Urinary markers of kidney injury and kidney function decline in HIV-infected women

Michael G. Shlipak, Rebecca Scherzer, Alison Gump Abraham, Phyllis C. Tien, Carl Grunfeld, Carmen A. Peralta, Prasad Devarajan, Michael Bennett, Anthony W. Butch, Kathryn Anastos, Mardge H. Cohen, Marek Nowicki, Anjali Sharma, Mary A. Young, Mark J. Sarnak, Chirag Parikh

Research output: Contribution to journalArticle

Abstract

Objective: HIV-infected persons have substantially higher risk of kidney failure than persons without HIV, but serum creatinine levels are insensitive for detecting declining kidney function. We hypothesized that urine markers of kidney injury would be associated with declining kidney function among HIV-infected women. Methods: In the Women's Interagency HIV Study, we measured concentrations of albumin-to-creatinine ratio, interleukin-18 (IL-18), kidney injury marker-1 (KIM-1), and neutrophil gelatinase-associated lipocalin from stored urine among 908 HIV-infected and 289 HIV-uninfected participants. Primary analyses used cystatin C-based estimated glomerular filtration rate (CKD-EPI eGFRcys) as the outcome, measured at baseline and 2 follow-up visits over 8 years; secondary analyses used creatinine (CKD-EPI eGFRcr). Each urine biomarker was categorized into tertiles, and kidney decline was modeled with both continuous and dichotomized outcomes. Results: Compared with the lowest tertiles, the highest tertiles of albumin-to-creatinine ratio (20.15 mL/min per 1.73 m2, P <0.0001), IL-18 (20.09 mL/min per 1.73 m2, P <0.0001) and KIM-1 (20.06 mL/min per 1.73 m2, P <0.001) were independently associated with faster eGFRcys decline after multivariate adjustment including all 3 biomarkers among HIV-infected women. Among these biomarkers, only IL-18 was associated with each dichotomized eGFRcys outcome: ≥3% (relative risk = 1.40; 95% confidence interval: 1.04 to 1.89); ≥5% (1.88; 1.30 to 2.71); and ≥10% (2.16; 1.20 to 3.88) for the highest versus lowest tertile. In alternative models using eGFRcr, the high tertile of KIM-1 had independent associations with 5% (1.71; 1.25 to 2.33) and 10% (1.78; 1.07 to 2.96) decline, and the high IL-18 tertile with 10% decline (1.97; 1.00 to 3.87). Conclusions: Among HIV-infected women in the Women's Inter-agency HIV Study cohort, novel urine markers of kidney injury detect risk for subsequent declines in kidney function.

Original languageEnglish (US)
Pages (from-to)565-573
Number of pages9
JournalJournal of Acquired Immune Deficiency Syndromes
Volume61
Issue number5
DOIs
StatePublished - Dec 15 2012

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HIV
Kidney
Wounds and Injuries
Interleukin-18
Creatinine
Urine
Biomarkers
Albumins
Cystatin C
Glomerular Filtration Rate
Renal Insufficiency
Cohort Studies
Confidence Intervals
Serum

Keywords

  • Albumin-to-creatinine ratio
  • Cystatin C
  • HIV
  • IL-18
  • Kidney injury
  • KIM-1
  • NGAL

ASJC Scopus subject areas

  • Infectious Diseases
  • Pharmacology (medical)
  • Medicine(all)

Cite this

Urinary markers of kidney injury and kidney function decline in HIV-infected women. / Shlipak, Michael G.; Scherzer, Rebecca; Abraham, Alison Gump; Tien, Phyllis C.; Grunfeld, Carl; Peralta, Carmen A.; Devarajan, Prasad; Bennett, Michael; Butch, Anthony W.; Anastos, Kathryn; Cohen, Mardge H.; Nowicki, Marek; Sharma, Anjali; Young, Mary A.; Sarnak, Mark J.; Parikh, Chirag.

In: Journal of Acquired Immune Deficiency Syndromes, Vol. 61, No. 5, 15.12.2012, p. 565-573.

Research output: Contribution to journalArticle

Shlipak, MG, Scherzer, R, Abraham, AG, Tien, PC, Grunfeld, C, Peralta, CA, Devarajan, P, Bennett, M, Butch, AW, Anastos, K, Cohen, MH, Nowicki, M, Sharma, A, Young, MA, Sarnak, MJ & Parikh, C 2012, 'Urinary markers of kidney injury and kidney function decline in HIV-infected women', Journal of Acquired Immune Deficiency Syndromes, vol. 61, no. 5, pp. 565-573. https://doi.org/10.1097/QAI.0b013e3182737706
Shlipak, Michael G. ; Scherzer, Rebecca ; Abraham, Alison Gump ; Tien, Phyllis C. ; Grunfeld, Carl ; Peralta, Carmen A. ; Devarajan, Prasad ; Bennett, Michael ; Butch, Anthony W. ; Anastos, Kathryn ; Cohen, Mardge H. ; Nowicki, Marek ; Sharma, Anjali ; Young, Mary A. ; Sarnak, Mark J. ; Parikh, Chirag. / Urinary markers of kidney injury and kidney function decline in HIV-infected women. In: Journal of Acquired Immune Deficiency Syndromes. 2012 ; Vol. 61, No. 5. pp. 565-573.
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T1 - Urinary markers of kidney injury and kidney function decline in HIV-infected women

AU - Shlipak, Michael G.

