Signals From Inflamed Perivascular Adipose Tissue Contribute to Small Vessel Dysfunction in Women Living With the Human Immunodeficiency Virus.

INTRODUCTION: People living with the human immunodeficiency virus (PWH) have microvascular disease. Since perivascular adipose tissue (PVAT) regulates microvascular function and adipose tissue is inflamed in PWH, we tested the hypothesis that PWH have inflamed PVAT that impairs the function of their small vessels. METHODS: Subcutaneous small arteries were dissected with or without (+ or -) PVAT from a gluteal skin biopsy from 11 women with treated HIV (WWH) aged < 50 years and 10 matched women without HIV and studied on isometric myographs. Nitric oxide (NO) and reactive oxygen species (ROS) were measured by fluorescence microscopy. Adipokines and markers of inflammation and ROS were assayed in PVAT. RESULTS: PVAT surrounding the small arteries in control women significantly (P < 0.05) enhanced acetylcholine (Ach)-induced endothelium dependent relaxation and NO and reduced contractions to thromboxane and endothelin-1. However, these effects of PVAT were reduced significantly (P < 0.05) in WWH whose PVAT released less adiponectin but more markers of ROS and inflammation. Moderation of contractions by PVAT were correlated positively with adipose adiponectin. CONCLUSION: PVAT from WWH has oxidative stress, inflammation and reduced release of adiponectin that may contribute to enhanced contractions and therefore could promote small artery dysfunction.

KDOQI US Commentary on the 2021 KDIGO Clinical Practice Guideline for the Management of Glomerular Diseases.

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.

Hemodialysis Emergencies: Core Curriculum 2021.

Since maintenance hemodialysis (HD) first became available in the United States in 1962, there has been tremendous growth in the population of patients with kidney failure. HD has become a routine treatment carried out in outpatient clinics, hospitals, nursing facilities, and in patients' homes. Although it is a complex procedure, HD is quite safe. Serious complications are uncommon due to the use of modern HD machines and water treatment systems as well as the development of strict protocols to monitor various aspects of the HD treatment. The practicing nephrologist must be knowledgeable about life-threatening complications that can occur during HD and be able to recognize, manage, and prevent them. This installment in the AJKD Core Curriculum in Nephrology reviews the pathogenesis, management, and prevention of 9 HD emergencies. The HD emergencies covered include dialyzer reactions, dialysis disequilibrium syndrome, uremic/dialysis-associated pericarditis, air embolism, venous needle dislodgement, vascular access hemorrhage, hemolysis, dialysis water contamination, and arrhythmia episodes.

Improving Primary Care Delivery for Patients Receiving Maintenance Hemodialysis.

The beneficial impact of primary care, focused on all aspects of a patient's health (rather than a disease-specific focus) is well established. Recognized benefits include greater receipt of preventive care and counseling, lower use of emergency care and hospitalization for ambulatory care-sensitive conditions, and decreased early mortality. Although the importance of primary care and care coordination at the primary care/specialty interface is well recognized, the role of primary care within traditional and emerging care models for patients receiving in-center maintenance hemodialysis remains ill-defined. In this perspective article, we will describe: (1) the role of primary care for patients receiving maintenance hemodialysis and the current evidence regarding the receipt of primary care among these patients; (2) the key challenges to delivery of primary care in these complex cases, including suboptimal care coordination between nephrology and primary care providers, the intensity of dialysis care, and the limited capacity of nephrologists and primary care providers to meet the broad health needs of hemodialysis patients; (3) potential strategies for improving the delivery of primary care for patients receiving hemodialysis; and (4) future research requirements to improve primary care delivery for this high-risk population.

Higher Prevalence of Concurrent Thrombocytopenia in Patients Receiving Continuous Renal Replacement Therapy in the Cardiac Intensive Care Unit.

