TY - JOUR
T1 - APOL1 genotype and glomerular and tubular kidney injury in women with HIV
AU - Jotwani, Vasantha
AU - Shlipak, Michael G.
AU - Scherzer, Rebecca
AU - Parekh, Rulan S.
AU - Kao, W. H.Linda
AU - Bennett, Michael
AU - Cohen, Mardge H.
AU - Nowicki, Marek
AU - Sharma, Anjali
AU - Young, Mary
AU - Tien, Phyllis C.
AU - Parikh, Chirag R.
AU - Estrella, Michelle M.
N1 - Publisher Copyright:
© 2015 National Kidney Foundation, Inc.
PY - 2015/6/1
Y1 - 2015/6/1
N2 - Background APOL1 genotype is associated with advanced kidney disease in African Americans, but the pathogenic mechanisms are unclear. Here, associations of APOL1 genotype with urine biomarkers of glomerular and tubular injury and kidney function decline were evaluated. Study Design Observational study. Setting & Participants 431 human immunodeficiency virus (HIV)-infected African American women enrolled in Women's Interagency HIV Study (WIHS). Predictor APOL1 genotype. Outcomes Albumin-creatinine ratio (ACR), 4 tubular injury biomarkers (interleukin 18 [IL-18], kidney injury molecule 1 [KIM-1], neutrophil gelatinase-associated lipocalin [NGAL], and α1-microglobulin [A1M]), and kidney function estimated using the CKD-EPI cystatin C equation. Measurements Participants were genotyped for APOL1 single-nucleotide polymorphisms rs73885319 (G1 allele) and rs71785313 (G2 allele). Urine biomarkers were measured using stored samples from 1999-2000. Cystatin C was measured using serum collected at baseline and 4- and 8-year follow-ups. Results At baseline, ACRs were higher among 47 women with 2 APOL1 risk alleles versus 384 women with 0/1 risk allele (median, 24 vs 11 mg/g; P < 0.001). Compared with women with 0/1 risk allele, women with 2 risk alleles had 104% higher ACRs (95% CI, 29-223 mg/g) and 2-fold greater risk of ACR > 30 (95% CI, 1.17-3.44) mg/g after multivariable adjustment. APOL1 genotype showed little association with urine IL-18:Cr ratio, KIM-1:Cr ratio, and NGAL:Cr ratio (estimates of -5% [95% CI, -24% to 18%], -20% [95% CI, -36% to -1%], and 10% [95% CI, -26% to 64%], respectively) or detectable urine A1M (prevalence ratio, 1.13; 95% CI, 0.65-1.97) in adjusted analyses. Compared with women with 0/1 allele, women with 2 risk alleles had faster eGFR decline, by 1.2 (95% CI, 0.2 to 2.2) mL/min/1.73 m2 per year, and 1.7- and 3.4-fold greater rates of incident chronic kidney disease (95% CI, 1.1 to 2.5) and 10% annual eGFR decline (95% CI, 1.7 to 6.7), respectively, with minimal attenuation after adjustment for glomerular and tubular injury biomarker levels. Limitations Results may not be generalizable to men. Conclusions Among HIV-infected African American women, APOL1-associated kidney injury appears to localize to the glomerulus, rather than the tubules.
AB - Background APOL1 genotype is associated with advanced kidney disease in African Americans, but the pathogenic mechanisms are unclear. Here, associations of APOL1 genotype with urine biomarkers of glomerular and tubular injury and kidney function decline were evaluated. Study Design Observational study. Setting & Participants 431 human immunodeficiency virus (HIV)-infected African American women enrolled in Women's Interagency HIV Study (WIHS). Predictor APOL1 genotype. Outcomes Albumin-creatinine ratio (ACR), 4 tubular injury biomarkers (interleukin 18 [IL-18], kidney injury molecule 1 [KIM-1], neutrophil gelatinase-associated lipocalin [NGAL], and α1-microglobulin [A1M]), and kidney function estimated using the CKD-EPI cystatin C equation. Measurements Participants were genotyped for APOL1 single-nucleotide polymorphisms rs73885319 (G1 allele) and rs71785313 (G2 allele). Urine biomarkers were measured using stored samples from 1999-2000. Cystatin C was measured using serum collected at baseline and 4- and 8-year follow-ups. Results At baseline, ACRs were higher among 47 women with 2 APOL1 risk alleles versus 384 women with 0/1 risk allele (median, 24 vs 11 mg/g; P < 0.001). Compared with women with 0/1 risk allele, women with 2 risk alleles had 104% higher ACRs (95% CI, 29-223 mg/g) and 2-fold greater risk of ACR > 30 (95% CI, 1.17-3.44) mg/g after multivariable adjustment. APOL1 genotype showed little association with urine IL-18:Cr ratio, KIM-1:Cr ratio, and NGAL:Cr ratio (estimates of -5% [95% CI, -24% to 18%], -20% [95% CI, -36% to -1%], and 10% [95% CI, -26% to 64%], respectively) or detectable urine A1M (prevalence ratio, 1.13; 95% CI, 0.65-1.97) in adjusted analyses. Compared with women with 0/1 allele, women with 2 risk alleles had faster eGFR decline, by 1.2 (95% CI, 0.2 to 2.2) mL/min/1.73 m2 per year, and 1.7- and 3.4-fold greater rates of incident chronic kidney disease (95% CI, 1.1 to 2.5) and 10% annual eGFR decline (95% CI, 1.7 to 6.7), respectively, with minimal attenuation after adjustment for glomerular and tubular injury biomarker levels. Limitations Results may not be generalizable to men. Conclusions Among HIV-infected African American women, APOL1-associated kidney injury appears to localize to the glomerulus, rather than the tubules.
KW - APOL1 genotype
KW - African American
KW - G1 allele
KW - G2 allele
KW - Women's Interagency HIV Study (WIHS)
KW - albumin-creatinine ratio (ACR)
KW - apolipoprotein L1
KW - glomerular injury
KW - kidney disease
KW - proteinuria
KW - renal function
KW - risk allele
KW - risk variant
KW - single-nucleotide polymorphism (SNP)
KW - tubular injury biomarker
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U2 - 10.1053/j.ajkd.2015.02.329
DO - 10.1053/j.ajkd.2015.02.329
M3 - Article
C2 - 25921719
AN - SCOPUS:84930473473
SN - 0272-6386
VL - 65
SP - 889
EP - 898
JO - American Journal of Kidney Diseases
JF - American Journal of Kidney Diseases
IS - 6
ER -
