Baseline renal insufficiency and mortality risk in HIV-positive adults in Zambia

Renal insufficiency has been found to be a risk factor for mortality in people with HIV. Understanding the prevalence and clinical implications this condition will have particular relevance in resource limited settings as programmes begin to introduce tenofovir as part of first line therapy.

A paper published in the September 12, 2008 edition of AIDS authored by Lloyd Mulenga and co-workers examined the association between baseline renal insufficiency and mortality in adults initiating ART in Lusaka, Zambia.

In this study, the investigators used the Cockcroft-Gault (CG) method, the Modification of Diet in Renal Disease (MDRD) equation, and serum creatinine to assess renal function. Creatinine clearance of at least 90ml/min was considered normal. Having a creatinine clearance of 60-89ml/min was catagorised as mild renal insufficiency; 30-59ml/min as moderate and less than 30 ml/min as severe.

This analysis included 25,779 patients enrolled in the Lusaka district programme, who started ART from May 2004 to September 2007, and who has a documented creatinine measurement at baseline.

When the investigators calculated creatinine clearance by the CG, they found a third of their patients (33.5%; 95%CI: 32.9%, 34.1%, n=8,456) had renal insufficiency. Of these, 6216 (73.5%) were mild, 1976 (23.4%) were moderate and 264 (3.1%) were severe.

In a multivariate analysis, the investigators found several covariates were associated with higher adjusted Hazard Rartos (AHR) of renal disease including: female sex (AHR=1.2; 95% CI: 1.1, 1.2), older age (AHR=1.5 per 10 years; 95% CI: 1.4, 1.5), hemoglobin less than 8 g/dl (AHR=1.5; 95% CI: 1.4, 1.6), BMI less than 16 kg/m2 (AHR=1.7; 95% CI: 1.6, 1.8), and WHO stage 3 (AHR=1.2; 95% CI: 1.2, 1.3) or stage 4 (AHR=1.3; 95% CI: 1.2, 1.4).

Additionally, they found a modest increase in the risk for renal insufficiency as CD4 cell counts declined.

In Kaplan-Meir analysis, renal insufficiency correlated with 2-year survival: 91% for patients with normal creatinine clearance, 85.8% for mild, 78.8% for moderate, and 61.2% for severe (p<0.001).

In an adjusted Cox proportional hazards model, risk for mortality less than 90 days increased for patients with mild (AHR=1.7; 95% CI: 1.5, 1.9), moderate (AHR=2.3; 95% CI: 2.0, 2.7), and severe (AHR= 4.3; 95% CI: 3.1, 5.5) reduction in creatinine clearance.

When compared with patients with normal renal function, the investigators noted similar risk in post-90 day mortality: mild insufficiency (AHR=1.4; 95% CI: 1.2, 1.6), moderate (AHR=1.9; 95% CI: 1.5, 2.3), and severe insufficiency (AHR=3.6; 95% CI: 2.4, 5.5).

They also found similar trends in secondary analyses when renal function was estimated with MDRD or serum creatinine.

The investigators noted that although these observational data do not establish a direct casual relationship between renal insufficiency and mortality they do suggest a need to further evaluate ART eligibility criteria.

They suggest that wherever feasible, screening for renal function should be instituted as part of ART programmes, particularly with the introduction of tenofovir. They add: “Algorithms for more aggressive assessment and management of renal insufficiency should also be developed specifically for settings with limited diagnostic capabilities.”

Mulengaa LB, Krusea G, Lakhib S et al. Baseline renal insufficiency and risk of death among HIV-infected adults on antiretroviral therapy in Lusaka, Zambia. AIDS 2008, 22:1821-1827.