ORIGINAL ARTICLE
Renal Function in Chronic Hepatitis B Patients Treated With Tenofovir Disoproxil Fumarate or Entecavir Monotherapy A Matched Case-Cohort Study Nghi B. Ha, PharmD, MPH,*w Kevin Ku, DO,z Nghiem B. Ha, BSc,y Kevin T. Chaung, BSc,w Huy N. Trinh, MD,8 and Mindie H. Nguyen, MD, MASz
Background and Aims: Tenofovir (TDF)-associated renal dysfunction has been described in various studies of human immunodeficiency virus–infected patients. Our goal is to examine the incidence and magnitude of decrease in renal function in chronic hepatitis B patients treated with TDF. Methods: We performed a case-cohort study of 103 patients on TDF 300 mg and 103 patients unexposed to TDF (Entecavir) at 4 centers, who were matched for age ± 10 years, sex, and baseline estimated glomerular filtration rate (eGFR) group. Calculation and evaluation of eGFR were performed with both the Cockcroft-Gault formula and the Modification of Diet in Renal Disease formula. Results: The exposed and unexposed populations were well matched with a similar mean age (44 ± 10 y), proportion of male patients (63.1%), and baseline eGFR groups (86.4% unimpaired). There was no significant difference in the proportion of patients reclassified to a more severe renal classification (RMSRC) or in the proportion of patients with decrease in eGFR of Z20% in those exposed to TDF versus control. The incidence density for RMSRC was 7.4 cases per 100 patient-years in the exposed group compared with 11.5 cases per 100 patient-years in the unexposed group (95% CI, 0.31-1.34). The relative risk of exposed to unexposed was 0.64 (95% CI, 0.31-1.34). On Cox proportional hazard analysis following adjustment for sex, age, baseline diagnosis hypertension, diabetes, impaired baseline renal function, and cirrhosis, TDF was not a predictor for RMSRC or decrease in eGFRZ20%. Conclusions: TDF treatment was not an independent predictor for significant deterioration of renal function. Renal function of chronic hepatitis B patients on antiviral therapy should be monitored, especially in those who are older and/or with mildly impaired renal function. Key Words: hepatitis B, tenofovir, renal dysfunction
(J Clin Gastroenterol 2015;49:873–877)
Received for publication September 1, 2014; accepted March 11, 2015. From the *School of Pharmacy, University of California, San Francisco, San Francisco; wPacific Health Foundation; 8San Jose Gastroenterology, San Jose; zDepartment of Medicine, Santa Clara Valley Medical Center, Santa Clara; ySchool of Medicine, University of California, Davis, Sacramento; and zDivision of Gastroenterology and Hepatology, Stanford University Medical Center, Palo Alto, CA. All authors contributed evenly to the study design, execution, analysis, and production of this manuscript. The authors declare that they have nothing to disclose. Reprints: Mindie H. Nguyen, MD, MAS, Medicine, Division of Gastroenterology and Hepatology, Stanford University Medical Center, 750 Welch Road, Suite 210, Palo Alto, CA 94304 (e-mail: [email protected]). Copyright r 2015 Wolters Kluwer Health, Inc. All rights reserved.
J Clin Gastroenterol
BACKGROUND AND AIMS It is estimated that 350 million people worldwide are chronically infected with hepatitis B virus (HBV).1 Approximately 15% to 40% of those with chronic hepatitis B (CHB) will develop chronic liver disease leading to cirrhosis and hepatocellular carcinoma.2 However, various treatment options are currently available for the treatment of CHB with the goal of eliminating or significantly suppressing HBV viral replication to prevent disease progression, major complications, and mortality.2,3 Current first-line oral monotherapy for CHB include entecavir (ETV) and tenofovir disoproxil fumarate (TDF) due to their high efficacy and low resistance. TDF is an acyclic nucleotide analogue that is structurally similar to adefovir dipivoxil (ADV).4 ADV has been replaced by TDF due to its lower efficacy in HBV DNA suppression and normalization of ALT, and higher incidence of resistance.2 ADV was also shown to be associated with increased incidence of renal dysfunction.5 Structural similarity between ADV and TDF could be an explanation for the concern of renal dysfunction in CHB patients treated with TDF. TDF-associated renal dysfunction has been described in several case reports and studies in human immunodeficiency virus (HIV)-infected patients.6–12 It is a nucleoside reverse-transcriptase inhibitor that is administered orally as a prodrug and eliminated from the body through glomerular filtration and tubular secretion.13,14 The main target of toxicity appears to be in the proximal tubule.13,15 Two potential mechanisms of tubule toxicity as previously described for adefovir and cidofovir include accumulation of TDF in tubular cells resulting in cytotoxicity of cells or depletion of mitochondrial DNA in proximal tubular cells.13,16–18 In severe cases, patients can develop Fanconi syndrome.13,15 More recently, a study of renal tubular dysfunction in ADV-treated or TDF-treated patients with CHB estimated a 10-year cumulative rate of renal tubular dysfunction of 15%.19 However, only 4 of 51 patients in this study were treated with TDF, limiting its conclusion regarding TDF. Published studies of renal events in CHB patients treated with TDF currently include: patients receiving TDF in combination with other nucleoside analogue, patients with significant preexisting renal insufficiency, and patients with high risk for renal impairment such as liver and kidney transplant patients.19,20 The goal of this study is to evaluate the incidence and magnitude of decrease in renal function among Asian American patients with CHB treated with TDF 300 mg daily.
