People living with both HIV and diabetes are much more likely to develop progressive chronic kidney disease (CKD) than people living with only one of the conditions, according to a study conducted by Veterans Healthcare Administration investigators and published ahead of print by the Journal of Acquired Immune Deficiency Syndromes.

"These results suggest that patients with both HIV and diabetes may benefit from more frequent screening of CKD, more rigorous follow-up of existing CKD, and more aggressive management of CKD risk factors," Christina Wyatt, MD, of Mount Sinai School of Medicine in New York City and her fellow authors conclude. "This hypothesis should be evaluated in future research studies."

About 15 percent of people living with HIV have diabetes. While several studies have suggested that HIV and diabetes have an additive effect on CKD progression, few research teams have looked closely at confounding factors that can potentially skew data, notably the prevalence of traditional risk factors for kidney disease among HIV-positive people (for example, high viral loads and low CD4 cell counts).

To explore this further, Wyatt and her colleagues followed more than 30,000 veterans for an average of five years, using estimated glomerular filtration rate (eGFR) calculations to monitor kidney function. All study subjects had normal eGFRs—greater than 45 milliliters per minute per 1.73 square meters of body-surface area (ml/min/1.732). The average eGFR, for all cohort participants at the start of the follow-up period, was 95 ml/min/1.732.

Roughly 13,500 veterans had neither HIV nor diabetes; 5,000 had diabetes but not HIV; 10,500 had HIV but not diabetes; and 1,800 were living with both HIV and diabetes.

On average, 7 percent of the cohort saw their eGFR drop below 45 ml/min/1.732—confirmed with two rounds of testing, 90 days apart—during the five-year follow-up period. Among those without HIV or diabetes, the rate of progression to kidney disease was less than 4 percent. However, among those with both HIV and diabetes, 18 percent progressed to chronic kidney disease.

Incidence rates—expressed as the number of eGFR-classified kidney disease cases per 100 person-years (PY) of follow-up—also differed between the four groups. Among those without HIV or diabetes, the incidence was 0.85 per 100 PY. Among those with HIV but not diabetes, the incidence was 1.9 per 100 PY. Among those with diabetes but not HIV, the incidence was 2.64 per 100 PY. And among those with both HIV and diabetes, the incidence was 4.37 per 100 PY.

These higher incidence rates ultimately translated into higher risk calculations. For example, compared with cohort subjects who didn’t have either condition, those with either HIV or diabetes saw their risk of CKD more than double and those with both conditions saw their risk of CKD more than quadruple.

Even when Wyatt and her colleagues used an even more conservative definition of CKD—two eGFR measurements, 90 days apart, below 30 ml/min/1.732—the compounded risk of HIV and diabetes was apparent. Compared with those without HIV or diabetes, the risk of CKD was more than three times higher among those with either HIV or diabetes and more than five times higher among those with both.

Limiting their analysis to the 7,328 people living with HIV in the cohort, researchers found that 711 saw their eGFR fall below 45 ml/min/1.732 during the five-year follow-up period. Though some traditional risk factors—notably older age, black race, high blood pressure, heart disease and hepatitis C virus (HCV) coinfection—increased the risk of kidney disease, diabetes was also found to be an independent risk factor for CKD.

Of note, Wyatt and her colleagues didn’t find a direct association between specific antiretrovirals—such as tenofovir (found in Viread, Truvada and Atripla)—and CKD risk in this cohort.

"In conclusion," the authors write, "DM [diabetes mellitus] and HIV are each risk factors for CKD. After adjustment for traditional risk factors for CKD progression and for competing risk of death, patients with both HIV and DM are at increased risk of CKD progression when compared to patients with only HIV or DM. Although not the focus of this analysis, other common comorbidities such as hypertension and HCV coinfection were also independently associated with increased risk of CKD progression in HIV-infected individuals.

"In order to optimize CKD screening and management in this population, future studies should determine the relative contribution of cumulative comorbidity, as well as the accompanying burden of [multi-drug regimens], to the risk of CKD in HIV-infected individuals."