Observational study of factors affecting Tacrolimus trough level in renal transplant patients
Hinal Rathod1, Ankita Metaliya1, Priyanka Lawngani1, M M Bahadur1, Ashay Shinagare1.
1Nephrology, Jaslok Hospital And Research Centre, Mumbai, India
Objective: Calcineurin inhibitors are widely used immunosuppressive drugs in various organ transplant patients including renal transplant patients.out of which Tacrolimus is commonly used in today’s era to for prevention of organ rejection.Use of Tacrolimus is complicated by its narrow therapeutic index which require frequent drug level monitoring in transplant patients.This study is aimed to determine the clinical and genetic factors affecting the Tacrolimus trough concentration in renal transplant patients ,hence to predict the proper dose of Tacrolimus to be given without over or under immunosuppression in post operative period.which will be helpful to stabilise the graft function in renal transplant patients.
Method: We enrolled the renal transplant patients as per inclusion and exclusion criteria described below.patients were followed up for 3 months with frequent blood reports as well as clinical monitoring.
Inclusion criteria:
(1) Age > 18 years
(2) patients undergoing deceased as well as live renal transplant
(3) patient with given consent to do follow up as required
Exclusion criteria:
(1) patients with combined organ transplant
(2) patients with liver disorders
Results: Tacrolimus trough concentrations were measured on post operative day 3,7,1st month and 3rd month for each recipient after renal transplantation.CYP3A5*GG carriers get the highest blood concentrations with the standard dose regimen.they were then treated with a continuously decreased dose .Regarding CYP3A5*AA/AG carriers, blood concentration of Tacrolimus was considerably lower then CYP3A5*GG patients.Patients with CYP3A5*AA variant had lowest Tacrolimus trough levels overall and require much high dose to maintain trough level compared to other patients.The frequency of these patient is low overall in study group.Along with the type of genotype we have studied other clinical factors also that affect the Tacrolimus levels in renal transplant patients.
Conclusion: A standard dose regimen as we follow in transplant patients based on body weight is not sufficient to maintain target trough level especially during early post operative period in renal transplant patients.Genotype pattern as well as various clinical parameters can cause inter individual variability in Tacrolimus drug concentration in renal transplant patients.During prescribing the dose we should consider all these parameters to adjust proper dose of Tacrolimus ,so that we can avoid CNI toxicity as well as dose sufficient to prevent rejection and can maintain stable graft function.