Volume 49, Number 10, November/December 2015
www.jcge.com |
Copyright r 2015 Wolters Kluwer Health, Inc. All rights reserved.
873
J Clin Gastroenterol
Ha et al
METHODS
Volume 49, Number 10, November/December 2015
This study was approved by the institutional review board at Stanford University (Stanford, CA).
Study Design We performed a matched case-cohort study of 103 consecutive CHB patients who were initiated on TDF 300 mg daily monotherapy and 103 consecutive CHB patients treated with ETV monotherapy at 2 communitybased gastroenterology clinics, 1 community hospital, and 1 tertiary medical center in the United States from January 2008 to May 2012. Patients were identified through electronic query using ICD-9 diagnosis codes for CHB and medical records were reviewed for patients treated with TDF or ETV. We queried and compiled a list of consecutive patients on TDF or ETV from January 2008 to May 2012 and abstracted only their age, sex, baseline serum Cr level, and weight. Matching of the ETV group to TDF group was based only on selected factors. Complete data abstraction were not done until all patients were matched. There was a 1:1 match of 103 cases and 103 controls. Cases were treatment-naive patients started with TDF 300 mg daily monotherapy with baseline estimated glomerular filtration rate (eGFR)Z50 mL/min. Controls were patients treated with ETV 0.5 or 1.0 mg daily monotherapy with baseline eGFRZ50 mL/min. Cases and controls were matched by their baseline characteristics including age ( ± 10 y), sex, and baseline eGFR classification (unimpaired: eGFRZ80 mL/min or mildly impaired: 50 mL/min < eGFR < 80 mL/min). The inclusion of patients treated with 1 single alternative agent as a control group was to avoid unnecessary heterogeneity in the comparison. Untreated patients were not selected as controls as they generally would not have regular laboratory monitoring that includes renal parameters. ETV was chosen as it is the other most commonly used antiviral therapy in our clinics and it has not been known to be associated with renal dysfunction. Patients with baseline eGFR < 50 mL/min, those with prior exposure to ADV or TDF, or those with TDF combination therapy were excluded from this study. Patients who had coinfection with hepatitis C virus (HCV), hepatitis D virus (HDV), and/or HIV were also excluded from this study.
Renal Classifications All available medical records were evaluated thoroughly and data were recorded using a case report form developed for this study. Renal function was monitored every 3 to 6 months in most patients and there were no significant differences in the frequencies of renal function tests between the cases and controls. Patient’s eGFR was calculated using the CockcroftGault formula ((140 age)(Wt in kg)(0.85 if female)/ (72Cr)) and the Modification of Diet in Renal Disease (MDRD) formula (170 (Cr 0.999)*(Age 0.176)(0.762 if Female)(1.180 if African American)(BUN 0.170) (Albumin0.318)). Patients were followed-up approximately every 6 months. Classification of eGFR is as follows: unimpaired (eGFR > 80 mL/min), mildly impaired (50 mL/ minreGFRr80 mL/min), moderately impaired (30 mL/ minreGFR < 50 mL/min), and severely impaired (eGFR < 30 mL/min). Incidence density analysis was performed to compare incidence of renal dysfunction in cases versus controls. Exposed time was measured in person-years. Date of entry was determined by baseline date, and date of exit was defined by treatment termination or termination of this study.
