Association of urine α1-microglobulin with kidney function decline and mortality in HIV-infected women

Clin J Am Soc Nephrol. 2015 Jan 7;10(1):63-73. doi: 10.2215/CJN.03220314. Epub 2014 Nov 4.

Abstract

Background and objectives: Despite advances in therapy, HIV-infected individuals remain at higher risk for kidney dysfunction than uninfected individuals. It was hypothesized that urine levels of α1-microglobulin, a biomarker of proximal tubular dysfunction, would predict kidney function decline and mortality risk in HIV-infected and uninfected women.

Design, setting, participants, & measurements: In the Women's Interagency HIV Study, urine α1-microglobulin and creatinine concentrations were measured in 903 HIV-infected and 287 uninfected women using stored urine from 1999 to 2000, when prevalence of tenofovir use was <1%. Participants were categorized into three categories by level of α1-microglobulin-to-creatinine ratio, and associations with kidney decline and all-cause mortality over 8 years were evaluated.

Results: Urine α1-microglobulin was detectable in 60% of HIV-infected and 40% of uninfected women (P<0.001). Among HIV-infected women, there were 177 (22%), 61 (7%), and 128 (14%) patients with incident CKD, with 10% annual eGFR decline, and who died, respectively. Compared with HIV-infected women in the lowest α1-microglobulin category, HIV-infected women in the highest α1-microglobulin category had a 2.1-fold risk of incident CKD (95% confidence interval, 1.3 to 3.4), 2.7-fold risk of 10% annual eGFR decline (95% confidence interval, 1.2 to 5.9), and 1.6-fold mortality risk (95% confidence interval, 1.0 to 2.6) in models adjusting for kidney risk factors, baseline eGFR, and albuminuria. Among uninfected women, the highest α1-microglobulin category was associated with 3% (relative risk, 2.2; 95% confidence interval, 1.4 to 3.5) and 5% (relative risk, 2.2; 95% confidence interval, 1.1 to 4.3) annual eGFR decline relative to the lowest α1-microglobulin category.

Conclusions: Proximal tubular dysfunction, indicated by urine α1-microglobulin, was independently associated with kidney function decline in HIV-infected and uninfected women and mortality risk among HIV-infected women.

Keywords: CKD; HIV nephropathy; proximal tubule.

Publication types

  • Multicenter Study
  • Research Support, N.I.H., Extramural

MeSH terms

  • AIDS-Associated Nephropathy / diagnosis*
  • AIDS-Associated Nephropathy / mortality*
  • AIDS-Associated Nephropathy / physiopathology
  • AIDS-Associated Nephropathy / urine
  • Adult
  • Alpha-Globulins / urine*
  • Biomarkers / urine
  • Case-Control Studies
  • Chi-Square Distribution
  • Creatinine / urine
  • Disease Progression
  • Female
  • Glomerular Filtration Rate
  • Humans
  • Kidney Function Tests
  • Kidney Tubules, Proximal / metabolism*
  • Kidney Tubules, Proximal / physiopathology
  • Linear Models
  • Middle Aged
  • Multivariate Analysis
  • Odds Ratio
  • Predictive Value of Tests
  • Proportional Hazards Models
  • Prospective Studies
  • Risk Assessment
  • Risk Factors
  • Sex Factors
  • Time Factors
  • United States / epidemiology

Substances

  • Alpha-Globulins
  • Biomarkers
  • alpha-1-microglobulin
  • Creatinine