Correlation of Base-Line Trough Tacrolimus Level With Early Rejection

The study was done at Muljibhai Patel Urological Hospital, Nadiad, Gujarat. It is a tertiary health care centre, for nephrology, with a well established hemodialysis unit. We have done about 1950 renal transplantation so far. Acute rejection is the most significant risk factor for chronic rejection and potential surrogate for longterm graft failure. Aim of our study was to analyze the association between the baseline through (C0) tacrolimus level in the first day post transplant, with early rejection in living donor transplants [110].


Data collection technique and tools
Demographic, baseline characteristics and outcome characteristics were collected throughout the first year posttransplant. Demographic data included donor and recipient age, gender, relation and underlying native kidney disease. Baseline transplant information included induction used, anti-proliferative used, number of HLA mismatches, graft renal artery number(single or dual), WIT and CIT. Data on complications was also collected including post transplant rejections, surgical complications, infections, liver dysfunctions, PTDM, TAC nephrotoxicity, and delayed graft functions (DGF). DGF was defined as need for dialysis in the first week post-transplant. PTDM was defined as requirement for oral hypoglycemic agents or insulin for the first time post-transplant. The outcome was assessed on the incidence and severity of acute rejection in correlation to base-line trough tacrolimus level measured on day 0 of transplantation. The sideeffects of the immunosuppressive therapy was also assessed in the form of; episodes of post-transplant infection and their severity; liver dysfunction; PTDM and its severity (transient or persistent; requiring OHAs or insulin) [31-40].

Data Analysis
Simple statistical tools were used for calculating demographic parameters. The difference between the two group means was tested using Student's t-test and the presence of episode within two groups by 2x2 Chi-square test. SPSS version 15.0 was used to carry the logistic regression analysis and to find the Pearson's correlation coefficients [41][42][43][44][45][46][47][48][49][50].      Our study showed a significant reduction in the incidence of early rejection as the baseline (pre-transplant) trough tacrolimus level increases. Patients in Group 3 had significantly lower rate of biopsy proven rejections than Group 1 (p=0.001). It also shows that with higher trough level severity of rejection also reduces and that there was no severe TIR and antibody mediated rejection when trough level was >15ng/ml [51][52][53][54][55][56][57][58][59][60].

Conclusion
i.
Incidences of early rejection reduces as the pretransplant trough tacrolimus level increases [71] ii.
With higher trough level severity of rejection also reduces and we did not encounter any severe TIR or antibody mediated rejection when trough level was >15ng/ml [72] iii. NOD was not different among various trough levels and trend towards higher nephrotoxicity with higher trough levels [73] iv. Only 18 % could achieve the trough level of >15ng/ml [74,75]

Recommendation
Our results suggest that targeting baseline (pretransplant) trough (T0) tacrolimus levels similar to those seen in Group 3 (>15ng/ml) immediately post-transplant can yield extremely low ACR rates in the long term. Thus, we propose that a target baseline trough tacrolimus levels similar to that seen in Group 3 would achieve the optimal balance between efficacy and toxicity.