Deceased-Donor Apolipoprotein L1 Renal-Risk Variants Have Minimal Effects on Liver Transplant Outcomes

Casey R Dorr, Barry I Freedman, Pamela J Hicks, W Mark Brown, Gregory B Russell, Bruce A Julian, Stephen O Pastan, Michael D Gautreaux, Amutha Muthusamy, Srinath Chinnakotla, Vera Hauptfeld, Robert A Bray, Allan D Kirk, Jasmin Divers, Ajay K Israni, Casey R Dorr, Barry I Freedman, Pamela J Hicks, W Mark Brown, Gregory B Russell, Bruce A Julian, Stephen O Pastan, Michael D Gautreaux, Amutha Muthusamy, Srinath Chinnakotla, Vera Hauptfeld, Robert A Bray, Allan D Kirk, Jasmin Divers, Ajay K Israni

Abstract

Background: Apolipoprotein L1 gene (APOL1) G1 and G2 renal-risk variants, common in populations with recent African ancestry, are strongly associated with non-diabetic nephropathy, end-stage kidney disease, and shorter allograft survival in deceased-donor kidneys (autosomal recessive inheritance). Circulating APOL1 protein is synthesized primarily in the liver and hydrodynamic gene delivery of APOL1 G1 and G2 risk variants has caused hepatic necrosis in a murine model.

Methods: To evaluate the impact of these variants in liver transplantation, this multicenter study investigated the association of APOL1 G1 and G2 alleles in deceased African American liver donors with allograft survival. Transplant recipients were followed for liver allograft survival using data from the Scientific Registry of Transplant Recipients.

Results: Of the 639 liver donors evaluated, 247 had no APOL1 risk allele, 300 had 1 risk allele, and 92 had 2 risk alleles. Graft failure assessed at 15 days, 6 months, 1 year and total was not significantly associated with donor APOL1 genotype (p-values = 0.25, 0.19, 0.67 and 0.89, respectively).

Conclusions: In contrast to kidney transplantation, deceased-donor APOL1 G1 and G2 risk variants do not significantly impact outcomes in liver transplantation.

Conflict of interest statement

Competing Interests: The authors have declared that no competing interests exist.

Figures

Fig 1. Allograft Survival Time with 0,…
Fig 1. Allograft Survival Time with 0, 1, or 2 APOL1 Renal Risk Variants in Donor Liver.
The number of censored events is the difference between the number of transplantations that started the year and the number of events observed during the year. These numbers are shown in parentheses at the bottom of the plot; each color corresponds to a specific APOL1 risk group. With a P-value of 0.6491 there is little correlation between liver allograft survival and the APOL1 renal risk variants. P-value is from the fully adjusted Cox proportional model.

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Source: PubMed

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