Laboratory Tests Laboratory tests were performed at one of the local community clinical laboratories operated by either Quest Diagnostics (San Juan Capistrano, CA) or LabCorp (Burlington, NC). Cirrhosis was defined by the presence of stage4 fibrosis on histology or by the presence of portal hypertension (platelet 0.0001 0.665 0.192 0.999 0.010 0.829 0.489
*Model inclusive of age, sex, presence of hypertension, presence of diabetes mellitus, presence of mild renal impairment at baseline (50 mL/minreGFRr80 mL/min), presence of cirrhosis, and therapy with TDF. CI indicates confidence interval; eGFR, estimated glomerular filtration rate; HR, hazard ratio; TDF, tenofovir.
mild renal impairment at baseline, rather than antiviral therapy (TDF or ETV), were significant independent predictors for a significant decline in renal function. When examining magnitude of decrease in eGFR, there was no significant difference in the cumulative incidence of patients with decrease in eGFR of Z20% using KaplanMeier survival analysis. A similar study found that there was no significant difference in the proportion of patients with decrease in eGFR of Z20%.20 A decrease in eGFR of Z20% resulted in treatment discontinuation of 2 patients in the TDF cohort versus none in the ETV cohort. Both patients that required treatment discontinuation had mildly impaired renal function at baseline, which may have contributed to their treatment discontinuation. TDF exposure was not a significant predictor for a decrease in eGFR of Z20%. There were limitations to this study. The follow-up duration was different between exposed versus control groups. However, incidence density and Kaplan-Meier survival analysis were used to account for the differences in exposure time between the 2 cohorts. There were also strengths in this study. All patients in the exposed cohort were only exposed to TDF and not in combination with any other anti-HBV medications. No patients in this study had significant preexisting renal disease and/or prior history of liver or kidney transplantation. In conclusion, we did not observe a significant difference in the proportion of patients reclassified to a more severe renal function classification or in the proportion of patients who experienced a decrease in eGFR of Z20% in those exposed to TDF versus ETV. However, renal function in patients treated with TDF should be monitored closely, especially in patients with preexisting renal dysfunction. Older age and preexisting renal impairment including mild cases independently predicted significant worsening of renal function in CHB patients but not TDF or ETV. REFERENCES 1. McMahon BJ. Chronic hepatitis B virus infection. Med Clin North Am. 2014;98:39–54. 2. Lok AS, McMahon BJ. Chronic hepatitis B: update 2009. Hepatology. 2009;50:661–662. 3. Keeffe EB, Dieterich DT, Han SH, et al. A treatment algorithm for the management of chronic hepatitis B virus infection in the United States: 2008 update. Clin Gastroenterol Hepatol. 2008;6:1315–1341. quiz 1286. 4. Gallant JE, Moore RD. Renal function with use of a tenofovircontaining initial antiretroviral regimen. AIDS. 2009;23:1971–1975.
Copyright
r
5. Ha NB, Garcia RT, Trinh HN, et al. Renal dysfunction in chronic hepatitis B patients treated with adefovir dipivoxil. Hepatology. 2009;50:727–734. 6. Horberg M, Tang B, Towner W, et al. Impact of tenofovir on renal function in HIV-infected, antiretroviral-naive patients. J Acquir Immune Defic Syndr. 2010;53:62–69. 7. Perazella MA. Drug-induced renal failure: update on new medications and unique mechanisms of nephrotoxicity. Am J Med Sci. 2003;325:349–362. 8. Peyriere H, Reynes J, Rouanet I, et al. Renal tubular dysfunction associated with tenofovir therapy: report of 7 cases. J Acquir Immune Defic Syndr. 2004;35:269–273. 9. Earle KE, Seneviratne T, Shaker J, et al. Fanconi’s syndrome in HIV + adults: report of three cases and literature review. J Bone Miner Res. 2004;19:714–721. 10. Gaspar G, Monereo A, Garcia-Reyne A, et al. Fanconi syndrome and acute renal failure in a patient treated with tenofovir: a call for caution. AIDS. 2004;18:351–352. 11. Malik A, Abraham P, Malik N. Acute renal failure and Fanconi syndrome in an AIDS patient on tenofovir treatment—case report and review of literature. J Infect. 2005;51:E61–E65. 12. Quimby D, Brito MO. Fanconi syndrome associated with use of tenofovir in HIV-infected patients: a case report and review of the literature. AIDS Read. 2005;15:357–364. 13. Gitman MD, Hirschwerk D, Baskin CH, et al. Tenofovirinduced kidney injury. Expert Opin Drug Saf. 2007;6:155–164. 