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Background: Recurrence of focal segmental glomerulosclerosis (FSGS) or steroid-resistant nephrotic syndrome (SRNS) after kidney transplant leads to significant morbidity and potentially earlier allograft loss. To date however, reported rates, risk factors and treatment outcomes have varied widely. Methods: We applied computational phenotypes to a multicenter aggregation of electronic health records data from 7 large pediatric health systems in the USA, to identify recurrence rates, risk factors, and treatment outcomes. We refined the data collection by chart review. Results: From > 7 million patients, we compared children with primary FSGS/SRNS who received a kidney transplant between 2009 and 2020 and who either developed recurrence (n = 67/165; 40.6%) or did not (n = 98/165). Serum albumin level at time of transplant was significantly lower and recipient HLA DR7 presence was significantly higher in the recurrence group. By 36 months post-transplant, complete remission occurred in 58.2% and partial remission in 17.9%. Through 6 years post-transplant, no remission after recurrence was associated with an increased risk of allograft loss over time (p < 0.0001), but any remission showed similar allograft survival and function decline to those with no recurrence. Since treatments were used in non-random fashion, using spline curves and multivariable non-linear analyses, complete + partial remission chance was significantly higher with greater plasmapheresis sessions, CTLA4-Ig doses or LDL-apheresis sessions. Only treatment with anti-CD20, CTLA4-Ig agents, or LDL-apheresis sessions were associated with complete remission. Excluding 25 patients with mutations did not significantly change our results. Conclusions: Our contemporary high-risk cohort had higher favorable response rates than most prior reports, from combinations of agents. [ABSTRACT FROM AUTHOR]

Background: Individuals with nephrotic syndrome (NS) are thought to have elevated cardiovascular risk because of a known association with hyperlipidemia. Unfortunately, no studies have compared the cardiovascular risk profiles of individual nephrotic syndromes. This study explores the prevalence and patterns of coronary artery disease (CAD) in patients with different types of NS, which may aid in developing risk reduction strategies., Methods: This retrospective study queried data from the National Inpatient Sample database spanning 2016-2020 and included patients over the age of 18 years with minimal change disease (MCD), membranous nephropathy (MN), and focal segmental glomerulosclerosis (FSGS). We analyzed the prevalence and trends of hyperlipidemia and CAD in the study population., Results: Of the 15,025 cohort, there were 3625 (24.1%) MCD, 4160 (27.7%) MN, and 7315 (48.7%) FSGS. Patients with MN were found to be older with a higher prevalence of hyperlipidemia and CAD compared to other groups. The odds of developing CAD when adjusting for confounding factors were increased in FSGS (adjusted odds [aOR] 1.570, 95% CI 1.406-1.753, p < 0.001) while reduced in MCD (aOR 0.671, 95% CI 0.580-0.777, p < 0.001) and MN (aOR 0.782, 95% CI 0.698-0.876, p < 0.001)., Conclusions: The divergent results of the different NS types highlight the need for targeted research to better understand and characterize the distinct cardiovascular risk profiles inherent in each type of nephrotic disease for risk stratification., Competing Interests: Declaration of competing interest No disclosures/conflicts of interest., (Copyright © 2024 Elsevier B.V. All rights reserved.)

Idiopathic membranous nephropathy is the most common cause of nephrotic syndrome in nondiabetic adults. The antibody most often implicated is the M‐type phospholipase A2 receptor (PLA2R) antibody, found in >70% of primary membranous nephropathy cases. First‐line therapy is immunosuppressive in nature, but for patients who are treatment‐resistant there is a significant risk of end‐stage renal disease and mortality. Hypercholesterolemia is not only a side effect of nephrotic syndrome, but also its presence may worsen renal function. A recent single‐arm observational study in Japan found that low‐density lipoprotein apheresis (LDL‐A) was able to ameliorate nephrotic syndrome in half of patients who were resistant to medication. We present a case of treatment resistant PLA2R negative membranous nephropathy who had significant improvement following two courses of LDL‐A. To our knowledge, this is the first such reported case in the United States. [ABSTRACT FROM AUTHOR]

