Search

Superoxide dismutase (SOD) is a potent scavenger of superoxide radicals produced during normothermic ischemia-reperfusion. Since it has a short half-life, its optimal effect is achieved when it is given prior to reperfusion. The inclusion of SOD in liposomes (lipo-SOD) prolongs its half-life (free SOD: 6 min; lipo-SOD: 4 h). The protective effect of lipo-SOD in a 60-min bilateral renal warm ischemia model was studied. We divided 60 male Wistar rats between two control groups and five study groups according to the drug used (SOD or lipo-SOD) and to the time of SOD administration (prior to ischemia or prior to reperfusion). SOD and lipo-SOD were both given at 20 mg/kg endovenously. Weight, diuresis, creatinine per 100 g (Cr/100 g), and creatinine clearance per 100 g (CrCl/100 g) were studied. Conventional renal histology was performed after reperfusion and on day 7. Renal malondialdehyde, 6 keto PGF 1 alpha, and TxB2 tissue levels were studied after reperfusion. Results showed that the renal protective effect of free SOD on warm ischemic-reperfusion injury depended on the time of administration, being more effective when given before reperfusion. On the other hand, the renal protective effect of liposomed SOD did not depend on the time of administration since efficacy was similar when given before reperfusion or before ischemia. The functional protective effect of liposomed SOD was similar to that of free SOD when they were given prior to reperfusion. Nevertheless, since histological damage observed with liposomed SOD was less than with free SOD, it is suggested that the liposomed galenic form may offer better protection against renal warm ischemia. In addition, liposomed SOD was better at preventing tissue prostanoid generation after renal warm ischemic-reperfusion injury than free SOD. We concluded that liposomed SOD shows a higher renal protective effect against warm ischemia than free SOD.

Different induction therapies have been used in renal transplantation to avoid cyclosporine (CsA) nephrotoxicity and early acute graft rejection. This study compares the efficacy of a short course of prophylactic OKT3 to that of antilymphocyte globulin (ALG) in preventing acute renal allograft rejection when administered concomitantly with CsA and steroids. Between March 1988 and December 1990, 140 first-cadaver renal transplant recipients were randomly allocated to two immunosuppression groups--ALG group (n = 68): ALG 15 mg/kg just before transplant surgery, ALG 12 mg/kg the first day after transplant, followed by four doses of 10 mg/kg on alternate days; and OKT3 group (n = 72): OKT3 5 mg just before transplant, followed by four doses of 5 mg/d. Both groups included low-dose CsA and steroids. The incidence of rejection during the first 3 months after transplantation was 15% in the ALG group and 19% in the OKT3 group (NS). Kaplan-Meier estimates of patients free of rejection at 2 years was 85% in the ALG group and 77% in the OKT3 group (NS). The 3-year actuarial graft survival was 82% and 85% (NS), and 3-year patient survival was 97% and 98% (NS), in the ALG and OKT3 groups, respectively. These results indicate that the concomitant association of CsA and ALG or OKT3 constitutes a safe and effective therapeutic strategy that provides a low incidence of rejection and gives good results for patient and graft survival.

Cyclosporin A (CsA) is a potent immunosuppressive drug whose effect is well known in the organ transplantation field. Treatment with CsA reduces the incidence of rejection and improves graft survival after renal transplantation (RT). However, to set against the clear advantages of CsA, a most important problem is nephrotoxicity [1, 3]. Scientists are therefore seeking new non-nephro-toxic Cs derivatives, but the search has not yet borne fruit.

DN is one of the most alarming complications of diabetes mellitus (DM) and a major cause of progressive renal disease (1). The clinical diagnosis has traditionally been based on persistent proteinuria. About 30 to 50% of patients with insulin dependent DM (type I) and somewhat fewer of those with non-insulin-dependent DM (type II) develop this complication.

In order to avoid cyclosporine (CsA) nephrotoxicity and rejection, especially during the early posttransplant periods, different immunosuppression regimens have been adopted. A prospective trial was conducted to evaluate the benefits of initially low CsA doses associated with antilymphoblast globulin and steroids in the first days after transplant, in comparison with higher doses of CsA and steroids. Between 1/86 and 1/88, two groups of first-cadaver renal transplant recipients were documented based on the immunosuppression regimen used. In group A (n = 50), oral CsA was started at 8 mg/kg/day and subsequent doses adjusted to maintain CsA whole-blood levels between 300 and 600 ng/ml. Horse ALG at 10 mg/kg was given the day after transplant and on alternate days to a maximum of 6 doses. After 3 doses, ALG was stopped if CsA blood levels were equal to or greater than 400 ng/ml. ALG dosage modifications were made in order to maintain peripheral CD3+ cells between 10 and 20%. Prednisone was given at 0.25 mg/kg/day. In group B (n = 50), oral CsA was started at 15 mg/kg/day. The CsA whole-blood levels were maintained between 300 and 800 ng/ml. Prednisone was administered at 0.5 mg/kg/day. The incidence of postransplant renal failure was the same in both groups (16%), but the duration of oliguria was lower in group A than in group B (3.3 +/- 2 vs. 16.2 +/- 10.7 days, P less than 0.05), as well as the incidence of acute rejection during the first 3 months (18% vs. 40%, P = 0.01. The cumulative doses of CsA and steroids were significantly lower in group A than in group B. Mean serum creatinine at 6 and 12 months remained similar in both groups. There was no difference between the 2 groups in the incidence of infection. There was no mortality in either group. The actuarial graft survival was significantly higher in group A than in group B at one (100% vs. 94%), two (97% vs. 87%), and three years (89% vs. 73%), respectively (P = 0.041). In summary, the triple regimen using simultaneously low-dose CsA, ALG, and steroids minimizes early graft dysfunction, provides efficient immunosuppression without severe infections, and gives good long-term patient and graft survival.