14. Gilead Sciences Inc., Viread (tenofovir disoproxil fumarate) prescribing information. 2013. 15. Hall AM, Hendry BM, Nitsch D, et al. Tenofovir-associated kidney toxicity in HIV-infected patients: a review of the evidence. Am J Kidney Dis. 2011;57:773–780. 16. Ortiz A, Justo P, Sanz A, et al. Tubular cell apoptosis and cidofovir-induced acute renal failure. Antivir Ther. 2005;10: 185–190. 17. Tanji N, Tanji K, Kambham N, et al. Adefovir nephrotoxicity: possible role of mitochondrial DNA depletion. Hum Pathol. 2001;32:734–740. 18. Bendele RA, Richardson FC. Adefovir nephrotoxicity and mitochondrial DNA depletion. Hum Pathol. 2002;33:574. 19. Gara N, Zhao X, Collins MT, et al. Renal tubular dysfunction during long-term adefovir or tenofovir therapy in chronic hepatitis B. Aliment Pharmacol Ther. 2012;35:1317–1325. 20. Gish RG, Clark MD, Kane SD, et al. Similar risk of renal events among patients treated with tenofovir or entecavir for chronic hepatitis B. Clin Gastroenterol Hepatol. 2012;10:941–946. quiz e968. 21. Padilla S, Gutierrez F, Masia M, et al. Low frequency of renal function impairment during one-year of therapy with tenofovir-containing regimens in the real-world: a case-control study. AIDS Patient Care STDS. 2005;19:421–424. 22. Antoniou T, Raboud J, Chirhin S, et al. Incidence of and risk factors for tenofovir-induced nephrotoxicity: a retrospective cohort study. HIV Med. 2005;6:284–290.
2015 Wolters Kluwer Health, Inc. All rights reserved.
www.jcge.com |
Copyright r 2015 Wolters Kluwer Health, Inc. All rights reserved.
877
Renal Function in Chronic Hepatitis B Patients Treated With Tenofovir Disoproxil Fumarate or Entecavir Monotherapy A Matched Case-Cohort Study Nghi B. Ha, PharmD, MPH,*w Kevin Ku, DO,z Nghiem B. Ha, BSc,y Kevin T. Chaung, BSc,w Huy N. Trinh, MD,8 and Mindie H. Nguyen, MD, MASz
Background and Aims: Tenofovir (TDF)-associated renal dysfunction has been described in various studies of human immunodeficiency virus–infected patients. Our goal is to examine the incidence and magnitude of decrease in renal function in chronic hepatitis B patients treated with TDF. Methods: We performed a case-cohort study of 103 patients on TDF 300 mg and 103 patients unexposed to TDF (Entecavir) at 4 centers, who were matched for age ± 10 years, sex, and baseline estimated glomerular filtration rate (eGFR) group. Calculation and evaluation of eGFR were performed with both the Cockcroft-Gault formula and the Modification of Diet in Renal Disease formula. Results: The exposed and unexposed populations were well matched with a similar mean age (44 ± 10 y), proportion of male patients (63.1%), and baseline eGFR groups (86.4% unimpaired). There was no significant difference in the proportion of patients reclassified to a more severe renal classification (RMSRC) or in the proportion of patients with decrease in eGFR of Z20% in those exposed to TDF versus control. The incidence density for RMSRC was 7.4 cases per 100 patient-years in the exposed group compared with 11.5 cases per 100 patient-years in the unexposed group (95% CI, 0.31-1.34). The relative risk of exposed to unexposed was 0.64 (95% CI, 0.31-1.34). On Cox proportional hazard analysis following adjustment for sex, age, baseline diagnosis hypertension, diabetes, impaired baseline renal function, and cirrhosis, TDF was not a predictor for RMSRC or decrease in eGFRZ20%. Conclusions: TDF treatment was not an independent predictor for significant deterioration of renal function. Renal function of chronic hepatitis B patients on antiviral therapy should be monitored, especially in those who are older and/or with mildly impaired renal function. Key Words: hepatitis B, tenofovir, renal dysfunction
(J Clin Gastroenterol 2015;49:873–877)
Received for publication September 1, 2014; accepted March 11, 2015. From the *School of Pharmacy, University of California, San Francisco, San Francisco; wPacific Health Foundation; 8San Jose Gastroenterology, San Jose; zDepartment of Medicine, Santa Clara Valley Medical Center, Santa Clara; ySchool of Medicine, University of California, Davis, Sacramento; and zDivision of Gastroenterology and Hepatology, Stanford University Medical Center, Palo Alto, CA. All authors contributed evenly to the study design, execution, analysis, and production of this manuscript. The authors declare that they have nothing to disclose. Reprints: Mindie H. Nguyen, MD, MAS, Medicine, Division of Gastroenterology and Hepatology, Stanford University Medical Center, 750 Welch Road, Suite 210, Palo Alto, CA 94304 (e-mail: [email protected]). Copyright r 2015 Wolters Kluwer Health, Inc. All rights reserved.