INTRODUCTION: Thrombocytopenia (TCP) is a common finding in patients receiving continuous renal replacement therapy (CRRT). OBJECTIVE: The purpose of this study was to assess the nature of TCP in patients receiving CRRT. METHODS: This is a single-center case-control observational study of 795 patients involving over 166,950 h of delivered CRRT at Johns Hopkins Hospital. Concurrent TCP in patients receiving CRRT was defined as a decrease in platelet count of ≥50% any time within 72 h of initiation of CRRT with strict exclusion criteria. RESULTS: There was a higher incidence of TCP in the cardiac intensive care unit (CICU) (22.5%) compared to medical ICU (MICU) (13.1%). Using logistic regression, the odds of developing concurrent TCP in patients receiving CRRT was 2.46 (95% CI 1.32-3.57, p < 0.05) times higher in the CICU compared with the MICU. There was no difference in the incidence of severe or profound TCP or timing of acute TCP between the CICU and MICU. CONCLUSION: Safe delivery of dialysis care in the ICU is paramount and creating awareness of potential risks such as concurrent TCP in patients receiving CRRT should be part of this care.

Burnout and Emotional Well-Being among Nephrology Fellows: A National Online Survey.

BACKGROUND: Physician burnout and emotional distress are associated with work dissatisfaction and provision of suboptimal patient care. Little is known about burnout among nephrology fellows. METHODS: Validated items on burnout, depressive symptoms, and well being were included in the American Society of Nephrology annual survey emailed to US nephrology fellows in May to June 2018. Burnout was defined as an affirmative response to two single-item questions of experiencing emotional exhaustion or depersonalization. RESULTS: Responses from 347 of 808 eligible first- and second-year adult nephrology fellows were examined (response rate=42.9%). Most fellows were aged 30-34 years (56.8%), male (62.0%), married or partnered (72.6%), international medical graduates (62.5%), and pursuing a clinical nephrology fellowship (87.0%). Emotional exhaustion and depersonalization were reported by 28.0% and 14.4% of the fellows, respectively, with an overall burnout prevalence of 30.0%. Most fellows indicated having strong program leadership (75.2%), positive work-life balance (69.2%), presence of social support (89.3%), and career satisfaction (73.2%); 44.7% reported a disruptive work environment and 35.4% reported depressive symptoms. Multivariable logistic regression revealed a statistically significant association between female gender (odds ratio [OR], 1.90; 95% confidence interval [95% CI], 1.09 to 3.32), poor work-life balance (OR, 3.97; 95% CI, 2.22 to 7.07), or a disruptive work environment (OR, 2.63; 95% CI, 1.48 to 4.66) and burnout. CONCLUSIONS: About one third of US nephrology fellows surveyed reported experiencing burnout and depressive symptoms. Further exploration of burnout-especially that reported by female physicians, as well as burnout associated with poor work-life balance or a disruptive work environment-is warranted to develop targeted efforts that may enhance the educational experience and emotional well being of nephrology fellows.

The Use of Erythropoiesis-Stimulating Agents in Patients With CKD and Cancer: A Clinical Approach.

Erythropoiesis-stimulating agents (ESAs) have been used to manage anemia in chronic kidney disease (CKD) to reduce transfusion requirements and anemia symptoms. Lack of objective benefit of normalizing hemoglobin (Hb) levels and increased evidence of ESA-induced complications in persons with anemia has resulted in clinicians generally attempting to maintain Hb levels in the 10- to 11-g/dL range. In 2000, concerns in patients with cancer arose attributable to associations of ESA use with increased mortality, thrombotic complications, and cerebrovascular accidents led to a change in US Food and Drug Administration oncology guidelines regarding limitation of ESA use for chemotherapy-induced anemia. No guidance was rendered for individuals with CKD and cancer. Persons with CKD with remote or active malignancy should receive the lowest ESA doses possible that achieve a maximum Hb level of 10g/dL. Based on current data, although ESAs may promote progression or worsen outcomes in some cancers, we lack data that ESAs increase the likelihood of developing new cancers in patients on dialysis or earlier stages of CKD.

KDOQI US Commentary on the 2017 ACC/AHA Hypertension Guideline.

Hypertension is a modifiable risk factor for cardiovascular morbidity and mortality and reduction of elevated blood pressure (BP) remains an important intervention for slowing kidney disease progression. Over the past decade, the most appropriate BP target for initiation and titration of BP-lowering medications has been an area of intense research and debate within the clinical community. In 2017, the American College of Cardiology and the American Heart Association (ACC/AHA) in conjunction with several other professional societies released new hypertension guidelines based on data from a systematic review of clinical trials and observational data. While many of the recommendations in the ACC/AHA hypertension guideline are relevant to nephrology practice, BP targets and management strategies for patients receiving dialysis are not discussed. This Kidney Disease Outcomes Quality Initiative (KDOQI) commentary focuses largely on recommendations from the ACC/AHA hypertension guidelines that are pertinent to individuals at risk of chronic kidney disease or with non-dialysis-dependent chronic kidney disease. This KDOQI commentary also includes a brief discussion of the consensus statement regarding hypertension diagnosis and management for adults receiving maintenance dialysis published by the European Renal and Cardiovascular Medicine Working Group of the European Renal Association-European Dialysis and Transplant Association (ERA-EDTA) and the Hypertension and the Kidney working group of the European Society of Hypertension. Overall, we support the vast majority of the ACC/AHA recommendations and highlight select areas in which best diagnosis and treatment options remain controversial.

