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Volume: 2 Issue: 2 December 2004 - Supplement - 1

FULL TEXT

EARLY EXPERIENCE WITH SIROLIMUS CONVERSION IN RENAL TRANSPLANTATION

Calcineurin inhibitors have been used extensively in renal transplantation. Although highly effective, their nephrotoxicity may lead to graft dysfunction. Sirolimus is a nonnephrotoxic, potent immunosuppressive agent that blocks the G1 to S cell cycle by inhibiting signal transduction via a specific target protein. Sirolimus is useful in the initial immunosuppressive protocol or, as a conversion therapy, to treat chronic allograft nephropathy, calcineurin-inhibitor–related nephrotoxicity, and steroid-resistant rejection episodes after kidney transplantation. This study included 11 renal transplantation patients (7 men and 4 women; mean age, 34.4 years) in whom drug conversion had been implemented. We switched from a calcineurin inhibitor to sirolimus owing to chronic allograft nephropathy in 4 patients and to calcineurin-inhibitor–related nephrotoxicity in 7 patients. In chronic allograft nephropathy, the immunosuppressive protocol consisted of sirolimus (blood trough levels between 12-15 ng/mL) and prednisolone (10 mg/day). In all other cases, low-dose calcineurin inhibitors combined with low-dose sirolimus and prednisolone were used. For the tacrolimus and sirolimus combination, the sum of both drugs’ blood trough levels was kept between 12-15 ng/mL. For the cyclosporine and sirolimus combination, sirolimus blood trough levels were maintained between 8-12 ng/mL, and cyclosporine blood trough levels were kept between 100-150 ng/mL. Mean follow-up was 8 months (range, 4-24 months). After conversion to sirolimus, mean serum creatinine levels fell from 3.3 mg/dL to 2.4 mg/dL. In the 9 patients in whom we had switched to sirolimus early in the postoperative period, wound complications were prominent. Four of 9 patients had perirenal fluid collection and 3 of them need to be drained. Two of them had extravasation from the ureter, which we treated with a nephrostomy catheter and a double-J catheter. Serum cholesterol and triglyceride levels rose to a mean value of 227 ± 45 mg/dL and 276 ± 48 mg/dL, respectively. We observed mild thrombocytopenia in 1 case, which recovered within 1 month. No infectious complications were encountered. Data from this study demonstrate that sirolimus conversion may decrease serum creatinine levels in patients with chronic allograft nephropathy and calcineurin-inhibitor–related nephrotoxicity. However, it may increase wound-related complications in the early postoperative period. If doses are administered at appropriate serum levels, sirolimus may be safely used even in combination with a calcineurin inhibitor.



Volume : 2
Issue : 2
Pages : 39


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