Analysis of renal function during telaprevir-based triple therapy for chronic hepatitis C

Kohjima,Motoyuki; Kurokawa,Miho; Enjoji,Munechika; Yoshimoto,Tsuyoshi; Nakamura,Tsukasa; Ohashi,Tomoko; Fukuizumi,Kunitaka; Harada,Naohiko; Murata,Yusuke; Matsunaga,Kazuhisa; Kato,Masaki; Kotoh,Kazuhiro; Nakamuta,Makoto

doi:10.3892/etm.2016.3133

Analysis of renal function during telaprevir-based triple therapy for chronic hepatitis C

Authors:
- Motoyuki Kohjima
- Miho Kurokawa
- Munechika Enjoji
- Tsuyoshi Yoshimoto
- Tsukasa Nakamura
- Tomoko Ohashi
- Kunitaka Fukuizumi
- Naohiko Harada
- Yusuke Murata
- Kazuhisa Matsunaga
- Masaki Kato
- Kazuhiro Kotoh
- Makoto Nakamuta
View Affiliations

Affiliations: Department of Gastroenterology, National Hospital Organization Kyushu Medical Center, Fukuoka 810‑8563, Japan, Faculty of Pharmaceutical Sciences, Fukuoka University, Fukuoka 814‑0180, Japan, Department of Medicine and Bioregulatory Science, Kyushu University, Fukuoka 812‑8582, Japan
Published online on: March 9, 2016 https://doi.org/10.3892/etm.2016.3133
Pages: 1781-1787

Metrics: Total Views: 0 (Spandidos Publications: | PMC Statistics: )

Metrics: Total PDF Downloads: 0 (Spandidos Publications: | PMC Statistics: )

Cited By (CrossRef): 0 citations Loading Articles...

Abstract

Telaprevir (TVR) is used for the treatment of chronic hepatitis C in a combination therapy with pegylated‑interferon and ribavirin. Although renal dysfunction is one of the critical adverse outcomes of this treatment, little is known regarding the mechanism of its onset. The present study assessed the association of renal function with TVR dose and viral response. Hematological, biochemical, urinary and virological parameters of renal function were examined during the TVR‑based triple therapy of patients infected with hepatitis C virus (HCV) genotype 1b. Serum creatinine levels were increased and the estimated glomerular filtration rate (eGFR) was decreased in every patient during TVR administration, but these values recovered to normal levels following cessation of TVR. Fractional excretion of sodium was <1% at days 3 and 7, appearing similar regardless of baseline renal function. Urinary β2‑microglobulin levels were elevated and were significantly higher in patients with renal dysfunction, as compared with those not exhibiting renal dysfunction (P<0.05). The reduction in renal function was milder in patients treated with a reduced TVR dose, and these patients had a significantly lower risk of developing renal dysfunction (P<0.05). Using a multivariate analysis, TVR dose and eGFR at the initiation of treatment were identified as significant contributory factors in the development of renal dysfunction. Reduction in TVR dose did not lead to a significant increase in the viral kinetics of HCV or detrimental effects on the sustained viral response (SVR) rate. It is hypothesized that renal dysfunction during TVR treatment is caused by damage of the renal tubule, in addition to pre‑renal dysfunction, and that reduction in TVR dose reduces the rate of renal dysfunction without causing a significant decrease in the SVR rate.