Primary Care Physicians' Perceived Barriers to Nephrology Referral and Co-management of Patients with CKD: a Qualitative Study.

BACKGROUND: Effective co-management of patients with chronic kidney disease (CKD) between primary care physicians (PCPs) and nephrologists is increasingly recognized as a key strategy to ensure the delivery of efficient and high-quality CKD care. However, the co-management of patients with CKD remains suboptimal. OBJECTIVE: We aimed to identify PCPs' perceptions of key barriers and facilitators to effective co-management of patients with CKD at the PCP-nephrology interface. STUDY DESIGN: Qualitative study SETTING AND PARTICIPANTS: Community-based PCPs in four US cities: Baltimore, MD; St. Louis, MO; Raleigh, NC; and San Francisco, CA APPROACH: We conducted four focus groups of PCPs. Two members of the research team coded transcribed audio-recorded interviews and identified major themes. KEY RESULTS: Most of the 32 PCPs (59% internists and 41% family physicians) had been in practice for > 10 years (97%), spent ≥ 80% of their time in clinical care (94%), and practiced in private (69%) or multispecialty group practice (16%) settings. PCPs most commonly identified barriers to effective co-management of patients with CKD focused on difficulty developing working partnerships with nephrologists, including (1) lack of timely adequate information exchange (e.g., consult note not received or CKD care plan unclear); (2) unclear roles and responsibilities between PCPs and nephrologists; and (3) limited access to nephrologists (e.g., unable to obtain timely consultations or easily contact nephrologists with concerns). PCPs expressed a desire for "better communication tools" (e.g., shared electronic medical record) and clear CKD care plans to facilitate improved PCP-nephrology collaboration. CONCLUSIONS: Interventions facilitating timely adequate information exchange, clear delineation of roles and responsibilities between PCPs and nephrologists, and greater access to specialist advice may improve the co-management of patients with CKD.

Use of Renin-Angiotensin System Blockade in Advanced CKD: An NKF-KDOQI Controversies Report.

Multiple clinical trials have demonstrated that renin-angiotensin system (RAS) blockade with either angiotensin-converting enzyme inhibitors or angiotensin receptor blockers effectively reduces chronic kidney disease (CKD) progression. However, most clinical trials excluded participants with advanced CKD (ie, estimated glomerular filtration rate [eGFR]<30mL/min/1.73m2). It is acknowledged that initiation of RAS blockade is often associated with an acute reduction in eGFR, which is thought to be functional, but may result in long-term preservation of kidney function through the reductions in glomerular intracapillary pressure conferred by these agents. In this National Kidney Foundation-Kidney Disease Outcomes Quality Initiative (NKF-KDOQI) report, we discuss the controversies regarding use of RAS blockade in patients with advanced kidney disease. We review available published data on this topic and provide perspective on the impact of RAS blockade on changes in eGFRs and potassium levels. We conclude that more research is needed to evaluate the therapeutic index of RAS blockade in patients with advanced CKD.

APOL1 Risk Variants and Cardiovascular Disease: Results From the AASK (African American Study of Kidney Disease and Hypertension).

