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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

Average estimated glomerular filtration rate in patients during and after telaprevir therapy, by baseline kidney function.3a. Baseline eGFR ≥ 90 mL/min/1.73m2 3b. Baseline eGFR < 90 mL/min/1.73m2. Mean eGFR (solid gray circle) and one-standard deviation error bars are shown with shading at baseline, on treatment (nadir), 12 weeks after finishing telaprevir, while still on PegIFN and RBV, and then one year after completing telaprevir, off all treatment. P < 0.01 for changes between baseline eGFR and eGFR while on telaprevir in both groups. There is no signficant difference between baseline eGFR and eGFR 12 weeks or one year post telaprevir. Fig 3a shows patients with baseline eGFR ≥ 90mL/min/1.73m2. (N = 44). 3b.) Includes patients with baseline eGFR < 90mL/min/1.73m2 (N = 34). Values that fell outside of one standard deviation are shown with hollow gray circles. eGFR = estimated glomerular filtration rate.
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pone.0124139.g003: Average estimated glomerular filtration rate in patients during and after telaprevir therapy, by baseline kidney function.3a. Baseline eGFR ≥ 90 mL/min/1.73m2 3b. Baseline eGFR < 90 mL/min/1.73m2. Mean eGFR (solid gray circle) and one-standard deviation error bars are shown with shading at baseline, on treatment (nadir), 12 weeks after finishing telaprevir, while still on PegIFN and RBV, and then one year after completing telaprevir, off all treatment. P < 0.01 for changes between baseline eGFR and eGFR while on telaprevir in both groups. There is no signficant difference between baseline eGFR and eGFR 12 weeks or one year post telaprevir. Fig 3a shows patients with baseline eGFR ≥ 90mL/min/1.73m2. (N = 44). 3b.) Includes patients with baseline eGFR < 90mL/min/1.73m2 (N = 34). Values that fell outside of one standard deviation are shown with hollow gray circles. eGFR = estimated glomerular filtration rate.

Mentions: When patients with eGFR < 90mL/min/1.73m2 at baseline were compared to those with eGFR ≥ 90 mL/min/1.73m2 at baseline the average decline in eGFR was, in fact, slightly lower in those with eGFR < 90 mL/min/1.73m2 compared to those with eGFR ≥ 90mL/min/1.73m2, 12 vs. 18mL/min/1.73m2, respectively, P = 0.047. Changes in eGFR during and after treatment stratified by baseline eGFR are shown in Fig 3A and 3B. When using a cutoff eGFR of 60mL/min/1.73m2 to define “renal impairment” as prior studies have done,[13] then unsurprisingly, the likelihood of this outcome was increased in the group with eGFR < 90 mL/min/1.73m2 (40% vs. 4.5%, P < 0.001). Baseline eGFR did not have an effect on the odds of significant creatinine rise during treatment in a multivariable logistic model (Table 2). There were no baseline demographic or clinical characteristics that were associated with the development of significant creatinine rise during telaprevir therapy.


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)

Average estimated glomerular filtration rate in patients during and after telaprevir therapy, by baseline kidney function.3a. Baseline eGFR ≥ 90 mL/min/1.73m2 3b. Baseline eGFR < 90 mL/min/1.73m2. Mean eGFR (solid gray circle) and one-standard deviation error bars are shown with shading at baseline, on treatment (nadir), 12 weeks after finishing telaprevir, while still on PegIFN and RBV, and then one year after completing telaprevir, off all treatment. P < 0.01 for changes between baseline eGFR and eGFR while on telaprevir in both groups. There is no signficant difference between baseline eGFR and eGFR 12 weeks or one year post telaprevir. Fig 3a shows patients with baseline eGFR ≥ 90mL/min/1.73m2. (N = 44). 3b.) Includes patients with baseline eGFR < 90mL/min/1.73m2 (N = 34). Values that fell outside of one standard deviation are shown with hollow gray circles. eGFR = estimated glomerular filtration rate.
© Copyright Policy
Related In: Results  -  Collection

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

pone.0124139.g003: Average estimated glomerular filtration rate in patients during and after telaprevir therapy, by baseline kidney function.3a. Baseline eGFR ≥ 90 mL/min/1.73m2 3b. Baseline eGFR < 90 mL/min/1.73m2. Mean eGFR (solid gray circle) and one-standard deviation error bars are shown with shading at baseline, on treatment (nadir), 12 weeks after finishing telaprevir, while still on PegIFN and RBV, and then one year after completing telaprevir, off all treatment. P < 0.01 for changes between baseline eGFR and eGFR while on telaprevir in both groups. There is no signficant difference between baseline eGFR and eGFR 12 weeks or one year post telaprevir. Fig 3a shows patients with baseline eGFR ≥ 90mL/min/1.73m2. (N = 44). 3b.) Includes patients with baseline eGFR < 90mL/min/1.73m2 (N = 34). Values that fell outside of one standard deviation are shown with hollow gray circles. eGFR = estimated glomerular filtration rate.
Mentions: When patients with eGFR < 90mL/min/1.73m2 at baseline were compared to those with eGFR ≥ 90 mL/min/1.73m2 at baseline the average decline in eGFR was, in fact, slightly lower in those with eGFR < 90 mL/min/1.73m2 compared to those with eGFR ≥ 90mL/min/1.73m2, 12 vs. 18mL/min/1.73m2, respectively, P = 0.047. Changes in eGFR during and after treatment stratified by baseline eGFR are shown in Fig 3A and 3B. When using a cutoff eGFR of 60mL/min/1.73m2 to define “renal impairment” as prior studies have done,[13] then unsurprisingly, the likelihood of this outcome was increased in the group with eGFR < 90 mL/min/1.73m2 (40% vs. 4.5%, P < 0.001). Baseline eGFR did not have an effect on the odds of significant creatinine rise during treatment in a multivariable logistic model (Table 2). There were no baseline demographic or clinical characteristics that were associated with the development of significant creatinine rise during telaprevir therapy.

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