Development of Proteinuria or Elevated Serum Creatinine and Mortality in HIV-Infected Women

Renal complications of HIV infection have been reported since 1984. However, data on the incidence and prognostic significance of renal dysfunction in HIV disease are limited. These are important issues, because renal dysfunction may be frequent but partially reversible once identified and treated. In the current study, researchers prospectively studied a cohort of 885 HIV-positive women without clinical AIDS and 425 HIV-negative women with a similar high-risk profile since 1993.

Researchers determined the incidence of proteinuria or elevated serum creatinine in the cohorts, to assess whether they were predictors of mortality in HIV-positive women, and to determine whether causes listed on death certificates differed between HIV-positive women with and without proteinuria or elevated serum creatinine. A woman was considered to have renal abnormalities if she had a serum creatinine level of 1.4 mg/dL or more, or a urine protein level of 2+ or more, or both.

Participants were from the general community or HIV care clinics in four U.S. urban locations: Bronx, N.Y.; Detroit, Mich.; Baltimore, Md.; and Providence, R.I. Roughly one-half of participants had high-risk sexual contacts, and one-half had injected drugs since 1985. Participants were seen at six-month intervals.

A significantly greater proportion of the HIV-infected (7.2 percent) women than uninfected women (2.4 percent) had renal abnormalities at baseline. Of the 64 HIV-positive women with renal abnormalities, 46 had proteinuria and 32 had high serum creatinine at baseline. HIV-infected women with renal abnormalities at baseline did not differ from HIV-infected women without renal abnormalities by percentage using antiretroviral therapy (34.4 percent vs. 34.3 percent), mean log viral load (3.43 vs. 3.17), or mean CD4 cell count (406 vs. 453 cells/mm3. No women were using HAART at baseline.

HIV-positive and -negative women differed in several ways by research visit 5. The cumulative percentage that had developed renal abnormalities, hypertension, or both were all significantly higher in HIV-positive women than in HIV-negative women. Of the 192 HIV-infected women with renal abnormalities, 148 (77 percent) did so prior to a CD4 cell count below 200 cells/mm3, and 95 percent of the time before clinical AIDS diagnosis. More of the women had proteinuria (158) than elevated serum creatinine (47) as an abnormality.

Over a mean 21-month follow-up, renal abnormalities developed in 128 of 821 (15.6 percent) HIV-positive women and 18 of 415 (4.3 percent) HIV-negative women. Most of the HIV-positive women's incident renal abnormalities were from proteinuria: 111 (13.5 percent) had proteinuria of 2+ or greater on one of the subsequent four visits, and 23 (2.8 percent) had a serum creatinine level of 1.4mg/dL or less on one of four subsequent visits. Of women without renal abnormalities at baseline, 15 percent developed them within a 21-month period before the widespread use of HAART.

Two hundred thirty-nine (27 percent) HIV-infected women and 7 (1.6 percent) HIV-uninfected women died over an average follow-up interval of 4.9 years. The small number of deaths precluded identification of risk factors among HIV-uninfected women. For the HIV-infected women, renal abnormalities were associated with a 2.5-fold excess mortality rate, controlling for all other mortality predictors in Cox regression analysis. Although only slightly more women with renal abnormalities died of an HIV- or AIDS-related cause than those without such abnormalities (58 percent vs. 47 percent), the former group had 11 times more renal causes recorded on the death certificate than the latter group.

"The high frequency with which elevated creatinine levels and proteinuria occurred... indicates the importance of closely monitoring serum and urine chemistries in HIV-infected patients, especially those with risk factors for renal dysfunction." The mortality data "suggest the utility of identifying women with even single abnormalities of serum creatinine or proteinuria, because women with such abnormalities had a significantly elevated mortality risk and a much greater frequency of renal causes listed on the death certificate," the researchers concluded.

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