Safe conversion of mycophenolate mofetil to azathioprine in kidney transplant recipients with sirolimus-based immunosuppression.

AIM: Mycophenolate mofetil (MMF) is a powerful immunosuppressive drug with established efficacy and safety. The long-term use of MMF may bring increased risk of for infection and malignancy and also increased cost of transplantation. The search for minimization of immunosuppressive protocol has led to an open randomized clinical trial of conversion from MMF to azathioprine (AZA). METHODS: A total of 50 kidney allograft recipients treated with prednisone, sirolimus and MMF were randomized into two groups: converted (AZA group) and continuing (MMF group). The average duration of MMF therapy prior to conversion was 43 months in each group. Inclusion criteria included: patients with serum creatinine levels of less than 200 micromol/L; no past history of acute vascular rejection or recent acute rejection 6 months before randomization; and normal liver function tests. RESULTS: Baseline demographics were similar in the two groups. During the 12 month observation period, there were no acute rejection episodes in either group. There were no significant differences in overall patient or graft survival or function. AZA-treated patients had a lower incidence of gastrointestinal complications (P=0.03). Daily cost reduction in the AZA group was more than $US8.79/day per patient. CONCLUSION: In general, replacing MMF with AZA in stable renal transplant recipients is well tolerated and was cost effective with no increased risk of rejection. As the this study was on relatively small samples, larger and longer follow-up studies will be needed to confirm these expected advantages for the long-term outcome and to assess the long-term safety of this minimization of immunosuppressive therapy.

Colchicine vs. omega-3 fatty acids for prevention of chronic cyclosporine nephrotoxicity in Sprague Dawley rats: an experimental animal model.

BACKGROUND: In view of the high cost of the new immunosuppressive drugs, which represents a challenge for both patients and governmental resources especially in developing countries, trials to prevent side effects of the first calcineurin inhibitor discovered (cyclosporine, Cs) are of particular interest. METHODS: In this prospective randomized experimental study, 60 male Sprague Dawley rats were enrolled. Group 1 served as negative control group and received olive oil. Group 2 received Cs orally 100 mg/kg for 80 days and served as positive control group. Group 3 was given daily colchicine (30 microg/kg/day) in addition to Cs. Group 4 was given omega-3 fatty acids (100 mg/kg/day) in addition to Cs. Animals were subjected every other week to laboratory assessment for serum creatinine, sodium, potassium, and Cs whole-blood through levels. At the end point, the animals were sacrificed, and kidney tissue was examined for histopathological changes. RESULTS: There were no significant differences in serum creatinine, creatinine clearance, and serum sodium and potassium in all groups. Histopathological examination of kidney tissues showed focal tubular atrophy and interstitial fibrosis in inner medulla and inner strip of the outer medulla in all Cs-treated animals. Morphological changes were significantly less in colchicine-treated rats compared to omega-3 fatty acid-treated rats and absent in the negative control group. Furthermore, immunostaining showed positive reactions for vimentin in Cs-treated animals only. CONCLUSIONS: Colchicine and omega-3 fatty acids are protective for the kidney against cyclosporine-induced nephropathy; however, colchicine is more protective than omega-3 fatty acid.