Abstract Objectives The course and long-term outcome of pure membranous lupus nephritis (MLN) are little understood. The aims of this study are to evaluate the clinical features, course, outcome and prognostic indicators in pure MLN and to determine the impact of ethnicity and the type of health insurance on the course and prognosis of pure MLN. Methods We conducted a retrospective review of medical records of 150 patients with pure MLN from Spain and the USA. Results Mean age was 34.2 ± 12.5 and 80% were women. Sixty-eight percent of patients had nephrotic syndrome at diagnosis. The average serum creatinine was 0.98 ± 0.78 mg/dl. Six percent of patients died and 5.3% developed end-stage renal disease (ESRD). ESRD was predicted by male sex, hypertension, dyslipidemia, high basal 24 h-proteinuria, high basal serum creatinine and a low basal creatinine clearance. Age, cardiac insufficiency, peripheral artheriopathy, hemodialysis and not having received mycophenolate mofetil or antimalarials for MLN predicted death. Conclusions Pure MLN frequently presents with nephrotic syndrome, high proteinuria and normal serum creatinine. Its prognosis is favourable in maintaining renal function although proteinuria usually persists over time. Baseline cardiovascular disease and not having a health insurance are related with poor prognosis. [ABSTRACT FROM AUTHOR]

Objectives-This report presents final 2020 data on the 10 leading causes of death in the United States by age, race and Hispanic origin, and sex. Leading causes of infant, neonatal, and postneonatal death are also presented. This report supplements "Deaths: Final Data for 2020," the National Center for Health Statistics' annual report of final mortality statistics. Methods-Data in this report are based on information from all death certificates filed in the 50 states and the District of Columbia in 2020. Causes of death classified by the International Classification of Diseases, 10th Revision (ICD-10) are ranked according to the number of deaths. Cause-of-death statistics are based on the underlying cause of death. Race and Hispanicorigin data are based on the Office of Management and Budget's 1997 standards for reporting race and Hispanic origin. Results-In 2020, many of the 10 leading causes of death changed rank order due to the emergence of COVID-19 as a leading cause of death in the United States. The 10 leading causes of death in 2020 were, in rank order: Diseases of heart; Malignant neoplasms; COVID-19; Accidents (unintentional injuries); Cerebrovascular diseases; Chronic lower respiratory diseases; Alzheimer disease; Diabetes mellitus; Influenza and pneumonia; and Nephritis, nephrotic syndrome and nephrosis. They accounted for 74.1% of all deaths occurring in the United States. Differences in the rankings are evident by age, race and Hispanic origin, and sex. Leading causes of infant death for 2020 were, in rank order: Congenital malformations, deformations and chromosomal abnormalities; Disorders related to short gestation and low birth weight, not elsewhere classified; Sudden infant death syndrome; Accidents (unintentional injuries); Newborn affected by maternal complications of pregnancy; Newborn affected by complications of placenta, cord and membranes; Bacterial sepsis of newborn; Respiratory distress of newborn; Diseases of the circulatory system; and Neonatal hemorrhage., (All material appearing in this report is in the public domain and may be reproduced or copied without permission; citation as to source, however, is appreciated.)

Focal segmental glomerulosclerosis (FSGS) is a pattern of kidney damage that can occur in individuals at any age, including children. Pediatric patients with FSGS require medication monitoring, growth, and psychological health. This article discusses the NP's role in the clinical presentation, diagnostic workup, and treatment of FSGS in pediatric patients. [ABSTRACT FROM AUTHOR]