AU - Scherzer, Rebecca

AU - Abraham, Alison Gump

AU - Tien, Phyllis C.

AU - Grunfeld, Carl

AU - Peralta, Carmen A.

AU - Devarajan, Prasad

AU - Bennett, Michael

AU - Butch, Anthony W.

AU - Anastos, Kathryn

AU - Cohen, Mardge H.

AU - Nowicki, Marek

AU - Sharma, Anjali

AU - Young, Mary A.

AU - Sarnak, Mark J.

AU - Parikh, Chirag

PY - 2012/12/15

Y1 - 2012/12/15

N2 - Objective: HIV-infected persons have substantially higher risk of kidney failure than persons without HIV, but serum creatinine levels are insensitive for detecting declining kidney function. We hypothesized that urine markers of kidney injury would be associated with declining kidney function among HIV-infected women. Methods: In the Women's Interagency HIV Study, we measured concentrations of albumin-to-creatinine ratio, interleukin-18 (IL-18), kidney injury marker-1 (KIM-1), and neutrophil gelatinase-associated lipocalin from stored urine among 908 HIV-infected and 289 HIV-uninfected participants. Primary analyses used cystatin C-based estimated glomerular filtration rate (CKD-EPI eGFRcys) as the outcome, measured at baseline and 2 follow-up visits over 8 years; secondary analyses used creatinine (CKD-EPI eGFRcr). Each urine biomarker was categorized into tertiles, and kidney decline was modeled with both continuous and dichotomized outcomes. Results: Compared with the lowest tertiles, the highest tertiles of albumin-to-creatinine ratio (20.15 mL/min per 1.73 m2, P <0.0001), IL-18 (20.09 mL/min per 1.73 m2, P <0.0001) and KIM-1 (20.06 mL/min per 1.73 m2, P <0.001) were independently associated with faster eGFRcys decline after multivariate adjustment including all 3 biomarkers among HIV-infected women. Among these biomarkers, only IL-18 was associated with each dichotomized eGFRcys outcome: ≥3% (relative risk = 1.40; 95% confidence interval: 1.04 to 1.89); ≥5% (1.88; 1.30 to 2.71); and ≥10% (2.16; 1.20 to 3.88) for the highest versus lowest tertile. In alternative models using eGFRcr, the high tertile of KIM-1 had independent associations with 5% (1.71; 1.25 to 2.33) and 10% (1.78; 1.07 to 2.96) decline, and the high IL-18 tertile with 10% decline (1.97; 1.00 to 3.87). Conclusions: Among HIV-infected women in the Women's Inter-agency HIV Study cohort, novel urine markers of kidney injury detect risk for subsequent declines in kidney function.

AB - Objective: HIV-infected persons have substantially higher risk of kidney failure than persons without HIV, but serum creatinine levels are insensitive for detecting declining kidney function. We hypothesized that urine markers of kidney injury would be associated with declining kidney function among HIV-infected women. Methods: In the Women's Interagency HIV Study, we measured concentrations of albumin-to-creatinine ratio, interleukin-18 (IL-18), kidney injury marker-1 (KIM-1), and neutrophil gelatinase-associated lipocalin from stored urine among 908 HIV-infected and 289 HIV-uninfected participants. Primary analyses used cystatin C-based estimated glomerular filtration rate (CKD-EPI eGFRcys) as the outcome, measured at baseline and 2 follow-up visits over 8 years; secondary analyses used creatinine (CKD-EPI eGFRcr). Each urine biomarker was categorized into tertiles, and kidney decline was modeled with both continuous and dichotomized outcomes. Results: Compared with the lowest tertiles, the highest tertiles of albumin-to-creatinine ratio (20.15 mL/min per 1.73 m2, P <0.0001), IL-18 (20.09 mL/min per 1.73 m2, P <0.0001) and KIM-1 (20.06 mL/min per 1.73 m2, P <0.001) were independently associated with faster eGFRcys decline after multivariate adjustment including all 3 biomarkers among HIV-infected women. Among these biomarkers, only IL-18 was associated with each dichotomized eGFRcys outcome: ≥3% (relative risk = 1.40; 95% confidence interval: 1.04 to 1.89); ≥5% (1.88; 1.30 to 2.71); and ≥10% (2.16; 1.20 to 3.88) for the highest versus lowest tertile. In alternative models using eGFRcr, the high tertile of KIM-1 had independent associations with 5% (1.71; 1.25 to 2.33) and 10% (1.78; 1.07 to 2.96) decline, and the high IL-18 tertile with 10% decline (1.97; 1.00 to 3.87). Conclusions: Among HIV-infected women in the Women's Inter-agency HIV Study cohort, novel urine markers of kidney injury detect risk for subsequent declines in kidney function.

KW - Albumin-to-creatinine ratio

KW - Cystatin C

KW - HIV

KW - IL-18

KW - Kidney injury

KW - KIM-1

KW - NGAL

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