Kidney Week

Abstract: TH-PO482

A Steep Slope: APOL1 High Risk Genotype and GFR Decline Among Black Patients With Membranous Nephropathy

Session Information

• Glomerular Diseases: Clinical, Outcomes, Trials - I
  November 03, 2022 | Location: Exhibit Hall, Orange County Convention Center‚ West Building
  Abstract Time: 10:00 AM - 12:00 PM

Category: Glomerular Diseases

• 1303 Glomerular Diseases: Clinical‚ Outcomes‚ and Trials

Authors

• Chen, Dhruti P., University of North Carolina System, Chapel Hill, North Carolina, United States

Dhruti P. Chen,

• Henderson, Candace Dione, University of North Carolina System, Chapel Hill, North Carolina, United States

Candace Dione Henderson,

• Collie, Mary Mcgowan, University of North Carolina System, Chapel Hill, North Carolina, United States

Mary Mcgowan Collie,

• Hu, Yichun, University of North Carolina System, Chapel Hill, North Carolina, United States

Yichun Hu,

• Hogan, Susan L., University of North Carolina System, Chapel Hill, North Carolina, United States

Susan L. Hogan,

• Falk, Ronald, University of North Carolina System, Chapel Hill, North Carolina, United States

Ronald Falk,

Background

Genetic variants in the Apolipoprotein L1 (APOL1) gene contribute to kidney disease burden in black patients, but the influence in membranous nephropathy (MN) has not been studied.

Methods

Black MN patients enrolled in the Glomerular Disease Collaborative Network or Cure Glomerulonephropathy Network with DNA or APOL1 genotyping and non-black MN patients were included. eGFR was calculated using the non-race-based CKD-Epi equation for adults >26 years and Schwartz for <18 years. For ages 18-26, equations were combined. eGFR slopes estimated using linear mixed effects models with random effect for each group, assuming an unstructured covariance and adjusting by group. Fisher’s exact, Wilcoxon rank, and Kaplan-Meier curves with log rank tests were used for time to ESKD.

Results

Among 118 black MN patients, 16 (14%) had high risk APOL1 risk alleles (2 APOL1 alleles), and 102 (86%) had low risk alleles (0 or 1 alleles, n= 53 and n = 49, respectively). High risk APOL1 patients were younger at disease onset compared to low risk APOL1 and non-black patients (n=573). Despite similar GFR at diagnosis, GFR decline was worse in those with 2 APOL1 risk alleles (-15.3mL/min/1.73m²/year) compared to black MN patients with 0 (-3.3mL/min/1.73m²/year) or 1 risk allele (-3.0mL/min/1.73m²/year) and non-black MN patients (-2.4mL/min/1.73m²/year). Time to ESKD was faster in the high risk APOL1 group compared to low risk APOL1 or non-black MN patients (logrank p<0.05).

Conclusion

The prevalence of high risk APOL1 variant among black MN patients is comparable to the general black population. The high risk APOL1 genotype conferred worse eGFR decline and faster time to ESKD in MN. Black patients with low risk APOL1 alleles had a similar GFR decline to the non-black MN patients. APOL1 is a valuable clinical prognostic marker in black patients with MN.

Funding

• NIDDK Support – Vertex Pharmaceuticals