Background: More than 30 genes can harbor rare exonic variants sufficient to cause nephrotic syndrome (NS), and the number of genes implicated in monogenic NS continues to grow. However, outside the first year of life, the majority of affected patients, particularly in ancestrally mixed populations, do not have a known monogenic form of NS. Even in those children classified with a monogenic form of NS, there is phenotypic heterogeneity. Thus, we have only discovered a fraction of the heritability of NS-the underlying genetic factors contributing to phenotypic variation. Part of the 'missing heritability' for NS has been posited to be explained by patients harboring coding variants across one or more previously implicated NS genes, insufficient to cause NS in a classical Mendelian manner, but that nonetheless have a sufficient impact on protein function to cause disease. However, systematic evaluation in patients with NS for rare or low-frequency risk alleles within single genes, or in combination across genes ('oligogenicity'), has not been reported. To determine whether, compared with a reference population, patients with NS have either a significantly increased burden of protein-altering variants ('risk-alleles'), or a unique combination of them ('oligogenicity'), in a set of 21 genes implicated in Mendelian forms of NS. Methods: In 303 patients with NS enrolled in the Nephrotic Syndrome Study Network (NEPTUNE), we performed targeted amplification paired with next-generation sequencing of 21 genes implicated in monogenic NS. We created a high-quality variant call set and compared it with a variant call set of the same genes in a reference population composed of 2,535 individuals from phase 3 of the 1000 Genomes Project. We created both a 'stringent' and a 'relaxed' pathogenicity-filtering pipeline, applied them to both cohorts, and computed the burden of variants in the entire gene set per cohort, the burden of variants in the entire gene set per individual, the burden of variants within a single gene per cohort, and unique combinations of variants across two or more genes per cohort. Results: With few exceptions when using the relaxed filter, and which are likely the result of confounding by population stratification, NS patients did not have a significantly increased burden of variants in Mendelian NS genes in comparison to a reference cohort, nor was there any evidence for oligogenicity. This was true when using both the relaxed and the stringent variant pathogenicity filter. Conclusion: In our study, there were no significant differences in the burden or particular combinations of low-frequency or rare protein-altering variants in a previously implicated Mendelian NS genes cohort between North American patients with NS and a reference population. Studies in larger independent cohorts or meta-analyses are needed to assess the generalizability of our discoveries and also address whether there is in fact small but significant enrichment of risk alleles or oligogenicity in NS cases that was undetectable with this current sample size. It is still possible that rare protein-altering variants in these genes, insufficient to cause Mendelian disease, still contribute to NS as risk alleles and/or via oligogenicity. However, we suggest that more accurate bioinformatic analyses and the incorporation of functional assays would be necessary to identify bona fide instances of this form of genetic architecture as a contributor to the heritability of NS. [ABSTRACT FROM AUTHOR]

The KDIGO 2021 Clinical Practice Guideline for the Management of Glomerular Diseases represents the first update to this set of recommendations since the initial set of KDIGO guideline recommendations was published in 2012. The pace of growth in our molecular understanding of glomerular disease has quickened and a number of newer immunosuppressive and targeted therapies have been introduced since the original set of guideline recommendations, making such an update necessary. Despite these updates, many areas of controversy remain. In addition, further updates since the publication of KDIGO 2021 have occurred which this guideline does not encompass. With this commentary, the KDOQI work group has generated a chapter-by-chapter companion opinion article that provides commentary specific to the implementation of the KDIGO 2021 guideline in the United States., (Copyright © 2023 National Kidney Foundation, Inc. Published by Elsevier Inc. All rights reserved.)

Background: Glomerular diseases are potentially fatal, requiring aggressive interventions and close monitoring. Urine is a readily-accessible body fluid enriched in molecular signatures from the kidney and therefore particularly suited for routine clinical analysis as well as development of non-invasive biomarkers for glomerular diseases.Methods: The Nephrotic Syndrome Study Network (NEPTUNE; ClinicalTrials.gov Identifier NCT01209000) is a North American multicenter collaborative consortium established to develop a translational research infrastructure for nephrotic syndrome. This includes standardized urine collections across all participating centers for the purpose of discovering non-invasive biomarkers for patients with nephrotic syndrome due to minimal change disease, focal segmental glomerulosclerosis, and membranous nephropathy. Here we describe the organization and methods of urine procurement and banking procedures in NEPTUNE.Results: We discuss the rationale for urine collection and storage conditions, and demonstrate the performance of three experimental analytes (neutrophil gelatinase-associated lipocalin [NGAL], retinol binding globulin, and alpha-1 microglobulin) under these conditions with and without urine preservatives (thymol, toluene, and boric acid). We also demonstrate the quality of RNA and protein collected from the urine cellular pellet and exosomes.Conclusions: The urine collection protocol in NEPTUNE allows robust detection of a wide range of proteins and RNAs from urine supernatant and pellets collected longitudinally from each patient over 5 years. Combined with the detailed clinical and histopathologic data, this provides a unique resource for exploration and validation of new or accepted markers of glomerular diseases.Trial Registration: ClinicalTrials.gov Identifier NCT01209000. [ABSTRACT FROM AUTHOR]

