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Abstract: TH-PO481

APOL1 Genotyping and Proteinuric Kidney Disease

Session Information

Category: Glomerular Diseases

  • 1303 Glomerular Diseases: Clinical‚ Outcomes‚ and Trials

Authors

  • Bramham, Kate, King's College London, London, United Kingdom
  • Audard, Vincent, Nephrology and Renal Transplantation Department, Institut National de la Santé et de la Recherche Médicale (INSERM) U955, Henri Mondor Hospital, Assistance Publique des Hôpitaux de Paris (AP-HP), Paris Est Créteil University, Créteil, France
  • Boffa, Jean-Jacques, Hôpital Tenon, Paris, France
  • Echeverri, Diego, South Florida Nephrology Associates, Lauderdale Lakes, Florida, United States
  • Knebelmann, Bertrand, Necker Hospital, APHP, Université Paris Cité, Paris, France
  • Mccafferty, Kieran, Bart’s Health NHS Trust, London, United Kingdom
  • Powell, Thomas, Columbia Nephrology Associates, Columbia, South Carolina, United States
  • Provenzano, Christopher, St. Clair Nephrology, Detroit, Michigan, United States
  • Shahid, Nauman, Eastern Nephrology Associates, Greenville, North Carolina, United States
  • Zaidan, Mohamad, Nephrology and Renal Transplantation Department, Bicêtre University Hospital, Assistance Publique des Hôpitaux de Paris (AP-HP), Paris Saclay University, Le Kremlin-Bicêtre, France
  • Bauman, John, Labcorp Drug Development, Morrisville, North Carolina, United States
  • Zamauskaite, Aurelia, Vertex Pharmaceuticals Incorporated, Boston, Massachusetts, United States
  • Manos, George, Vertex Pharmaceuticals Incorporated, Boston, Massachusetts, United States
  • Krause, Silva, Vertex Pharmaceuticals Incorporated, Boston, Massachusetts, United States
  • Faria-Urbina, Mariana, Vertex Pharmaceuticals Incorporated, Boston, Massachusetts, United States
  • Egbuna, Ogo I., Vertex Pharmaceuticals Incorporated, Boston, Massachusetts, United States
  • Chertow, Glenn, Stanford University School of Medicine, Palo Alto, California, United States
Background

Two toxic gain-of-function variants (G1 or G2) in APOL1 are genetic factors driving a progressive, proteinuric nephropathy referred to as APOL1-mediated kidney disease (AMKD). APOL1 variants are common in persons of recent African ancestry, but APOL1 genotyping is not routine and therefore their prevalence is not well-known. We report interim data of a trial estimating the prevalence of APOL1 genotypes in participants with chronic kidney disease (CKD).

Methods

Up to 2,500 participants of recent African ancestry or geographic origin with focal segmental glomerulosclerosis (FSGS) or other nondiabetic kidney disease (NDKD) and a urine protein to creatinine ratio of ≥0.1g/g will be enrolled (Table). Blood samples are used to determine genotypes using a polymerase chain reaction (PCR) assay; Sanger sequencing is used to confirm accuracy of the PCR assay. We will assess the percent of participants with 2 APOL1 variants.

Results

Interim analysis included 738 participants, 213 (28.9%) with FSGS and 525 (71.1%) with NDKD, of whom 110 (51.6%) and 124 (23.6%), respectively, have 2 APOL1 variants (G1 or G2). The table shows the distribution of participants with 2 APOL1 variants by disease state and region.

Conclusion

Using a highly sensitive genotyping assay to generate one of the largest APOL1 genotyping datasets, we show preliminary data on the noteworthy prevalence of 2 APOL1 variants in participants with proteinuric CKD and recent African ancestry across geographies. These results underscore the importance of APOL1 genotyping in routine care to identify AMKD, optimize patients’ disease management, and enable referral for clinical trials of APOL1 inhibitors.

Funding

  • Commercial Support