A Unifying Approach for GFR Estimation: Recommendations of the NKF-ASN Task Force on Reassessing the Inclusion of Race in Diagnosing Kidney Disease.

BACKGROUND: In response to a national call for re-evaluation of the use of race in clinical algorithms, the National Kidney Foundation (NKF) and the American Society of Nephrology (ASN) established a Task Force to reassess inclusion of race in the estimation of glomerular filtration rate (GFR) in the United States and its implications for diagnosis and management of patients with, or at risk for, kidney diseases. PROCESS & DELIBERATIONS: The Task Force organized its activities over 10 months in phases to (1) clarify the problem and evidence regarding GFR estimating equations in the United States (described previously in an interim report), and, in this final report, (2) evaluate approaches to address use of race in GFR estimation, and (3) provide recommendations. We identified 26 approaches for the estimation of GFR that did or did not consider race and narrowed our focus, by consensus, to 5 of those approaches. We holistically evaluated each approach considering 6 attributes: assay availability and standardization; implementation; population diversity in equation development; performance compared with measured GFR; consequences to clinical care, population tracking, and research; and patient centeredness. To arrive at a unifying approach to estimate GFR, we integrated information and evidence from many sources in assessing strengths and weaknesses in attributes for each approach, recognizing the number of Black and non-Black adults affected. RECOMMENDATIONS: (1) For US adults (>85% of whom have normal kidney function), we recommend immediate implementation of the CKD-EPI creatinine equation refit without the race variable in all laboratories in the United States because it does not include race in the calculation and reporting, included diversity in its development, is immediately available to all laboratories in the United States, and has acceptable performance characteristics and potential consequences that do not disproportionately affect any one group of individuals. (2) We recommend national efforts to facilitate increased, routine, and timely use of cystatin C, especially to confirm estimated GFR in adults who are at risk for or have chronic kidney disease, because combining filtration markers (creatinine and cystatin C) is more accurate and would support better clinical decisions than either marker alone. If ongoing evidence supports acceptable performance, the CKD-EPI eGFR-cystatin C (eGFRcys) and eGFR creatinine-cystatin C (eGFRcr-cys_R) refit without the race variables should be adopted to provide another first-line test, in addition to confirmatory testing. (3) Research on GFR estimation with new endogenous filtration markers and on interventions to eliminate race and ethnic disparities should be encouraged and funded. An investment in science is needed for newer approaches that generate accurate, unbiased, and precise GFR measurement and estimation without the inclusion of race, and that promote health equity and do not generate disparate care. IMPLEMENTATION: This unified approach, without specification of race, should be adopted across the United States. High-priority and multistakeholder efforts should implement this solution.

A Unifying Approach for GFR Estimation: Recommendations of the NKF-ASN Task Force on Reassessing the Inclusion of Race in Diagnosing Kidney Disease.

BACKGROUND: In response to a national call for re-evaluation of the use of race in clinical algorithms, the National Kidney Foundation (NKF) and the American Society of Nephrology (ASN) established a Task Force to reassess inclusion of race in the estimation of GFR in the United States and its implications for diagnosis and management of patients with, or at risk for, kidney diseases. PROCESS DELIBERATIONS: The Task Force organized its activities over 10 months in phases to ( 1 ) clarify the problem and evidence regarding eGFR equations in the United States (described previously in an interim report), and, in this final report, ( 2 ) evaluate approaches to address use of race in GFR estimation, and ( 3 ) provide recommendations. We identified 26 approaches for the estimation of GFR that did or did not consider race and narrowed our focus, by consensus, to five of those approaches. We holistically evaluated each approach considering six attributes: assay availability and standardization; implementation; population diversity in equation development; performance compared with measured GFR; consequences to clinical care, population tracking, and research; and patient centeredness. To arrive at a unifying approach to estimate GFR, we integrated information and evidence from many sources in assessing strengths and weaknesses in attributes for each approach, recognizing the number of Black and non-Black adults affected. RECOMMENDATIONS: ( 1 ) For US adults (>85% of whom have normal kidney function), we recommend immediate implementation of the CKD-EPI creatinine equation refit without the race variable in all laboratories in the United States because it does not include race in the calculation and reporting, included diversity in its development, is immediately available to all laboratories in the United States, and has acceptable performance characteristics and potential consequences that do not disproportionately affect any one group of individuals. ( 2 ) We recommend national efforts to facilitate increased, routine, and timely use of cystatin C, especially to confirm eGFR in adults who are at risk for or have CKD, because combining filtration markers (creatinine and cystatin C) is more accurate and would support better clinical decisions than either marker alone. If ongoing evidence supports acceptable performance, the CKD-EPI eGFR-cystatin C (eGFRcys) and eGFR creatinine-cystatin C (eGFRcr-cys_R) refit without the race variables should be adopted to provide another first-line test, in addition to confirmatory testing. ( 3 ) Research on GFR estimation with new endogenous filtration markers and on interventions to eliminate race and ethnic disparities should be encouraged and funded. An investment in science is needed for newer approaches that generate accurate, unbiased, and precise GFR measurement and estimation without the inclusion of race, and that promote health equity and do not generate disparate care. IMPLEMENTATION: This unified approach, without specification of race, should be adopted across the United States. High-priority and multistakeholder efforts should implement this solution.

