TY - JOUR
T1 - APOL1 Nephropathy Risk Variants Through the Life Course
T2 - A Review
AU - Itoku, Ai
AU - Isaac, Jaya
AU - Wilson, Scott
AU - Reidy, Kimberly
AU - Kaskel, Frederick
N1 - Publisher Copyright:
© 2024 National Kidney Foundation, Inc.
PY - 2024
Y1 - 2024
N2 - Two variant alleles of the gene apolipoprotein L1 (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, HIV, Salmonella, and leishmaniasis. However, the effects of carrying 1 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 the life span. 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 are those with kidney disease who lack 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 RVs at different stages of life.
AB - Two variant alleles of the gene apolipoprotein L1 (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, HIV, Salmonella, and leishmaniasis. However, the effects of carrying 1 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 the life span. 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 are those with kidney disease who lack 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 RVs at different stages of life.
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U2 - 10.1053/j.ajkd.2023.12.014
DO - 10.1053/j.ajkd.2023.12.014
M3 - Review article
C2 - 38341125
AN - SCOPUS:85188736664
SN - 0272-6386
JO - American Journal of Kidney Diseases
JF - American Journal of Kidney Diseases
ER -