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 75th 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
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
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
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