Tenofovir Use and Urinary Biomarkers Among HIV-Infected Women in the Women's Interagency HIV Study (WIHS)

Abstract

Background Tenofovir has been associated with renal tubular injury. Biomarkers that signal early tubular dysfunction are needed because creatinine rise lags behind tenofovir-associated kidney dysfunction. We examined several urinary biomarkers to determine if rises accompanying tenofovir initiation preceded creatinine changes. Methods Three urinary biomarkers of tubular impairment- neutrophil gelatinase-associated lipocalin (NGAL), N-acetyl- β -D-glucosaminidase (NAG), and β-2-microglobulin (β2MG)-were measured across three time points (one pre-tenofovir visit and two post tenofovir visits) in one hundred and thirty two HIV-positive women from the Women's Interagency HIV Study (WIHS). Women initiating HAART containing tenofovir were propensity score matched to women initiating HAART without tenofovir and women not on HAART. Results There were no differences between groups for NGAL or NAG but β2MG was 19 times more likely to be elevated among tenofovir users at the 2nd post tenofovir visit compared to non-TDF users at the pre-tenofovir visit (p<0.01). History of proteinuria was associated with elevated NGAL (p <0.01). Factors associated with elevated NAG were GFR<60 ml/min, history of proteinuria, hepatitis C (p<0.01 for all) and diabetes mellitus (p=0.05). Factors associated with increased odds of elevated β2MG were HIV RNA>100,000 copies/ml, hepatitis C, boosted protease inhibitor (PI) use, and GFR<60 ml/min (p≤0.01 for all). Conclusions β2MG levels are elevated in women on tenofovir indicating probable early renal dysfunction. Biomarker elevation is additionally associated with baseline chronic kidney disease, uncontrolled viremia, and boosted PI use. Future studies are needed to explore urinary biomarker thresholds in identifying treated HIV-infected individuals at risk for renal dysfunction.

Tenofovir monotherapy for hepatitis B after 1 year does not produce renal dysfunction, but is associated with hyperparathyroidism not related to vitamin D

“…Changes in its urinary and plasmatic concentrations have been used to implicate kidney dysfunction and tubulopathy [40,41]. NGAL is produced by neutrophils and its urinary level is considered a marker of kidney injury [42,43]. β2-Microglobulin is a small protein located in all nucleated cell membranes.…”

The case of chronic hepatitis B treatment with tenofovir: an update for nephrologists

“…Moreover, since the known mechanisms of TDF renal toxicity are expressed in the proximal tubule, new markers of tubular dysfunction such as neutrophil gelatinase associated lipocalin (NGAL) could be used to early detect a TDF related kidney damage, although the results of the few studies using NGAL as a biomarker of tubular damage in HIV patients have reported contrasting results [67][68][69][70]. There is lack of knowledge on the topic in HBV-infected patients [68].…”

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

“…In this study, renal impairment and PRTD began to improve as early as three months after discontinuation of nucleotide analogue as seen from the rising TmPO 4 /GFR representing improved tubular reabsorption of phosphate and the declining 24-hour urinary protein and urinary 2-microglobulin, which is a 12 kDA tubular protein with a component of major histocompatibility complex class I molecule [32]. Urinary 2-microglobulin is known to be a specific marker of proximal renal tubular dysfunction, which has been studied in HIV patients who developed antiretroviral agents related to PRTD [28,[32][33][34]. The rapid decline of renal losses of urinary protein and 2-microglobulin after cessation of nucleotide analogue signified the restoration of proximal renal tubular structure and function.…”