Low CD4 cell count and hepatitis C coinfection risk factors for acute kidney failure in HIV-infected patients

Michael Carter
Published: 19 July 2006

HIV-positive individuals who are receiving treatment with potent antiretroviral therapy have an increased risk of experiencing acute kidney failure if they have a low CD4 cell count, US investigators report in the July edition of the Journal of Acquired Immune Deficiency Syndromes. The investigators further found that patients who were coinfected with hepatitis C virus had particularly elevated rates of acute kidney failure.

In the period before potent anti-HIV therapy became available, severe immune suppression, indicated by a very low CD4 cell count, and AIDS-defining opportunistic infections were associated with acute renal failure in HIV-positive individuals. Although potent antiretroviral therapy can improve the immune function of HIV-positive patients, reducing the incidence of opportunistic infections, many HIV-infected individuals may remain vulnerable to acute kidney failure because of coinfections, drug toxicities, life-style factors and continuing susceptibility to some infections.

Researchers at the University of North Carolina’s Centre for AIDS Research conducted an observational study involving 705 HIV-positive individuals between 2000 – 2002. with a primary aim of assessing the effect of a low CD4 cell count on the incidence of acute renal failure.

Acute renal failure was defined as an increase in serum creatinine for at least two days of 0.5mg/dl in individuals whose baseline level was less than 2.0mg/dl; 1.0mg/dl for patients whose baseline creatinine was between 2.0mg/dl – 5.0mg/dl; and, 1.5mg/dl for individuals with a baseline creatinine level of 5.0mg/dl or higher.

CD4 cell counts were measured at least three months before entry to the study and at regular intervals thereafter. Patients were also tested for infection with hepatitis C virus and hepatitis B virus.

The investigators also gathered data on the patients’ age, race, sex, previous-AIDS defining illnesses, blood pressure, the prevalence of diabetes, and history of injecting drug use. These were included in their later statistical analyses.

Median age of the patients included in the study was 40 years, 69% were male, and 61% were African American. Baseline CD4 cell count was 352 cells/mm3, and approximately a third of individuals had a CD4 cell count below 200 cells/mm3, indicating an increased susceptibility to opportunistic infections.

Baseline median creatinine was 0.7mg/dl and did not differ by CD4 cell count. Approximately 25% of patients were coinfected with hepatitis C virus, 17% had chronic high blood pressure, and 6% had diabetes.

Anti-HIV therapy was used to treat 93% of patients by the end of follow-up, the median duration of exposure to antiretrovirals being five and a half years. The median number of anti-HIV drugs used was five. Only 38% of patients had a viral load below 400 copies/ml.

A total of 109 instances of acute kidney failure were observed in 69 patients during the two-year period of the study, providing an overall unadjusted incidence rate was 6.4 per 100 patient years.

Acute renal failure was associated with a low CD4 cell count: the unadjusted incidence rate being 15 per 100 patient years for individuals with a CD4 cell count below 100 cells/mm3 compared to 1 per 100 patient years amongst patients with a CD4 cell count of 500 cells/mm3 or more.

An even higher rate of acute renal failure was seen amongst patients coinfected with hepatitis C virus, the unadjusted incidence rate being 25 per 100 patient years for patients with a CD4 cell count below 100 cells/mm3. Moreover, in their adjusted analysis they noted very similar, and significantly elevated, incidence rates of kidney failure in coinfected patients with CD4 cell counts above and below 200 cells/mm3 (4.3 per 100 person years versus 3.7 per 100 person years).

Patients in their first year of anti-HIV therapy had the highest incidence of acute kidney failure (19 per 100 person years versus 3 per 100 person years for subsequent years of therapy), and the investigators therefore recommend that the kidney function of patients should be intensively monitored during the first twelve months of antiretroviral treatment.

The investigators repeated their statistical analysis, adjusting it for possible confounding factors. They found that a low CD4 cell count (p < 0.001), and number of years of previous antiretroviral therapy, an indicator of long-term HIV infection and immune suppression (p < 0.001), and coinfection with hepatitis C virus (p = 0.02) were all significantly associated with an increased risk of kidney failure.

“A low CD4 cell count is…a strong predictor for experiencing an incident acute renal failure event”, write the investigators, adding “we observed that increased acute renal failure incidence rates may be a more substantial concern for patients with relatively preserved immune function. These findings have clinical implications for the care of HIV-1-infected individuals, because acute renal failure by itself is associated with increased morbidity and mortality”

Reference

Franceschini N et al. Immunosuppression, hepatitis C infection, and acute renal failure in HIV-infected patients. J Acquir Immune Defic Syndr 42: 368 – 372, 2006.

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