J Clin Gastroenterol
BACKGROUND AND AIMS It is estimated that 350 million people worldwide are chronically infected with hepatitis B virus (HBV).1 Approximately 15% to 40% of those with chronic hepatitis B (CHB) will develop chronic liver disease leading to cirrhosis and hepatocellular carcinoma.2 However, various treatment options are currently available for the treatment of CHB with the goal of eliminating or significantly suppressing HBV viral replication to prevent disease progression, major complications, and mortality.2,3 Current first-line oral monotherapy for CHB include entecavir (ETV) and tenofovir disoproxil fumarate (TDF) due to their high efficacy and low resistance. TDF is an acyclic nucleotide analogue that is structurally similar to adefovir dipivoxil (ADV).4 ADV has been replaced by TDF due to its lower efficacy in HBV DNA suppression and normalization of ALT, and higher incidence of resistance.2 ADV was also shown to be associated with increased incidence of renal dysfunction.5 Structural similarity between ADV and TDF could be an explanation for the concern of renal dysfunction in CHB patients treated with TDF. TDF-associated renal dysfunction has been described in several case reports and studies in human immunodeficiency virus (HIV)-infected patients.6–12 It is a nucleoside reverse-transcriptase inhibitor that is administered orally as a prodrug and eliminated from the body through glomerular filtration and tubular secretion.13,14 The main target of toxicity appears to be in the proximal tubule.13,15 Two potential mechanisms of tubule toxicity as previously described for adefovir and cidofovir include accumulation of TDF in tubular cells resulting in cytotoxicity of cells or depletion of mitochondrial DNA in proximal tubular cells.13,16–18 In severe cases, patients can develop Fanconi syndrome.13,15 More recently, a study of renal tubular dysfunction in ADV-treated or TDF-treated patients with CHB estimated a 10-year cumulative rate of renal tubular dysfunction of 15%.19 However, only 4 of 51 patients in this study were treated with TDF, limiting its conclusion regarding TDF. Published studies of renal events in CHB patients treated with TDF currently include: patients receiving TDF in combination with other nucleoside analogue, patients with significant preexisting renal insufficiency, and patients with high risk for renal impairment such as liver and kidney transplant patients.19,20 The goal of this study is to evaluate the incidence and magnitude of decrease in renal function among Asian American patients with CHB treated with TDF 300 mg daily.
Volume 49, Number 10, November/December 2015
www.jcge.com |
Copyright r 2015 Wolters Kluwer Health, Inc. All rights reserved.
873
J Clin Gastroenterol
Ha et al
METHODS
Volume 49, Number 10, November/December 2015
This study was approved by the institutional review board at Stanford University (Stanford, CA).
