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Eur J Clin Invest 2011; 41 (9): 971–978 Abstract 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.

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

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).

Studies on living donor kidney transplantation primarily address the recipients; few publications focus on kidney donors. The aim of the present study was to detect changes in and compensations of defined parameters of anemia and inflammation in the immediate postnephrectomy period. We included six living kidney donors who underwent an open anterior-extraperitoneal nephrectomy. We excluded donors with complications, such as significant blood loss or infection. Blood samples were taken before nephrectomy as well as on postoperative days 1, 3, 5, and 7, and at discharge for measurements of hemoglobin (Hb), serum erythropoietin (Epo), reticulocytes (Reti), pentraxin 3 (PTX3), and C-reactive protein (CRP). There was a significant decrease in Hb (>3 g/dL), reaching a maximum on day 3 followed by a significant threefold increase in Epo levels on day 5 and a nonsignificant elevation of Reti count. CRP increased approximately 80-fold on day 3. PTX3 showed a similar course, peaking on day 3 with an approximate 70-fold increase. After living donor nephrectomy, there was an unexpectedly pronounced inflammatory reaction in the absence of any signs of bacterial infection simultaneous with a significant decrease in Hb. These parameters improved during the hospital stay, in some cases they achieved the prenephrectomy level at discharge. These data may assist in interpreting laboratory results after nephrectomy among living kidney donors.

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.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.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.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.

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.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.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-Agor = 20/200.000 cells) and 100% (PCRor =30.000 copies/ml). Transfusion of2 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.Therefore, pp65-antigenemia and plasma PCR with a cut-off could be useful for monitoring preemptive therapy.

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.

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 (p0.05) but CYT-DRA did resulting in a significant poor graft outcome 3 months after transplantation (p0.001).

We evaluated survival and renal function of cadaveric donor grafts according to donor age. The median age of the pediatric donors was 7.0 (0.7-16) years in 46 patients [median age 11.8 years (range) 3-16.8 years]. The median age of the adult donors was 34.4 (19-54) years in 59 patients [median age 12.1 years (range) 7-17.3 years]. Thirty patients were treated with azathioprine and prednisolone and 75 with cyclosporine A and prednisolone. The glomerular filtration rate (GFR) and the effective renal plasma flow (ERPF) were determined by the clearances of 51chromium-EDTA and 125iodine-hippurate 1-48 months after kidney transplantation. There was no difference in graft survival between pediatric and adult grafts. There were also no differences in GFR in patients receiving grafts from pediatric or adult donors; 2-3 months after transplantation the GFR in recipients of pediatric grafts was 62 +/- 20 ml/min per 1.73 m2 compared with 61 +/- 21 in those receiving adult grafts. The ERPF in recipients of adult grafts was significantly higher in the 1st month after transplantation: 486 +/- 239 versus 362 +/- 158 ml/min per 1.73 m2. From the 4th to the 6th month after transplantation this difference disappeared: the ERPF of grafts from pediatric donors was 279 +/- 131 ml/min per 1.73 m2 compared with 273 +/- 123 ml/min per 1.73 m2 in grafts from adult donors. Using the single-kidney GFR and ERPF on an age-matched group of probands with minor diseases as references, 2-3 months after transplant the mean GFR of grafts from pediatric donors increased to 118% +/- 51%, whereas the GFR of adult donor grafts fell to 60% +/- 22% over the same period. After 4-6 months the ERPF in pediatric grafts was 96% +/- 55% compared with 50% +/- 22% in adult grafts. We conclude that graft survival and function in children with either a pediatric or an adult graft may not differ because graft function adapts to the requirement of the recipient.