.60) and 1.23 times (95% CI: 1.01, 1.54) higher than MHNO phenotype in female subjects, respectively. Conclusion The odds of CKD were higher in MUNO and MUO phenotypes. Therefore, lifestyle modification is recommended to control normal weight and healthy metabolism.
 
Article
Background Patients on maintenance hemodialysis (HD) exhibit a high risk of death, cardiovascular and cerebrovascular diseases (CCDs). Previous studies indicated complement activation associated with the increased risk of cardiovascular diseases in HD patients. This study aimed to explore whether the critical complement factors were associated with the adverse outcomes in HD patients. Methods A total of 108 HD patients were included and followed up for 52 months. The baseline clinical characteristics and plasma C3c, C1q, CFH, CFB, C4, MAC, C5a, C3a and MBL were measured. The three endpoints were death, cardiovascular and cerebrovascular events (CCEs) and the composition of them. Univariate and multivariate Cox regression identified factors associated with the three endpoints respectively. X-tile analyses determined the optimal cut-off values for high risks. Restricted cubic spline plots illustrated the dose–response relationships. Correlations between the complement factors and risk factors for CCDs were analyzed. Results Baseline plasma C4 was finally selected by univariate and multivariate Cox regression analyses for three endpoints, including all-cause mortality, CCEs and the composition of them. When baseline plasma C4 exceeded 0.47 (P = 0.001) or 0.44 (P = 0.018) g/L respectively, the risks for death or achieving the composite endpoint enhanced significantly. The relationships of C4 and HR for the three endpoints showed a positive linear trend. Plasma C4 had prominent correlations with blood TG (r = 0.62, P < 0.001) and HDL (r = -0.38, P < 0.001). Conclusions A higher baseline plasma C4 level was significantly associated with the future incidence of decease, CCEs and either of them. Plasma C4 level correlated with blood TG and HDL.
 
Flow chart indicates patient enrollment and study design
Kaplan-Meier survival estimates of all-cause mortality between the two total indoxyl sulfate subgroups divided by the optimal cutoff value generated by the X-tile program
Kaplan-Meier survival estimates of cardiovascular mortality between the two total indoxyl sulfate subgroups divided by the optimal cutoff value generated by the X-tile program
The dose-response relationship of total indoxyl sulfate with the risk of cardiovascular disease mortality, estimated by restricted cubic spline models. The red solid line and the shaded area represent the estimated HRs and their 95% CIs, respectively
The dose-response relationship of total indoxyl sulfate with the risk of all-cause mortality, estimated by restricted cubic spline models. The red solid line and the shaded area represent the estimated HRs and their 95% CIs, respectively
Article
Background The association between serum total indoxyl sulfate (tIS), and cardiovascular disease (CVD) and all-cause mortality is a matter of debate. In the current study we sought to determine the association, if any, between serum tIS, and all-cause and CVD-associated mortality in patients on maintenance hemodialysis (MHD). Methods A prospective cohort study was conducted involving 500 MHD patients at Dalian Municipal Central Hospital from 31 December 2014 to 31 December 2020. Serum tIS levels were measured at baseline and classified as high (≥44.16 ng/ml) or low (< 44.16 ng/ml) according to the “X-tile” program. Besides, the associations between continuous serum tIS and outcomes were also explored. Predictors were tested for colinearity using variance inflation factor analysis. Hazard ratios (HRs) and 95% confidence intervals (CIs) were calculated using Cox proportional hazards regression models. Restricted cubic spline model was performed to assess dose-response relationships between tIS concentration and all-cause and CVD mortality. Results During a 58-month median follow-up period, 224 deaths (132 CVD deaths) were documented. After adjustment for potential confounders, the serum tIS level was positively associated with all-cause mortality (HR = 1.02, 95% = 1.01–1.03); however, we did not detect a significant association when tIS was a dichotomous variable. Compared with the MHD population with a serum tIS level < 44.16 ng/ml, the adjusted HR for CVD mortality among those with a serum tIS level ≥ 44.16 ng/ml was 1.76 (95% = 1.10–2.82). Furthermore, we also noted the same association when the serum tIS level was a continuous variable. Conclusion The serum tIS level was associated with higher risk of all-cause and CVD mortality among MHD patients. Further prospective large-scale studies are required to confirm this finding.
 
Flow diagram
Article
Background Engagement in exercise by haemodialysis (HD) patients has been shown to generate benefits both in terms of improved functional capacity and in the health-related quality of life. The use of non-immersive virtual reality (VR) games represents a new format for the implementation of intradialysis exercise. Some studies have shown that engaging in exercise for 6 months reduces the consumption of antihypertensive drugs and decreases the time spent admitted to hospital among individuals receiving HD treatments. The objective of this study was to evaluate changes in the consumption of healthcare resources and micro-costing for patients on HD who completed a VR exercise program. Materials and methods Design: This study is a secondary analysis of a clinical trial. The participants performed an intradialysis exercise program with non-immersive virtual reality for 3 months. The variables were recorded in two periods: 12 months before and 12 months after the start of the exercise program. Results The micro-costing analysis showed a significant decrease in the mean cost, in euros, for the consumption of laboratory tests − 330 (95% CI:[− 533, − 126];p = 0.003), outpatient visits − 351 ([− 566, − 135];p = 0.003), and radiology tests − 111 ([− 209, − 10];p = 0.03) in the 12 months after the implementation of the exercise program relative to the 12 months prior to its start. Conclusion The implementation of intradialysis exercise programs decreased the expenditure of some healthcare resources. Future studies could help clarify if longer interventions would have a stronger impact on these cost reductions.
 