Reassessing the Inclusion of Race in Diagnosing Kidney Diseases: An Interim Report from the NKF-ASN Task Force.

For almost two decades, equations that use serum creatinine, age, sex, and race to eGFR have included "race" as Black or non-Black. Given considerable evidence of disparities in health and healthcare delivery in African American communities, some regard keeping a race term in GFR equations as a practice that differentially influences access to care and kidney transplantation. Others assert that race captures important non GFR determinants of serum creatinine and its removal from the calculation may perpetuate other disparities. The National Kidney Foundation (NKF) and American Society of Nephrology (ASN) established a task force in 2020 to reassess the inclusion of race in the estimation of GFR in the United States and its implications for diagnosis and subsequent management of patients with, or at risk for, kidney diseases. This interim report details the process, initial assessment of evidence, and values defined regarding the use of race to estimate GFR. We organized activities in phases: (1) clarify the problem and examine evidence, (2) evaluate different approaches to address use of race in GFR estimation, and (3) make recommendations. In phase one, we constructed statements about the evidence and defined values regarding equity and disparities; race and racism; GFR measurement, estimation, and equation performance; laboratory standardization; and patient perspectives. We also identified several approaches to estimate GFR and a set of attributes to evaluate these approaches. Building on evidence and values, the attributes of alternative approaches to estimate GFR will be evaluated in the next phases and recommendations will be made.

Reassessing the Inclusion of Race in Diagnosing Kidney Diseases: An Interim Report From the NKF-ASN Task Force.

For almost 2 decades, equations that use serum creatinine, age, sex, and race to estimate glomerular filtration rate (GFR) have included "race" as Black or non-Black. Given considerable evidence of disparities in health and health care delivery in African American communities, some regard keeping a race term in GFR equations as a practice that differentially influences access to care and kidney transplantation. Others assert that race captures important non-GFR determinants of serum creatinine and its removal from the calculation may perpetuate other disparities. The National Kidney Foundation (NKF) and American Society of Nephrology (ASN) established a task force in 2020 to reassess the inclusion of race in the estimation of GFR in the United States and its implications for diagnosis and subsequent management of patients with, or at risk for, kidney diseases. This interim report details the process, initial assessment of evidence, and values defined regarding the use of race to estimate GFR. We organized activities in phases: (1) clarify the problem and examine evidence, (2) evaluate different approaches to address use of race in GFR estimation, and (3) make recommendations. In phase 1, we constructed statements about the evidence and defined values regarding equity and disparities; race and racism; GFR measurement, estimation, and equation performance; laboratory standardization; and patient perspectives. We also identified several approaches to estimate GFR and a set of attributes to evaluate these approaches. Building on evidence and values, the attributes of alternative approaches to estimate GFR will be evaluated in the next phases and recommendations will be made.

Proteinuria Reduction and Kidney Survival in Focal Segmental Glomerulosclerosis.

