Diabetes increases risk of chronic kidney disease for people with HIV: effect greater than for either disease alone

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 employed.

Moreover, the 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 authors.

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.

• HIV alone.

• Diabetes alone.

• HIV and 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 conditions.

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, 4.34-6.99).

Restricting analysis 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”.