Long-term outcome of ATG vs. Basiliximab induction.

BACKGROUND: An evaluation of the long-term efficacy and incidence of adverse events after induction therapy with antithymocyte globulin (ATG) vs. Basiliximab in renal transplant patients. METHODS: Sixty recipients receiving ATG induction and a dual immunosuppression with Tacrolimus and steroids were compared retrospectively with 60 patients treated with Basiliximab. The following characteristics were evaluated: concomitant immunosuppression, recipient age, donor age, time on dialysis, cold ischemia time, year of transplantation and HLA mismatches. RESULTS: The 6-year patient survival in the ATG group was 91·7% compared to 85% in the Basiliximab group (not significant, n.s.). Graft survival at 6 years was 89·7% and. 83·6% in the ATG and the Basiliximab group (n.s.), respectively. Incidence of biopsy proven acute rejection episodes (33·3% vs. 26·7%) and delayed graft function (30% vs. 33·3%) were similar in both groups. Kidney function was not significantly different at 1 and 6 years. CMV infections were more prevalent in the ATG arm (22% vs. 5%; P = 0·05), and a significantly higher rate of haematological complications was observed following ATG induction. CONCLUSIONS: ATG induction was associated with an improved (but n.s.) trend in patient and graft survival. Patients induced with ATG had a higher rate of CMV infections and haematological complications.

Factors impacting short and long-term kidney graft survival: modification by single intra-operative -high-dose induction with ATG-Fresenius.

BACKGROUND: A majority of recipients benefited from the intra-operative single high-dose induction (HDI) with ATG-Fresenius (ATG-F) still leaving a group of recipients who did not profit from this kind of induction. Therefore the aim of this retrospective analysis was 1st to identify the risk factors impacting short and long-term graft survival, and 2nd to assess the efficacy of this type of induction in kidney graft recipients with or without these risk factors. MATERIAL/METHODS: A total of 606 recipients receiving two different immunosuppressive treatment regimens (1st: Triple drug therapy [TDT, n=196] consisting mainly of steroids, azathioprine and cyclosporine; 2nd: TDT + 9 mg/kg ATG-F intra-operatively [HDI, n=410]) were included in this analysis and grouped according to their kidney graft survival time (short GST: ≤1 yr, n=100 and long GST: >5 yrs, n=506). RESULTS: The main risk factors associated with a shortened graft survival were pre-transplant sensitization, re-transplantation, rejections (in particular vascular or mixed ones) and the necessity of a long-term anti-rejection therapy. Adding ATG-F single high dose induction to TDT was more efficient in prolonging kidney graft survival than TDT alone not only in recipients without any risk factors (p<0.005) but also in recipients with at least one risk factor (p<0.021). Only in 4.6% of recipients having two or more risk factors this effect could not be demonstrated. CONCLUSIONS: The intra-operative single high-dose induction with ATG-F significantly improves the kidney graft survival in recipients with or without risk factors and can therefore be recommended.

Improved long-term survival after intra-operative single high-dose ATG-Fresenius induction in renal transplantation: a single centre experience.

BACKGROUND: In organ grafts donor-specific sensitization is initiated immediately after revascularization. Therefore, in 1990 we introduced the intra-operative single high-dose ATG-Fresenius (ATG-F) induction in addition to standard triple drug therapy (TDT) consisting of steroids, azathioprine and cyclosporin. A total of 778 first renal transplantations from deceased donors, performed between 1987 and 1998, were included in this evaluation. MATERIAL/METHODS: This retrospective analysis of clinic records and electronic databases presents data of all recipients of first kidney grafts who received two different ATG-F inductions (1(st) group: 9 mg/kg body weight as single high-dose intra-operatively, n=484; 2(nd) group: 3 mg/kg body weight on 7 or 8 consecutive days as multiple-dose starting also intra-operatively, n=78) and standard TDT alone (3(rd) group: TDT alone, n=216). RESULTS: The 10-year patient survival rates were 72.6+/-2.6% (TDT + ATG-F single high-dose), 79.5+/-5.1% (TDT + ATG-F multiple-dose) and 67.2+/-3.7%% (TDT alone; Kaplan-Meier estimates with standard errors; ATG-F vs TDT alone, p=0.001). The 10-year graft survival rates with censoring of patients that died with a functioning graft were 73.8+/-2.4%, 57.7+/-5.8% and 58.4+/-3.6% (Kaplan-Meier estimates with standard errors; 1(st) vs 2(nd )and 3(rd) group, respectively, p<0.001) and the 10-year graft survival rates with patient death counted as graft failure were 58.3+/-2.7%, 55.7+/-5.8% and 48.2+/-3.5% (Kaplan-Meier estimates with standard errors; ATG-F single high-dose vs TDT, p=0.023). In pre-sensitized recipients there were also significant differences in favour of ATG-F, more notably in the single high-dose ATG-F induction. A total of 69% of the patients in the two cohorts receiving ATG-F did not experience any transplant rejections compared to 56% in patients undergoing TDT alone (p=0.018). The incidence of infectious complications was comparable across all groups. CONCLUSIONS: According to evidence obtained from the routine documentation of 778 renal transplantations, ATG-F induction therapy administered as a part of immunosuppressive therapy significantly improves patient survival and reduces the risk of graft failure and transplant rejections.