RATIONALE & OBJECTIVE: Remission of proteinuria has been shown to be associated with lower rates of kidney disease progression among people with focal segmental glomerulosclerosis (FSGS). The goal of this study was to evaluate whether reductions in proteinuria after treatment are associated with greater kidney survival. STUDY DESIGN: Cohort analysis of clinical trial participants. SETTING & PARTICIPANTS: Patients with steroid-resistant FSGS enrolled in a randomized treatment trial that compared cyclosporine with mycophenolate mofetil plus dexamethasone. PREDICTORS: Reduction in proteinuria measured during 26 weeks after initiating treatment. OUTCOMES: Repeated assessments of estimated glomerular filtration rate (eGFR) and time to a composite outcome of kidney failure or death assessed between 26 weeks and 54 months after randomization. ANALYTICAL APPROACH: Multivariable linear mixed-effects models with participant-specific slope and intercept to estimate the association of change in proteinuria over 26 weeks while receiving treatment with the subsequent slope of change in eGFR. Multivariable time-varying Cox proportional hazards models were used to estimate the association of changes in proteinuria with time to the composite outcome. RESULTS: 138 of 192 trial participants were included. Changes in proteinuria over 26 weeks were significantly related to eGFR slope. A 1-unit reduction in log-transformed urinary protein-creatinine ratio was associated with a 3.90mL/min/1.73m2 per year increase in eGFR (95% CI, 2.01-5.79). This difference remained significant after adjusting for complete remission. There was an analogous relationship between time-varying proteinuria and time to the composite outcome: the HR per 1-unit reduction in log-transformed urinary protein-creatinine ratio was 0.23 (95% CI, 0.12-0.44). LIMITATIONS: Limited to individuals with steroid-resistant FSGS followed up for a maximum of 5 years. CONCLUSIONS: These findings provide evidence for the benefit of urinary protein reduction in FSGS. Reductions in proteinuria warrant further evaluation as a potential surrogate for preservation of kidney function that may inform the design of future clinical trials.

Advancing Nephrology: Division Leaders Advise ASN.

New treatments, new understanding, and new approaches to translational research are transforming the outlook for patients with kidney diseases. A number of new initiatives dedicated to advancing the field of nephrology-from value-based care to prize competitions-will further improve outcomes of patients with kidney disease. Because of individual nephrologists and kidney organizations in the United States, such as the American Society of Nephrology, the National Kidney Foundation, and the Renal Physicians Association, and international nephrologists and organizations, such as the International Society of Nephrology and the European Renal Association-European Dialysis and Transplant Association, we are beginning to gain traction to invigorate nephrology to meet the pandemic of global kidney diseases. Recognizing the timeliness of this opportunity, the American Society of Nephrology convened a Division Chief Retreat in Dallas, Texas, in June 2019 to address five key issues: (1) asserting the value of nephrology to the health system; (2) productivity and compensation; (3) financial support of faculty's and divisions' educational efforts; (4) faculty recruitment, retention, diversity, and inclusion; and (5) ensuring that fellowship programs prepare trainees to provide high-value nephrology care and enhance attraction of trainees to nephrology. Herein, we highlight the outcomes of these discussions and recommendations to the American Society of Nephrology.

Acute Kidney Injury and Risk of CKD and Hypertension after Pediatric Cardiac Surgery.

BACKGROUND AND OBJECTIVES: The association of AKI after pediatric cardiac surgery with long-term CKD and hypertension development is unclear. The study objectives were to determine whether AKI after pediatric cardiac surgery is associated with incident CKD and hypertension. DESIGN, SETTING, PARTICIPANTS, & MEASUREMENTS: This was a prospective cohort study of children of 1 month to 18 years old who were undergoing cardiac surgery at two tertiary care centers (Canada, United States). Participants were recruited before cardiac surgery and were followed during hospitalization and at 3, 12, 24, 36, and 48 months after discharge. Exposures were postoperative AKI, based on the Kidney Disease Improving Global Outcomes (KDIGO) definition, and age <2 years old at surgery. Outcomes and measures were CKD (low eGFR or albuminuria for age) and hypertension (per the 2017 American Academy of Pediatrics guidelines) at follow-up, with the composite outcome of CKD or hypertension. RESULTS: Among 124 participants, 57 (46%) developed AKI. AKI versus non-AKI participants had a median (interquartile range) age of 8 (4.8-40.8) versus 46 (6.0-158.4) months, respectively, and higher preoperative eGFR. From the 3- to 48-month follow-up, the cohort prevalence of CKD was high (17%-20%); hypertension prevalence was also high (22%-30%). AKI was not significantly associated with the development of CKD throughout follow-up. AKI was associated with hypertension development at 12 months after discharge (adjusted relative risk, 2.16; 95% confidence interval, 1.18 to 3.95), but not at subsequent visits. Children aged <2 years old at surgery had a significantly higher prevalence of hypertension during follow-up than older children (40% versus 21% at 3-month follow-up; 32% versus 13% at 48-month follow-up). CONCLUSIONS: CKD and hypertension burden in the 4 years after pediatric cardiac surgery is high. Young age at surgery, but not AKI, is associated with their development.