Study Design We performed a matched case-cohort study of 103 consecutive CHB patients who were initiated on TDF 300 mg daily monotherapy and 103 consecutive CHB patients treated with ETV monotherapy at 2 communitybased gastroenterology clinics, 1 community hospital, and 1 tertiary medical center in the United States from January 2008 to May 2012. Patients were identified through electronic query using ICD-9 diagnosis codes for CHB and medical records were reviewed for patients treated with TDF or ETV. We queried and compiled a list of consecutive patients on TDF or ETV from January 2008 to May 2012 and abstracted only their age, sex, baseline serum Cr level, and weight. Matching of the ETV group to TDF group was based only on selected factors. Complete data abstraction were not done until all patients were matched. There was a 1:1 match of 103 cases and 103 controls. Cases were treatment-naive patients started with TDF 300 mg daily monotherapy with baseline estimated glomerular filtration rate (eGFR)Z50 mL/min. Controls were patients treated with ETV 0.5 or 1.0 mg daily monotherapy with baseline eGFRZ50 mL/min. Cases and controls were matched by their baseline characteristics including age ( ± 10 y), sex, and baseline eGFR classification (unimpaired: eGFRZ80 mL/min or mildly impaired: 50 mL/min < eGFR < 80 mL/min). The inclusion of patients treated with 1 single alternative agent as a control group was to avoid unnecessary heterogeneity in the comparison. Untreated patients were not selected as controls as they generally would not have regular laboratory monitoring that includes renal parameters. ETV was chosen as it is the other most commonly used antiviral therapy in our clinics and it has not been known to be associated with renal dysfunction. Patients with baseline eGFR < 50 mL/min, those with prior exposure to ADV or TDF, or those with TDF combination therapy were excluded from this study. Patients who had coinfection with hepatitis C virus (HCV), hepatitis D virus (HDV), and/or HIV were also excluded from this study.
Renal Classifications All available medical records were evaluated thoroughly and data were recorded using a case report form developed for this study. Renal function was monitored every 3 to 6 months in most patients and there were no significant differences in the frequencies of renal function tests between the cases and controls. Patient’s eGFR was calculated using the CockcroftGault formula ((140 age)(Wt in kg)(0.85 if female)/ (72Cr)) and the Modification of Diet in Renal Disease (MDRD) formula (170 (Cr 0.999)*(Age 0.176)(0.762 if Female)(1.180 if African American)(BUN 0.170) (Albumin0.318)). Patients were followed-up approximately every 6 months. Classification of eGFR is as follows: unimpaired (eGFR > 80 mL/min), mildly impaired (50 mL/ minreGFRr80 mL/min), moderately impaired (30 mL/ minreGFR < 50 mL/min), and severely impaired (eGFR < 30 mL/min). Incidence density analysis was performed to compare incidence of renal dysfunction in cases versus controls. Exposed time was measured in person-years. Date of entry was determined by baseline date, and date of exit was defined by treatment termination or termination of this study.
Laboratory Tests Laboratory tests were performed at one of the local community clinical laboratories operated by either Quest Diagnostics (San Juan Capistrano, CA) or LabCorp (Burlington, NC). Cirrhosis was defined by the presence of stage4 fibrosis on histology or by the presence of portal hypertension (platelet 0.0001 0.665 0.192 0.999 0.010 0.829 0.489
*Model inclusive of age, sex, presence of hypertension, presence of diabetes mellitus, presence of mild renal impairment at baseline (50 mL/minreGFRr80 mL/min), presence of cirrhosis, and therapy with TDF. CI indicates confidence interval; eGFR, estimated glomerular filtration rate; HR, hazard ratio; TDF, tenofovir.
mild renal impairment at baseline, rather than antiviral therapy (TDF or ETV), were significant independent predictors for a significant decline in renal function. When examining magnitude of decrease in eGFR, there was no significant difference in the cumulative incidence of patients with decrease in eGFR of Z20% using KaplanMeier survival analysis. A similar study found that there was no significant difference in the proportion of patients with decrease in eGFR of Z20%.20 A decrease in eGFR of Z20% resulted in treatment discontinuation of 2 patients in the TDF cohort versus none in the ETV cohort. Both patients that required treatment discontinuation had mildly impaired renal function at baseline, which may have contributed to their treatment discontinuation. TDF exposure was not a significant predictor for a decrease in eGFR of Z20%. There were limitations to this study. The follow-up duration was different between exposed versus control groups. However, incidence density and Kaplan-Meier survival analysis were used to account for the differences in exposure time between the 2 cohorts. There were also strengths in this study. All patients in the exposed cohort were only exposed to TDF and not in combination with any other anti-HBV medications. No patients in this study had significant preexisting renal disease and/or prior history of liver or kidney transplantation. In conclusion, we did not observe a significant difference in the proportion of patients reclassified to a more severe renal function classification or in the proportion of patients who experienced a decrease in eGFR of Z20% in those exposed to TDF versus ETV. However, renal function in patients treated with TDF should be monitored closely, especially in patients with preexisting renal dysfunction. Older age and preexisting renal impairment including mild cases independently predicted significant worsening of renal function in CHB patients but not TDF or ETV. REFERENCES 1. McMahon BJ. Chronic hepatitis B virus infection. Med Clin North Am. 2014;98:39–54. 2. Lok AS, McMahon BJ. Chronic hepatitis B: update 2009. Hepatology. 2009;50:661–662. 3. Keeffe EB, Dieterich DT, Han SH, et al. A treatment algorithm for the management of chronic hepatitis B virus infection in the United States: 2008 update. Clin Gastroenterol Hepatol. 2008;6:1315–1341. quiz 1286. 4. Gallant JE, Moore RD. Renal function with use of a tenofovircontaining initial antiretroviral regimen. AIDS. 2009;23:1971–1975.
