Abstract: SA-PO288
ARF Caused by Tacrolimus Nephrotoxicity Due to Enhanced Absorption Mediated by Ledipasvir Inhibition of Gut Permeability-Glycoprotein
Session Information
- Trainee Case Reports - VI
October 27, 2018 | Location: Exhibit Hall, San Diego Convention Center
Abstract Time: 10:00 AM - 12:00 PM
Category: Trainee Case Reports
- 103 AKI: Mechanisms
Authors
- Khan, Usman A., University of Oklahoma Health Science Center, Oklahoma City, Oklahoma, United States
- Lau, Kai, University of Oklahoma Health Sciences Center, Oklahoma cty, Oklahoma, United States
- Syed, Taseen Ahmed, University of Oklahoma Health Sciences Center, Oklahoma cty, Oklahoma, United States
- Khakwani, Aemen Shams, University of Oklahoma Health Sciences Center, Oklahoma city, Oklahoma, United States
Introduction
Recently discovered Novel Direct-acting antivirals (DAA’s) have completely changed the spectrum of Hep.C treatment with multiple studies showing sustained virological response of over 90% in many genotypes.Treatment of hepatitis C with DAA’s in renal transplant has been associated with nephrotoxicity at the pharmacodynamic level due to indirect interaction with immunosuppressive medications especially tacrolimus.We report a case of acute renal failure from increased tacrolimus plasma levels secondary to Harvoni mediated inhibition of gut permeability- glycoprotein.
Case Description
65-yo M with a h/o renal transplant for ESRD due to DM and HTN and hep.C being treated with Harvoni (ledipasvir/sofosbuvir) was admitted for incidental ARF when presented initially for lesions on his AVF.His immunosuppression was tacrolimus 5 mg q 12 h and MMF 1 g bid.Physical exam was within normal limits.Lab was remarkable for an acute bump in Cr from his baseline of 1.5 to 2.1 mg%, along with blood tacrolimus level of 14 ng/ml.There were no identifiable nephrotoxic insults or medications.The clinical diagnosis of tacrolimus nephrotoxicty was made and was attributed to excessive gut tacrolimus absorption because ledipasvir is known to inhibit the gut p-Glycoprotein which normally limits the absorption of tacrolimus.His dose was gradually reduced from the home regimen of 5 mg bid to 2 mg bid,with a subsequent drop in his tacrolimus levels and recovery of serum creatinine to baseline of 1.5 mg% at a tacrolimus level of 7.8 ng/ml.After resolution of his ARF, he was discharged on 2 mg bid with the target tacrolimus level 6-8 ng/ml while he was still getting Harvoni.After the completion of his 12-week course of Harvoni,he was put back on a higher dose of tacrolimus,to avoid allograft rejection due to inadequate tacrolimus level secondary to the sudden drop in gut absorption without ledipasvir.
Discussion
Emerging DAAs seem to have a reduced potential for drug interactions, which will facilitate their use in the treatment of HCV in renal transplant patient.Close monitoring and dose titration of immunosuppressive medication especially Tacrolimus in renal transplant HCV infected patients being treated with DAA’s is important to prevent Nephrotoxicity from higher plasma levels and renal rejection from lower plasma levels of tacrolimus.