Background: Nephrotic syndrome (NS) is among the most common kidney diseases seen in children. The major complications of NS include infection, acute kidney injury (AKI), and thromboembolism (TE). The objective of this study was to analyze long-term trends in the epidemiology of major complications of pediatric NS. Methods: We used the Healthcare Cost and Utilization Project Kids’ Inpatient Database for the years 2000–2009 to perform an analysis of U.S. hospitalizations of children diagnosed with NS with or without infection, AKI or TE. Results: The frequency of NS hospitalizations complicated by AKI increased by 158 % between 2000 and 2009 ( p < 0.001). The frequency of NS hospitalizations with infection and TE remained stable overall. Pneumonia was the most common infectious complication while peritonitis decreased by 50 % ( p < 0.001). Importantly, development of any of these major complications of NS resulted in ∼2–3-fold increases in both hospital charges and length of stay. Conclusions: It is concerning that the frequency of AKI in children hospitalized with NS has more than doubled in the past decade. Strategies to prevent or initiate earlier treatments for complications of NS could have a major impact on both morbidity and health care expenses. [ABSTRACT FROM AUTHOR]

Background and Objectives: Recovery of kidney function after the start of maintenance dialysis can occur, but data on the incidence and risk factors for restarting dialysis after recovery of kidney function in this population are limited., Design, Setting, Participants, & Measurements: We conducted a retrospective study of adult Medicare beneficiaries who started dialysis between 2005 and 2015 according to the United States Renal Data System but who had recovery of kidney function (defined as a ≥90-day dialysis-free interval). We identified risk factors that were associated with the risk for the reinitiation of dialysis within a 3-year time frame following the recovery of kidney function and at any time during follow-up using Cox proportional hazards models., Results: Of the 34,530 individuals previously on dialysis who had recovery of kidney function, 7217 (21%) restarted dialysis (absolute rate of 11.5 per 100 person-years) within 3 years of recovery of kidney function, and 9120 (26%) restarted dialysis during the entire follow-up period (absolute rate of 8.8 per 100 person-years). Among those with CKD stage 1 or 2 after recovery of kidney function, 10% of individuals restarted dialysis within 3 years of their recovery of kidney function, whereas among those with CKD stage 3, 4, or 5, 13%, 27%, and 36% of individuals restarted dialysis within 3 years of recovery of kidney function, respectively. Age at first dialysis, cause of kidney disease, history of CKD or nephrology care prior to starting dialysis, presence of heart failure, CKD stage following recovery of kidney function, and location of first dialysis initiation (inpatient versus outpatient) were some of the risk factors that were strongly associated with the risk of restarting dialysis after the recovery of kidney function., Conclusions: Over one in five patients with recovery of kidney function after kidney failure restarted dialysis within 3 years., (Copyright © 2022 by the American Society of Nephrology.)

Background: Mesangial deposition of IgA (MCA) is a very rare finding in minimal change disease and has previously been considered a pure coincidence. In the US and Europe only anecdotal case reports exist. To date, there has been no consensus on nomenclature and categorization of this entity. We describe 2 cases of MCA with analogue histological findings but relevant differences in clinical presentation, and we discuss the clinical implications of mesangial IgA deposition in minimal change nephrotic syndrome. Patients: A 47 year-old fe male was admitted to hospital with nephrotic syndrome, microscopic hematuria, arterial hypertension and slight impairment of renal function 3 weeks after an unspecific upper air way infection. A 42-year-old male presented with nephrotic syndrome, microscopic hematuria, normotension and normal renal function. Both of the nephrotic syndromes were steroid-responsive and steroid-dependent. Findings: The clinical presentation of the male patient was consistent with the features of minimal change glomerulopathy, whereas the female patient combined signs of minimal change disease and IgA nephropathy. Light microscopy revealed mesangial IgA immune deposits and slight mesangial hypercellularity. Electron microscopic studies of MCA patients disclose diffuse effacement of glomerular foot processes. Conclusion: Our cases and a review of the literature indicate that the histological diagnosis of MCA may comprise different pathogenetic entities. From the clinical point of view, MCA has to be regarded as a minimal change nephrotic syndrome with symptomatic or asymptomatic mesangial IgA deposition. IgA deposition constitutes a risk factor for impairment of renal function and indicates a frequently relapsing course. [ABSTRACT FROM AUTHOR]