APOL1 Long-term Kidney Transplantation Outcomes Network (APOLLO): Design and Rationale.

INTRODUCTION: Much of the higher risk for end-stage kidney disease (ESKD) in African American individuals relates to ancestry-specific variation in the apolipoprotein L1 gene (APOL1). Relative to kidneys from European American deceased-donors, kidneys from African American deceased-donors have shorter allograft survival and African American living-kidney donors more often develop ESKD. The National Institutes of Health (NIH)-sponsored APOL1 Long-term Kidney Transplantation Outcomes Network (APOLLO) is prospectively assessing kidney allograft survival from donors with recent African ancestry based on donor and recipient APOL1 genotypes. METHODS: APOLLO will evaluate outcomes from 2614 deceased kidney donor-recipient pairs, as well as additional living-kidney donor-recipient pairs and unpaired deceased-donor kidneys. RESULTS: The United Network for Organ Sharing (UNOS), Association of Organ Procurement Organizations, American Society of Transplantation, American Society for Histocompatibility and Immunogenetics, and nearly all U.S. kidney transplant programs, organ procurement organizations (OPOs), and histocompatibility laboratories are participating in this observational study. APOLLO employs a central institutional review board (cIRB) and maintains voluntary partnerships with OPOs and histocompatibility laboratories. A Community Advisory Council composed of African American individuals with a personal or family history of kidney disease has advised the NIH Project Office and Steering Committee since inception. UNOS is providing data for outcome analyses. CONCLUSION: This article describes unique aspects of the protocol, design, and performance of APOLLO. Results will guide use of APOL1 genotypic data to improve the assessment of quality in deceased-donor kidneys and could increase numbers of transplanted kidneys, reduce rates of discard, and improve the safety of living-kidney donation.

Psychiatric Illness and Mortality in Hospitalized ESKD Dialysis Patients.

BACKGROUND AND OBJECTIVES: Limited existing data on psychiatric illness in ESKD patients suggest these diseases are common and burdensome, but under-recognized in clinical practice. DESIGN, SETTING, PARTICIPANTS, & MEASUREMENTS: We examined hospitalizations with psychiatric diagnoses using inpatient claims from the first year of ESKD in adult and pediatric Medicare recipients who initiated treatment from 1996 to 2013. We assessed associations between hospitalizations with psychiatric diagnoses and all-cause death after discharge in adult dialysis patients using multivariable-adjusted Cox proportional hazards regression models. RESULTS: In the first ESKD year, 72% of elderly adults, 66% of adults and 64% of children had at least one hospitalization. Approximately 2% of adults and 1% of children were hospitalized with a primary psychiatric diagnosis. The most common primary psychiatric diagnoses were depression/affective disorder in adults and children, and organic disorders/dementias in elderly adults. Prevalence of hospitalizations with psychiatric diagnoses increased over time across groups, primarily from secondary diagnoses. 19% of elderly adults, 25% of adults and 15% of children were hospitalized with a secondary psychiatric diagnosis. Hazards ratios of all-cause death were higher in all dialysis adults hospitalized with either primary (1.29; 1.26 to 1.32) or secondary (1.11; 1.10 to 1.12) psychiatric diagnoses than in those hospitalized without psychiatric diagnoses. CONCLUSIONS: Hospitalizations with psychiatric diagnoses are common in pediatric and adult ESKD patients, and are associated with subsequent higher mortality, compared with hospitalizations without psychiatric diagnoses. The prevalence of hospitalizations with psychiatric diagnoses likely underestimates the burden of mental illness in the population.

Albuminuria, Proteinuria, and Renal Disease Progression in Children with CKD.

