Cystatin C-based renal function changes after antiretroviral initiation: a substudy of a randomized trial

Area of Science:

• Nephrology
• Pharmacology
• Infectious Diseases

Background:

• The impact of antiretroviral (ARV) therapies on renal function estimates, particularly those utilizing cystatin C, remains largely uncharacterized.
• Understanding these effects is crucial for accurate patient monitoring and management.

Purpose of the Study:

• To investigate the influence of different antiretroviral drug combinations on renal function estimates.
• To compare the performance of various creatinine and cystatin C-based equations in assessing ARV-associated renal changes.

Main Methods:

• A substudy (A5224s) of 269 treatment-naive patients (Study A5202) was analyzed.
• Patients were randomized to receive either abacavir/lamivudine or tenofovir/emtricitabine, combined with open-label atazanavir/ritonavir or efavirenz.
• Renal function changes were assessed using creatinine and cystatin C-based estimating equations, including Cockcroft-Gault, Modification of Diet in Renal Disease (MDRD), and Chronic Kidney Disease Epidemiology Collaboration (CKD-EPI) equations.

Main Results:

• Abacavir/lamivudine treatment was associated with significantly better renal function changes compared to tenofovir/emtricitabine, as indicated by the Cockcroft-Gault and CKD-EPI equations (P = .016 to P = .025).
• Efavirenz use resulted in significantly improved renal function changes compared to atazanavir/ritonavir across all assessed equations (P < .001).
• Specific ARV combinations, such as tenofovir/emtricitabine with atazanavir/ritonavir, showed varying degrees of renal function decline depending on the estimating equation used, with estimates ranging from -14.9 mL/min to +8.9 mL/min.

Conclusions:

• Antiretroviral therapy can induce changes in renal function, with the magnitude and direction of these changes being dependent on the specific drug combination and the estimating equation employed.
• The choice of renal function estimating equation is critical when evaluating ARV-associated renal effects, as different equations yield divergent results.