Abstract: Recurrence of nephrotic syndrome (NS) after transplantation (Tx) occurs in 20–50% of renal transplant recipients, with a median time to recurrence of 14 days and a 50% rate of graft loss. We performed a retrospective analysis of 22 pediatric patients with NS who received renal transplants at the Children's Hospital, Boston, between 1982 and 1999. During the first 14 days following Tx, 13 (59%) patients developed clinical recurrent nephrotic syndrome (RNS). RNS developed in 50% of living donor recipients and in 70% of cadaveric donor recipients (p= non-significant). Seven of the 13 patients with RNS were treated with plasmapheresis, while six received standard immunosuppressive induction therapy only. Two of the seven treated patients and one of the six untreated patients lost their grafts to RNS, yielding a total RNS graft loss rate of 23%. However, patients with RNS who achieved remission had significantly higher cumulative graft survival at 5 yr than did RNS patients who did not achieve remission (p< 0.001). Overall cumulative graft survival at 5 yr was not significantly different between the two groups: 67% in those with non-recurrent nephrotic syndrome (NRNS) vs. 64% in those with RNS, p= non-significant. We conclude that successful reversal of early RNS improves long-term graft survival in pediatric RNS. Multi-center studies are sorely needed to develop novel, less toxic therapies for native and recurrent NS. [ABSTRACT FROM AUTHOR]

A simple method to detect an albumin permeability factor in the idiopathic nephrotic syndrome. Background. Several investigators have detected an albumin permeability factor in the serum of patients with the idiopathic nephrotic syndrome (INS), that is, minimal change disease (MCD) or focal segmental glomerulosclerosis (FSGS), but the methods used have been complex. Methods. We describe here a simpler method using cultured rat glomerular epithelial cell monolayers grown to confluence on Millicell filters, which allow sampling of apical and basolateral media. 125I-labeled human serum albumin (125I-HSA) was added to the basolateral compartment, and its leakage across the epithelial cell monolayer into the apical compartment was measured. Results. In untreated cells (negative control), the albumin leakage reached 5.3% at 18 hours. Cell monolayers fixed with 95% ethanol (positive control) showed 62% leakage. Sera from three out of four patients with MCD and three out of four with FSGS resulted in considerable albumin leakage, whereas sera from nine patients with other types of nephrotic renal disease and five normal subjects caused no leakage. Conclusion. This study shows that the Millicell system provides a simple and useful method to screen for permeability factors in the INS. [ABSTRACT FROM AUTHOR]

Background: Nephrotic syndrome (NS) is a rare kidney syndrome with high morbidity. Although a common contributor to the burden of chronic kidney disease, the direct and indirect costs of NS to patients and family caregivers are unrecognized. The objective was to characterize the direct and indirect costs of NS to patients., Methods: Adults with NS and family caregivers of children with NS were eligible to participate if they had a diagnosis of primary NS, had disease for at least 1 year, and had no other severe health conditions. Data-collection surveys were generated with input from the Kidney Research Network Patient Advisory Board, and surveys were mailed to the eligible participants. Participants were provided $50 for the return of completed surveys. Costs were defined as either direct out-of-pocket costs or indirect costs ( e.g. , time). Descriptive statistics, including percentage and median (interquartile range [IQR]) are reported., Results: Respondents included 28 adult patients and 17 caregivers of patients who were minors. Reported health insurance coverage included 35 (78%) with private insurance, 12 (27%) with public insurance, six (13%) with Children's Special Health Care Services, and one (2%) uninsured. Median annual direct costs were $3464 ($844-$5865) for adult patients and $1687 (IQR $1035-$4763) for caregivers. Of these costs, diet-associated costs contributed $1140 (IQR $600-$2400). The most substantial indirect cost was from the time spent planning/prepping meals (adults: 183 h/yr [IQR 114-331]; caregivers: 173 h/yr [IQR 84-205])., Conclusions: Adults and caregivers of children with NS face substantial disease-related direct and indirect costs beyond those covered by insurance. Following replication, the study will help health care providers, systems, and payers gain a better understanding of the financial and time burden incurred by those living with NS, consider barriers when treating patients, and develop supportive strategies., Competing Interests: D.S. Gipson reports consultancy between the University of Michigan and AstraZeneca, Boehringer-Ingelheim, Genentech, Goldfinch Bio, Roche, Travere, and Vertex (no individual consultancy agreements); research funding to the University of Michigan from BoehringerIngelheim, Goldfinch Bio, Novartis, Reata, and Travere; being a scientific advisor for or a member of AstraZeneca, Goldfinch Bio, and Vertex; and other interests/relationships with the Nephrotic Syndrome Patient Reported Outcome Consortium (public-private partnership, with Goldfinch Bio, GSK, Pfizer, and Zyversa; NephCure Kidney International). S. Massengill reports consultancy agreements with Guidepoint Network and being a scientific advisor for or a member of the Editorial Board of online Glomerular Disease Journal (Karger Publishers). All remaining authors have nothing to disclose., (Copyright © 2022 by the American Society of Nephrology.)

