Randomized Controlled Trial
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World J Nephrol. Aug 6, 2014; 3(3): 107-113
Published online Aug 6, 2014. doi: 10.5527/wjn.v3.i3.107
Long-term outcome of ketoconazole and tacrolimus co-administration in kidney transplant patients
Enver Khan, Mary Killackey, Damodar Kumbala, Heather LaGuardia, Yong-Jun Liu, Huai-Zhen Qin, Brent Alper, Anil Paramesh, Joseph Buell, Rubin Zhang
Enver Khan, Mary Killackey, Damodar Kumbala, Heather LaGuardia, Yong-Jun Liu, Huai-Zhen Qin, Brent Alper, Anil Paramesh, Joseph Buell, Rubin Zhang, Section of Nephrology, Department of Medicine, New Orleans, LA 70112, United States
Author contributions: Khan L, Killackey M, Kumbala D and LaGuardia H participated in data collection; Liu YJ and Qin HZ participated in data analysis; Alper B, Paramesh A and Buell J participated in editing; Zhang R participated in research design and writing.
Correspondence to: Rubin Zhang, MD, FASN, Professor of Clinical Medicine, Section of Nephrology, Department of Medicine, 1430 Tulane Ave, Box SL-45, New Orleans, LA 70112, United States. rzhang@tulane.edu
Telephone: +1-504-9881457 Fax:+1-504-9881105
Received: April 4, 2014
Revised: June 25, 2014
Accepted: July 27, 2014
Published online: August 6, 2014
Processing time: 198 Days and 9.3 Hours
Abstract

AIM: To study the long-term outcome of ketoconazole and tacrolimus combination in kidney transplant recipients.

METHODS: From 2006 to 2010, ketoconazole was given in 199 patients and was continued for at least 1 year or until graft failure (Group 1), while 149 patients did not receive any ketoconazole (Group 2). A combination of tacrolimus, mycophenolate and steroid was used as maintenance therapy. High risk patients received basiliximab induction.

RESULTS: Basic demographic data was similar between the 2 groups. The 5-year cumulative incidence of biopsy-confirmed and clinically-treated acute rejection was significantly higher in Group 1 than in Group 2 (34% vs 18%, P = 0.01). The 5-year Kaplan-Meier estimated graft survival (74.3% vs 76.4%, P = 0.58) and patient survival (87.8% vs 87.5%, P = 0.93) were not different between the 2 groups. Multivariable analyses identified ketoconazole usage as an independent risk of acute rejection (HR = 2.33, 95%CI: 1.33-4.07; P = 0.003) while tacrolimus dose in the 2nd month was protective (HR = 0.89, 95%CI: 0.75-0.96; P = 0.041).

CONCLUSION: Co-administration of ketoconazole and tacrolimus is associated with significantly higher incidence of acute rejection in kidney transplant recipients.

Keywords: Kidney transplant; Rejection; Survival; Tacrolimus Ketoconazole; Pharmacokinetics; Cytochrome P450

Core tip: Tacrolimus is mainly metabolized by cytochrome P450 enzymes and ketoconazole is a potent inhibitor of P450. Transplant programs often use ketoconazole to reduce the tacrolimus dose and financial cost. Small short-term studies had previously supported such practice, but the long-term outcome are still lacking. We hereby report our center’s experience of this combination in kidney transplant recipients. Our study suggests that co-administration of ketoconazole and tacrolimus is associated with significantly higher incidence of acute rejection in kidney transplant recipients.