Efficacy and Safety of the Intra-operative High-dose Induction with ATG-Fresenius in Older Kidney Graft Recipients

Jürgen Kaden, Gottfried May, Andreas Völp, Claus Wesslau
Aim/Background: With respect to the immunosuppressive treatment of older kidney graft recipients no unique recommendations are available or generally accepted. At our centre we developed a renal sparing regimen which combined the highly efficacious intra-operative single high-dose induction using ATG-Fresenius (9 mg/kg body weight) with a low cyclosporine trough level throughout the first post-operative week (median: 162 ng/ml; n=518 recipients). The results of a retrospective analysis
more » ... e analysis comparing the long-term outcomes in older and in younger recipients showed the efficacy and safety of this treatment protocol. Material/Methods: In order to stronger underline the age difference, two clearly defined different patient cohorts were analysed: cohort 1: n=40 recipients ≥ 60 years; cohort 2: n=205 recipients aged between 20 to 40 years. All patients received the same basic immunosuppression consisting of CsA, azathioprine and steroids and an intra-operative single high dose ATG-F. There were no systematic differences in donor characteristics with respect to age, sex, cold ischemia time and HLA-mismatches. The recipients' characteristics were also comparable except for age (mean 63±2.7 vs 31.6±5.3 years). Results: The patient survival (censored at 120 months) was significantly longer in younger than in older recipients (mean: 109.6 vs 87.4 months; 95% confidence interval: 105.4-113.8 vs 72.2-102.6 months; p<0.001), long-term death censored graft survival did not reach statistical significance (p=0.067). The incidence of death censored graft loss within 10 years was lower in the older recipients (4/40 vs 56/205, p=0.02), but a higher proportion of death with functioning graft (11/40 vs 11/205) was noted.The rates of biopsy confirmed rejections of any type were comparable (10/40 vs 69/205), just as were the rates of malignancies (0/40 vs 1/205), PTLD (0/40 vs 1/205), CMV diseases (9/40 vs 40/205) and viral pneumonias (2/40 vs 2/205). Bacterial pneumonias were more frequent in older recipients (3/40 vs 2/205, p=0.008). Using the same initial cyclosporine dose in both cohorts a higher blood trough level was observed in the older cohort (median: 211 vs 141 ng/ml, p=0.001) during the first post-operative week indicating that older recipients may need initial lower cy-closporine doses than younger recipients in order to achieve comparable target levels. Conclusions: In older kidney graft recipients with age 60 and above receiving the intra-operative single high-dose induction with ATG combined with a basic triple-drug immunosuppression, survival and a safety profile comparable to the younger recipients has been observed. Therefore, this type of induction can be recommended. Effizienz und Sicherheit der intraoperativen Hochdosisinduktion mit ATG-Fresenius bei älteren Empfängern von Nierentransplantaten Zielsetzung/Hintergrund: Für die immunsuppressive Behandlung älterer Nierentransplant-Emp-fänger gibt es bislang keine allgemein akzeptierten Behandlungsprotokolle. In unserem Zentrum wurde eine Transplantat-schützende Therapie entwickelt, die die intraoperative Hochdosisindukti-on mit ATG-Fresenius (9 mg/kg) mit einem niedrigen Cyclosporin-Talspiegel während der ersten postoperativen Woche (Median: 162 ng/ml; n=518 Rezipienten) kombiniert. Die retrospektive Analyse der Langzeitergebnisse belegt, dass sowohl Effizienz als auch Sicherheit dieses Protokolls bei älteren und jüngeren Transplantatempfängern vergleichbar sind. Patientengut und Methoden: Um eindeutig unterschiedliche Altersgruppen zu haben, wurden nur folgende zwei Patientenkohorten analysiert: Kohorte 1: n=40 Rezipienten ≥ 60 Jahre; Kohorte 2: n=205 Rezipienten zwischen 20 und 40 Jahren. Alle Patienten erhielten eine Dreifachtherapie mit Cyclosporin, Azathioprin und Steroiden sowie eine intraoperative singuläre hochdosierte (9 mg/kg)