Rapid Progression of Focal Segmental Glomerulosclerosis in Patients with High-Risk APOL1 Genotypes : Clinical Journal of the American Society of Nephrology

Journal Logo

Advanced Search
Original Article: Glomerular and Tubulointerstitial Diseases

Rapid Progression of Focal Segmental Glomerulosclerosis in Patients with High-Risk APOL1 Genotypes

Kallash, Mahmoud; Wang, Yujie; Smith, Abigail; Trachtman, Howard; Gbadegesin, Rasheed; Nester, Carla; Canetta, Pietro; Wang, Chen; Hunley, Tracy E.; Sperati, C. John; Selewski, David; Ayoub, Isabelle; Srivastava, Tarak; Mottl, Amy K.; Kopp, Jeffrey; Gillespie, Brenda; Robinson, Bruce; Chen, Dhruti; Steinke, Julia; Twombley, Katherine; Reidy, Kimberly; Mucha, Krzysztof; Greenbaum, Larry A.; Blazius, Brooke; Helmuth, Margaret; Yonatan, Peleg; Parekh, Rulan S.; Hogan, Susan; Royal, Virginie; D'Agati, Vivette; Chishti, Aftab; Falk, Ronald; Gharavi, Ali; Holzman, Lawrence; Klein, Jon; Smoyer, William; Kretzler, Matthias; Gipson, Debbie; Kidd, Jason M.;  on behalf of CureGN*

Author Information

1Division of Pediatric Nephrology, Nationwide Children's Hospital, Columbus, Ohio

2University of Michigan, Ann Arbor, Michigan

3Arbor Research Collaborative for Health, Ann Arbor, Michigan

4Division of Nephrology, Department of Pediatrics, University of Michigan, Ann Arbor, Michigan

5Department of Pediatric Nephrology, Duke Children's Hospital and Health Center, Durham, North Carolina

6Division of Pediatric Nephrology, Dialysis and Transplantation, Stead Family Department of Pediatrics, University of Iowa, Iowa City, Iowa

7Division of Nephrology, Department of Medicine, Columbia University College of Physicians and Surgeons, New York, New York

8Division of Pediatric Nephrology, Vanderbilt University Medical Center, Nashville, Tennessee

9Division of Nephrology, Johns Hopkins University School of Medicine, Baltimore, Maryland

10Department of Pediatric Nephrology, Medical University of South Carolina, Charleston, South Carolina

11Department of Medicine, Division of Nephrology, The Ohio State University Wexner Medical Center, Columbus, Ohio

12Children's Mercy Hospital and University of Missouri-Kansas City School of Medicine, Kansas City, Missouri

13Division of Nephrology and Hypertension, Kidney Center, Department of Medicine, University of North Carolina, Chapel Hill, North Carolina

14Kidney Disease Section, Kidney Diseases Branch, National Institute of Diabetes and Digestive and Kidney Diseases, National Institutes of Health, Bethesda, Maryland

15Department of Biostatistics, School of Public Health, University of Michigan, Ann Arbor, Michigan

16Division of Medical Subspecialties, Section of Pediatric Nephrology, Helen DeVos Children's Hospital, Grand Rapids, Michigan

17Department of Pediatric Nephrology, Children's Hospital at Montefiore, Albert Einstein College of Medicine, Bronx, New York

18Department of Immunology, Transplantology and Internal Diseases, Medical University of Warsaw, Warsaw, Poland

19Institute of Biochemistry and Biophysics, Polish Academy of Sciences, Warsaw, Poland

20Division of Pediatric Nephrology, Department of Pediatrics, Emory University and Children's Healthcare of Atlanta, Atlanta, Georgia

21Division of Pediatric Nephrology, Hospital for Sick Children, Toronto, Ontario, Canada

22Child Health Evaluative Sciences, Research Institute, Hospital for Sick Children, Toronto, Ontario, Canada

23Department of Medicine, Division of Nephrology, University Health Network, Toronto, Ontario, Canada

24Division of Pathology, Hôpital Maisonneuve-Rosemont, Université de Montréal, Montréal, Québec, Canada

25Department of Pathology, Columbia University Medical Center, New York, New York

26Division of Nephrology, Hypertension and Renal Transplantation, University of Kentucky, Lexington, Kentucky

27Department of Internal Medicine, University of Pennsylvania School of Medicine, Philadelphia, Pennsylvania

28Department of Medicine-Renal, University of Louisville School of Medicine, Louisville, Kentucky

29Division of Nephrology, Department of Internal Medicine, University of Michigan, Ann Arbor, Michigan

30Division of Nephrology, Virginia Commonwealth University, Richmond, Virginia

Correspondence: Dr. Jason M. Kidd, Division of Nephrology, Department of Internal Medicine, Virginia Commonwealth University, PO Box 980160, 1101 E. Marshall Street, Richmond, VA 23298. Email: [email protected]

Published online ahead of print. Publication date available at www.cjasn.org.

*The list of nonauthor contributors is extensive and has been provided in Supplemental Summary 1.

Clinical Journal of the American Society of Nephrology 18(3):p 344-355, March 2023. | DOI: 10.2215/CJN.0000000000000069
  • Buy
  • Infographic

Abstract

Background 

FSGS is a heterogeneous diagnosis with a guarded prognosis. Polymorphisms in the apolipoprotein L1 (APOL1) gene are associated with developing FSGS and faster progression to kidney failure in affected patients. Better understanding the natural history of patients with FSGS and APOL1 risk alleles is essential to improve patient care and support the design and interpretation of interventional studies. The objective of this study was to evaluate the quantitative association between APOL1 and kidney disease progression and the interaction with other clinical and laboratory factors.

Methods 

CureGN cohort study participants with biopsy diagnosis of FSGS, regardless of self-identified race, were included. The exposure of interest was two APOL1 risk alleles (high risk) versus zero to one risk alleles (low risk). The primary outcome was eGFR slope categorized as rapid progressor (eGFR slope ≤−5 ml/min per year), intermediate progressor (slope between 0 and −5), or nonprogressor (slope ≥0). Multivariable ordinal logistic and linear regressions were used for adjusted analyses. Missing data were addressed using multiple imputation.

Results 

Of 650 participants, 476 (73%) had genetic testing, among whom 87 (18%) were high risk. High-risk participants were more likely to have lower median eGFR (62 [interquartile range, 36–81] versus low-risk participants 76 ml/min per 1.73 m2 [interquartile range, 44–106]; P<0.01). In adjusted analysis, the odds of more rapid progression of eGFR was 2.75 times higher (95% confidence interval, 1.67 to 4.53; P<0.001) in the high-risk versus low-risk groups.

Conclusions 

In patients with FSGS, high-risk APOL1 genotype is the predominant factor associated with more rapid loss of kidney function.

Visual Abstract

Abstract
Export

Copyright © 2023 by the American Society of Nephrology

Full Text Access for Subscribers:

ASN Member Login
ASN Member Login

Not a Subscriber?

Buy
Request Permissions

You can read the full text of this article if you:

Access through Ovid