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Abstract: PO1327

Effect of ApoL1 Genotype on Kidney Failure and eGFR Decline in Patients with All-Cause CKD

Session Information

Category: Genetic Diseases of the Kidneys

  • 1002 Genetic Diseases of the Kidneys: Non-Cystic

Authors

  • Elliott, Mark, Columbia University Irving Medical Center, New York, New York, United States
  • Marasa, Maddalena, Columbia University Irving Medical Center, New York, New York, United States
  • Cocchi, Enrico, Columbia University Irving Medical Center, New York, New York, United States
  • Zhang, Junying, Columbia University Irving Medical Center, New York, New York, United States
  • Khan, Atlas, Columbia University Irving Medical Center, New York, New York, United States
  • Kiryluk, Krzysztof, Columbia University Irving Medical Center, New York, New York, United States
  • Gharavi, Ali G., Columbia University Irving Medical Center, New York, New York, United States

Group or Team Name

  • Gharavi Lab
Background

ApoL1 risk variants G1 and G2 associate with an increased risk of kidney failure and a higher rate of eGFR loss. We assess the effect of ApoL1 genotype in African American and Latino individuals with chronic kidney disease (CKD) in New York City.

Methods

ApoL1 genotype determined by sequencing. CKD cases with high-risk ApoL1 genotype (n= 242) were compared to CKD cases with a low-risk ApoL1 genotype (n=885) and African ancestry per Admixture. Kaplan-Meier survival analyses assessed time to kidney failure followed by Adjusted Cox-proportional hazard model and competing risk regression against death both incorporating covariates. Linear mixed-effects modelling evaluated CKD-EPI eGFRCr decline rate using the same covariates.

Results

Cases with a high-risk ApoL1 genotype reach kidney failure 10-15 years earlier than low-risk cases. G1/G1 reach kidney failure earliest, followed by G1/G2 and G2/G2 (Fig 1). These data are supported across multiple risk models (Table 1). Cases with a high-risk genotype have a higher eGFR decline rate than low-risk cases with a similar trend per specific genotype (Fig 2). The addition of self-declared or genetically defined ancestry did not confer additional risk.

Conclusion

High-risk ApoL1 genotypes increase the risk of kidney failure at an earlier age, likely due to a higher eGFR decline rate. G1/G1 genotypes appear most affected and G2/G2 least.

Table 1. Modelling Results by ApoL1 Genotype
ApoL1 GenotypeAge at Kidney Failure (Median, 95% CI, Years)Unadjusted HR of Kidney FailureAdjusted HR of Kidney FailureCompeting Risk HR of Kidney FailureeGFR Decline Rate (mL/min/year)
Control54.6 (52 – 56.7)1112.68
High Risk41.4 (39.4 – 46)1.83***1.90***1.90***3.89*
G1/G140.7 (34.3 – 43.9)1.89***1.95**1.95***4.56*
G1/G243.5 (37.6 – 49.2)1.84***2.002.013.52
G2/G245.5 (39.4 – inf)1.621.42***1.42***3.91

*p <0.05 **p <0.001 ***p < 0.0001

Funding

  • Government Support – Non-U.S.