A novel clinical assay for detection of APOL1 renal risk alleles

Affinergy, Llc, Durham NC

Investigators

Abstract

SUMMARY/ABSTRACT African Americans are disproportionately affected by chronic and end stage kidney disease; while 35% of patients on dialysis are African American, only 13.2% of the U.S. population is African American. One factor contributing to this disparity are genetic variations in apolipoprotein L1 (APOL1). APOL1 is a plasma protein protective against human sleeping sickness caused by the parasite Trypanosoma brucei rhodesiense. In humans, there are three allelic variants of APOL1: G0 (wildtype), G1, and G2. The G1 and G2 APOL1 alleles (i.e. renal risk alleles) impart resistance to sleeping sickness, while the G0 allele promotes parasite survival and infection. For this reason, the G1 and G2 alleles are found almost exclusively in African and African American populations. While beneficial for resisting sleeping sickness, the G1 and G2 variants are also associated with a greatly increased risk for end stage renal disease. Moreover, in the renal transplantation setting, the presence of any two risk alleles (G1/G1, G2/G2 or G1/G2) in the donor kidney is strongly associated with poor graft survival, whereas the presence of just one copy of the G0 allele completely eliminates this increased risk (G0/G0, G1/G0, G2/G0). As a result, African Americans are at a higher risk for end stage renal disease and donor kidneys containing two APOL1 renal risk alleles may not be suitable for transplantation. It is therefore essential that donors are screened for APOL1 renal risk alleles prior to kidney donation. Unfortunately, the current gold standard for genotyping APOL1 requires gene sequencing and is technically infeasible during the limited time frame for triaging deceased donor organs. Structural differences in the APOL1 variants, in combination with differential binding to a parasite protein, make this system a suitable target for assay development. Affinergy plans to develop a simple, rapid, and affordable peptide-based detection system for the qualitative assessment of APOL1 G0 status to improve risk stratification during renal transplantation. At the conclusion of Phase 1, we expect to have a technology that can be developed into a diagnostic assay in Phase 2 for use by clinicians and researchers to quickly assess for kidney disease risk through the rapid detection of APOL1 G0 in plasma.