BACKGROUND AND OBJECTIVES: The role of albuminuria as an indicator of progression has not been investigated in children with CKD in the absence of diabetes. DESIGN, SETTING, PARTICIPANTS, & MEASUREMENTS: Children were enrolled from 49 centers of the CKD in Children study between January of 2005 and March of 2014. Cross-sectional multivariable linear regression (n=647) was used to examine the relationship between urine protein-to-creatinine (UP/C [milligrams per milligram]) and albumin-to-creatinine (ACR [milligrams per gram]) with eGFR (milliliters per minute per 1.73 m2). Parametric time-to-event analysis (n=751) was used to assess the association of UP/C, ACR, and urine nonalbumin-to-creatinine (Unon-alb/cr [milligrams per gram]) on the time to the composite endpoint of initiation of RRT or 50% decline in eGFR. RESULTS: The median follow-up time was 3.4 years and 202 individuals experienced the event. Participants with a UP/C≥0.2 mg/mg and ACR≥30 mg/g had a mean eGFR that was 16 ml/min per 1.73 m2 lower than those with a UP/C<0.2 mg/mg and ACR<30 mg/g. Individuals with ACR<30 mg/g, but a UP/C≥0.2 mg/mg, had a mean eGFR that was 9.3 ml/min per 1.73 m2 lower than those with a UP/C<0.2 mg/mg and ACR<30 mg/g. When categories of ACR and Unon-alb/cr were created on the basis of clinically meaningful cutoff values of UP/C with the same sample sizes for comparison, the relative times (RTs) to the composite end-point were almost identical when comparing the middle (RT=0.31 for UP/C [0.2-2.0 mg/mg], RT=0.38 for ACR [56-1333 mg/g], RT=0.31 for Unon-alb/cr [118-715 mg/g]) and the highest (RT=0.08 for UP/C [>2.0 mg/mg], RT=0.09 for ACR [>1333 mg/g], RT=0.07 for Unon-alb/cr [>715 mg/g]) levels to the lowest levels. A similar trend was seen when categories were created on the basis of clinically meaningful cutoff values of ACR (<30, 30-300, >300 mg/g). CONCLUSIONS: In children with CKD without diabetes, the utility of an initial UP/C, ACR, and Unon-alb/cr for characterizing progression is similar.

Kidney outcomes three years after bariatric surgery in severely obese adolescents.

A significant number of severely obese adolescents undergoing bariatric surgery have evidence of early kidney damage. To determine if kidney injury is reversible following bariatric surgery, we investigated renal outcomes in the Teen-Longitudinal Assessment of Bariatric Surgery cohort, a prospective multicenter study of 242 severely obese adolescents undergoing bariatric surgery. Primary outcomes of urine albumin-to-creatinine ratio and cystatin C-based estimated glomerular filtration rate (eGFR) were evaluated preoperatively and up to 3 years following bariatric surgery. At surgery, mean age of participants was 17 years and median body mass index (BMI) was 51 kg/m2. In those with decreased kidney function at baseline (eGFR under 90 mL/min/1.73m2), mean eGFR significantly improved from 76 to 102 mL/min/1.73m2 at three-year follow-up. Similarly, participants with albuminuria (albumin-to-creatinine ratio of 30 mg/g and more) at baseline demonstrated significant improvement following surgery: geometric mean of ACR was 74 mg/g at baseline and decreased to 17 mg/g at three years. Those with normal renal function and no albuminuria at baseline remained stable throughout the study period. Among individuals with a BMI of 40 kg/m2 and more at follow-up, increased BMI was associated with significantly lower eGFR, while no association was observed in those with a BMI under 40 kg/m2. In adjusted analysis, eGFR increased by 3.9 mL/min/1.73m2 for each 10-unit loss of BMI. Early kidney abnormalities improved following bariatric surgery in adolescents with evidence of preoperative kidney disease. Thus, kidney disease should be considered as a selection criteria for bariatric surgery in severely obese adolescents who fail conventional weight management.

Assessment of dietary intake of children with chronic kidney disease.

OBJECTIVE: Our aim was to characterize the nutrient intake of children with chronic kidney disease (CKD) relative to recommended intake levels. METHODS: We conducted a cross-sectional study of dietary intake assessed by Food Frequency Questionnaire (FFQ) in The North American Chronic Kidney Disease in Children (CKiD) prospective cohort study. Nutrient intake was analyzed to estimate the daily consumption levels of various nutrients and compared with national guidelines for intake. RESULTS: There were 658 FFQs available for analysis; 69.9 % of respondents were boys, with a median age [Interquartile range (IQR)] of 11 years (8-15). Median daily sodium, potassium, and phosphorus intake was 3089 mg (2294-4243), 2384 mg (1804-3076), and 1206 mg (894-1612) respectively. Sodium and phosphorus consumptions were higher than recommended in all age groups. Caloric intake decreased with dropping glomerular filtration rate (GFR) (p = 0.003). The median daily caloric intakes were 1307 kcal in male children 2-3 years old, 1875 kcal in children 4-8 years old, 1923 kcal in those 9-13 years old, and 2427 kcal in those 14-18 years old. Respective levels for girls were 1467 kcal, 1736 kcal, 1803 kcal, and 2281 kcal. Median protein intake exceeded recommended levels in all age groups, particularly among younger participants. Younger children were more likely than older children to exceed the recommended intakes for phosphorus (p < 0.001) and the age-specific recommended caloric intake (p < 0.001). Macronutrient distribution (carbohydrate:fat:protein) was consistent with recommendation. CONCLUSIONS: Children in the CKiD cohort consumed more sodium, phosphorus, protein, and calories than recommended. The gap between actual consumption and recommendations indicates a need for improved nutritional counseling and monitoring.

