Search

Forty-three biopsies were performed between 30 and 60 min after reperfusion. Patients (22 males/21 females, mean age 41 +/- 12 years, mean donor age 32 +/- 14 years) were treated either with antilymphocytic globulin, cyclosporin, and prednisolone (24 cases), or OKT3, cyclosporin, and prednisolone (19 cases). Ten patients had delayed post-transplant renal function (DPRF), defined as haemodialysis requirements after surgery, and seven patients had acute rejection 11 +/- 16 days post-transplant. Kidneys were perfused with a hypertonic solution containing mannitol. All patients were followed up for at least 30 months. During follow-up, five patients lost their grafts due chronic rejection, two patients due to noncompliance and one due to recurrence of focal segmental glomerulosclerosis. One patient died from heart infarction. Biopsies were stained with H&E, Masson's trichrome, periodic acid-Schiff (PAS) and silver methenamine. Interstitial fibrosis, interstitial oedema, tubular vacuolization, and peritubular capillary oedema were measured using a semiquantitative scale. Five 400 x magnification micrographs of cortical interstitium from silver-methenamine-stained sections were used to measure percentage of interstitial surface with a morphometer. Interstitial surface was 18.7 +/- 6.2% (range 3.2-35.3%). A positive correlation was found between interstitial surface and donor age (r = 0.469, P = 0.0015). No relationship was found between warm and cold ischaemia times and tubular vacuolization or peritubular capillary oedema.(ABSTRACT TRUNCATED AT 250 WORDS)

Background. Discontinuation of steroids has long been a goal of transplant teams. However, whether this strategy is associated or not with a higher risk of long-term graft loss has not been resolved. Methods. The authors analyzed a cohort of 91 renal allograft recipients who underwent transplantation between 1993 and 1997. They were treated with cyclosporine and mycophenolate mofetil (MMF) and then had steroids withdrawn. Inclusion criteria were as follows: serum creatinine lower than 133 μM, first or second renal transplants, no or only one acute rejection episode (borderline or Ia grade), and a peak of panel reactive antibodies under 50%. Prednisone was gradually tapered off and then discontinued over a period of 2 to 4 months. Results. There were no episodes of acute rejection after steroid withdrawal. Whether steroids were withdrawn before (early) or after (late) 6 months of renal transplantation did not influence outcome. By Kaplan-Meier analysis, patient survival was 93.6% and 100% at 5 years and 93.6% and 97.6% at 10 years in the early and late steroid withdrawal groups, respectively. Graft survival was 94.3% and 98.1% at 5 years and 87.6% and 82.4% at 10 years in the early and late steroid-withdrawal groups, respectively. Risk factors for graft loss in multivariate analysis were peak of panel reactive antibodies (relative risk, 1.074; 95% confidence interval, 1.017–1.134; P=0.01) and acute rejection (relative risk, 16.5; 95% confidence interval, 1.8–147; P=0.01). Conclusions. Early and late steroid withdrawal in low-immunologic-risk renal allografts treated with cyclosporine and MMF can be achieved without risk of acute rejection and with excellent long-term results.

THE AREA UNDER the CsA concentration time curve (AUC) is a better measure of systemic drug exposure than trough concentrations (C0) and has been shown to correlate better with clinical outcome. However, therapeutic monitoring of CsA based on AUC is impractical because collection of multiple blood samples is required. For this reason C0 concentrations are used in most centers for the adjustment of CsA dosage. Recently, several reports suggest that monitoring of markers of neoral absorption such as AUC0–4h are more sensitive than C0 for optimizing the effect of CsA. 3–4

Background. In renal transplantation the beneficial immunosuppressive effects of cyclosporin (CsA) may be curtailed by its nephrotoxicity, specially in patients receiving a cadaveric allograft from suboptimal donors or at risk of delayed graft function. Mycophenolate mofetil (MMF) and antithymocyte globulin (ATG) have each demonstrated to be potent immuno-suppressants in renal transplantation. In a prospective analysis we have studied the results at 6 months of the combination of MMF, ATG and low-dose steroids in patients with low immunological risk receiving a first cadaveric renal allograft from a suboptimal donor or at risk of delayed graft function. Methods. Patients with preformed reactive antibodies

Background Because of the shortage of kidneys available for transplantation, we began in 1986 to harvest kidneys from non-heartbeating (NHB) donors. Methods. We compared the results of a group of 66 kidney recipients from NHB donors (NHB group) with 122 kidney recipients from heartbeating donors (HB group). We analyzed, in the NHB group, the influence of ischemia times in graft survival and we tested the best cut-offs by receiver operating characteristic curves. We also studied, using a univariate and multivariate Cox hazard model, the capacity of different variables to predict graft loss. Results. Patient and graft survival were similar in both groups during the follow-up. The percentage of delayed graft function was the only significant difference between both groups (NHB group 62% vs. HB group 32%; P=0.0001). Delayed graft function, in the NHB group, is influenced by the warm ischemia time, which is directly related to the number of days to achieve a serum creatinine

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.

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.

The present study describes 3 adult patients with hemolytic uremic syndrome (HUS) leading to chronic renal failure. Following renal transplantation, the 3 patients developed microangiopathic hemolytic anemia associated with acute rejection crises and graft failure. In 2 patients the renal histology of the transplanted kidney was consistent with HUS. It is concluded that, in adult patients, HUS may recur after renal transplantation and contribute to renal graft failure.