Proximal Renal Tubular Dysfunction Related to Antiretroviral Therapy Among HIV-Infected Patients in an HIV Clinic in Mexico

Abstract

Proximal renal tubular dysfunction (PRTD) of varying severity has been associated with antiretroviral toxicity, especially related to the use of tenofovir (TDF). The aim of this study was to investigate whether HIV-infected patients who use a tenofovir-based regimen are at increased risk of tubular dysfunction. We conducted an observational, comparative, longitudinal, prospective study. Estimated glomerular filtration rate (eGFR) and markers of tubular damage to assess tubular dysfunction (fractional excretion of phosphate and uric acid, glycosuria, and proteinuria) were measured at baseline and at weeks 12 and 24. Of 111 participants, PRTD was found in 6.3% at week 12 and 9% at week 24, with no statistically significant difference between those on an abacavir (ABC)-containing regimen or a TDF-containing regimen. We also found an increase in triglycerides associated with the ABC-containing regimen compared with the TDF group. The use of an ABC- or TDF-containing regimen was independently associated with tubular dysfunction, but we found no significant differences between these groups, except when TDF was combined with a protease inhibitor. A better and more complete assessment of renal function is needed, because the presence of tubular dysfunction and proteinuria without impairment of eGFR may affect the renal safety of HIV-infected patients.

Nucleotide Analogue-Related Proximal Renal Tubular Dysfunction during Long-Term Treatment of Chronic Hepatitis B: A Cross-Sectional Study

“…Overt proximal RTD was seen in an estimated 10% of patients. The prevalence of nucleotide analogue-related proximal RTD in our study was higher than a previous report (15%), which may be due to the different criteria of proximal RTD in our study [17, 23, 24] and the other report [19]. On contrary, previous studies did not report significant reduction in renal function after long-term nucleotide analogue treatment in CHB [13–15, 26].…”

“…FEPO 4 >18% was used for the criteria of tubular phosphate loss in our study [24], while tubular reabsorption of phosphate (TRP) <82% was an alternative criterion used in some other reports [19, 23, 28]. In addition, the problem of severe tubular phosphate loss in subclinical and overt proximal RTD was confirmed with low TmPO 4 /GFR (<2.8 mg/dL) in our study.…”

Complications of Treatment in Youth with HIV

“…Similarly, a longitudinal, observational study of subjects on either ABC or TDF showed no significant differences in the rates of tubular dysfunction between the groups except where PIs were used in conjunction with TDF •[23]. Lastly, the final results of GS-US-104-0321 were recently published, which was the open-label TDF extension phase that followed the randomized, placebo-controlled, double-blind trial of TDF or placebo with optimized background regimen for 48 weeks in HIV-infected adolescents 12–17 years old [24].…”

809 Reversal of Proximal Renal Tubular Dysfunction After Nucleotide Analogue Withdrawal in Chronic Hepatitis B

“…Renal loss of protein, glucose, phosphate, uric acid, potassium, and bicarbonate was defined via laboratory assays. PRTD was diagnosed when at least two of these criteria were present [10,16,20,27]. Subclinical PRTD was defined at two criteria present, and overt PRTD was defined with ≥3 criteria [20].…”

“…Despite the safety profile of 10 mg ADV from large clinical trials [4][5][6], ADV-induced Fanconi's syndrome, proximal renal tubular dysfunction (PRTD), and hypophosphatemia have been reported in CHB patients [7][8][9][10][11][12][13]. PRTD, hypophosphatemia, and Fanconi's syndrome are also common in human immunodeficiency virus-(HIV-) infected patients receiving TDF as a part of highly active antiretroviral therapy [14][15][16]. A recent meta-analysis study revealed no significant differences between ETV and TDF treatment in CHB patients in terms of renal safety profiles and hypophosphatemia; however, the short duration of the study limited the power of the conclusions [4][5][6]17].…”