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Short and long-term effects of telaprevir on kidney function in patients with hepatitis C virus infection: a retrospective cohort study.

Sise ME, Backman ES, Wenger JB, Wood BR, Sax PE, Chung RT, Thadhani R, Kim AY - PLoS ONE (2015)

Bottom Line: The majority completed the prescribed twelve weeks of telaprevir therapy; 32% discontinued due to side effects.Thirty-one percent experienced a significant creatinine rise during therapy.Decline in kidney function during therapy with telaprevir is common and is not associated with baseline eGFR < 90mL/min/1.73m2 as previously reported.

View Article: PubMed Central - PubMed

Affiliation: Division of Nephrology, Department of Medicine, Massachusetts General Hospital, Harvard University, Boston, MA, United States of America.

ABSTRACT

Background: Recent reports suggest that telaprevir, a protease inhibitor used to treat hepatitis C infection, is associated with decline in kidney function during therapy, particularly in patients with baseline renal impairment.

Methods: Patients treated with telaprevir in a single healthcare network were retrospectively reviewed. Kidney function was determined at baseline, during therapy, and twelve weeks and twelve months after telaprevir discontinuation. Significant creatinine rise during therapy was defined as an increase in serum creatinine ≥ 0.3mg/dL from baseline during treatment with telaprevir.

Results: Between July 2011 to January 2013,seventy-eight patients began treatment. The majority completed the prescribed twelve weeks of telaprevir therapy; 32% discontinued due to side effects. The average rise in serum creatinine during therapy was 0.22mg/dL (standard deviation 0.22mg/dL). Thirty-one percent experienced a significant creatinine rise during therapy. Decline in estimated glomerular filtration rate (eGFR) was lower in those with baseline eGFR < 90 mL/min/1.73m2 compared to the group with baseline eGFR ≥ 90 mL/min/1.73m2 (12 vs. 18 mL/min/1.73m2, P = 0.047). Serum creatinine fully normalized by twelve weeks after cessation of telaprevir in 83% of patients, however experiencing a significant creatinine rise during telaprevir use was associated with a 6.6mL/min/1.73m2 decrease in estimated glomerular filtration rate at twelve months in an adjusted model.

Conclusions: Decline in kidney function during therapy with telaprevir is common and is not associated with baseline eGFR < 90mL/min/1.73m2 as previously reported.

No MeSH data available.


Related in: MedlinePlus

Timeline of Triple Therapy, Short and Long-term Follow-up.Patients were prescribed triple therapy (telaprevir, Peg-IFN, and ribavirin) for twelve weeks. Based on clinical characteristics and at the providers discretion patients then continue Peg-IFN and ribavirin for a total of 24–48 weeks. Short-term follow-up was obtained 12 weeks after telaprevir was discontinued (at week 24). Long-term follow-up was obtained 12 months after telaprevir was discontinued (at week 62).
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pone.0124139.g001: Timeline of Triple Therapy, Short and Long-term Follow-up.Patients were prescribed triple therapy (telaprevir, Peg-IFN, and ribavirin) for twelve weeks. Based on clinical characteristics and at the providers discretion patients then continue Peg-IFN and ribavirin for a total of 24–48 weeks. Short-term follow-up was obtained 12 weeks after telaprevir was discontinued (at week 24). Long-term follow-up was obtained 12 months after telaprevir was discontinued (at week 62).

Mentions: At the discretion of the treating physician, triple therapy with telaprevir, PegIFN and RBV was prescribed for 12 weeks, followed by dual therapy with PegIFN and RBV for either 24 or 48 weeks total (Fig 1). Serum creatinine values were obtained during therapy with telaprevir and the maximum values used to determine the presence of significant creatinine rise during telaprevir use. A significant creatinine rise was defined as a ≥ 0.3mg/dL increase from baseline. This cutoff was chosen as it is the same magnitude of rise that has been shown to have significant effect on chronic kidney disease development and progression in the setting of acute kidney injury[16]. Patients were considered to have cirrhosis if it was demonstrated on liver biopsy or if the treating physician determined it to be likely based on clinical findings, imaging, and fibrosis score. Sustained viral response (SVR), or cure of hepatitis C, was defined as undetectable HCV RNA 12 weeks after therapy[17]. Short-term kidney function recovery was determined based on serum creatinine between 4–12 weeks after discontinuation of telaprevir, at this time point,patients were still on PegIFN and RBV unless they had prematurely discontinued therapy due to side effects. Normalization of kidney function was defined as return of eGFR to at least 90% of prior baseline within 12 weeks after discontinuing telaprevir. Long-term kidney function recovery was determined based on serum creatinine between twelve months after discontinuation of telaprevir. See Fig 1 for a schematic representation of treatment course and follow-up time-points.


Short and long-term effects of telaprevir on kidney function in patients with hepatitis C virus infection: a retrospective cohort study.

