Diabetes increases the
risk of the progression of chronic kidney disease for patients with HIV, US
investigators report in the online edition of the Journal of Acquired Immune Deficiency Syndromes.
The association was
significant even after controlling for traditional risk factors for kidney
disease and when a more stringent set of diagnostic criteria for kidney disease was
investigators found that people with both HIV and diabetes had a higher risk
of kidney disease than patients with either condition alone.
“Patients with both
HIV and diabetes mellitus are at increased risk of chronic kidney disease
progression when compared to patients with only HIV or diabetes,” comment the
Chronic kidney disease
is an increasingly important cause of illness and death in people with HIV.
Prevalence of diabetes in HIV-positive people is estimated to be in the
region of 15% and approximately 45% of incident end-stage renal disease in
people with HIV is believed to have diabetes as its underlying cause.
There is also some
evidence that HIV and diabetes have an additive effective on chronic kidney
disease progression. However, research exploring this question may be limited
because it did not control for other risk factors.
Investigators from the
US Department of Veterans Affairs therefore designed a study involving 31,072
patients. None had chronic kidney disease at baseline.
Over a median of five
years of follow-up, the authors monitored the participants’ risk of kidney disease
progression (an estimated glomerular filtration rate, or eGFR, below 45ml/min/1.73m2).
The participants were
divided into four groups according to their HIV and diabetes status:
- Neither HIV nor diabetes.
Overall, 7% of
participants developed chronic kidney disease. The rate of progression was 4% among
people with neither HIV nor diabetes, compared to 18% for people with both
The rate of
progression also differed according to disease status. It was lowest for
people without HIV or diabetes (0.85 per 100 person-years), but was markedly
higher for individuals with HIV only (1.95 per 100 person-years) and diabetes
only (2.64 per 100 person-years). It was highest of all for people with both
HIV and diabetes (4.37 per 100 person-years).
Compared to people without HIV or diabetes, the risk of chronic kidney disease was
increased for patients with diabetes alone (HR = 2.48; 95% CI, 2.19-2.80) and
HIV only (HR = 2.80; 95% CI, 2.50-3.15). However, the risk was over four-fold
higher for people with both HIV and diabetes (HR = 4.47; 95% CI, 3.87-5.17).
Because both HIV and
diabetes were associated with the progression of kidney disease, the
investigators stratified their results according to HIV status. Diabetes
remained associated with the risk of kidney disease regardless of HIV status. However,
the magnitude of the association was somewhat higher among HIV-negative
people (HR = 2.43; 95% CI, 2.14-2.75) than HIV-positive individuals (HR =
1.67; 95% CI, 1.46-1.49).
Black race has been
associated with an increased risk of kidney disease (kidney disease has been observed at higher prevalence among African Americans and some African populations). But stratifying for race
did not affect the investigators’ findings.
The investigators then
used a more stringent definition of chronic kidney disease (eGFR below 30
ml/min/1.73m3). There was a more than three-fold increase in the
risk of chronic kidney disease for participants with HIV alone (HR = 3.51; 95% CI,
2.89-4.27) and diabetes only (HR = 3.10; 95% CI, 2.51-3.83). The risk was
highest of all for individuals with both HIV and diabetes (HR = 5.51; 95% CI,
to people with HIV confirmed that diabetes increased the risk of chronic
kidney disease. This was independent of CD4 cell count, viral load, use of
antiretroviral therapy and history of AIDS-defining illness. There was no
evidence that tenofovir (Viread), atazanavir (Reyataz), indivinavir (Crixivan) or lopinavir (Kaletra), all of which
have been associated with renal side-effects, increased the risk of chronic
kidney disease. However, older age, black race, viral load, blood pressure,
heart failure and co-infection with hepatitis C were significant risk factors.
“We have demonstrated
a significant and graduated association between HIV and diabetes mellitus
status and the risk of progression to [chronic kidney disease], even after
adjustment for other factors,” write the investigators. “Concurrent HIV and
diabetes mellitus have a greater effect on the risk of chronic kidney disease
than would be expected from either disease alone.”
The authors call for
further research “to determine the relative contribution of cumulative
comorbidity, as well as the accompanying burden of polypharmacy, to the risk of
chronic kidney disease in HIV-infected individuals”.