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Abstract: SA-PO735

Progression of Focal Segmental Glomerulosclerosis in Patients With High Risk APOL1 Genotypes: A CureGN Study

Session Information

Category: Glomerular Diseases

  • 1304 Glomerular Diseases: Podocyte Biology


  • Kallash, Mahmoud, Nationwide Children's Hospital, Columbus, Ohio, United States
  • Wang, Yujie, University of Michigan, Ann Arbor, Michigan, United States
  • Smith, Abigail R., University of Michigan, Ann Arbor, Michigan, United States
  • Trachtman, Howard, University of Michigan, Ann Arbor, Michigan, United States
  • Nester, Carla Marie, The University of Iowa Hospitals and Clinics Department of Pathology, Iowa City, Iowa, United States
  • Gbadegesin, Rasheed A., Duke University Medical Center, Durham, North Carolina, United States
  • Canetta, Pietro A., Columbia University Irving Medical Center, New York, New York, United States
  • Wang, Chen, Columbia University Irving Medical Center, New York, New York, United States
  • Hunley, Tracy E., Vanderbilt University Medical Center, Nashville, Tennessee, United States
  • Sperati, John, Johns Hopkins University School of Medicine, Baltimore, Maryland, United States
  • Selewski, David T., University of South Carolina System, Columbia, South Carolina, United States
  • Ayoub, Isabelle, The Ohio State University Wexner Medical Center, Columbus, Ohio, United States
  • Srivastava, Tarak, Mercy Children's Hospital Springfield, Springfield, Missouri, United States
  • Mottl, Amy K., Cincinnati Children's Hospital Medical Center James M Anderson Center for Health Systems Excellence, Cincinnati, Ohio, United States
  • Kopp, Jeffrey B., National Institute of Diabetes and Digestive and Kidney Diseases, Bethesda, Maryland, United States
  • Royal, Virginie, Hopital Maisonneuve-Rosemont, Montreal, Quebec, Canada
  • Gipson, Debbie, University of Michigan, Ann Arbor, Michigan, United States
  • Kidd, Jason M., VCU Medical Center Main Hospital, Richmond, Virginia, United States

Polymorphism in APOL1 is a risk factor for disease progression in FSGS. This study evaluated the association of APOL1 genotypes on kidney disease progression in patients with FSGS.


Cure Glomerulonephropathy participants with a biopsy diagnosis of FSGS were included. Whole genome sequencing was performed with 150 bp paired end reads on Illumina NovaSeq 6000 instruments targeting 30X read depth. eGFR decline was categorized as <-5, 0 to -5, and >0ml/min/yr. Multivariable ordinal logistic regression was used to assess the association with APOL1 high-risk (HR, 2 risk alleles) vs low risk (LR, 0-1 risk alleles).


Of 650 participants, 13% were HR, 60% were LR (APOL1 status missing for 27%, Table). HR participants' biopsies showed more collapsing FSGS (p<0.001), greater interstitial inflammation (p<0.001) and interstitial fibrosis and tubular atrophy (p=0.02). The odds of rapid progression was 2.76 times higher in the HR group after adjustment. Proteinuria at biopsy was not associated with progression category, however, within the first year post-enrollment, higher nadir proteinuria (OR=1.09, p=0.02), need for multiple immunosuppressive agents (OR=1.35, p=0.001) and uncontrolled hypertension (OR=1.61, p=0.04) were associated with rapid progression.


In addition to APOL1 genotype, degree of proteinuria reduction, use of multiple immunosuppressive agents and uncontrolled hypertension are additional risk factors for rapid progression of FSGS. A better understanding of the natural history of FSGS in the context of high risk APOL1 genotypes will improve patient care and inform the design of interventional studies.