2010 - TTS International Congress


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Induction Immunosuppression

89.6 - Short- and long term kidney graft survival: the impact of intra-operative high-dose ATG-Fresenius induction and identification of important predictors

Presenter: Juergen, Kaden, Berlin, Germany
Authors: Kaden J., May G., Völp A., Wesslau C., Abendroth D.

SHORT- AND LONG TERM KIDNEY GRAFT SURVIVAL: THE IMPACT OF INTRA-OPERATIVE HIGH-DOSE ATG-FRESENIUS INDUCTION AND IDENTIFICATION OF IMPORTANT PREDICTORS

INDUCTION IMMUNOSUPPRESSION

J. Kaden1, G. May1, A. Völp2, C. Wesslau3, D.K. Abendroth4
1Renal Transplant Centre, Friedrichshain Hospital (formerly), Berlin/GERMANY, 2Scientific Services, Psy Consult, Frankfurt/GERMANY, 3Region Nordost, Deutsche Stiftung Organtransplantation, Berlin/GERMANY, 4Zentrum Für Chirurgie, Universitätsklinik Ulm, Ulm/GERMANY

Body: Purpose: The induction with intra-operative single high-dose ATG-Fresenius (ATG-F: 9 mg/kg body weight) in addition to the standard triple drug immunosuppression (TDT) reduces the risk of graft failure. The aim of this study was to identify characteristic predictors for long-term graft survival associated with this specific type of induction. Methods: Retrospective analysis of clinic records of all cadaveric renal transplantations whose induction regimen did or did not include ATG-F in addition to TDT consisting of steroids, azathioprine and cyclosporine. Materials: 510 renal transplantations that involved TDT in combination with an ATG-F single high-dose induction (HDI, n=249), or with an ATG-F multiple-dose induction (MDI, n=61), or TDT alone (n=200) were evaluated. The following variables were included in the analysis: first vs. re-grafts, age, cold ischemia time, panel-reactive lymphocytotoxic antibodies (PRA), post-transplant graft function, number of rejections and duration of anti-rejection therapy, HLA-mismatches, all kinds of infections as well as blood levels of creatinine, C-reactive protein (mg/l), T-cells, IL-6, IL-2R, endogeneous cortisol and kynurenine (µmol/ml; indicating the activity of the anti-inflammatory acting enzyme Idoleamin 2,3-dioxigenase; IDO) at post-transplant days 5±1, 10±1 and 20±2. According to kidney graft survival (KGS) recipients were grouped as high (<1yr, n=91), intermediate (>1-5yrs, n=53) and low risk (>5yrs, n=366). Results:
1. Risk factors associated with shortened KGS were re-grafting, pre-Tx sensitization, rejections (in particular vascular rejection) and the necessity of a long-term anti-rejection therapy.
2. Whereas in the TDT-group 23.9% (42/176) of all recipients experienced a shortened KGS, in the high-dose ATG-F induction group only 11.5% (25/226) of all recipients did so. This is a difference of 12.5% in favour to this special ATG-F induction.
3. Using decision tree methods the criteria ‘no rejection’, ‘PRA ≤73%’ and ‘single high-dose ATG-F’ were associated with an improved long-term KGS (>5-year graft survival in 94.7% of the patients with this combination).
Conclusions:
1. From all serum or cellular parameters tested detailed analyses showed that only IDO (and to a lesser extend CRP) serum concentrations within the first three post-Tx weeks were predictive of long-term KGS.
2. Intra-operative high-dose induction with ATG-F compensates for the negative influence of risk factors regarding KGS.

Disclosure: All authors have declared no conflicts of interest.


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