APOL1 Nephropathy Risk Variants Through the Life Course: A Review

Two variant alleles of the gene APOL1, known as risk variants (RVs), are a major contributor to kidney disease burden in those of African descent. The APOL1 protein contributes to innate immunity and may protect against trypanosoma, human immunodeficiency virus, salmonella, and leishmaniasis. However, the effects of carrying one or more RVs contribute to a variety of disease processes starting as early as in utero and can be exacerbated by other factors (or “second hits”). Indeed, these genetic variations interact with environmental exposures, infections, and systemic disease to modify health outcomes across one’s lifespan. This review focuses on APOL1-associated diseases through the life-course perspective and discusses how early exposure to “second hits” can impact long-term outcomes. APOL1-related kidney disease typically presents in adolescents to young adults, and individuals harboring RVs are more likely to progress to kidney failure than those with kidney disease but lacking APOL-1 RVs. Ongoing research is aimed at elucidating the association of APOL1 RV effects with adverse donor and recipient kidney transplant outcomes. Unfortunately, there is currently no established treatment for APOL1-associated nephropathy. Long-term research is needed to evaluate the risk and protective factors associated with APOL1 risk variants at different stages of life.