Background: Primary nephrotic syndromes are rare diseases which can impede adequate sample size for observational patient-oriented research and clinical trial enrollment. A computable phenotype may be powerful in identifying patients with these diseases for research across multiple institutions., Methods: A comprehensive algorithm of inclusion and exclusion ICD-9 and ICD-10 codes to identify patients with primary nephrotic syndrome was developed. The algorithm was executed against the PCORnet CDM at three institutions from January 1, 2009 to January 1, 2018, where a random selection of 50 cases and 50 noncases (individuals not meeting case criteria seen within the same calendar year and within 5 years of age of a case) were reviewed by a nephrologist, for a total of 150 cases and 150 noncases reviewed. The classification accuracy (sensitivity, specificity, positive and negative predictive value, F1 score) of the computable phenotype was determined., Results: The algorithm identified a total of 2708 patients with nephrotic syndrome from 4,305,092 distinct patients in the CDM at all sites from 2009 to 2018. For all sites, the sensitivity, specificity, and area under the curve of the algorithm were 99% (95% CI, 97% to 99%), 79% (95% CI, 74% to 85%), and 0.9 (0.84 to 0.97), respectively. The most common causes of false positive classification were secondary FSGS (nine out of 39) and lupus nephritis (nine out of 39)., Conclusion: This computable phenotype had good classification in identifying both children and adults with primary nephrotic syndrome utilizing only ICD-9 and ICD-10 codes, which are available across institutions in the United States. This may facilitate future screening and enrollment for research studies and enable comparative effectiveness research. Further refinements to the algorithm including use of laboratory data or addition of natural language processing may help better distinguish primary and secondary causes of nephrotic syndrome., Competing Interests: C. Tran reports being a scientific advisor or member of Frontiers in Pediatrics Review Editor on the Editorial Board of Pediatric Nephrology. D. Gipson reports having consultancy agreements, through the University of Michigan, with AstraZeneca, Boehringer Ingelheim, Roche/Genentech, and Vertex Pharmaceuticals; reports receiving research funding, through the University of Michigan, from Atrium Health Medical Foundation, Boehringer Ingelheim, Centers for Disease Control, Food and Drug Administration, Goldfinch Bio, National Institutes of Health, Novartis, Reata, and Travere; and reports being a scientific advisor or member of the American Society of Pediatric Nephrology, American Society of Nephrology, and International Society of Pediatric Nephrology. H. Desmond reports receiving research funding through a percentage of salary from the University of Michigan, funded by Boehringer Ingelheim. I. Ayoub reports receiving honoraria from the American College of Rheumatology; reports being a scientific advisor or member of the Journal of Clinical Nephrology (Editorial Board) and the Lupus Foundation of America (advisory board). L. Mariani reports having consultancy agreements with, and receiving honoraria from, Calliditas Therapeutics Advisory Board, CKD Advisory Committee, Reata Pharmaceuticals, and Travere Therapeutics Advisory Board; reports receiving research funding from Boehringer Ingelheim; reports receiving honoraria from American Society of Nephrology Board Review Course and Update; and reports being a scientific advisor or member of Calliditas Therapeutics, Reata Pharmaceuticals, and Travere Therapeutics. M. Denburg reports having consultancy agreements with Trisalus Life Sciences (spouse); reports having an ownership interest in In-Bore LLC (spouse) and Precision Guided Interventions LLC (spouse); reports receiving research funding from Mallinckrodt; reports being a scientific advisor or member of NKF Delaware Valley Medical Advisory Board and Trisalus Life Sciences Scientific Advisory Board (spouse); and reports other interests/relationships with the American Society of Pediatric Nephrology Research and Program Committees and the National Kidney Foundation Pediatric Education Planning Committee. M. Matheny reports consultancy agreements with National Institutes of Health- Veterans Affairs- Department of Defense Pain Management Grant Consortium (PMC3); reports being a scientific advisor or member of Scientific Merit Review Board Study Section, VA Health Services Research and Development (HSR&D), Informatics and Methods Section, the Steering Committee of Indianapolis VA HSR&D Center of Innovation; and the Steering Committee of VA HSR&D VA Information Resource Center. S. Almaani reports having consultancy agreements with Aurinia Pharmaceuticals and Kezar Life Sciences; reports receiving research funding from Gilead Sciences; reports being a scientific advisor or member Clinical Nephrology Editorial Board; and reports speakers bureau from Aurinia Pharmaceuticals. S. Massengill reports having consultancy agreements with Guidepoint Group; reports being a scientific advisor or member of the Editorial Board of online Glomerular Disease Journal (Karger Publishers). All remaining authors have nothing to disclose., (Copyright © 2021 by the American Society of Nephrology.)

