APOL1 genotype and glomerular and tubular kidney injury in women with HIV

Vasantha Jotwani, Michael G. Shlipak, Rebecca Scherzer, Rulan S. Parekh, W. H.Linda Kao, Michael Bennett, Mardge H. Cohen, Marek Nowicki, Anjali Sharma, Mary Young, Phyllis C. Tien, Chirag R. Parikh, Michelle M. Estrella

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13 Scopus citations

Abstract

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.

Original languageEnglish (US)
Pages (from-to)889-898
Number of pages10
JournalAmerican Journal of Kidney Diseases
Volume65
Issue number6
DOIs
Publication statusPublished - Jun 1 2015
Externally publishedYes

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Keywords

  • APOL1 genotype
  • African American
  • G1 allele
  • G2 allele
  • Women's Interagency HIV Study (WIHS)
  • albumin-creatinine ratio (ACR)
  • apolipoprotein L1
  • glomerular injury
  • kidney disease
  • proteinuria
  • renal function
  • risk allele
  • risk variant
  • single-nucleotide polymorphism (SNP)
  • tubular injury biomarker

ASJC Scopus subject areas

  • Nephrology

Cite this

Jotwani, V., Shlipak, M. G., Scherzer, R., Parekh, R. S., Kao, W. H. L., Bennett, M., ... Estrella, M. M. (2015). APOL1 genotype and glomerular and tubular kidney injury in women with HIV. American Journal of Kidney Diseases, 65(6), 889-898. https://doi.org/10.1053/j.ajkd.2015.02.329