Glomerular Diseases: Registries and Clinical Trials.

Nephrology has conducted few high-quality clinical trials, and the trials that have been conducted have not resulted in the approval of new treatments for primary or inflammatory glomerular diseases. There are overarching process issues that affect the conduct of all clinical trials, but there are also some specialty-specific issues. Within nephrology, primary glomerular diseases are rare, making adequate recruitment for meaningful trials difficult. Nephrologists need better ways, beyond histopathology, to phenotype patients with glomerular diseases and stratify the risk for progression to ESRD. Rigorous trial design is needed for the testing of new therapies, where most patients with glomerular diseases are offered the opportunity to enroll in a clinical trial if standard therapies have failed or are lacking. Training programs to develop a core group of kidney specialists with expertise in the design and implementation of clinical trials are also needed. Registries of patients with glomerular disease and observational studies can aid in the ability to determine realistic estimates of disease prevalence and inform trial design through a better understanding of the natural history of disease. Some proposed changes to the Common Rule, the federal regulations governing the ethical conduct of research involving humans, and the emerging use of electronic health records may facilitate the efficiency of initiating multicenter clinical trials. Collaborations among academia, government scientific and regulatory agencies, industry, foundations, and patient advocacy groups can accelerate therapeutic development for these complex diseases.

Social Determinants of Racial Disparities in CKD.

Significant disparities in CKD rates and outcomes exist between black and white Americans. Health disparities are defined as health differences that adversely affect disadvantaged populations, on the basis of one or more health outcomes. CKD is the complex result of genetic and environmental factors, reflecting the balance of nature and nurture. Social determinants of health have an important role as environmental components, especially for black populations, who are disproportionately disadvantaged. Understanding the social determinants of health and appreciating the underlying differences associated with meaningful clinical outcomes may help nephrologists treat all their patients with CKD in an optimal manner. Altering the social determinants of health, although difficult, may embody important policy and research efforts, with the ultimate goal of improving outcomes for patients with kidney diseases, and minimizing the disparities between groups.

Complete Remission in the Nephrotic Syndrome Study Network.

BACKGROUND AND OBJECTIVES: This analysis from the Nephrotic Syndrome Study Network (NEPTUNE) assessed the phenotypic and pathology characteristics of proteinuric patients undergoing kidney biopsy and defined the frequency and factors associated with complete proteinuria remission (CRever). DESIGN, SETTING, PARTICIPANTS, & MEASUREMENTS: We enrolled adults and children with proteinuria ≥0.5 g/d at the time of first clinically indicated renal biopsy at 21 sites in North America from April 2010 to June 2014 into a prospective cohort study. NEPTUNE central pathologists assigned participants to minimal-change disease (MCD), FSGS, membranous nephropathy, or other glomerulopathy cohorts. Outcome measures for this analysis were (1) CRever with urine protein-to-creatinine ratio (UPC) <0.3 g/g with preserved native kidney function and (2) ESRD. Continuous variables are reported as median and interquartile range (IQR; 25th, 75th percentile). Cox proportional hazards modeling was used to assess factors associated with CRever. RESULTS: We enrolled 441 patients: 116 (27%) had MCD, 142 (32%) had FSGS, 66 (15%) had membranous nephropathy, and 117 (27%) had other glomerulopathy. The baseline UPC was 4.1 g/g (IQR, 1.9, 7.7) and the eGFR was 81 ml/min per 1.73 m(2) (IQR, 50, 105). Median duration of observation was 19 months (IQR, 11, 30). CRever occurred in 46% of patients, and 4.6% progressed to ESRD. Multivariate analysis demonstrated that higher prebiopsy proteinuria (hazard ratio, 0.3; 95% confidence interval, 0.2 to 0.5) and pathology diagnosis (FSGS versus MCD; hazard ratio, 0.2; 95% confidence interval, 0.1 to 0.5) were inversely associated with CRever. The effect of immunosuppressive therapy on remission varied by pathology diagnosis. CONCLUSIONS: In NEPTUNE, the high frequency of other pathology in proteinuric patients affirms the value of the diagnostic kidney biopsy. Clinical factors, including level of proteinuria before biopsy, pathology diagnosis, and immunosuppression, are associated with complete remission.