OBJECTIVE: Among African Americans, the apolipoprotein L1 (APOL1) risk variants have been associated with various types of kidney disease and chronic kidney disease progression. We aimed to determine whether these same risk variants also confer an increased risk for cardiovascular disease. APPROACH AND RESULTS: In a cohort of African Americans with hypertension-attributed chronic kidney disease followed for up to 12 years, we used Cox proportional hazards models to estimate the relative hazard of a composite cardiovascular disease outcome (cardiovascular death or hospitalization for myocardial infarction, cardiac revascularization procedure, heart failure, or stroke) for the APOL1 high- (2 risk variants) versus low-risk (0-1 risk variant) genotypes. We adjusted for age, sex, ancestry, smoking, heart disease history, body mass index, cholesterol, randomized treatment groups, and baseline and longitudinal estimated glomerular filtration rate, systolic blood pressure, and proteinuria. Among 693 participants with APOL1 genotyping available (23% high risk), the high-risk group had lower mean estimated glomerular filtration rate (44.7 versus 50.1 mL/min per 1.73 m2) and greater proteinuria (median 0.19 versus 0.06) compared with the low-risk group at baseline. There was no significant association between APOL1 genotypes and the composite cardiovascular disease outcome in both unadjusted (hazard ratio=1.23; 95% confidence interval: 0.83-1.81) and fully adjusted (hazard ratio=1.16; 95% confidence interval: 0.77-1.76) models; however, in using an additive model, APOL1 high-risk variants were associated with increased cardiovascular mortality. CONCLUSIONS: Among African Americans with hypertension-attributed chronic kidney disease, APOL1 risk variants were not associated with an overall risk for cardiovascular disease although some signals for cardiovascular mortality were noted.

Oral Anticoagulants to Prevent Stroke in Nonvalvular Atrial Fibrillation in Patients With CKD Stage 5D: An NKF-KDOQI Controversies Report.

Stroke risk may be more than 3-fold higher among patients with chronic kidney disease stage 5D (CKD-5D) compared to the general population, with the highest stroke rates noted among those 85 years and older. Atrial fibrillation (AF), a strong risk factor for stroke, is the most common arrhythmia and affects >7% of the population with CKD-5D. Warfarin use is widely acknowledged as an important intervention for stroke prevention with nonvalvular AF in the general population. However, use of oral anticoagulants for stroke prevention in patients with CKD-5D and nonvalvular AF continues to be debated by the nephrology community. In this National Kidney Foundation-Kidney Disease Outcomes Quality Initiative (NKF-KDOQI) controversies report, we discuss the existing observational studies that examine warfarin use and associated stroke and bleeding risks in adults with CKD-5D and AF. Non-vitamin K-dependent oral anticoagulants and their potential use for stroke prevention in patients with CKD-5D and nonvalvular AF are also discussed. Data from randomized clinical trials are urgently needed to determine the benefits and risks of oral anticoagulant use for stroke prevention in the setting of AF among patients with CKD-5D.

Comparative Effect of Contrast Media Type on the Incidence of Contrast-Induced Nephropathy: A Systematic Review and Meta-analysis.

BACKGROUND: Iodine contrast media are essential components of many imaging procedures. An important potential side effect is contrast-induced nephropathy (CIN). PURPOSE: To compare CIN risk for contrast media within and between osmolality classes in patients receiving diagnostic or therapeutic imaging procedures. DATA SOURCES: PubMed, EMBASE, Cochrane Library, Clinical Trials.gov, and Scopus through June 2015. STUDY SELECTION: Randomized, controlled trials that reported CIN-related outcomes in patients receiving low-osmolar contrast media (LOCM) or iso-osmolar contrast media for imaging. DATA EXTRACTION: Independent study selection and quality assessment by 2 reviewers and dual extraction of study characteristics and results. DATA SYNTHESIS: None of the 5 studies that compared types of LOCM reported a statistically significant or clinically important difference among study groups, but the strength of evidence was low. Twenty-five randomized, controlled trials found a slight reduction in CIN risk with the iso-osmolar contrast media agent iodixanol compared with a diverse group of LOCM that just reached statistical significance in a meta-analysis (pooled relative risk, 0.80 [95% CI, 0.65 to 0.99]; P = 0.045). This comparison's strength of evidence was moderate. In a meta regression of randomized, controlled trials of iodixanol, no relationship was found between route of administration and comparative CIN risk. LIMITATIONS: Few studies compared LOCM. Procedural details about contrast administration were not uniformly reported. Few studies specified clinical indications or severity of baseline renal impairment. CONCLUSION: No differences were found in CIN risk among types of LOCM. Iodixanol had a slightly lower risk for CIN than LOCM, but the lower risk did not exceed a criterion for clinical importance. PRIMARY FUNDING SOURCE: Agency for Healthcare Research and Quality.

Effectiveness of Prevention Strategies for Contrast-Induced Nephropathy: A Systematic Review and Meta-analysis.

