Duska Dragun. Nephrologie & internistische Intensivmedizin Charité Campus Virchow Klinikum

Transkript

1 ASN 2008 Highlights - Nierentransplantation Duska Dragun Nephrologie & internistische Intensivmedizin Charité Campus Virchow Klinikum duska.dragun@charite.de

2 Determinanten des individuellen Transplantationserfolges im Langzeitverlauf Komorbiditäten des Empfängers Kardiovaskuläre Komplikationen Tumoren Infektionen (CMV) Immunologische Mechanismen Späte Abstoßungen Non-Compliance Reduktion der Immunsuppressiva Organqualität Alter des Spenders Ischämieschäden GN-Rekurrenz Toxische Wirkungen von Immunsuppressiva Lebendspende

3 Häufig verwendete Kombinationstherapien Erhaltungskombinationen mit CNI (CyA oder Tac) + MPA ohne CNI (mtor-inh + MPA) - primär - sekundär mit Steroiden ohne Steroide - sekundär Ziel: Reduktion von Nebenwirkungen ohne Beeinträchtigung des Transplantatüberlebens

4 Everolimus/EC-MPS therapy after calcineurin inhibitor withdrawel in de novo transplant patients: Final outcomes of the ZEUS study DESIGN Baseline Month 4.5 Anti IL-2R + CsA + EC-MPS + CS stepwise conversion (2 weeks) n = 145 n = 155 Cyclosporine A + EC-MPS + CS Everolimus + EC-MPS + CS CsA trough level ng/ml CS = Corticosteroids. Anti IL-2R = Basiliximab Everolimus trough level 6-10 ng/ml TH-FC041 ZEUS Study

5 Everolimus/EC-MPS therapy after calcineurin inhibitor withdrawel in de novo transplant patients: Final outcomes of the ZEUS study OUTCOME Absolute values at month 12* p <.0001 ml / min Cyclosporine Everolimus N = 145 N = 155 GFR Nankivell * no significant difference at baseline TH-FC041 ZEUS Study

6 Comparison of interstitial fibrosis (IF) at 1 year in renal transplant recipients with Csa discontinuation and SRL introduction - The CONCEPT trial - n=193 Randomization at week 12 Csa + MMF Csa + SRL 52 weeks N Mean IF (%) Grade I (% patients) Grade II (% patients) Grade III (% patients) Serum creatinine clearance by MDRD (ml/min/1.73m²) SRL ± ±15.7 CsA ± ±16.2 TH-FC040 A. Servais et al.

7 Determinanten des individuellen Transplantationserfolges im Langzeitverlauf Komorbiditäten des Empfängers Kardiovaskuläre Komplikationen Tumoren Infektionen (CMV) Immunologische Mechanismen Späte Abstoßungen Non-Compliance Reduktion der Immunsuppressiva Organqualität Alter des Spenders Ischämieschäden GN-Rekurrenz Toxische Wirkungen von Immunsuppressiva Lebendspende

8 Impact of CMV infection on acute rejection and long term allograft function n= CMV infections at 1 year PROTOCOL BIOPSY No difference between CMV- and CMV+ 6 weeks 3 months 6 months + diagnostic biopsies Majority within 3 months CMV-/AR- GFR=56.0 ml/min p=0.047 CMV+/AR+ GFR=48.0 ml/min TH-P0584 U. Erdbruegger,, W. Gwinner

9 CMV resistance in the era of prophylaxis French study n=211 at their first CMV infection 78 with prophylaxis 133 without prophylaxis 20 VCV 58 VGCV days Clinical resistance 15/211 (7.1%) Genetic resistance 9/211 (4.2%) 7/9 D+/R- 3.8% WITHOUT 5.1% WITH VCV or VGCV did not influence the resistance rate TH-P0580 S. Hantz,, S. Alain

10 Coronary calcifications predict cardiovascular events in renal transplant recipients n=281 renal transplant recipients 16-slice HR-CT check at baseline years follow-up TH-FC033 S. Henrard et al.

11 Transplantnephrectomy is associated with improved survival among patients returning to dialysis with failed renal allograft USRDS Overall mortality in the cohort 34.5% 10,951 patients 35% Tx-Nephrektomie NTx Dialys sis younger more likely with infectious complications, anemia after covariate adjustment RR for death (95% CI: ) 32.5% reduction in relative mortality risk F-FC191 SC Ayus et al.

12 Pregnancy outcomes after kidney donation donation University of Minnesota questionnaire on pregnancy outcomes adressing fetal and maternal complications comparison of maternal and fetal outcomes before and after donation 2,025 female donors 965 ever pregnant 822 with 2416 pregnancies before donation 223 with 459 pregnancies after donation Pre-donation pregnancy with higher likelihood of full-term delivery + Lower likelihood of fetal loss 83.7% vs. 72.3% p= % vs. 19.8% p=0.006 Risk for gestational hypertension, gestational diabetes, and preeclampsia F-FC190 SK Akkina et al.

13 Soluble urokinase receptor (supar) is a circulating glomerular disease recurrence factor Release in inflammatory environment Antagonizes urokinase actions WT upar -/- upar -/- SA-FC454 C. Wei,, J. Reiser

14 Soluble urokinase receptor (supar) is a circulating glomerular disease recurrence factor WT LPS MCN Foot process effacement Deposition of supar WT supar FSGS proteinuria upar -/- upar -/- 3. supar levels in patients with relapsing MCN and recurrent FSGS in transplants SA-FC454 C. Wei,, J. Reiser