Poor kidney function increases cardiovascular disease risk for patients with HIV

Poor kidney function is associated with an increased risk of cardiovascular disease in patients with HIV, US investigators report in the January 28^th edition of AIDS.

A key measure of kidney function – estimated glomerular filtration rate – was correlated with an increased risk of heart attack or stroke.

“Our study highlights the existence of a strong link between kidney function and cardiovascular disease risk in HIV-infected individuals, an association that is at least as strong, if not stronger than that reported in the general population,” comment the investigators. They add, “no previous study has correlated kidney function with cardiovascular events in HIV patients.”

The introduction of effective antiretroviral therapy in the late 1990s brought about a substantial and sustained fall in the amount of HIV-related illness and death seen in industrialised countries.

At the same time, the proportion of deaths caused by cardiovascular disease among people with HIV has increased. There are a number of possible reasons for this including the ageing of the HIV-positive population, the inflammatory effects of HIV, the side-effects of some anti-HIV drugs, and the high prevalence of risk behaviours such as smoking.

Poor kidney function demonstrated by reduced estimated glomerular filtration rate and proteinuria (protein in the urine) is strongly associated with an increased risk of cardiovascular disease in HIV-negative individuals.

However, the association between these two markers of kidney function and cardiovascular disease in patients with HIV has never previously been explored, despite the fact that a high proportion of people living with HIV in the United States suffer from chronic kidney disease.

The condition is particularly prevalent among African-Americans, and in 2000 the US National Institute of Diabetes and Digestive and Kidney Diseases reported that HIV-associated kidney disease, or nephropathy, had become the third most frequent cause of end-stage renal disease among African-Americans aged 20 to 64. A 2008 study found that although African-Americans with HIV were only slightly more likely to develop kidney dysfunction than Caucasians, they had a much higher risk of subsequent progression to end-stage renal disease than Caucasians.

A recent French study found that kidney function was impaired in 39% of patients receiving long-term antiretroviral therapy, but did not deteriorate with a longer duration of treatment.

In order to elucidate the relationship between kidney function and cardiovascular risk in people living with HIV, investigators at Johns Hopkins University in Baltimore performed a retrospective case-controlled study that compared kidney function between 63 HIV-positive patients who had had either a heart attack or stroke, and 252 HIV-positive controls who had not experienced a cardiovascular event.

The two groups of patients had similar demographic characteristics. However, those who experienced a cardiovascular event were more likely to have a CD4 cell count below 200 cells/mm³ (49% vs 25%, p < 0.001) and a viral load above 50,000 copies/ml (39% vs 20%, p < 0.007).

Moreover, they also had a higher prevalence than the control patients of established risk factors for cardiovascular disease such as diabetes, high blood pressure, and high lipids and were also more likely to have had a previous cardiovascular event (41% vs 7%, p < 0.001).

Several markers showed that the patients who experienced a cardiovascular event had poorer kidney function than the controls. Their mean creatinine levels were higher (2.4 mg/dl vs 1.1 mg/dl, p < 0.001) and their estimated glomerular filtration rate was poorer (68.4 ml/min per 1.73 m ² vs 103.2 ml/min per 1.73 m², p < 0.001).

After taking into account possible confounding factors, such as diabetes and high blood pressure, the researchers found that estimated glomerular filtration rate below 60 ml/min per 1.73 m² was associated with a significant increase in the risk of a major cardiovascular event (OR = 6.4, p < 0.001). The investigators used two alternative equations for measuring estimated glomerular filtration rate and both showed the same results.

Protein was present in the urine of 51% of the patients who had a heart attack or stroke but only 25% of the controls. Even after taking into account the presence of other risk factors for cardiovascular disease, proteinuria more than doubled the risk of heart attack or stroke (OR = 2.2, p = 0.038).

Patients who had both estimated glomerular filtration rate below 60 ml/min per 1.73 m² and protein in their urine had their risk of a cardiovascular event increased 41-fold compared to patients who had an estimated glomerular filtration rate above 90 ml/min per 1.73 m² and no protein in their urine, p < 0.001.

The investigators observed a clear association between declining estimated glomerular filtration from the normal level of 120 ml/min per 1.73 m² and an increased risk of cardiovascular disease. Even after taking into account other cardiovascular risk factors, each 10 ml/min per 1.73 m² fall in estimated glomerular filtration rate increased the risk of cardiovascular disease by 20% (p = 0.009).

Statistical analysis that controlled for confounding factors also showed that a CD4 cell count below 200 cells/mm³(p = 0.019), diabetes (p = 0.037) and a previous history of cardiovascular illness (p < 0.001) significantly increased the risk of heart attack or stroke.

“Decreasing estimated glomerular filtration rate was associated with a significantly increased risk of cardiovascular events independent of traditional cardiovascular risk factors and highly active antiretroviral therapy”, comment the investigators.

Noting that their study was limited by its small sample size, they conclude, “our findings require further confirmation but suggest the potential value of early screening and treatment of chronic kidney disease in HIV-1-infected patients, particularly those with other cardiovascular risk factors.”