Poor kidney function at the time HIV treatment is started is associated with an increased risk of death, a study conducted amongst US women and published in the online edition of the Journal of Acquired Immune Deficiency Syndromes suggests.
Women who had an AIDS-defining illness and kidney disease when they started antiretroviral therapy were twice as likely to die as women with normal kidney function.
“Our study demonstrates that established CKD [chronic kidney disease] at HAART [highly active antiretroviral therapy] initiation is associated with higher mortality risk independent of HIV-related risk factors for death”, comment the study’s authors.
Researchers from the Women’s Interagency HIV Study (WIHS) had already shown that the presence of chronic kidney disease increased the risk of death for HIV-positive women in both the era before HIV treatment became available, and in the early years after the introduction of potent, multi-drug antiretroviral therapy.
They now wished to see if kidney function at the time modern HIV treatment was started was associated with subsequent risk of death.
A retrospective analysis was performed involving 1415 women with HIV, all of whom had their creatinine measured within 15 months of starting antiretroviral treatment.
Chronic kidney disease ( defined as an estimated glomerular filtration rate [eGFR] below 60ml/min/1.73 m2) was present in 44 women at the time antiretroviral therapy was started.
These individuals were older (44 vs. 39) than those without kidney disease. They also had a lower CD4 cell count (171 vs 271 cells/mm3), lower serum albumin (3.6 vs. 4.2 mg/dl), and were in generally poorer health, being more likely to have progressed to AIDS, have diabetes, or high blood pressure (all comparisons p < 0.05).
The median follow-up period was significantly shorter for women with kidney disease than those without (3.5 vs. 7.2 years, p < 0.01). The investigators believe this was because of the higher mortality rate amongst women with kidney dysfunction.
Indeed, during 8184 person years of follow-up, there were 335 deaths. The investigators calculated that the mortality risk was doubled for women with kidney disease (hazard ratio [HR] = 2.23; 95% CI, 1.45-3.43).
However, adjustment for the presence of hypertension and diabetes weakened this association to the point where it was of borderline significance (HR = 1.89; 95% CI, 0.94-3.80).
Kidney failure was the cause of death for 17% of women with renal disease. Heart disease was the cause of death of 11% of women with kidney disease, but only 6% of those with normal kidney function.
The investigators highlighted this finding, commenting: “many of the same risk factors that lead to CKD also lead to cardiovascular disease. These CKD risk factors and CKD itself may lead to activation of the angiotensin system, inflammation, extraskeletal calcification, and dyslipidemia, which, in turn, culminate in endothelial dysfunction.”
In all 14% of women without kidney disease died of cancer compared to none of the women with renal impairment. “Perhaps, women with CKD were more likely to die of other causes before having the opportunity to develop cancer”, comment the authors.
The investigators’ findings were modified when they included factors traditionally associated with HIV-related death into their models.
Each 20% decrease in eGFR at the time HIV treatment was started was associated with a 28% increase in the risk of death for women with an AIDS diagnosis (HR = 1.28; 95% CI, 1.33-1.44).
But the association between poorer kidney function and death was weaker for women who had not progressed to AIDS before starting antiretroviral therapy (HR = 1.1; 95% CI, 1.06-1.17). When this result was adjusted to include a history of diabetes or hypertension, it ceased to be significant.
“Kidney function level at HAART initiation is independently associated with mortality in those with a history of AIDS”, comment the investigators.
They conclude, “our study underscores the importance of early screening for kidney disease in HIV-infected women before HAART initiation.”
Estrella MM et al. The impact of kidney function at highly active antiretroviral therapy initiation on mortality in HIV-infected women. J Acquir Immune Defic Syndr, advance online publication, 2010.