View Figures

View References

1	Alter HJ: HCV natural history: The retrospective and prospective in perspective. J Hepatol. 43:550–552. 2005. View Article : Google Scholar : PubMed/NCBI
2	Kumada T, Toyoda H, Honda T, Kuzuya T, Katano Y, Nakano I and Goto H: Treatment of chronic hepatitis C with interferon alone or combined with ribavirin in Japan. Intervirology. 49:112–118. 2006. View Article : Google Scholar : PubMed/NCBI
3	Aghemo A, Rumi MG and Colombo M: Pegylated IFN-alpha2a and ribavirin in the treatment of hepatitis C. Expert Rev Anti Infect Ther. 7:925–935. 2009. View Article : Google Scholar : PubMed/NCBI
4	McHutchison JG, Everson GT, Gordon SC, Jacobson IM, Sulkowski M, Kauffman R, McNair L, Alam J and Muir AJ: PROVE1 Study Team: Telaprevir with peginterferon and ribavirin for chronic HCV genotype 1 infection. N Engl J Med. 360:1827–1838. 2009. View Article : Google Scholar : PubMed/NCBI
5	Hayashi N, Okanoue T, Tsubouchi H, Toyota J, Chayama K and Kumada H: Efficacy and safety of telaprevir, a new protease inhibitor, for difficult-to-treat patients with genotype 1 chronic hepatitis C. J Viral Hepat. 19:e134–e142. 2012. View Article : Google Scholar : PubMed/NCBI
6	Kumada H, Toyota J, Okanoue T, Chayama K, Tsubouchi H and Hayashi N: Telaprevir with peginterferon and ribavirin for treatment-naive patients chronically infected with HCV of genotype 1 in Japan. J Hepatol. 56:78–84. 2012. View Article : Google Scholar : PubMed/NCBI
7	Rajani AK, Ravindra BK and Dkhar SA: Telaprevir: Changing the standard of care of chronic hepatitis C. J Postgrad Med. 59:42–47. 2013. View Article : Google Scholar : PubMed/NCBI
8	Kleinknecht D, Landais P and Goldfarb B: Drug-associated acute renal failure. A prospective collaborative study of 81 biopsied patients. Adv Exp Med Biol. 212:125–128. 1987. View Article : Google Scholar : PubMed/NCBI
9	Choudhury D and Ahmed Z: Drug-associated renal dysfunction and injury. Nat Clin Pract Nephrol. 2:80–91. 2006. View Article : Google Scholar : PubMed/NCBI
10	Prowle J, Bagshaw SM and Bellomo R: Renal blood flow, fractional excretion of sodium and acute kidney injury: Time for a new paradigm? Curr Opin Crit Care. 18:585–592. 2012. View Article : Google Scholar : PubMed/NCBI
11	Nakamoto S, Kanda T, Yonemitsu Y, Arai M, Fujiwara K, Fukai K, Kanai F, Imazeki F and Yokosuka O: Quantification of hepatitis C amino acid substitutions 70 and 91 in the core coding region by real-time amplification refractory mutation system reverse transcription-polymerase chain reaction. Scand J Gastroenterol. 44:872–877. 2009. View Article : Google Scholar : PubMed/NCBI
12	Kohjima M, Enjoji M, Yoshimoto T, Yada R, Fujino T, Aoyagi Y, Fukushima N, Fukuizumi K, Harada N, Yada M, et al: Add-on therapy of pitavastatin and eicosapentaenoic acid improves outcome of peginterferon plus ribavirin treatment for chronic hepatitis C. J Med Virol. 85:250–260. 2013. View Article : Google Scholar : PubMed/NCBI
13	Fahal IH, Murry N, Chu P and Bell GM: Acute renal failure during interferon treatment. BMJ. 306:9731993. View Article : Google Scholar : PubMed/NCBI
14	Jadoul M, Piessevaux H, Ferrant A, Cosyns JP and van Ypersele de Strihou C: Renal thrombotic microangiopathy in patients with chronic myelogenous leukaemia treated with interferon-alpha 2b. Nephrol Dial Transplant. 10:111–113. 1995.PubMed/NCBI
