Deferred pre-emptive switch from calcineurin inhibitor to sirolimus leads to improvement in GFR and expansion of T regulatory cell population: a randomized, controlled trial
Author(s)
Type
Journal Article
Abstract
BACKGROUND: Measures to prevent chronic calcineurin inhibitor (CNI) toxicity have included limiting exposure by switching to sirolimus (SIR). SIR may favorably influence T regulator cell (T(reg)) population. This randomized controlled trial compares the effect of switching from CNI to SIR on glomerular filtration rate (GFR) and T(reg) frequency. METHODS: In this prospective open label randomized trial, primary living donor kidney transplant recipients on CNI-based immunosuppression were randomized to continue CNI or switched to sirolimus 2 months after surgery; 29 were randomized to receive CNI and 31 to SIR. All patients received mycophenolate mofetil and steroids. The main outcome parameter was estimated GFR (eGFR) at 180 days. T(reg) population was estimated by flowcytometry. RESULTS: Baseline characteristics in the two groups were similar. Forty-eight patients completed the trial. At six months, patients in the SIR group had significantly higher eGFR as compared to those in the CNI group (88.94 ± 11.78 vs 80.59 ± 16.51 mL/min, p = 0.038). Patients on SIR had a 12 mL/min gain of eGFR of at the end of six months. Patients in the SIR group showed significant increase in T(reg) population at 30 days, which persisted till day 180. There was no difference in the adverse events in terms of number of acute rejection episodes, death, infections, proteinuria, lipid profile, blood pressure control and hematological parameters between the two groups. Four patients taking SIR developed enthesitis. No patient left the study or switched treatment because of adverse event. CONCLUSIONS: A deferred pre-emptive switch over from CNI to SIR safely improves renal function and T(reg) population at 6 months in living donor kidney transplant recipients. Registered in Clinical Trials Registry of India (CTRI/2011/091/000034).
Date Issued
2013-10-11
Online Publication Date
2020-08-05T09:18:42Z
Date Acceptance
2013-08-09
ISSN
1932-6203
Publisher
Public Library of Science (PLoS)
Journal / Book Title
PLoS One
Volume
8
Issue
10
Copyright Statement
© 2013 Bansal et al. This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.
License URI
Identifier
https://www.ncbi.nlm.nih.gov/pubmed/24146762
PONE-D-13-16968
Subjects
Adult
Calcineurin
Calcineurin Inhibitors
Cell Proliferation
Drug Substitution
Enzyme Inhibitors
Female
Glomerular Filtration Rate
Humans
Immunosuppressive Agents
Kidney
Kidney Transplantation
Living Donors
Male
Mycophenolic Acid
Prospective Studies
Sirolimus
T-Lymphocytes, Regulatory
Time Factors
Kidney
Humans
Mycophenolic Acid
Sirolimus
Calcineurin
Immunosuppressive Agents
Enzyme Inhibitors
Glomerular Filtration Rate
Kidney Transplantation
Prospective Studies
Cell Proliferation
Time Factors
Adult
Living Donors
Female
Male
T-Lymphocytes, Regulatory
Drug Substitution
Calcineurin Inhibitors
Adult
Calcineurin
Calcineurin Inhibitors
Cell Proliferation
Drug Substitution
Enzyme Inhibitors
Female
Glomerular Filtration Rate
Humans
Immunosuppressive Agents
Kidney
Kidney Transplantation
Living Donors
Male
Mycophenolic Acid
Prospective Studies
Sirolimus
T-Lymphocytes, Regulatory
Time Factors
General Science & Technology
Publication Status
Published
Country
United States
Article Number
ARTN e75591