The Clinical Study On A New Immunosuppressive Agent Of Rapamycin In Human Renal Transplantation

Objective: To observe the efficacy and side-effect of two immunosuppression schemes in renal transplant recipients. To compare the safety and influence of allograft of Rapamycin (RPM, Sirolimus, SRL)-based therapy with that of common dose of cyclosporine A (CsA) -based therapy in prevention of renal acute rejection (AR) episodes.Methods: The study was conducted in two groups after renal transplantation over 6 months. Twenty-five cases of the first renal transplant recipients were treated with SRL combined with low dose of CsA(5-6mg.kg~-1d~-1) and prednisone(Pred) (SRL Group).A loading dose of SRL of 6ml was administered within 48hours after renal transplantation ,maintained at 2 ml.d~-1 thereafter. Another Thirty-five cases of the first renal transplant recipients were treated with MMF (0.5g, thrice day) combined with common dose of cyclosporine A (CsA) (6-8mg.kg~-1.d~-1) and Pred ( MMF group).There are no statistical differences in two groups for age, sex, cold ischemia time/heat ischemia time of donor kidney, complement dependent cyctoxicity (CDC) and level of panel reactive antibody (PRA).Renal and liver function, level of cholesterol and triglyceride, serum concentration of CsA and RPM, incidence of acute refection episodes, side effect during 6 months and recipients/grafts survival wereobserved in two groups over 6 months after transplantation. Results:1. Twenty recipients have completely been observed over 6 months in SRL group.5 recipients withdrew from the therapy combined with Rapamycin and changed into other immunosuppression schemes because of adverse events and other reasons, including lip numbness and poststernum burning pain after dosed(2 cases),delayed graft function(DGF)(l case),liver and renal function(l case) and pulmonary infection(l case). All cases in MMF groups have reached the end of course. Recipient/grafts survival rates were 100%/100% in two groups after renal transplantation.2. The counts of serum creatinine of 20 recipients in SRL group completely returned to normal within four weeks after renal transplantation. The counts of serum creatinine of 29 patients within 1 week and 6 patients within 2 weeks in MMF group returned to normal after renal transplantation respectively. There were not significant differences of recovery renal function in two groups during a follow-up period.3. The incidence rates of biopsy-confirmed acute rejection were 10% and 11.4% in SRL group and MMF group over 6 months after renal transplantation, respectively. There were not significant differences of incidence rate of AR between two groups during a follow-up period.4. Hyperlipidemia was one of the most frequently accounted side-effects induced by Rapamycin and changed relatively accompanied by blood trough level of RPM. There was not significant difference of incidence of hyperlipidemia between pre-transplantation and post-transplantation in MMF group (P>0.05 ) .5. The incidence of gastrointestinal reactions was very closed and high between two groups. Rapamycin were discontinued in 2 patients before the completion of 6 months study period even though gastrointestinal reaction of SRL group was nothigher than one of MMF group.6. There was no serious infection was found in two groups during a follow-up period.The incidence of infection-based disease was similar (p>0.05) and no malignancywas reported in two groups.Conclusion:1. The immunosuppression scheme of SRL group including low dose of CsA has definitely therapeutical effectiveness in prevention of AR episodes after renal transplantation for Chinese.2. The adverse effects of SRL group are not increased. Immunoprophylaxis using Rapamycin is safety for renal recipients.3. Hyperlipidemia is apparently observed adverse events in these patients of SRL group, especially hypercholesteraemia, usually attributed to dosage of Rapamycin.4. There are a high recipient/graft survival rates and not significant difference between two groups over 6 months after renal transplantation.5. Two recipients withdraw ahead of schedule from SRL group because of bad taste and gastrointestinal symptom.