BACKGROUND: N-acetylcysteine, sodium bicarbonate, statins, and ascorbic acid have been studied for reducing contrast-induced nephropathy (CIN). PURPOSE: To evaluate the comparative effectiveness of interventions to reduce CIN in adults receiving contrast media. DATA SOURCES: MEDLINE, EMBASE, Cochrane Library, ClinicalTrials.gov, and Scopus databases through June 2015. Risk of bias and overall strength of evidence (SOE) of studies were assessed. STUDY SELECTION: Randomized, controlled trials of N-acetylcysteine, sodium bicarbonate, statins, or ascorbic acid that used intravenous (IV) or intra-arterial contrast media and defined CIN with enough data for meta-analysis. DATA EXTRACTION: Two reviewers independently extracted data and assessed study quality. DATA SYNTHESIS: Low-dose N-acetylcysteine plus IV saline compared with IV saline (risk ratio [RR], 0.75 [95% CI, 0.63 to 0.89]; low SOE), N-acetylcysteine plus IV saline compared with IV saline in patients receiving low-osmolar contrast media (RR, 0.69 [CI, 0.58 to 0.84]; moderate SOE), and statins plus N-acetylcysteine plus IV saline versus N-acetylcysteine plus IV saline (RR, 0.52 [CI, 0.29 to 0.93]; low SOE) had clinically important and statistically significant benefits. The following 3 comparisons suggested a clinically important difference that was not statistically significant: sodium bicarbonate versus IV saline in patients receiving low-osmolar contrast media (RR, 0.65 [CI, 0.33 to 1.25]; low SOE), statins plus IV saline versus IV saline (RR, 0.68 [CI, 0.39 to 1.20]; low SOE), and ascorbic acid versus IV saline (RR, 0.72 [CI, 0.48 to 1.01]; low SOE). Strength of evidence was generally insufficient for comparisons of the need for renal replacement, cardiac events, and mortality. LIMITATION: Too few studies were done in patients receiving IV contrast media. CONCLUSION: The greatest reduction in CIN was seen with N-acetylcysteine plus IV saline in patients receiving LOCM and with statins plus N-acetylcysteine plus IV saline. PRIMARY FUNDING SOURCE: Agency for Healthcare Research and Quality.

APOL1 risk variants, race, and progression of chronic kidney disease.

BACKGROUND: Among patients in the United States with chronic kidney disease, black patients are at increased risk for end-stage renal disease, as compared with white patients. METHODS: In two studies, we examined the effects of variants in the gene encoding apolipoprotein L1 (APOL1) on the progression of chronic kidney disease. In the African American Study of Kidney Disease and Hypertension (AASK), we evaluated 693 black patients with chronic kidney disease attributed to hypertension. In the Chronic Renal Insufficiency Cohort (CRIC) study, we evaluated 2955 white patients and black patients with chronic kidney disease (46% of whom had diabetes) according to whether they had 2 copies of high-risk APOL1 variants (APOL1 high-risk group) or 0 or 1 copy (APOL1 low-risk group). In the AASK study, the primary outcome was a composite of end-stage renal disease or a doubling of the serum creatinine level. In the CRIC study, the primary outcomes were the slope in the estimated glomerular filtration rate (eGFR) and the composite of end-stage renal disease or a reduction of 50% in the eGFR from baseline. RESULTS: In the AASK study, the primary outcome occurred in 58.1% of the patients in the APOL1 high-risk group and in 36.6% of those in the APOL1 low-risk group (hazard ratio in the high-risk group, 1.88; P<0.001). There was no interaction between APOL1 status and trial interventions or the presence of baseline proteinuria. In the CRIC study, black patients in the APOL1 high-risk group had a more rapid decline in the eGFR and a higher risk of the composite renal outcome than did white patients, among those with diabetes and those without diabetes (P<0.001 for all comparisons). CONCLUSIONS: Renal risk variants in APOL1 were associated with the higher rates of end-stage renal disease and progression of chronic kidney disease that were observed in black patients as compared with white patients, regardless of diabetes status. (Funded by the National Institute of Diabetes and Digestive and Kidney Diseases and others.).

Ultrafiltration Rate Thresholds in Maintenance Hemodialysis: An NKF-KDOQI Controversies Report.

