POS-753 LONG TERM BENEFITS OF PRESERVED GRAFT FUNCTIONS AFTER LATE WITHDRAWAL OF CALCINEURIN INHIBITORS IN LIVE DONOR KIDNEY TRANSPLANT RECIPIENTS.

Abstract

With the use of calcineurin inhibitors (CNI) and induction therapy , graft survival has reached over 90% at 1 year. Despite short and medium term improvement , long term graft survival has not shown proportionate improvement. There is debate about role of CNI induced nephrotoxicity and long term graft dysfunction and there is no uniformity in renal outcome after CNI minimization or withdrawal 1 year after transplantation, especially in live donor transplants and well matched kidneys. This retrospective data analyses the long term outcome of patient and graft survival after CNI withdrawal from triple drug therapy of CNI, prednisolone and azathioprine /mycophenolate mofetyl (MMF) Twenty two adults (M:F- 16: 6) who had kidney from live donor and no rejections with stable renal function at one year after transplant were evaluated in this retrospective study. 6 recipients for financial reasons opted for CNI withdrawal which was done over 8 weeks. In the transition period prednisolone and azathioprine dose was stepped up. In another 12 patients CNI was withdrawn over 1-2 years post transplantation for gradually rising serum creatinine. In the remaining 4 patients CNI was withdrawn after graft biopsy revealed no evidence of rejection and histological changes suggestive of CNI toxicity,48-140 months( mean 90 +/-40) after transplant.Patients were followed up regularly for estimation of renal functions. Withdrawal of CNI after 12 months and even in late withdrawal did not result in graft rejection and all patients tolerated the intervention well. At time of early withdrawal at 12 months in 6 patients(Group A) serum creatinine ranged from 1.12 –1.6 mg/dl (Mean1.28 +/-0.16) and eGFR of 65.16 +/-12.81ml/mt. In12 patients (Group-B) in whom CNI was withdrawn between12-24 months serum creatinine ranged from 1.3-1.75 mg/dl (mean 1.51+/- 0.15) and eGFR 56.16 +/-7.1 ml/mt. In remaining 4 patients (group 3) who had evidence of toxicity,CNI was withdrawn 48 to140 months after transplant.Their serum creatinine was1.3 -1.75 mg/dl (mean 1.57+/-0.19) and eGFR 47+/-7.63ml/mt. At the end of follow up ranging from 60-348 months (mean 170+/-72 months ) all the patients had well preserved renal functions with their mean GFR of 65, 56 and 47 ml/mt in respective group with serum creatinine1.02 to 5.2 mg/dl (mean 1.86 +/- 0.99) There were 9 deaths after a follow up of 82-300 months (mean 200 +/- 75.2 )months.Three patients had carcinoma tongue of whom one had achieved prolonged remission after therapy but during follow up along with 2others reached ESRD and were initiated on hemodialysis.Cardiovascular events in 3 and infections in other 2 patients accounted for their mortality. Recipients of kidney from live donors with at least 1 haplo match and who did not have rejections in the1st year of transplant had excellent long term graft survival with 2 drugs only without CNI.In selected live donor transplant recipients who do not have rejection in first year calceinurin inhibitors can safely be withdrawn at least one year after transplant which helps in ameliorating CNI induced renal injury and prevents further deterioration of renal functions. In patients with graft dysfunction with histological features of CNI toxicity this beneficial effect of CNI withdrawal can sometimes be seen even many years after transplantation.