Background: Few data exist for the genetic variants underlying the risk for steroid-sensitive nephrotic syndrome (SSNS) in children. The objectives of this study were to evaluate HLA-DQA1 and APOL1 variants as risk factors for SSNS in African American children and use classic HLA antigen types and amino acid inference to refine the HLA-DQA1 association., Study Design: Case-control study., Setting & Participants: African American children with SSNS or steroid-resistant nephrotic syndrome (SRNS) were enrolled from Duke University and centers participating in the Midwest Pediatric Nephrology Consortium., Factor: Genetic variants in HLA-DQA1 (C34Y [rs1129740]; F41S [rs1071630]) and APOL1 high-risk alleles., Outcomes: SSNS and SRNS., Measurements: Direct sequencing for the HLA-DQA1 and APOL1 variants in 115 African American children (65 with SSNS and 50 with SRNS). Imputation of classic HLA alleles and amino acids was done in 363 South Asian children., Results: The 2 HLA-DQA1 variants were significantly associated with SSNS in African American children (C34Y: P=5.7 × 10 -11 ; OR, 3.53; 95% CI, 2.33-5.42; F41S: P=1.2 × 10 -13 ; OR, 4.08; 95% CI, 2.70-6.28), but not with SRNS (C34Y: P=0.6; F41S: P=0.2). APOL1 high-risk variants were not associated with SSNS (P=0.5) but showed significant associations with SRNS (P=1.04 × 10 -7 ; OR, 4.17; 95% CI, 2.23-7.64). HLA-DQA1*0201, HLA-DQB1*0201, and HLA-DRB1*0701 were the classic HLA alleles with the most significant associations with SSNS risk. The most significantly associated amino acid positions were HLA-DQα1 56 and 76 (both P=2.8 × 10 -7 ). Conditional analysis revealed that these variants most likely account for the observed association., Limitations: Modest sample size and limited statistical power to detect small to moderate effect sizes. Children studied may not be representative of all African American children in the United States., Conclusions: HLA-DQA1 is a risk locus for SSNS, but not SRNS, in African American children, consistent with its role in SSNS risk in children of European, Asian, and African ancestries. There is little evidence of a significant role for the APOL1 high-risk alleles in childhood SSNS in African American children. Refinement of the HLA-DQA1 association identified the critical classic HLA antigen types and amino acids of the HLA-DQ α1 molecule., (Copyright © 2017 National Kidney Foundation, Inc. All rights reserved.)

The article provides updates on developments related to medical research. The mechanism by which the contaminant resulted in severe clinical outcomes reminds nephrologists of the importance of voluntary reporting of adverse events to the U.S. Food and Drug Administration has been investigated. Meanwhile, response to hypoxia involves increased synthesis of erythropoietin. The lipopolysaccharide-induced nephrotic syndrome in severe combined immunodeficiency disease has been examined.

