Five-year cumulative TDF exposure is associated with CKD in people living with HIV: a propensity score-matched study supporting UACR-based renal screening

Background Tenofovir disoproxil fumarate (TDF)-based antiretroviral therapy (ART) remains the cornerstone of HIV treatment; however, prolonged exposure is associated with insidious nephrotoxicity. Estimated glomerular filtration rate (eGFR) declines only after substantial renal injury, and both a validated TDF exposure threshold and routine screening biomarkers for people living with HIV (PLWH) remain scarce. Methods In this cross-sectional study, 3,519 PLWH receiving TDF-based ART were screened; after excluding patients on lopinavir/ritonavir and those with diabetes, hypertension, or cardiovascular disease, 2,814 were evaluable. Chronic kidney disease (CKD) was defined as urinary albumin-to-creatinine ratio (UACR) ≥30 mg/g or eGFR <60 mL/min/1.73m², persisting for 3 months or more. CKD cases were 1:1 propensity score-matched to controls for age, sex, CD4 count, HIV-1 RNA, and third-agent class. Logistic regression, Spearman correlation, and stratified analyses were performed. Results Among 2,814 evaluable PLWH, 292 (10.4%) met CKD criteria. The matched cohort (n = 584) was 84.9% male, with a median age of 43 years (interquartile range [IQR] 35–55), median CD4 count of 470 cells/μL (IQR 301–609), and 94.0% virological suppression. Compared with controls, CKD cases presented prolonged TDF exposure (4.78 vs. 4.06 years; P < 0.001), lower median eGFR (96.81 vs. 102.24 mL/min/1.73m²; P = 0.013) and significantly elevated median UACR (66.13 vs. 9.94 mg/g; P < 0.001). Notably, eGFR <60 mL/min/1.73m² was only detected in 6.2% of CKD patients ( P < 0.001), and albuminuria was far more common among CKD cases (97.3% vs. 0.3%, P < 0.001). TDF duration was independently associated with CKD: relative to <2 years’ exposure, longer durations conferred increased odds (>5 years: OR 1.580, 95% CI 1.023–2.440, P = 0.039). Cumulative TDF exposure correlated positively with UACR ( P = 0.001). Conclusions Cumulative TDF exposure is independently associated with CKD in Chinese PLWH; five years of therapy may serve as a practical cut-point for intensifying renal surveillance. UACR, as an accessible screening biomarker, was more frequently abnormal than eGFR in identifying early renal injury and may be integrated into routine HIV care to prompt confirmatory evaluation and timely ART adjustment.