Calcineurin Inhibitor–Free Immunosuppression in Renal Transplantation

Abstract

Purpose. To describe our initial results using a calcineurin inhibitor-free immunosuppression protocol in renal transplants. Patients and methods. Between October 2001 and June 2003, 56 recipients of a renal allografts were started on an immunosuppression protocol without calcineurin inhibitors, consisting of basiliximab, sirolimus, mycophenolate mofetil, and steroids. We analyzed patient and graft survival, acute rejection episodes, and renal function. Results. The mean follow-up was 19.6 months. Actuarial patient survival at 1 and 2 years was 98.1% and 95.3%, respectively. Actuarial graft survival at 1 and 2 years was 92.9% and 87.6%, respectively. Acute rejection occurred in 27.8% of the patients, usually Banff 1 (73.3%). There was stable renal function with mean serum creatinine of 1.3, 1.4, 1.3, and 1.3 mg/dL at 1, 6, 12, and 24 months after transplant. Conclusions. The use of immunosuppression free of calcineurin inhibitors is effective and safe. Further follow-up is needed to evaluate the impact on long-term results.K IDNEY TRANSPLANT OUTCOMES have steadily improved over the past decade 1 due to modern immunosuppression protocols and better prophylaxis and treatment of common posttransplant infections. 2 The introduction of calcineurin inhibitors (CNIs)-cyclosporine (CsA) and tacrolimus (Tac)-in the last two decades has resulted in a significant decrease in acute rejection and an improvement in short-term graft survival 3 with most centers now achieving 85% to 90% 1-year graft survival. 4 However, long-term graft loss due to chronic allograft nephropathy (CAN) remains a major problem in renal transplantation. 5 While there appear to be many contributors to CAN, many studies emphasize the nephrotoxicity associated with CNIs. 6 -8 Several studies of CNI-free immunosuppression 2,9 -13 or early CsA withdrawal 14 -16 have been reported, with good patient and graft survival and without drug-induced nephrotoxicity. In this report, we describe our initial results using a CNI-free immunosuppression protocol in renal transplants. PATIENTS AND METHODSBetween October 2001 and June 2003, 56 recipients of a first renal allograft were enrolled in this prospective study, which had obtained local ethics committee approval and written informed consent from each patient. Exclusion criteria consisted of prior transplantation or exposure to immunosuppressants, type I diabeties, severe hyperlipidemia prior to transplantation (serum cholesterol level greater than 350 mg/dL or serum triglycerides over 400 mg/dL), white blood cells less than 3000/mm 3 , or platelets less than 100,000/mm 3 .Immunosuppressive protocol included basiliximab 20 mg (days 0 and 4), mycophenolate mofetil (1 g two times per day), steroids, and sirolimus (5 mg daily after a 20 mg loading dose). Sirolimus doses were then adjusted to achieve target through levels between 10 and 15 ng/mL for 6 months and 5 to 10 ng/mL thereafter. All clinical rejections were biopsy-proven and Banff scored prior to initiation of therapy with high-dose steroids. Prim...

Cyclosporine Withdrawal Improves Renal Function in Heart Transplant Patients on Reduced-Dose Cyclosporine Therapy

“…The present study shows that CNI‐free immunosuppression is safe, relatively well tolerated and results in improved renal function as shown by decrease of serum creatinine and increase of calculated creatinine clearance. This is in line with similar studies in renal transplant patients (20,21) and case reports and uncontrolled retrospective data analyses in cardiac transplant recipients (13–15,22) previously on full‐dose CsA regimen. It furthermore emphasizes the fact that even though patients switched to low‐dose CNI therapy show improvement of renal function as compared to standard‐dose CNI immunosuppression, complete cessation of CsA medication improves renal function even further suggesting the absence of a CNI nephrotoxicity ‘threshold’ effect.…”