Monitoring of human cytomegalovirus, HHV-6 and HHV-7 infection in kidney transplant recipients by molecular methods to predict HCMV disease after transplantation: a prospective study.

OBJECTIVES: Recently, highly sensitive molecular assays to detect HCMV, HHV-6 and HHV-7 have been developed but their ability to detect patients at high risk for disease is unclear. METHODS: The positive predictive values (PPV) of pp65-antigenemia, quantitative plasma DNA and pp67-mRNA for CMV-disease were prospectively compared in 82 transplant recipients (72 renal, 10 pancreas-kidney) without CMV-prophylaxis. In addition, the prevalence of HHV-6 and HHV-7 infection were assessed using qualitative PCR. The assays were performed weekly. RESULTS: Three patients (3,7%) developed CMV-disease and were effectively treated. They were positive in all three CMV-assays. The PPVs of pp65-Ag, DNA viral load and pp67-mRNA were 33%, 20% and 25% in CMV-positive and 100%, 67% and 50% in seronegative recipients. Sensitivity and negative predictive value were 100% for all assays. Using cut-offs, PPVs were 75% (pp65-Ag > or = 20/200.000 cells) and 100% (PCR > or =30.000 copies/ml). Transfusion of >2 packed red cells, rejection and non-functioning graft were risk factors for CMV Five patients and one patient were positive for HHV-6 and HHV-7 resp.; both were symptomless and did not have a HCMV infection. CONCLUSIONS: Therefore, pp65-antigenemia and plasma PCR with a cut-off could be useful for monitoring preemptive therapy.

The dynamics of antidonor antibody formation early after clinical kidney transplantation measured by flow cytometry and microcytotoxicity test.

To study the dynamics of antidonor sensitization 92 patients were monitored for antibodies against donor T and B spleen lymphocytes before transplantation, within the first month after transplantation and 3 months after transplantation. Patients were monitored for donorreactive antibodies (DRA) of immunoglobulin G (IgG), IgA, and IgM isotype using flow cytometry (FC) and the standard microcytotoxicity test (CYT). Graft function was followed for at least 2 yrs, 51% of patients for 3 yrs after transplantation. Within the first month after transplantation the percentage of patients with antidonor sensitization detected by FC rose dramatically, so that the overall sensitization rate increased from 28 (30.4%) of 92 patients prior to transplantation to 63 (68.5%) of 92 patients after transplantation. Whereas preoperatively only one isotype (IgM for T lymphocytes, IgG for B lymphocytes) and only one target cell type (either T or B lymphocytes) dominated, the postoperative patterns of positive FC results were more variable regarding target and isotype, whereby FC-DRA of the IgA class substantially contributed. Appearance of donor-directed antibodies early after kidney transplantation is a frequent event. In our cases, sensitization with FC-DRA per se seemed not to be detrimental to the graft outcome (p > 0.05) but CYT-DRA did resulting in a significant poor graft outcome 3 months after transplantation (p < 0.001).

Kidney transplantation at the Charité: long tradition, elderly patients and the duration of hospitalization.

Since the sixties kidneys have been transplanted successfully at the 2 predecessors of today's transplant center at the Charité. So far, 1,290 kidneys were transplanted resulting in 89.8% overall graft survival at one year and 78.6% at 5 years. Several factors were associated with these results. Ischemia times were very short (11.9 +/- 7.3 hours). Patients with diabetic nephropathy were rarely transplanted without combined pancreas transplantation. Combined with a pancreas transplantation, kidney grafts fared even better than those of non-diabetic patients. The share of living donation is still rising and is associated with a better outcome than cadaveric grafts. In contrast, the effect of HLA mismatches was not very pronounced. Zero- and one-mismatch transplantations had a clear benefit over those with 2-3 mismatches, but higher numbers of mismatches did not lead to worse results. To expand the donor pool with kidneys from old donors (> 64 years) we participate in the Eurotransplant Senior Program (ESP) where these kidneys are allocated locally to recipients aged 65 years and older without HLA matching. The ischemia times for ESP kidneys were shorter (7.3 +/- 3.0 hours) but transplants were less well matched (4.2 +/- 2.1 mismatches). Graft survival was not different from controls aged 60 years and older who received a kidney from a donor under age 65. The ESP patients do not require prolonged hospitalization for transplantation (30.6 +/- 14.6 days versus 35.3 +/- 26.0 days in patients below 60 years). With the introduction of the ESP the number of transplantations in recipients aged 60 years and above have risen considerably.