Does HIV infection promote early kidney injury in women?

Abstract

Background: In HIV-infected women, urine concentrations of novel tubulointerstitial injury markers, interleukin-18 (IL-18) and kidney injury marker-1 (KIM-1), are associated with kidney function decline and all-cause mortality. We hypothesized that HIV-infected individuals with preserved kidney filtration function would have more extensive kidney injury, as determined by urine injury markers, compared to the uninfected controls, and that risk factors for tubulointerstitial injury would differ from risk factors for albuminuria.

Methods: In this cross-sectional study, we compared urine concentrations of IL-18, KIM-1 and albumin-to-creatinine ratio (ACR) in 908 HIV-infected and 289 HIV-uninfected women enrolled in the Women's Interagency HIV Study, utilizing stored urine specimens from visits between 1999 and 2000.

Results: After multivariate-adjusted linear regression analysis, mean urine concentrations were higher in HIV-infected individuals by 38% for IL-18 (P<0.0001), 12% for KIM-1 (P=0.081) and 47% for ACR (P<0.0001). Higher HIV RNA level (15% per 10-fold increase; P<0.0001), lower CD4(+) lymphocyte count (8% per doubling; P=0.0025), HCV infection (30%; P=0.00018) and lower high-density lipoprotein (5% per 10 mg/dl; P=0.0024) were each associated with higher IL-18 concentrations. In contrast, hypertension (81%; P<0.0001) and diabetes (47%; P=0.018) were among the strongest predictors of higher ACR, though HIV RNA level (15% per 10-fold increase; P=0.0004) was also associated with higher ACR.

Conclusions: HIV-infected women had more extensive tubulointerstitial and glomerular injury than uninfected women, but the associated factors differed among the urine biomarkers. Combinations of urinary biomarkers should be investigated to further characterize early kidney injury in HIV-infected women.

Figure 1. Association of HIV infection with urine biomarkers among HIV-infected (N=908) and uninfected (N=289) WIHS participants

Note: Bars represent median urine biomarker concentrations with 95% confidence intervals. P-values from Mann-Whitney U test. Abbreviations: ACR, albumin-to-creatinine ratio; IL-18, interleukin-18; KIM-1, kidney injury molecule-1; NGAL, neutrophil gelatinase-associated lipocalin.