IMPORTANCE: Focal segmental glomerulosclerosis (FSGS) is a common cause of end-stage kidney disease (ESKD) across the lifespan. While 10% to 15% of children and 3% of adults who develop ESKD have FSGS, it remains uncertain whether the natural history differs in pediatric vs adult patients, and this uncertainty contributes to the exclusion of children and adolescents in clinical trials.
OBJECTIVE: To examine whether there are differences in the kidney health outcomes among children, adolescents, and adults with FSGS.
DESIGN, SETTING, AND PARTICIPANTS: This cohort study used pooled and parallel analyses, completed July 5, 2022, from 3 complimentary data sources: (1) Nephrotic Syndrome Rare Disease Clinical Research Network (NEPTUNE); (2) FSGS clinical trial (FSGS-CT); and (3) Kidney Research Network (KRN). NEPTUNE is a multicenter US/Canada cohort study; FSGS-CT is a multicenter US/Canada clinical trial; and KRN is a multicenter US electronic health record-based registry from academic and community nephrology practices. NEPTUNE included 166 patients with incident FSGS enrolled at first kidney biopsy; FSGS-CT included 132 patients with steroid-resistant FSGS randomized to cyclosporine vs dexamethasone with mycophenolate; and KRN included 184 patients with prevalent FSGS. Data were collected from November 2004 to October 2019 and analyzed from October 2020 to July 2022.
EXPOSURES: Age: children (age <13 years) vs adolescents (13-17 years) vs adults (≥18 years). Covariates of interest included sex, disease duration, APOL1 genotype, urine protein-to-creatinine ratio, estimated glomerular filtration rate (eGFR), edema, serum albumin, and immunosuppressive therapy.
MAIN OUTCOMES AND MEASURES: ESKD, composite outcome of ESKD or 40% decline in eGFR, and complete and/or partial remission of proteinuria.
RESULTS: The study included 127 (26%) children, 102 (21%) adolescents, and 253 (52%) adults, including 215 (45%) female participants and 138 (29%) who identified as Black, 98 (20%) who identified as Hispanic, and 275 (57%) who identified as White. Overall, the median time to ESKD was 11.9 years (IQR, 5.2-19.1 years). There was no difference in ESKD risk among children vs adults (hazard ratio [HR], 0.67; 95% CI, 0.43-1.03) or adolescents vs adults (HR, 0.85; 95% CI, 0.52-1.36). The median time to the composite end point was 5.7 years (IQR 1.6-15.2 years), with hazard ratio estimates for children vs adults of 1.12 (95% CI, 0.83-1.52) and adolescents vs adults of 1.06 (95% CI, 0.75-1.50).
CONCLUSIONS AND RELEVANCE: In this study, the association of FSGS with kidney survival and functional outcomes was comparable at all ages.
|Original language||English (US)|
|Journal||JAMA Network Open|
|State||Published - Aug 25 2022|
Bibliographical noteFunding Information:
Funding/Support: Analytic work for this study was supported by grant UL1TR002240 from NCATS for the Michigan Institute for Clinical and Health Research to Dr Troost. NEPTUNE is part of the Rare Diseases Clinical Research Network (RDCRN), funded by the NIH and led by NCATS through its Office of Rare Diseases Research. NEPTUNE is funded by grant U54DK083912, a collaboration between NCATS and NIDDK. Additional funding and/or programmatic support is provided by the University of Michigan, NephCure Kidney International and the Halpin Foundation. All RDCRN consortia are supported by the RDCRN Data Management and Coordinating Center (DMCC) via grant U2CTR002818. The FSGS clinical trial (FSGS-CT) was supported by grants U01DK063385, U01DK063490, U01DK063455, and U01DK063549 from NIH/NIDDK. This study was supported by many NCATS-and NIH-funded institutions for the conduct of study visits, nursing, laboratory, and outpatient research facilities throughout the trial. The Kidney Research Network registry enrollment, data collection, analytic design, interpretation of data, and writing of this manuscript are supported by the Atrium Health Medical Foundation and the University of Michigan.
of the recently completed American Society of Nephrology, Kidney Health Initiative project on focal segmental glomerulosclerosis (FSGS). Dr Troost reported receiving grants from the National Center for Advancing Translational Sciences (NCATS) during the conduct of the study. Dr Spino reported receiving grants from University of Michigan during the conduct of the study. Dr Tarnoff reported reporting holding stock in Creegh Pharmaceuticals outside the submitted work and serving as board chairman of Creegh Pharmaceuticals and chief executive officer of NephCure Kidney International. Dr Massengill reported serving on the Travere advisory board. Dr Lafayette reported receiving personal fees from Omeros, Calliditas, Travere, Chinook, Vera, and Aurinia outside the submitted work. Dr Adler reported receiving grants from Lundquist Research Institute at Harbor-UCLA Medical Center during the conduct of the study. Dr P. Gipson reported receiving grants from NIH and the Levine Medical Foundation during the conduct of the study and receiving grants from Goldfinch and Travere outside the submitted work. Dr Brown reported holding a patent for FSGS genetic test with royalties paid from Boston Children’s Hospital. Dr Reidy reported receiving grants from NIH during the conduct of the study and receiving grants from Advicienne and Travere Therapeutics outside the submitted work. Dr Tuttle reported grants from NIH/National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK) during the conduct of the study and grants from Travere outside the submitted work. Dr Gibson reported consulting for Travere and Aurinia outside the submitted work and serving as a nonpaid member of the Kidney Disease—Improving Global Outcomes (KDIGO) Glomerulonephritis Guidelines Writing Group. Dr Greenbaum reported receiving grants from NIH during the conduct of the study and receiving personal fees and grants from Alexion, Roche, and Novartis and receiving personal fees from Cara Therapeutics outside the submitted work. Dr Atkinson reported receiving personal fees from GlaxoSmithKline outside the submitted work. Dr Srivastava reported receiving grants from Travere Therapeutics, Apellis Pharmaceuticals, and Bristol Myers Squibb during the conduct of the study. Dr Meyers reported receiving grants from the NIH/Nephrotic Syndrome Rare Disease Clinical Research Network III (NEPTUNE) during the conduct of the study. Dr Dell reported other serving as a site principal investigator for Travere outside the submitted work. Dr Wang reported grants from NIH/NIDDK during the conduct of the study. Dr Sampson reported receiving grants from NIDDK and consulting with Maze Therapeutics outside the submitted work as well as serving on the scientific advisory board of Natera. Dr Gbadegesin reported consulting for Reata Pharmaceutical outside the submitted work. Dr Rheault reported receiving grants from Chinook, Travere, Reata, Sanofi, and Kaneka and consulting for Visterra outside the submitted work. Dr Trachtman reported consulting for Angion, Goldfinch Bio, Natera, Travere Therapeutics, Walden, and Otsuka outside the submitted work; being chair of the data monitoring committee for Otsuka pediatric trials; and serving on the board of the Kidney Health Initiative. No other disclosures were reported.
© 2022 American Medical Association. All rights reserved.
- Apolipoprotein L1
- Cohort Studies
- Glomerulosclerosis, Focal Segmental/complications
- Kidney Failure, Chronic/complications
- Nephrotic Syndrome/drug therapy
- Outcome Assessment, Health Care
PubMed: MeSH publication types
- Randomized Controlled Trial
- Multicenter Study
- Journal Article
- Research Support, N.I.H., Extramural