Comparing Kidney Health Outcomes in Children, Adolescents, and Adults With Focal Segmental Glomerulosclerosis

Debbie S. Gipson, Division of Nephrology, Department of Pediatrics, University of Michigan, Ann Arbor.
Jonathan P. Troost, Michigan Institute for Clinical and Health Research, University of Michigan, Ann Arbor.
Cathie Spino, School of Public Health, Department of Biostatistics, University of Michigan, Ann Arbor.
Samara Attalla, Division of Nephrology, Department of Pediatrics, University of Michigan, Ann Arbor.
Joshua Tarnoff, NephCure Kidney International, King of Prussia, Pennsylvania.
Susan Massengill, Division of Pediatric Nephrology, Department of Pediatrics, Levine Children's Hospital, Atrium Health, Charlotte, North Carolina.
Richard Lafayette, Department of Internal Medicine, Division of Nephrology, Stanford University, Palo Alto, California.
Virginia Vega-Warner, Division of Nephrology, Department of Internal Medicine, University of Michigan, Ann Arbor.
Sharon Adler, Division of Nephrology and Hypertension, Los Angeles Biomedical Research Institute at Harbor-University of California, Torrance.
Patrick Gipson, Division of Nephrology, Department of Pediatrics, University of Michigan, Ann Arbor.
Matthew Elliott, Metrolina Nephrology Associates, Charlotte, North Carolina.
Frederick Kaskel, Division of Nephrology, Children's Hospital at Montefiore; Albert Einstein College of Medicine, Bronx, New York.
Damian Fermin, Division of Nephrology, Department of Internal Medicine, University of Michigan, Ann Arbor.
Marva Moxey-Mims, Division of Nephrology, Children's National Hospital, Department of Pediatrics, The George Washington University School of Medicine, Washington, DC.
Richard N. Fine, Renaissance School of Medicine at Stony Brook University, Stony Brook University Medical Center, Stony Brook, New York.
Elizabeth J. Brown, Division of Nephrology, Department of Pediatrics, UT Southwestern Medical Center, Dallas, Texas.
Kimberly Reidy, Division of Nephrology, Department of Pediatrics, Albert Einstein College of Medicine, Montefiore Medical Center, New York, New York.
Katherine Tuttle, Providence Medical Research Center, Providence Health Care, Spokane, Washington.
Keisha Gibson, University of North Carolina Kidney Center at Chapel Hill.
Kevin V. Lemley, Department of Pediatrics, USC Keck School of Medicine, Children's Hospital Los Angeles, Los Angeles, California.
Larry A. Greenbaum, Division of Pediatric Nephrology, Department of Pediatrics, Emory University School of Medicine and Children's Healthcare of Atlanta, Atlanta, Georgia.
Meredith A. Atkinson, Division of Pediatric Nephrology, Johns Hopkins University School of Medicine, Baltimore, Maryland.
Sangeeta Hingorani, Department of Pediatrics, University of Washington and Division of Nephrology, Seattle Children's, Seattle.
Tarak Srivastava, Section of Nephrology, Children's Mercy Hospital and University of Missouri at Kansas City.
Christine B. Sethna, Pediatric Nephrology, Cohen Children's Medical Center of New York, Zucker School of Medicine at Hofstra/Northwell, Hempstead, New York.
Kevin Meyers, Division of Nephrology, Children's Hospital of Philadelphia, Philadelphia, Pennsylvania.
Cheryl Tran, Children's Center, Pediatric and Adolescent Medicine, Mayo Clinic, Rochester, Minnesota.
Katherine M. Dell, Center for Pediatric Nephrology, Cleveland Clinic Children's, Cleveland, Ohio.
Chia-Shi Wang, Division of Pediatric Nephrology, Department of Pediatrics, Emory University School of Medicine and Children's Healthcare of Atlanta, Atlanta, Georgia.
Jennifer Lai Yee, Division of Nephrology, Department of Pediatrics, University of Michigan, Ann Arbor.
Matthew G. Sampson, Division of Nephrology, Boston Children's Hospital, Harvard Medical School, Boston, Massachusetts.
Rasheed Gbadegesin, Pediatric Nephrology, Duke University Hospital, Durham, North Carolina.

Document Type

Journal Article

Publication Date

8-1-2022

Journal

JAMA network open

Volume

5

Issue

8

DOI

10.1001/jamanetworkopen.2022.28701

Abstract

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.

Department

Pediatrics

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