Comparison of Tacrolimus with everolimus or Mycophenolate mofetil or Steroid regimen and their association with Tryptophan metabolism :A Pilot study

An abstract article submitted at ASN 2016 for a pilot study. I performed the Tryptophan metabolism using qRT-PCR for the department of nephrology.

Background: Assess graft survival and safety profile at one year. Explore Tryptophan metabolism pathway as a clinical tool to predict graft survival.

Methods: All patients received induction therapy with thymoglobulin(3mg/kg). They received Tacrolimus, mycophenolate mofetil, steroid and were randomised into three groups at the end of 3 months. Group 1 (control) patients received Tacrolimus /Mycophenolate/Steroid. Group 2: Tacrolimus/Mycophenolate Mofetil/Everolimus and group 3: Tacrolimus/Everolimus/Steroid. Patients were assessed with RFT, Hemogram, Urine R/M, Lipid profile, Blood Sugar levels, Serum Tacrolimus/ Everolimus levels. Adverse events such as anaphylaxis, life-threatening infections were noted. Tryptophan metabolite measurement was done using Quantitative real-time RT-PCR.

Results: Graft survival at one year: Control group 1: 7/11 patients had stable graft outcomes, 1 patient had ATN & 3 were lost to follow-up. Group 2:4/ 6 patients had stable graft outcomes & 2 had ATN. Group 3: 4/7 patients had stable graft outcome, 1 had ACR+ AMR. Safety: No patient had serious adverse events. One patient with Dyslipidemia was reported in each of the Groups 2 & 3. Furunculosis was noted more in group 3. Tryptophan metabolism enzyme levels: Control Group: No changes were seen in various enzymes levels for the 9 patients available. Group 2 & Group 3: Various enzymes showed low expression, but no association was observed with graft survival. Low expression of IDO 1 was observed in 5 patients out of which 4 patients were associated with stable graft outcome & 1 with graft dysfunction. No significant difference was observed in drug levels, Haemoglobin, Creatinine, TLC, Platelets, Triglycerides & Total Cholesterol levels among different groups (p= NS)

Conclusions: The larger study is needed to establish the role of Tryptophan metabolising enzyme as a predictive biomarker for graft survival. IDO 1 may possibly show some association. Corticosteroid-sparing immunosuppressant regimen(Tac+MMF+EVE) appear to be safe as compared to Steroid containing immunosuppressant regimens (Tac+MMF+Steroid/Tac+EVL+ Steroid)


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