Proteinuria as a potential early marker of tenofovir-related renal toxicity

Researchers from UCL reported on a ptoential early marker for tenofovir-associated renal toxicity.

Ana Milinkovic and colleagues from University College London, presented results from routine monitoring for tenofovir-related renal toxicity which since 2006 has involved serum creatinine (SCr), eGFR, urine protein (UP/C) and serum phosphate.

In patients with abnormal changes, tests for renal tbule dysfunction (includingurine retinaol binding protein) and phosphate reabsorption capacity are used to diagnose tenofovir-associated renal toxicity.

Abnormal results from the cohort of almost 1300 patients with data were screened for proximal tubular dysfunction including tubular proteinuria and phosphate excretion.

The retrospective case note review identified 103/1293 patients (8%) who had stopped tenofovir, 29 of who (2.2% of the cohort) who discontinued due to renal toxicity. The decision to stop tenofovir in this group and analysis had been based on clinical judgement rather than laboratory results. Median duration of tenofovir use was 1054 days (IQR 834-1266).

Median (IQR) baseline characteristics included: male 82%, white 63%, age 41 years (IQR 34-46), CD4 count 330 cells/mm3 (220-500).

In multivariate analysis, UP/C (per two-fold increase: aHR 3.38; 95%CI 2.69-5.51), SCr (per 10 u/mol increase: aHR 1.36; 95%CI 1.33-1.64) and recent PI use (aHR 3.34; 95%CI 1.24 – 9.41) were associated with tenofovir related renal toxicity.

Of note, half of these patients maintained eGFR levels >75 mL/min/1.732 and elevated UP/C in this group remained predictive leading the authors to conclude that proteinuria is an early marker of tenofovir associated renal toxicity, supporting rountine UP/C ratios for patients on tenofovir, even when eGFR remains normal.

Milinkovic A et al. Proteinuria as an early marker of tenofovir renal toxicity. 14th IWCADR, 19-21 July 2012, Washington. Oral abstract 005. Antiviral therapy 2012; 17 Suppl 2:A5.