APOL1 Risk Alleles Are Associated with Exaggerated Age-Related Changes in Glomerular Number and Volume in African-American Adults: An Autopsy Study

Abstract

APOL1 genetic variants contribute to kidney disease in African Americans. We assessed correlations between APOL1 profiles and renal histological features in subjects without renal disease. Glomerular number (N glom) and mean glomerular volume (V glom) were measured by the dissector/fractionator method in kidneys of African-American and non-African-American adults without renal disease, undergoing autopsies in Jackson, Mississippi. APOL1 risk alleles were genotyped and the kidney findings were evaluated in the context of those profiles. The proportions of African Americans with none, one, and two APOL1 risk alleles were 38%, 43%, and 19%, respectively; 38% of African Americans had G1 allele variants and 31% of African Americans had G2 allele variants. Only APOL1-positive African Americans had significant reductions in N glom and increases in V glom with increasing age. Regression analysis predicted an annual average loss of 8834 (P=0.03, sex adjusted) glomeruli per single kidney over the first 38 years of adult life in African Americans with two risk alleles. Body mass index above the group medians, but below the obesity definition of ≥ 30 kg/m(2), enhanced the expression of age-related changes in N glom in African Americans with either one or two APOL1 risk alleles. These findings indicate that APOL1 risk alleles are associated with exaggerated age-related nephron loss, probably decaying from a larger pool of smaller glomeruli in early adult life, along with enlargement of the remaining glomeruli. These phenomena might mark mechanisms of accentuated susceptibility to kidney disease in APOL1-positive African Americans.

Keywords: APOL1 risk alleles; African Americans; glomerular enlargement; glomerular number.

Figure 1.

Proportions of obesity, hypertension, cardiovascular deaths and deaths by misadventure in African Americans aged 18–67 years at autopsy, by sex and number of APOL1 risk alleles, adjusted for age. p1, P value of F-test for linear trend (Additive model) from age-adjusted logistic regression. p2, P value for the Dominant model from age-adjusted logistic regression.

Figure 2.

Age-related change in N_glom and V_glom. N_glom (A) and V_glom (B) at autopsy age 20–57 years, by race, number of APOL1 risk allele profiles and sex, adjusted for age. N_glom, estimated total number of glomeruli per kidney; V_glom, estimated mean glomerular volume (µm³×10⁶).

Figure 3.

Comparison of fractional annual age changes at autopsy age 20–57 years in N_glom and V_glom, in those with BMI ≥ and < their group median, by race and APOL1 risk allele profiles, adjusted by age and sex. The group median BMI for African Americans with no risk alleles was 28.8 kg/m² and for African Americans in groups with risk alleles it ranged from 25.6 to 27.6 kg/m². N_glom, estimated total number of glomeruli per kidney; V_glom, estimated mean glomerular volume (µm³×10⁶). AA, African American.

Figure 4.

Age-related change in N_glom in African Americans with one or two APOL1 risk alleles at autopsy age 18–67 years. Age-related change in N_glom in African Americans without hypertension (A) and without a cardiovascular cause of death (B), adjusted for age and sex. N_glom, estimated total number of glomeruli per kidney; N, number of subjects; P, P value of modeled age.