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. 2020 Nov;29(6):645-655.
doi: 10.1097/MNH.0000000000000653.

Apolipoprotein L1: role in the evaluation of kidney transplant donors

Krista L Lentine  1 , Roslyn B Mannon  2
Affiliations

Apolipoprotein L1: role in the evaluation of kidney transplant donors

Krista L Lentine et al. Curr Opin Nephrol Hypertens. 2020 Nov.

Abstract

Purpose of review: To summarize the current state of evidence regarding the role of apolipoprotein L1 (APOL1) genotyping in evaluating donors for kidney transplantation.

Recent findings: African ancestry is associated with an increased risk of kidney failure following living donation. Moreover, kidney transplants from African ancestry deceased donors have an increased risk of graft failure. Preliminary evidence suggests that APOL1 genotype may mediate at least a portion of this racial variation, with high-risk APOL1 genotypes defined by presence of two renal risk variants (RRVs). A pilot study 136 African ancestry living donors found that those with APOL1 high-risk genotypes had lower baseline kidney function and faster rates of kidney function decline after donation. To date, three retrospective studies identified a two-to-three times greater risk of allograft failure associated with kidneys from donors with high-risk APOL1 genotype. Active research initiatives seek to address unanswered questions, including reproducibility in large national samples, the role of 'second hits' injuries, and impact of recipient genotype, with a goal to build consensus on applications for policy and practice.

Summary: As evidence evolves, APOL1 genotyping may have applications for organ quality scoring in deceased donor kidney allocation, and for the evaluation and selection of living donor candidates.

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Conflict of interest statement

Conflicts of interest: K.L.L. is a consultant for CareDx, Inc. and serves on a Sanofi speakers’ bureau. RBM has no relevant conflicts of interest to declare.

Figures

Figure 1.
Figure 1.
Example of application of APOL1 genotyping with integrated risk projection tools in the evaluation of a young AA living donor candidate. “Predonation” risk refers to risk in the absence of donation. A tool for estimating projected 15-year and lifetime ESKD risk, based on 10 demographic (“race”, age, sex) and health factors, was developed by Grams et al. Projected postdonation risk can be estimated by multiplying by the best available estimate for donation attributable risk (e.g. Grams et al report a multiple of 3.5 to 5.3), or by using a postdonation tool developed with a more limited set of five factors. Identification low-risk APOL1 genotype could suggest lower than average risk for the AA candidate.
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