Efficacy and safety of early tacrolimus conversion to sirolimus after kidney transplantation: Long-term results of a prospective randomized study

Abstract

We report a prospective, open-label, randomized study to evaluate the safety and efficacy of converting patients with a stable renal function from tacrolimus (Tac)-based regimen to a sirolimus (SRL)-based regimen after kidney transplantation. Fifty-eight low-risk renal allograft recipients who receiving Tac 6 months posttransplant, were randomly assigned to continue Tac (n = 29) or convert to SRL (n = 29). We evaluated the 3-year outcomes including patient and graft survival, graft function, and safety profile. Three-year patient and graft survival in SRL and Tac groups were 93.1% versus 100% (P = 0.32), and 89.7% versus 100% (P = 0.11), respectively. However, the SRL group had a significantly better renal function, from the 2nd year posttransplant until the last follow-up. Four (13.8%) patients in the SRL group and 3 (10.3%) in the Tac group (P = 0.5) developed biopsy-proven acute rejection. Mean urinary protein excretion increased significantly after SRL conversion. Diastolic blood pressure was significantly lower at the end of the study in patients who eliminated Tac (80.4 vs. 75.6 mmHg in Tac and SRL group, respectively) (P = 0.03). Mean hemoglobin concentrations decreased after SRL conversion and remained significantly lower from 12 months to 36 months (P = 0.01). The mean serum cholesterol (540 ± 44 mg/dl) and triglyceride (177 ± 27 mg/dl) increased significantly in the SRL group, compared to Tac group (487 ± 62 mg/dl) (P = 0.03) and (141 ± 26 mg/dl) (P = 0.04). Our experience demonstrates that conversion to SRL from calcineurin inhibitors-based therapy may result in better renal function and blood pressure control in renal transplant recipients without an increased risk of acute rejection. However, these benefits have not resulted in a growing advantage in graft or patient survival.

Programmed Cell Death 1 (PD-1) Inhibitors in Renal Transplant Patients with Advanced Cancer: A Double-Edged Sword?

“…Calcineurin inhibitor (CNI) minimization or elimination is a critical strategy to decrease CNI toxicities, such as nephrotoxicity, the worsening risk of cardiovascular disease, new-onset diabetes, increased incidence of neoplasms, and viral infections. Some studies have demonstrated well-maintained graft functions without increased rates of graft rejection and failure after CNI elimination using sirolimus in kidney transplantation [37,38]. In addition, the mTOR signaling pathway plays a vital role in tumor initiation and progression.…”

Factors Contributing to Kidney Allograft Loss and Associated Consequences among Post Kidney Transplantation Patients

“…According to Liu et al [77]; El-Agroudy et al [85]; Shihab et al [20]; Thomas [10] calcineurin inhibitors (CNIs) used to prevent kidney rejection, may initially protect the renal transplant against immunologic injury but may subsequently cause damage as a result of long-term nephrotoxicity. According to these authors, the low early acute rejection rates achieved using CNIs are not accompanied by improvements in long-term outcomes.…”

Personalized dosing protocol for extended-release tacrolimus in kidney transplant recipients in the early postoperative period

“…Для решения данной задачи многими авторами предлагаются различные стратегии снижения нагрузки ингибиторов кальциневрина в раннем посттрансплантационном периоде. Одной из них является назначение низких доз такролимуса (с достижением целевой концентрации в пределах 3-8 нг/мл) в комбинации с ингибиторами mTOR сразу после трансплантации [10][11][12]. По нашему мнению, включение этих препаратов в иммуносупрессивные схемы отдаленного послеоперационного периода для снижения эффекта нефротоксичности CNI в ряде случаев безусловно оправдано, однако в первые дни после трансплантации использование ингибиторов mTOR может быть связано с повышенным риском раневых инфекционных осложнений.…”