Sise ME, Backman ES, Wenger JB, Wood BR, Sax PE, Chung RT, Thadhani R, Kim AY - PLoS ONE (2015)

Timeline of Triple Therapy, Short and Long-term Follow-up.Patients were prescribed triple therapy (telaprevir, Peg-IFN, and ribavirin) for twelve weeks. Based on clinical characteristics and at the providers discretion patients then continue Peg-IFN and ribavirin for a total of 24–48 weeks. Short-term follow-up was obtained 12 weeks after telaprevir was discontinued (at week 24). Long-term follow-up was obtained 12 months after telaprevir was discontinued (at week 62).
© Copyright Policy
Related In: Results  -  Collection

License
Show All Figures
getmorefigures.php?uid=PMC4414554&req=5

pone.0124139.g001: Timeline of Triple Therapy, Short and Long-term Follow-up.Patients were prescribed triple therapy (telaprevir, Peg-IFN, and ribavirin) for twelve weeks. Based on clinical characteristics and at the providers discretion patients then continue Peg-IFN and ribavirin for a total of 24–48 weeks. Short-term follow-up was obtained 12 weeks after telaprevir was discontinued (at week 24). Long-term follow-up was obtained 12 months after telaprevir was discontinued (at week 62).
Mentions: At the discretion of the treating physician, triple therapy with telaprevir, PegIFN and RBV was prescribed for 12 weeks, followed by dual therapy with PegIFN and RBV for either 24 or 48 weeks total (Fig 1). Serum creatinine values were obtained during therapy with telaprevir and the maximum values used to determine the presence of significant creatinine rise during telaprevir use. A significant creatinine rise was defined as a ≥ 0.3mg/dL increase from baseline. This cutoff was chosen as it is the same magnitude of rise that has been shown to have significant effect on chronic kidney disease development and progression in the setting of acute kidney injury[16]. Patients were considered to have cirrhosis if it was demonstrated on liver biopsy or if the treating physician determined it to be likely based on clinical findings, imaging, and fibrosis score. Sustained viral response (SVR), or cure of hepatitis C, was defined as undetectable HCV RNA 12 weeks after therapy[17]. Short-term kidney function recovery was determined based on serum creatinine between 4–12 weeks after discontinuation of telaprevir, at this time point,patients were still on PegIFN and RBV unless they had prematurely discontinued therapy due to side effects. Normalization of kidney function was defined as return of eGFR to at least 90% of prior baseline within 12 weeks after discontinuing telaprevir. Long-term kidney function recovery was determined based on serum creatinine between twelve months after discontinuation of telaprevir. See Fig 1 for a schematic representation of treatment course and follow-up time-points.

Bottom Line: The majority completed the prescribed twelve weeks of telaprevir therapy; 32% discontinued due to side effects.Thirty-one percent experienced a significant creatinine rise during therapy.Decline in kidney function during therapy with telaprevir is common and is not associated with baseline eGFR < 90mL/min/1.73m2 as previously reported.

View Article: PubMed Central - PubMed

Affiliation: Division of Nephrology, Department of Medicine, Massachusetts General Hospital, Harvard University, Boston, MA, United States of America.

ABSTRACT

Background: Recent reports suggest that telaprevir, a protease inhibitor used to treat hepatitis C infection, is associated with decline in kidney function during therapy, particularly in patients with baseline renal impairment.

Methods: Patients treated with telaprevir in a single healthcare network were retrospectively reviewed. Kidney function was determined at baseline, during therapy, and twelve weeks and twelve months after telaprevir discontinuation. Significant creatinine rise during therapy was defined as an increase in serum creatinine ≥ 0.3mg/dL from baseline during treatment with telaprevir.

Results: Between July 2011 to January 2013,seventy-eight patients began treatment. The majority completed the prescribed twelve weeks of telaprevir therapy; 32% discontinued due to side effects. The average rise in serum creatinine during therapy was 0.22mg/dL (standard deviation 0.22mg/dL). Thirty-one percent experienced a significant creatinine rise during therapy. Decline in estimated glomerular filtration rate (eGFR) was lower in those with baseline eGFR < 90 mL/min/1.73m2 compared to the group with baseline eGFR ≥ 90 mL/min/1.73m2 (12 vs. 18 mL/min/1.73m2, P = 0.047). Serum creatinine fully normalized by twelve weeks after cessation of telaprevir in 83% of patients, however experiencing a significant creatinine rise during telaprevir use was associated with a 6.6mL/min/1.73m2 decrease in estimated glomerular filtration rate at twelve months in an adjusted model.

Conclusions: Decline in kidney function during therapy with telaprevir is common and is not associated with baseline eGFR < 90mL/min/1.73m2 as previously reported.

No MeSH data available.


Related in: MedlinePlus