A cross-sectional comparison of renal function in patients on stable abacavir (ABC) or tenofovir (TDF) containing therapy

Purpose of the stud

Renal toxicity is an important complication of both HIV infection and antiretroviral therapy; drug-related toxicity may differ by NRTI backbone. We analysed markers of renal function in patients stable on ABC or TDF.

Methods

Prospective, cross-sectional, single-centre study of patients stable for >6 months on ABC- or TDF-based therapy (naïve to TDF and ABC, respectively) and <50 cps/ml. Renal markers collected: plasma urea, creatinine, cystatin-c (endogenous cysteine proteinase inhibitor produced at a constant rate). Individuals underwent 24-hour urine collection (creatinine clearance and protein quantification) or spot urine for protein and N-acetyl-beta-glucosaminidase (NAG):creatinine ratio. NAG, secreted by renal tubular cells, is a sensitive marker of proximal tubular damage; measuring NAG:creatinine ratio controls for urine volume. Demographics, drug history, CD4 and VL were collected. Parameters independently significantly associated with abnormal renal function by univariate analysis (p < 0.15) were entered into a multivariable regression model. Measured CrCl and eGFR have been presented previously.

Summary of results

391 subjects (145 on ABC, 246 on TDF) were recruited. Most were male (95% on ABC, 92% on TDF); median age (48 vs. 46 years; p = 0.021) and CD4 count (552 vs. 475; p = 0.007) were higher in ABC recipients. By multivariable modelling, factors associated with MDRD eGFR <90 were older age (>53 vs. <46 years; p < 0.001) and elevated cystatin c (>0.86 vs. <0.68; p = 0.037). Five subjects on ABC (3.4%) and nine on TDF (3.7%) had MDRD GFR <60 (p = ns). Cystatin c was elevated (>0.96) in 7.6% and 10.2% of ABC and TDF recipients, respectively (OR for ABC 0.73; p = 0.396); there was no relationship between cystatin c elevations and duration of ABC or TDF. By multivariable analysis, there was a trend to greater risk of elevated cystatin c with increased age (p = 0.065 for <40 vs. >53 years). Hypophosphataemia (≤0.8 mmol/l) was detected in 13% and 16.5% of ABC and TDF treated subjects, respectively (OR for ABC 0.76; p = 0.361). Seven subjects had grade 3 hypophosphataemia (0.33–0.64 mmol/l), three on ABC (2.2%) and four on TDF (1.7%). NAG:creatinine ratio was measured in 296 patients from spot urine and was elevated (≥2.4) in 7% on ABC and 7.1% on TDF (p = ns).

Conclusion

Significant renal abnormalities were infrequent. For renal end-points we did not detect a statistically significant or clinically relevant safety difference between the ABC and TDF in our cohort.