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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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 α<inf>1</inf>-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 m<sup>2</sup> 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
StatePublished - Jun 1 2015
Externally publishedYes

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Genotype
HIV
Kidney
Alleles
Wounds and Injuries
Biomarkers
Urine
African Americans
Cystatin C
Interleukin-18
Lipocalin 1
Kidney Diseases
Chronic Renal Insufficiency
Observational Studies
Single Nucleotide Polymorphism
Albumins
Creatinine
Serum
Lipocalin-2

Keywords

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

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

APOL1 genotype and glomerular and tubular kidney injury in women with HIV. / Jotwani, Vasantha; Shlipak, Michael G.; Scherzer, Rebecca; Parekh, Rulan S.; Kao, W. H Linda; Bennett, Michael; Cohen, Mardge H.; Nowicki, Marek; Sharma, Anjali; Young, Mary; Tien, Phyllis C.; Parikh, Chirag R.; Estrella, Michelle M.

In: American Journal of Kidney Diseases, Vol. 65, No. 6, 01.06.2015, p. 889-898.

Research output: Contribution to journalArticle

Jotwani, V, Shlipak, MG, Scherzer, R, Parekh, RS, Kao, WHL, Bennett, M, Cohen, MH, Nowicki, M, Sharma, A, Young, M, Tien, PC, Parikh, CR & Estrella, MM 2015, 'APOL1 genotype and glomerular and tubular kidney injury in women with HIV', American Journal of Kidney Diseases, vol. 65, no. 6, pp. 889-898. https://doi.org/10.1053/j.ajkd.2015.02.329
Jotwani V, Shlipak MG, Scherzer R, Parekh RS, Kao WHL, Bennett M et al. APOL1 genotype and glomerular and tubular kidney injury in women with HIV. American Journal of Kidney Diseases. 2015 Jun 1;65(6):889-898. https://doi.org/10.1053/j.ajkd.2015.02.329
Jotwani, Vasantha ; Shlipak, Michael G. ; Scherzer, Rebecca ; Parekh, Rulan S. ; Kao, W. H Linda ; Bennett, Michael ; Cohen, Mardge H. ; Nowicki, Marek ; Sharma, Anjali ; Young, Mary ; Tien, Phyllis C. ; Parikh, Chirag R. ; Estrella, Michelle M. / APOL1 genotype and glomerular and tubular kidney injury in women with HIV. In: American Journal of Kidney Diseases. 2015 ; Vol. 65, No. 6. pp. 889-898.
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title = "APOL1 genotype and glomerular and tubular kidney injury in women with HIV",
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.",
keywords = "African American, albumin-creatinine ratio (ACR), APOL1 genotype, apolipoprotein L1, G1 allele, G2 allele, glomerular injury, kidney disease, proteinuria, renal function, risk allele, risk variant, single-nucleotide polymorphism (SNP), tubular injury biomarker, Women's Interagency HIV Study (WIHS)",
author = "Vasantha Jotwani and Shlipak, {Michael G.} and Rebecca Scherzer and Parekh, {Rulan S.} and Kao, {W. H Linda} and Michael Bennett and Cohen, {Mardge H.} and Marek Nowicki and Anjali Sharma and Mary Young and Tien, {Phyllis C.} and Parikh, {Chirag R.} and Estrella, {Michelle M.}",
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language = "English (US)",
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pages = "889--898",
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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.

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 - African American

KW - albumin-creatinine ratio (ACR)

KW - APOL1 genotype

KW - apolipoprotein L1

KW - G1 allele

KW - G2 allele

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

KW - Women's Interagency HIV Study (WIHS)

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JO - American Journal of Kidney Diseases

JF - American Journal of Kidney Diseases

SN - 0272-6386

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