Are There Differences in the Development of Proteinuria after Everolimus Initiation and Calcineurin Withdrawal or Not in Heart Transplantation?

Abstract

Purpose Proliferation signal inhibitors(PSI) used after heart transplantation(HT) are useful in long-term complications. Proteinuria associated with use of PSI and possible deterioration of renal function may be related to use of calcineurin inhibitors (CNI). Purpose To determine the incidence of proteinuria after 1year of initiation everolimus (EVE) and analyze its relationship with CNI withdrawal and type of CNI. Methods and Materials Retrospective study of 54HT patients receiving EVE in late phase. 4patients were excluded due to basal pathological proteinuria and 7patients for CNI reintroduction. Immunosuppression was Cyclosporine (CyA) vs Tacrolimus (FK), MMF vs Azathioprine and prednisone. Proterinuria was determined using urine dipstick method and value Results 43HT patients analyzed(91% men, mean age 61±11 years), mean time between HT-EVE starting 5,5±4,8 years, CNI was discontinued in 10patients. Mean time of CNI withdrawal 24.7±17,4 days. Mean initial proteinuria(pre-EVE): 13’1 mg/dl(1,5-29,8). Incidence of proteinuria after EVE starting in patients with CNI/non-CNI at 3, 6 and 12 months was: 6(18%)/2(20%); 7(21%)/2(22%); 10(31%)/5(56%),p=NS; and with a median of 15,5(4-93)/25’5 (4-61); 15(7-53)/14(4-98); 19(7,7-93)/27(5-132), p=NS. Regarding to the CNI type (n=33; CyA12 and FK21), the incidence of proteinuria at 3,6 and 12 months in patients with CyA/FK was: 3(25%)/3(14%); 3(25%)/4(19%); 4(33%)/6(30%); and with a median of 19(8-33)/15(4-93); 14(9-52)/18(7-48); 22(8-92)/16(8-64), p=NS. Conclusions Incidence of proteinuria after 1year of EVE initiation in long-term HT is 34,8%. Combination of CNI with EVE does not increase significantly the development of proteinuria, although an increasing trend in the CNI withdrawal is observed. Comparison between CyA/FK also showed no significant differences. Further studies are needed to corroborate this hypothesis.