Mild kidney problems in patients with HIV can identify patients with hardening of the arteries

Emergent kidney dysfunction is associated with an increased risk of hardening of the arteries in patients with HIV, Spanish researchers show in the online edition of the Journal of Acquired Immune Deficiency Syndromes.

“Our findings provide support for the hypothesis that mild abnormalities of renal function can independently predict an increased atherosclerotic burden and behave as a useful surrogate marker of subclinical atherosclerosis,” write the investigators.

Kidney disease is an increasingly important cause of serious illness and death in patients with HIV. The exact causes are uncertain but appear to include the effects of HIV, lifestyle factors and possibly the side-effects of some anti-HIV drugs.

Research has established an association between renal dysfunction and an increased risk of cardiovascular disease in HIV-positive patients. However, most HIV-positive individuals with kidney problems experience only mild abnormalities. Nevertheless, studies conducted in the general population have shown that the presence of low-grade albuminuria and a low eGFR are associated with death due to cardiovascular causes.

Investigators in Madrid therefore hypothesised that mild deterioration in kidney function, or incipient renal impairment, would predict hardening of the arteries in HIV-positive patients.

They therefore designed a cross sectional study involving 145 individuals who received HIV care between 2009 and 2010.

Incipient renal impairment was defined as eGFR below 90 ml/min, a rate of eGFR decrease above 3% annually over a three-year period, and an albumin/creatine urine ratio above 5 mg/g. Patients with carotid artery intima media thickness (cIMT) above the 75^th percentile or plaques were classified as having sub-clinical atherosclerosis.

Most of the patients (88%) were male and their average age was 41 years. There was a high prevalence of cardiovascular risk factors. The most common was smoking (47%), followed by elevated triglycerides (43%), high cholesterol (39%), hypertension (17%) and diabetes (9%). Nearly all the patients (91%) were taking antiretroviral therapy and 77% had an undetectable viral load.

Plaques were detected in the coronary arteries of 6% of patients and 31% were classified as having sub-clinical atherosclerosis. Incipient renal impairment was identified in almost two-thirds of patients (64%).

The emergence of kidney dysfunction was associated with a number of recognised cardiovascular risk factors, including waist circumference (p = 0.038), diabetes (p = 0.032), high triglycerides (p = 0.013), and metabolic syndrome (p = 0.031).

Some HIV-related factors were also significant. These included lipodystrophy (p = 0.017), nadir CD4 cell count (p = 0.046), a detectable viral load (p = 0.036) and not taking antiretroviral therapy (p = 0.017).

Longer use of all the main classes of antiretrovirals was also associated with the development of mild renal impairment. However, the investigators were unable to find an association with specific drugs, including tenofovir (Viread, also in the combination pills Truvada and Atripla).

Incipient renal impairment was significantly associated with the hardening of the arteries (OR = 4.3; 95% CI, 1.7-10.6; p = 0.001). This association was still highly significant after the investigators controlled for factors known to increase the risk of kidney disease, such as age, and diabetes, as well as cumulative exposure to HIV therapy (OR = 3.8; 95% CI, 1.3-11.0; p = 0.013).

“In our study,” write the authors, “individuals with incipient renal impairment…had a 4-fold higher risk of subclinical atherosclerosis.” They note that this risk was present with even mild kidney dysfunction.

The authors believe their findings have immediate clinical implications and suggest “periodic monitoring of eGFR and albumin/creatine urine ratio might help to better identify subjects at increased risk of cardiovascular disease in order to initiate aggressive management of risk factors.”