Inter-Individual Variability of Tacrolimus Tough Level May be Due to Differential P-glycoprotein Expression on PBMCs in Renal Transplant Recipient

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Abstract

Objective

Tacrolimus (TAC) is a most widely used immunosuppressive drug in transplantation. It is a challenging task for clinicians to achieve an optimal dose of TAC to reduce the chance of rejection and toxicity due to Inter-individual variability. The objective of this study was to evaluate the P-glycoprotein (P-gp) expression on PBMCs, CD4 and CD8 cells and correlate with Tacrolimus trough concentration whose pharmacokinetic characteristics display large inter-individual variations in renal allograft recipients.

Methods

We recruited 54 renal transplant recipients, of them 35 achieved (group A), 12 high (group B) and 6 low (group C) TAC level. All patients were on triple immunosuppressive TAC, MMF and prednisolone. TAC level, Dose adjusted Co, TAC dose given in. Those patients were administered with drugs which hinder TAC level was excluded. P-gp expression and functionality were analyzed on flowcytometer.

Results

Of the 54 patients, 29 had glomerulonephritis,19 had interstitial nephropathy, 5 had diabetic nephropathy and 1 had polycystic kidney disease.

Results

P-gp was significantly high in group B (p=0.049) and low in group C (p=0.236) as compared to group A. The relative fluorescence intensity (RFI) were significantly high in high Tac level (group B; p<0.001) compare to group A and C. When we analyze absolute P-gp expression we found significantly higher expression in group B (p=0.004) and lower in group C (p=0.032) than group A. The functionality of P-gp was also high in high Tac level group B (p=0.044) than that of low Tac level group C (p=0.064) in lymphocyte population.

Results

CD4+, CD8+ and CD4+/CD8+ ratio were slightly low in low Tac level group but there were not any significant difference in the groups (p 0.486, 0.087, 0.358 respectively). However, P-gp positivity on CD4+ and CD8+ cell were significantly high (p 0.043, 0.001 respectively) in high Tac level group than that of low Tac level group.

Conclusion

P-gp monitoring predicts the optimal dose of tacrolimus in renal transplant recipients and may predict the initial daily dose needed by individual patients to obtain adequate immunosuppression.

Conclusion

Indian Council of Medical Research, New Delhi, INDIA.

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