Skip to main page content
U.S. flag

An official website of the United States government

Dot gov

The .gov means it’s official.
Federal government websites often end in .gov or .mil. Before sharing sensitive information, make sure you’re on a federal government site.

Https

The site is secure.
The https:// ensures that you are connecting to the official website and that any information you provide is encrypted and transmitted securely.

Access keys NCBI Homepage MyNCBI Homepage Main Content Main Navigation
Randomized Controlled Trial
. 2022 Aug 1;5(8):e2228701.
doi: 10.1001/jamanetworkopen.2022.28701.

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

Debbie S Gipson  1 , Jonathan P Troost  2 , Cathie Spino  3 , Samara Attalla  1 , Joshua Tarnoff  4 , Susan Massengill  5 , Richard Lafayette  6 , Virginia Vega-Warner  7 , Sharon Adler  8 , Patrick Gipson  1 , Matthew Elliott  9 , Frederick Kaskel  10 , Damian Fermin  7 , Marva Moxey-Mims  11 , Richard N Fine  12 , Elizabeth J Brown  13 , Kimberly Reidy  14 , Katherine Tuttle  15   16 , Keisha Gibson  17 , Kevin V Lemley  18 , Larry A Greenbaum  19 , Meredith A Atkinson  20 , Sangeeta Hingorani  21 , Tarak Srivastava  22 , Christine B Sethna  23 , Kevin Meyers  24 , Cheryl Tran  25 , Katherine M Dell  26 , Chia-Shi Wang  19 , Jennifer Lai Yee  1 , Matthew G Sampson  27   28 , Rasheed Gbadegesin  29 , J J Lin  30 , Tammy Brady  20 , Michelle Rheault  31 , Howard Trachtman  1
Affiliations
Randomized Controlled Trial

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

Debbie S Gipson et al. JAMA Netw Open. .

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.

PubMed Disclaimer

Conflict of interest statement

Conflict of Interest Disclosures: Dr D. S. Gipson reported receiving grants from the National Institutes of Health (NIH) and Levine Children’s Hospital Medical Foundation during the conduct of the study; receiving grants from Travere, Goldfinch Bio, Novartis, and Certa; consulting with Roche/Genentech and AstraZeneca through her institution; serving on a trial steering committee with Vertex outside the submitted work; and serving as a member 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.

Figures

Figure 1.
Figure 1.. Time to End-Stage Kidney Disease or 40% Reduction in Estimated Glomerular Filtration Rate by Age
Nephrotic Syndrome Rare Disease Clinical Research Network (NEPTUNE) included 166 participants, with 56 events; Focal segmental glomerulosclerosis clinical trial (FSGS-CT) included 132 participants, with 52 events; Kidney Research Network (KRN) included 184 participants, with 121 events. The pooled analysis included 482 participants with 229 events.
Figure 2.
Figure 2.. Results of Linear Mixed-Effects Models of Estimated Glomerular Filtration Rate (eGFR)
Values shown are regression estimates, with shaded areas indicating 95% CIs. Nephrotic Syndrome Rare Disease Clinical Research Network (NEPTUNE) included 166 participants, with 1827 observations; focal segmental glomerulosclerosis clinical trial (FSGS-CT) included 132 participants, with 1992 observations; Kidney Research Network (KRN) included 184 participants, with 3082 observations. The pooled analysis included 482 participants, with 6901 observations.
Figure 3.
Figure 3.. Time to Complete Remission by Age
Nephrotic Syndrome Rare Disease Clinical Research Network (NEPTUNE) included 166 participants, with 64 events; focal segmental glomerulosclerosis clinical trial (FSGS-CT) included 132 participants, with 50 events. The pooled analysis included 298 participants with 114 events.
Figure 4.
Figure 4.. Time to Complete Remission or Urine Protein–to-Creatine Ratio Less Than 1.5 g/g and 40% Reduction in Urine Protein–to-Creatine Ratio by Age
Nephrotic Syndrome Rare Disease Clinical Research Network (NEPTUNE) included 166 participants, with 114 events; focal segmental glomerulosclerosis clinical trial (FSGS-CT) included 132 participants, with 88 events. The pooled analysis included 298 participants with 202 events.
See this image and copyright information in PMC

References

    1. Baigent C, Herrington WG, Coresh J, et al. ; KDIGO Controversies Conference on Challenges in the Conduct of Clinical Trials in Nephrology Conference Participants . Challenges in conducting clinical trials in nephrology: conclusions from a Kidney Disease-Improving Global Outcomes (KDIGO) Controversies Conference. Kidney Int. 2017;92(2):297-305. doi: 10.1016/j.kint.2017.04.019 - DOI - PMC - PubMed
    1. Chen S, Meng XF, Zhang C. Role of NADPH oxidase-mediated reactive oxygen species in podocyte injury. Biomed Res Int. 2013;2013:839761. doi: 10.1155/2013/839761 - DOI - PMC - PubMed
    1. Gaspar N, Marshall LV, Binner D, et al. ; Members of Working Group 1 of the Paediatric Platform of ACCELERATE . Joint adolescent-adult early phase clinical trials to improve access to new drugs for adolescents with cancer: proposals from the multi-stakeholder platform-ACCELERATE. Ann Oncol. 2018;29(3):766-771. doi: 10.1093/annonc/mdy002 - DOI - PMC - PubMed
    1. Bellanti F, Della Pasqua O. Modelling and simulation as research tools in paediatric drug development. Eur J Clin Pharmacol. 2011;67(suppl 1):75-86. doi: 10.1007/s00228-010-0974-3 - DOI - PMC - PubMed
    1. Cattran DC, Rao P. Long-term outcome in children and adults with classic focal segmental glomerulosclerosis. Am J Kidney Dis. 1998;32(1):72-79. doi: 10.1053/ajkd.1998.v32.pm9669427 - DOI - PubMed

Publication types

LinkOut - more resources