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The diagnosis of nephrotic syndrome relies on clinical presentation and descriptive patterns of injury on kidney biopsies, but not specific to underlying pathobiology. Consequently, there are variable rates of progression and response to therapy within diagnoses. Here, an unbiased transcriptomic-driven approach was used to identify molecular pathways which are shared by subgroups of patients with either minimal change disease (MCD) or focal segmental glomerulosclerosis (FSGS). Kidney tissue transcriptomic profile-based clustering identified three patient subgroups with shared molecular signatures across independent, North American, European, and African cohorts. One subgroup had significantly greater disease progression (Hazard Ratio 5.2) which persisted after adjusting for diagnosis and clinical measures (Hazard Ratio 3.8). Inclusion in this subgroup was retained even when clustering was limited to those with less than 25% interstitial fibrosis. The molecular profile of this subgroup was largely consistent with tumor necrosis factor (TNF) pathway activation. Two TNF pathway urine markers were identified, tissue inhibitor of metalloproteinases-1 (TIMP-1) and monocyte chemoattractant protein-1 (MCP-1), that could be used to predict an individual's TNF pathway activation score. Kidney organoids and single-nucleus RNA-sequencing of participant kidney biopsies, validated TNF-dependent increases in pathway activation score, transcript and protein levels of TIMP-1 and MCP-1, in resident kidney cells. Thus, molecular profiling identified a subgroup of patients with either MCD or FSGS who shared kidney TNF pathway activation and poor outcomes. A clinical trial testing targeted therapies in patients selected using urinary markers of TNF pathway activation is ongoing., (Copyright © 2022 International Society of Nephrology. All rights reserved.)

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 (eGFR cys ) and eGFR creatinine-cystatin C (eGFR cr-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., (Copyright © 2021 National Kidney Foundation, Inc and the American Society of Nephrology. Published by Elsevier Inc. All rights reserved.)

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., (Copyright © 2021 by the American Society of Nephrology and National Kidney Foundation, Inc. All rights reserved.)

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., (Copyright © 2021 by the American Society of Nephrology.)