High hemodialysis ultrafiltration rate (UFR) is increasingly recognized as an important and modifiable risk factor for mortality among patients receiving maintenance hemodialysis. Recently, the Kidney Care Quality Alliance (KCQA) developed a UFR measure to assess dialysis unit care quality. The UFR measure was defined as UFR≥13mL/kg/h for patients with dialysis session length less than 240 minutes and was endorsed by the National Quality Forum as a quality measure in December 2015. Despite this, implementation of a UFR threshold remains controversial. In this NKF-KDOQI (National Kidney Foundation-Kidney Disease Outcomes Quality Initiative) Controversies Report, we discuss the concept of the UFR, which is governed by patients' interdialytic weight gain, body weight, and dialysis treatment time. We also examine the potential benefits and pitfalls of adopting a UFR threshold as a clinical performance measure and outline several aspects of UFR thresholds that require further research.

25-Hydroxyvitamin D testing and supplementation in CKD: an NKF-KDOQI controversies report.

The benefits of and thresholds for 25-hydroxyvitamin D administration in individuals with chronic kidney disease (CKD) remain uncertain. In this report, NKF-KDOQI (National Kidney Foundation-Kidney Disease Outcomes Quality Initiative) endeavors to provide health care providers with the latest information on a controversial area in the management of CKD, the role for nutritional vitamin D. Although knowledge of the biological mechanisms of vitamin D for bone maintenance in individuals with all stages of CKD has expanded, no consensus currently exists within the medical community regarding methods for 25-hydroxyvitamin D supplementation or optimal 25-hydroxyvitamin D levels in individuals with CKD. Within this report, existing CKD guidelines are summarized and scrutinized and ongoing clinical trials are cited as sources for future guidance on the optimal management of vitamin D in CKD.

Apolipoprotein L1 gene variants associate with hypertension-attributed nephropathy and the rate of kidney function decline in African Americans.

Despite intensive antihypertensive therapy there was a high incidence of renal end points in participants of the African American Study of Kidney Disease and Hypertension (AASK) cohort. To better understand this, coding variants in the apolipoprotein L1 (APOL1) and the nonmuscle myosin heavy chain 9 (MYH9) genes were evaluated for an association with hypertension-attributed nephropathy and clinical outcomes in a case-control study. Clinical data and DNA were available for 675 AASK participant cases and 618 African American non-nephropathy control individuals. APOL1 G1 and G2, and MYH9 E1 variants along with 44 ancestry informative markers, were genotyped with allele frequency differences between cases and controls analyzed by logistic regression multivariable models adjusting for ancestry, age, and gender. In recessive models, APOL1 risk variants were significantly associated with kidney disease in all cases compared to controls with an odds ratio of 2.57. In AASK cases with more advanced disease, such as a baseline urine protein to creatinine ratio over 0.6 g/g or a serum creatinine over 3 mg/dl during follow-up, the association was strengthened with odds ratios of 6.29 and 4.61, respectively. APOL1 risk variants were consistently associated with renal disease progression across medication classes and blood pressure targets. Thus, kidney disease in AASK participants was strongly associated with APOL1 renal risk variants.

Design of the Nephrotic Syndrome Study Network (NEPTUNE) to evaluate primary glomerular nephropathy by a multidisciplinary approach.

The Nephrotic Syndrome Study Network (NEPTUNE) is a North American multicenter collaborative consortium established to develop a translational research infrastructure for nephrotic syndrome. This includes a longitudinal observational cohort study, a pilot and ancillary study program, a training program, and a patient contact registry. NEPTUNE will enroll 450 adults and children with minimal change disease, focal segmental glomerulosclerosis, and membranous nephropathy for detailed clinical, histopathological, and molecular phenotyping at the time of clinically indicated renal biopsy. Initial visits will include an extensive clinical history, physical examination, collection of urine, blood and renal tissue samples, and assessments of quality of life and patient-reported outcomes. Follow-up history, physical measures, urine and blood samples, and questionnaires will be obtained every 4 months in the first year and biannually, thereafter. Molecular profiles and gene expression data will be linked to phenotypic, genetic, and digitalized histological data for comprehensive analyses using systems biology approaches. Analytical strategies were designed to transform descriptive information to mechanistic disease classification for nephrotic syndrome and to identify clinical, histological, and genomic disease predictors. Thus, understanding the complexity of the disease pathogenesis will guide further investigation for targeted therapeutic strategies.