Tenofovir (TDF) is associated with treatment-limiting renal tubulopathy (RT) which may manifest as proximal tubulopathy (PT) and/or acute tubular injury (ATI) on renal biopsy. The risk factors for RT remain poorly defined.
Cases of TDF treatment limiting PT (≥2 of normoglycaemic glycosuria, hypophosphataemia <2 mg/dL, protein-creatinine ratio >300 mg/g) and/or ATI were identified retrospectively in 7 major HIV treatment centres contributing to the UK CHIC cohort. Poisson regression was used to investigate factors associated with RT; age; ethnicity; calendar year of TDF start (fixed covariates); hepatitis B/C status; CD4 cell count; HIV RNA; time on TDF and protease inhibitor (PI) based regimes (time-updated covariates) were considered for inclusion in the model.
15983 subjects received TDF for >4 weeks, of whom 69 (0.4%) were diagnosed with treatment limiting RT between Oct 2002-July 2013 (PT: n=52; ATI: n=17) after a median (IQR) of 43 (26, 67) months of TDF exposure. At presentation, RT was characterised by normoglycaemic glycosuria (83%), hypophosphataemia (67%) and proteinuria (94%); eGFR decline >25% from baseline (start of TDF-containing regimen) was present in 54% of cases and exposure to ritonavir-boosted PI (44% lopinavir, 35% atazanavir, 16% darunavir, 5% other) in 83% of cases. Compared to subjects without RT, those with RT were older (mean age 45.7 vs. 40.7 years), more likely to be white (91% vs. 74%), male (90% vs. 80%), have a prior AIDS diagnosis (41% vs. 26%) and lower nadir CD4 cell count (median 129 vs. 190 cells/mm3) (p<0.01 for all). No differences in baseline HBV/HCV status, HIV RNA and eGFR (95 vs. 96 mL/min/1.73m2) were observed. In multivariable analysis, older age, ethnicity, time on TDF, CD4 cell count and PI based regimes remained independently associated with the development of RT (Table 1).
Severe TDF-associated RT was uncommon in this cohort and accompanied by significant eGFR decline in only half of all cases. Age and PI co-administration were risk factor for the development of RT, and black ethnicity was protective. Baseline eGFR did not identify subjects at increased risk of treatment-limiting RT.