15	Shah M, Jenis EH, Mookerjee BK, Schriber JR, Baer MR, Herzig GP and Wetzler M: Interferon-alpha-associated focal segmental glomerulosclerosis with massive proteinuria in patients with chronic myeloid leukemia following high dose chemotherapy. Cancer. 83:1938–1946. 1998. View Article : Google Scholar : PubMed/NCBI
16	Russo MW and Fried MW: Side effects of therapy for chronic hepatitis C. Gastroenterology. 124:1711–1719. 2003. View Article : Google Scholar : PubMed/NCBI
17	Willson RA: Nephrotoxicity of interferon alfa-ribavirin therapy for chronic hepatitis C. J Clin Gastroenterol. 35:89–92. 2002. View Article : Google Scholar : PubMed/NCBI
18	Gervasoni C, Milazzo L, Pezzani D, Fucile S and Cattaneo D: Telaprevir therapy, renal impairment, and their effects on the pharmacokinetics of tenofovir in HIV/hepatitis C virus coinfected patients. AIDS. 28:285–287. 2014. View Article : Google Scholar : PubMed/NCBI
19	Mauss S, Hueppe D and Alshuth U: Renal impairment is frequent in chronic hepatitis C patients under triple therapy with telaprevir or boceprevir. Hepatology. 59:46–48. 2014. View Article : Google Scholar : PubMed/NCBI
20	Pariente A, Rémy AJ, Lesgourgues B and Hagège H: APROVVIE group of the Association Nationale des Gastroentérologues des Hôpitaux Généraux (ANGH): Risk factors for severe anaemia during telaprevir-based triple therapy: Is acquired renal dysfunction the missing link? Liver Int. 34:e163–e164. 2014. View Article : Google Scholar : PubMed/NCBI
21	Tempestilli M, Lionetti R, D'Offizi G, Montalbano M, Giaffreda A, Fazio S and Pucillo LP: Increased plasma concentration of ribavirin as a result of renal dysfunction in hepatitis C virus patients treated with telaprevir. Hepatology. 60:1109–1110. 2014. View Article : Google Scholar : PubMed/NCBI
22	Karino T, Ozeki I, Hige S, Kimura M, Arakawa T, Nakajima T, Kuwata Y, Sato T, Ohmura T and Toyota J: Telaprevir impairs renal function and increases blood ribavirin concentration during telaprevir/pegylated interferon/ribavirin therapy for chronic hepatitis C. J Viral Hepat. 21:341–347. 2014. View Article : Google Scholar : PubMed/NCBI
23	Carrier P, Chambaraud T, Vong C, Guillaudeau A, Debette-Gratien M, Jacques J, Legros R, Sautereau D, Essig M and Loustaud-Ratti V: Severe renal impairment during triple therapy with telaprevir. Clin Res Hepatol Gastroenterol. 38:e69–e71. 2014. View Article : Google Scholar : PubMed/NCBI
24	Kainuma M, Furusyo N, Kajiwara E, Takahashi K, Nomura H, Tanabe Y, Satoh T, Maruyama T, Nakamuta M, Kotoh K, et al: Kyushu University Liver Disease Study Group: Pegylated interferon α-2b plus ribavirin for older patients with chronic hepatitis C. World J Gastroenterol. 16:4400–4409. 2010. View Article : Google Scholar : PubMed/NCBI
25	Honda T, Katano Y, Shimizu J, Ishizu Y, Doizaki M, Hayashi K, Ishigami M, Itoh A, Hirooka Y, Nakano I, et al: Efficacy of peginterferon-alpha-2b plus ribavirin in patients aged 65 years and older with chronic hepatitis C. Liver Int. 30:527–537. 2010. View Article : Google Scholar : PubMed/NCBI
26	Furusyo N, Ogawa E, Nakamuta M, Kajiwara E, Nomura H, Dohmen K, Takahashi K, Satoh T, Azuma K, Kawano A, et al: Kyushu University Liver Disease Study (KULDS) Group: Telaprevir can be successfully and safely used to treat older patients with genotype 1b chronic hepatitis C. J Hepatol. 59:205–212. 2013. View Article : Google Scholar : PubMed/NCBI
27	Kunze A, Huwyler J, Camenisch G and Gutmann H: Interaction of the antiviral drug telaprevir with renal and hepatic drug transporters. Biochem Pharmacol. 84:1096–1102. 2012. View Article : Google Scholar : PubMed/NCBI