Hypertension and blood pressure variability (BPV; SD and average real variability) in primary proteinuric glomerulopathies are not well described. Data were from 433 participants in the NEPTUNE (Nephrotic Syndrome Study Network). Hypertensive BP status was defined as previous history of hypertension or BP ≥140/90 mm Hg for adults/≥95th percentile for children at baseline. BPV was measured in participants with ≥3 visits in the first year. Two-hundred ninety-six adults (43 years [interquartile range, 32-57.8 years], 61.5% male) and 147 children (11 years [interquartile range, 5-14 years], 57.8% male) were evaluated. At baseline, 64.8% of adults and 46.9% of children were hypertensive. Histological diagnosis was associated with hypertensive status in adults ( P =0.036). In adults, hypertensive status was associated with lower hazard of complete remission (hazard ratio, 0.36; 95% confidence interval, 0.19-0.68) and greater hazard of achieving the composite end point (end-stage renal disease or estimated glomerular filtration rate decline >40%; hazard ratio, 4.1; 95% confidence interval, 1.4-12). Greater systolic and diastolic SD and average real variability were also associated with greater hazard of reaching the composite end point in adults (all P <0.01). In children, greater BPV was an independent predictor of composite end point (determined by systolic SD and average real variability) and complete remission (determined by systolic and diastolic average real variability; all P <0.05). Hypertensive status was common among adults and children enrolled in NEPTUNE. Differences in hypertensive status prevalence, BPV, and treatment were found by age and histological diagnosis. In addition, hypertensive status and greater BPV were associated with poorer clinical outcomes., (© 2017 American Heart Association, Inc.)

Background: The incidence and distribution of primary glomerulonephropathies vary throughout the world and by race and ethnicity. We sought to evaluate the distribution of primary glomerulonephropathies among a large racially and ethnically diverse population of the United States., Study Design: Case series from January 1, 2000, through December 31, 2011., Setting & Participants: Adults (aged ≥ 18 years) of an integrated health system who underwent native kidney biopsy and had kidney biopsy findings demonstrating focal segmental glomerulosclerosis (FSGS), membranous glomerulonephritis (MGN), minimal change disease (MCD), immunoglobulin A nephropathy (IgAN), and other., Outcomes: Rates and characteristics of the most common primary glomerulonephropathies overall and by race and ethnicity., Results: 2,501 patients with primary glomerulonephropathy were identified, with a mean age 50.6 years, 45.7% women, 36.1% Hispanics, 31.2% non-Hispanic whites, 17.4% blacks, and 12.4% Asians. FSGS was the most common glomerulonephropathy (38.9%) across all race and ethnic groups, followed by MGN (12.7%), MCD (11.0%), IgAN (10.2%), and other (27.3%). The FSGS category had the greatest proportion of blacks, and patients with FSGS had the highest rate of poverty. IgAN was the second most common glomerulonephropathy among Asians (28.6%), whereas it was 1.2% among blacks. Patients with MGN presented with the highest proteinuria (protein excretion, 8.3g) whereas patients with FSGS had the highest creatinine levels (2.6mg/dL). Overall glomerulonephropathy rates increased annually in our 12-year observation period, driven by FSGS (2.7 cases/100,000) and IgAN (0.7 cases/100,000). MGN and MCD rates remained flat., Limitations: Missing data for urine albumin and sediment, indication bias in performing kidney biopsies, and inexact classification of primary versus secondary disease., Conclusions: Among a racially and ethnically diverse cohort from a single geographical area and similar environment, FSGS was the most common glomerulonephropathy, but there was variability of other glomerulonephropathies based on race and ethnicity., (Copyright © 2016 The Authors. Published by Elsevier Inc. All rights reserved.)

The Nephrology Quiz and Questionnaire (NQ&Q) remains an extremely popular session for attendees of the Annual Meeting of the American Society of Nephrology. As in past years, the conference hall of the 2013 meeting was overflowing with interested audience members. Topics covered by expert discussants included electrolyte and acid-base disorders, glomerular disease, ESRD/dialysis, and transplantation. Complex cases representing each of these categories, along with single best answer questions, were prepared by a panel of experts. Before the meeting, program directors of United States nephrology training programs answered questions through an Internet-based questionnaire. A new addition to the NQ&Q was participation in the questionnaire by nephrology fellows. To review the process, members of the audience test their knowledge and judgment on a series of case-oriented questions prepared and discussed by experts. Their answers are compared in real time using audience response devices with the answers of nephrology fellows and training program directors. The correct and incorrect answers are then briefly discussed after the audience responses and the results of the questionnaire are displayed. This article recapitulates the session and reproduces its educational value for CJASN readers. Enjoy the clinical cases and expert discussions.