878 Renal Dysfunction During Peg-Ifn + Rbv+ TVR Treatment

Renal dysfunction associated with telaprevir-containing triple therapy for chronic hepatitis C

“…We showed that the minimum eGFR can be predicted precisely from basal and week 2 determination of serum creatinine, information not available in the work of Mauss et al [6], who did not have serum creatinine values before the 12th week of treatment. This is in agreement with Japanese studies, which showed that eGFR is significantly reduced as early as the seventh [11,12] or ever the third day of treatment [13]. The decrease in eGFR was similar irrespective of the baseline eGFR, and there was a median increase of one stage according to the KDIGO classification.…”

“…In a Japanese study of 115 patients, the independent predictors of renal failure were basal serum creatinine and TVR dose (a reduced dose of 1500 mg/day being administered to the patients older than 65 years) [13]. In accordance with this observation, the Japanese authors showed that the TVR dose by weight (which was highly correlated with TVR serum concentration at day 7 [12]) was higher in patients developing renal failure and significantly correlated with eGFR [11,12].…”

“…First, it is in part because of a prerenal dysfunction as the fractional excretion of sodium was early and constantly less than 1% in Nakamura et al's [13] study; this was, however, observed in all patients, whether or not they developed renal failure. Second, TVR inhibits renal tubular drug transporter OCT2, which could lead to a decrease in the tubular secretion of creatinine, increasing the concentration of serum creatinine without affecting glomerular filtration [13].…”

“…First, it is in part because of a prerenal dysfunction as the fractional excretion of sodium was early and constantly less than 1% in Nakamura et al's [13] study; this was, however, observed in all patients, whether or not they developed renal failure. Second, TVR inhibits renal tubular drug transporter OCT2, which could lead to a decrease in the tubular secretion of creatinine, increasing the concentration of serum creatinine without affecting glomerular filtration [13]. Finally, a tubular toxicity is probable as urinary β2 microglobulin was markedly increased in patients receiving TVR and higher in patients developing renal function [13]; there is no indication of glomerular damage in the literature, or in four of our patients in whom urine analysis was available.…”