High blood pressure and diabetes have become the predominant cause of kidney disease in HIV-positive individuals, concludes a small retrospective cohort study that mainly included African American injecting drug users, and published in the August 1st edition of Clinical Infectious Diseases. The study also found that a viral load measurement below 400 copies/ml may be used as a crude diagnostic tool in order to differentiate between the likelihood of HIV-associated nephropathy (HIVAN) and kidney disease due to other causes.
Until recently, chronic kidney disease in HIV-positive people was a subject very much 'under the radar', especially since the prevalence of liver-related problems is much higher. More recent data suggest that the number of people with kidney-related problems may be increasing as people with HIV live longer (for an overview see this article on aidsmap.com).
Historically, HIV-associated nephropathy (HIVAN) has been the most prevalent cause of kidney disease in HIV-positive individuals, although experts have predicated that non-HIVAN kidney diseases would overtake HIVAN in the era of potent antiretroviral therapy. This is because non-HIVAN kidney problems are not generally improved by potent antiretroviral therapy, unlike HIVAN; kidney disease can be a side-effect of certain drugs used to treat HIV and AIDS; and the metabolic side-effects of anti-HIV therapy may increase the likelihood of experiencing high blood pressure and diabetes, which can result in kidney disease.
Kidney biopsy is currently the 'gold standard' for accurately diagnosing the severity of kidney disease, as well as for differentiating between HIVAN and non-HIVAN. However, this is an invasive process that may not be available routinely. Consequently, investigators from the Johns Hopkins School of Medicine in the United States sought to determine whether HIV viral load measurements can be a useful prognostic tool in order to help to differentiate between HIVAN and non-HIVAN renal pathology.
Between January 1995 and August 2004, 263 HIV-positive individuals were referred to the Johns Hopkins Renal Clinic of whom 152 underwent kidney biopsy. Of these, 86 patients who also had HIV viral loads measured within two months of the biopsy, and who had detailed clinical records, were included in this retrospective cohort study. Most of the participants were African American and around half had a history of injecting drug use.
The investigators divided participants into those with an HIV viral load above or below 400 copies/ml. This cut-off value was used since more sensitive viral load testing only became routine during the later years of the study. A total of 23 patients had viral loads below 400 copies/mL (the 'undetectable' group), of whom 22 were on potent antiretroviral therapy, and 63 had viral loads of 400 copies/mL or higher (the 'detectable' group), of whom 48 were on potent antiretroviral therapy.
There were a few significant differences between the two groups. The 'undetectable' group included a greater proportion of people with diabetes (34.7% vs. 15.9%; p=0.06) but only one individual diagnosed with HIVAN (p
In univariate analysis, a viral load above 400 copies/mL was strongly associated with HIVAN (OR, 15.5; p=0.009), but this was no longer significant in multivariate analysis (OR, 7.8; p= .076) due to the wide 95% confidence intervals (0.80-77.11). They also calculated that an HIV viral load greater than 400 copies/mL was highly sensitive for HIVAN (sensitivity, 95.8%; negative predictive value, 95.7%), although it was non-specific (specificity, 35.5%).
The investigators conclude that "although no single test other than renal biopsy can definitively diagnose HIVAN", HIV viral load may be "a useful measure for differentiating between HIVAN and non-HIVAN renal disease," because they found "that HIVAN is unlikely among patients with HIV-1 RNA levels of
Of interest, the investigators found a wide variety of kidney disease in both viral load groups. The most prevalent problem seen in the 'undetectable' group was hypertensive vascular disease. This may be a result of high blood pressure caused by hardening of the arteries, or, conversely, the kidney disease itself may be causing the hypertension. Four patients with viral loads of
"In fact," write the investigators, "hypertensive vascular disease surpassed HIVAN as the single most common biopsy finding among all patients. This observation may reflect an evolving profile of renal diseases affecting HIV-infected patients as a result of systemic nonantiviral effects of HAART or a shift towards more traditional causes of chronic kidney disease."
Although both groups had a similar number of participants with high blood pressure, a greater proportion in the 'undetectable' group had "at least moderate-to-severe hypertensive vascular disease pathologically (43.5% vs. 23.8%)," they write, suggesting that antiretroviral therapy exposure may be the cause. They suggest a similar reason for the greater proportion of patients in the 'undetectable' group having diabetic glomerulosclerosis (17.4% vs. 4.8%).
However, there were some limitations to this study which may not make the results generalisable to the general population, in particular the high number of African American patients, who are genetically at a higher risk of kidney disease than other ethnicities. The investigators also failed to provide information on the class of antiretroviral drugs used, or whether there was a history of other kidney-toxic medicines that might affect outcome.
The investigators conclude that "for patients with contraindications to renal biopsy, the combination of clinical history and HIV-1 RNA level of
Estrella M et al. HIV Type 1 RNA level as a clinical indicator of renal pathology in HIV-infected patients. Clin Infect Dis 43: 377-380, 2006.