Human Heredity and Health (H3) in Africa Kidney Disease Research Network: A Focus on Methods in Sub-Saharan Africa.

CKD affects an estimated 14% of adults in sub-Saharan Africa, but very little research has been done on the cause, progression, and prevention of CKD there. As part of the Human Heredity and Health in Africa (H3Africa) Consortium, the H3Africa Kidney Disease Research Network was established to study prevalent forms of kidney disease in sub-Saharan Africa and increase the capacity for genetics and genomics research. The study is performing comprehensive phenotypic characterization and analyzing environmental and genetic factors from nine clinical centers in four African countries (Ghana, Nigeria, Ethiopia, and Kenya) over a 5-year period. Approximately 4000 participants with specified kidney disease diagnoses and 4000 control participants will be enrolled in the four African countries. In addition, approximately 50 families with hereditary glomerular disease will be enrolled. The study includes both pediatric and adult participants age <1 to 74 years across a broad spectrum of kidney diseases secondary to hypertension-attributed nephropathy, diabetes, HIV infection, sickle cell disease, biopsy-proven glomerular disease, and CKD of unknown origin. Clinical and demographic data with biospecimens are collected to assess clinical, biochemical, and genetic markers of kidney disease. As of March 2015, a total of 3499 patients and controls have been recruited and 1897 had complete entry data for analysis. Slightly more than half (50.2%) of the cohort is female. Initial quality control of clinical data collection and of biosample and DNA analysis is satisfactory, demonstrating that a clinical research infrastructure can be successfully established in Africa. This study will provide clinical, biochemical, and genotypic data that will greatly increase the understanding of CKD in sub-Saharan Africa.

Hyperuricemia and Progression of CKD in Children and Adolescents: The Chronic Kidney Disease in Children (CKiD) Cohort Study.

BACKGROUND: Hyperuricemia is associated with essential hypertension in children. No previous studies have evaluated the effect of hyperuricemia on progression of chronic kidney disease (CKD) in children. STUDY DESIGN: Prospective observational cohort study. SETTING & PARTICIPANTS: Children and adolescents (n=678 cross-sectional; n=627 longitudinal) with a median age of 12.3 (IQR, 8.6-15.6) years enrolled at 52 North American sites of the CKiD (CKD in Children) Study. PREDICTOR: Serum uric acid level (<5.5, 5.5-7.5, and >7.5mg/dL). OUTCOMES: Composite end point of either >30% decline in glomerular filtration rate (GFR) or initiation of renal replacement therapy. MEASUREMENTS: Age, sex, race, blood pressure status, GFR, CKD cause, urine protein-creatinine ratio (<0.5, 0.5-<2.0, and ≥2.0mg/mg), age- and sex-specific body mass index > 95th percentile, use of diuretics, and serum uric acid level. RESULTS: Older age, male sex, lower GFR, and body mass index > 95th percentile were associated with higher uric acid levels. 162, 294, and 171 participants had initial uric acid levels < 5.5, 5.5 to 7.5, or >7.5 mg/dL, respectively. We observed 225 instances of the composite end point over 5 years. In a multivariable parametric time-to-event analysis, compared with participants with initial uric acid levels < 5.5mg/dL, those with uric acid levels of 5.5 to 7.5 or >7.5mg/dL had 17% shorter (relative time, 0.83; 95% CI, 0.62-1.11) or 38% shorter (relative time, 0.62; 95% CI, 0.45-0.85) times to event, respectively. Hypertension, lower GFR, glomerular CKD cause, and elevated urine protein-creatinine ratio were also associated with faster times to the composite end point. LIMITATIONS: The study lacked sufficient data to examine how use of specific medications might influence serum uric acid levels and CKD progression. CONCLUSIONS: Hyperuricemia is a previously undescribed independent risk factor for faster progression of CKD in children and adolescents. It is possible that treatment of children and adolescents with CKD with urate-lowering therapy could slow disease progression.