The urinary ultrasound showed enhanced echo of bilateral renal collecting system
Direct sequencing results of KCNJ1. Compound mutations c.65G > T and c.89G > A in KCNJ1 gene (NM_153767) in the proband (a), originated form his father and mother. The sites as normal control were shown in (b)
Phylogenetic comparison of protein encoded by KCNJ 1 across species
Homology modeling of wild-type and mutant KCNJ 1 variants. A Modeled structure of the ROMK protein; B Neighboring residues of Arg22 in the wild type of KCNJ1. Arg22 is shown in green; C Neighboring residues of Met22 in mutant KCNJ 1. Met22 is shown in yellow. D Neighboring residues of Cys30 in the wild type of KCNJ1. Cys30 is shown in white; E Neighboring residues of Tyr30 in mutant KCNJ1. Tyr30 is shown in magenta. Predicted H bonds are indicated by yellow dashed lines
Structural model of ROMK1 channel protein and the position of the two variants identified in this study shown in red, the variants of ROMK1 detected in ref. [7]
in green
Article
Nephrolithiasis is not common in children, but the incidence is gradually increased in these years. Urinary tract malformations, urinary infection, dietary habits, geographic region and genetic factor are involved in the etiology of nephrolithiasis. For the affected child, it is especially important to elucidate the etiology, which may provide an accurate diagnosis, a personalized therapy and effective follow-up strategy. Here to seek the etiology of a ten-year-old boy incidentally found with nephrolithiasis, next generation sequencing (NGS) including a panel with 248 genes involved in hereditary kidney diseases was performed for the boy and identified two mutations of KCNJ1, c.89G > A (p.C30Y) and c.65G > T (p.R22M), and the later was a novel missense mutation originated from his father. The child was confirmed with type II Bartter syndrome (BS) caused by KCNJ1 mutations. Our study suggests that BS may be difficult to get diagnosed at an early stage based on clinical manifestations or biochemical laboratory tests, and NGS is an efficient way to determine the etiology and provide further treatment and guide fertility counseling for the affected family.
 
Physical examination of the patient. A and B Deformities of finger and toe joints (claw-shaped). C Fish scale-like skin
Liver biopsy. A Haematoxylin–eosin (HE) staining (200X); B Cytokeratin 19 (CK19)-labelled tissues showed the absence of a bile duct (black arrow)
Electron microscopy of the liver tissue showed that the gross bile ducts were severely dilated
Article
Background Arthrogryposis-renal dysfunction-cholestasis (ARC) syndrome is a rare disease with a high mortality rate caused by VPS33B or VIPAS39 mutations. ARC syndrome typically presents with arthrogryposis, renal tubular leak and neonatal cholestatic jaundice, and most patients with this disease do not survive beyond one year. Case presentation Here, we report the case of a 13-year-old girl with ARC featuring an incomplete and mild phenotype with novel compound heterozygous mutations of VPS33B. The patient presented with arthrogryposis (claw-shaped limbs), ichthyosis, jaundice, and pruritus. Laboratory tests revealed highly evaluated levels of total bilirubin (TB), direct bilirubin (DB), and total bile acid (TBA) as well as normal levels of gamma-glutamyltransferase (GGT). However, signs of renal dysfunction, as well as other manifestations of ARC syndrome, including nervous system abnormalities, deafness, and failure to thrive, were not observed. The patient’s clinical symptoms of jaundice and pruritus were significantly alleviated by administration of ursodeoxycholic acid. Whole-exome sequencing (WES) revealed novel compound heterozygous mutations of VPS33B, c.1081 C > T (p.Q361X,257)/c.244 T > C (p.C82R). Both variants were predicted to be pathogenic in silico and have never been reported previously. To date, the patients’ cholestatic jaundice has been well controlled with continuous treatment of ursodeoxycholic acid. Conclusions We report the case of a Chinese female with ARC including novel compound heterozygous mutations of VPS33B and an incomplete and mild phenotype. Early diagnosis and suitable symptomatic therapies are critical for the management of ARC patients with mild manifestations and prolonged lifespan.
 
Top-cited authors
Bernard G Jaar
  • Johns Hopkins Medicine
Mohan M Rajapurkar
  • Muljibhai Patel Society for Research in Nephro-Urology
Alan F Almeida
  • P.D Hinduja National Hospital & Medical Research Centre
David Wayne Johnson
  • Princess Alexandra Hospital (Queensland Health)
Neil R Powe
  • University of California, San Francisco