Copyright
r
5. Ha NB, Garcia RT, Trinh HN, et al. Renal dysfunction in chronic hepatitis B patients treated with adefovir dipivoxil. Hepatology. 2009;50:727–734. 6. Horberg M, Tang B, Towner W, et al. Impact of tenofovir on renal function in HIV-infected, antiretroviral-naive patients. J Acquir Immune Defic Syndr. 2010;53:62–69. 7. Perazella MA. Drug-induced renal failure: update on new medications and unique mechanisms of nephrotoxicity. Am J Med Sci. 2003;325:349–362. 8. Peyriere H, Reynes J, Rouanet I, et al. Renal tubular dysfunction associated with tenofovir therapy: report of 7 cases. J Acquir Immune Defic Syndr. 2004;35:269–273. 9. Earle KE, Seneviratne T, Shaker J, et al. Fanconi’s syndrome in HIV + adults: report of three cases and literature review. J Bone Miner Res. 2004;19:714–721. 10. Gaspar G, Monereo A, Garcia-Reyne A, et al. Fanconi syndrome and acute renal failure in a patient treated with tenofovir: a call for caution. AIDS. 2004;18:351–352. 11. Malik A, Abraham P, Malik N. Acute renal failure and Fanconi syndrome in an AIDS patient on tenofovir treatment—case report and review of literature. J Infect. 2005;51:E61–E65. 12. Quimby D, Brito MO. Fanconi syndrome associated with use of tenofovir in HIV-infected patients: a case report and review of the literature. AIDS Read. 2005;15:357–364. 13. Gitman MD, Hirschwerk D, Baskin CH, et al. Tenofovirinduced kidney injury. Expert Opin Drug Saf. 2007;6:155–164. 14. Gilead Sciences Inc., Viread (tenofovir disoproxil fumarate) prescribing information. 2013. 15. Hall AM, Hendry BM, Nitsch D, et al. Tenofovir-associated kidney toxicity in HIV-infected patients: a review of the evidence. Am J Kidney Dis. 2011;57:773–780. 16. Ortiz A, Justo P, Sanz A, et al. Tubular cell apoptosis and cidofovir-induced acute renal failure. Antivir Ther. 2005;10: 185–190. 17. Tanji N, Tanji K, Kambham N, et al. Adefovir nephrotoxicity: possible role of mitochondrial DNA depletion. Hum Pathol. 2001;32:734–740. 18. Bendele RA, Richardson FC. Adefovir nephrotoxicity and mitochondrial DNA depletion. Hum Pathol. 2002;33:574. 19. Gara N, Zhao X, Collins MT, et al. Renal tubular dysfunction during long-term adefovir or tenofovir therapy in chronic hepatitis B. Aliment Pharmacol Ther. 2012;35:1317–1325. 20. Gish RG, Clark MD, Kane SD, et al. Similar risk of renal events among patients treated with tenofovir or entecavir for chronic hepatitis B. Clin Gastroenterol Hepatol. 2012;10:941–946. quiz e968. 21. Padilla S, Gutierrez F, Masia M, et al. Low frequency of renal function impairment during one-year of therapy with tenofovir-containing regimens in the real-world: a case-control study. AIDS Patient Care STDS. 2005;19:421–424. 22. Antoniou T, Raboud J, Chirhin S, et al. Incidence of and risk factors for tenofovir-induced nephrotoxicity: a retrospective cohort study. HIV Med. 2005;6:284–290.
2015 Wolters Kluwer Health, Inc. All rights reserved.
www.jcge.com |
Copyright r 2015 Wolters Kluwer Health, Inc. All rights reserved.
877
