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Randomized Controlled Trial
. 2013 Oct 11;8(10):e75591.
doi: 10.1371/journal.pone.0075591. eCollection 2013.

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

Dinesh Bansal  1 , Ashok K Yadav, Vinod Kumar, Mukut Minz, Vinay Sakhuja, Vivekanand Jha
Affiliations
Randomized Controlled Trial

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

Dinesh Bansal et al. PLoS One. .

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).

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Conflict of interest statement

Competing Interests: The authors have the following interests. The study was funded by Biocon Nephrology. The following drugs used in this study are manufactured by Biocon: Tacrograf, Cyclophil ME, and mycophenolate mofetil. There are no further patents, products in development or marketed products to declare. This does not alter the authors' adherence to all the PLOS ONE policies on sharing data and materials, as detailed online in the guide for authors.

Figures

Figure 1
Figure 1. Study design, randomization, and follow up.
Figure 2
Figure 2. Graph showing estimated glomerular filtration rate (mL/min/1.73 m2) at different time points in the two groups.
Patients in the SIR group showed a significant improvement in GFR over baseline, and the difference between groups was significant at 6 months.
Figure 3
Figure 3. A. Dot plot showing analysis of (Treg) by flowcytometry and B. Graph showing Treg number and frequency at different time points in the study in the two groups.
Compared to baseline, SIR group showed higher Treg number and frequency at all time points whereas there was no change in the CNI group. Compared to CNI group, SIR group showed higher Treg number and frequency.
See this image and copyright information in PMC

References

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