Medium-grade Tubular Proteinuria is Common in HIV-positive Patients and Specifically Associated with Exposure to Tenofovir Disoproxil Fumarate

Objectives: The aim of this cross-sectional study was to evaluate the prevalence and risk factors of medium-grade proteinuria (100-500 mg/g creatinine) among HIV-positive adults.

Methods: Spot urine samples of HIV-positive adults without known renal disease were analyzed quantitatively between January 2009 and February 2011. Demographic and medical data were collected. Multivariate regression models for different patterns of proteinuria were constructed.

Results: Among 411 patients, 18 (4.4 %) presented albuminuria >300 mg/g creatinine and/or proteinuria >500 mg/g creatinine and were excluded from further analyses. Among the study population of 393 patients, 181 (46.1 %) had no significant proteinuria or albuminuria (<100 and <30 mg/g creatinine, respectively), 60 (15.3 %) had moderate albuminuria, while 152 (38.7 %) had proteinuria without albuminuria, suggesting tubular proteinuria. Independent predictors for medium-grade tubular proteinuria in multivariate analysis were exposure to tenofovir (DF), a CD4 nadir <500/µl, older age, and anti-HCV-antibodies. There was no association with classic renal risk factors like diabetes mellitus and arterial hypertension, or with estimated glomerular filtration rate (eGFR).

Conclusions: We detected significant proteinuria in 230 (56.0 %) of 411 HIV-positive patients. Among this group, 152 (66.1 %) had medium-grade proteinuria without albuminuria, which was significantly associated with exposure to tenofovir, older age, a lower CD4 nadir and Hepatitis C. Nephrologic or HIV treatment guidelines fail to detect most of these patients but rather identify patients with high cardiovascular risk. In the absence of an association with eGFR the role of medium-grade tubular proteinuria as a potential early marker of chronic kidney disease remains unclear. Prospective studies are needed.