Zusammenfassung
HINTERGRUND: Es gibt Hinweise für eine Bedeutung humoraler Alloreaktivität in der Pathogenese der chronischen Transplantat-Nephropathie. Kürzlich wurde in einer kleinen Fallserie über den günstigen Effekt einer Rescue-Therapie mit Tacrolimus in Kombination mit Mycophenolat Mofetil auf den Verlauf der chronischen humoralen Abstoßungsreaktion berichtet. METHODEN: In unsere Studie wurden elf Nierentransplantatempfänger mit bioptisch verifizierter C4d-positiver chronischer Transplantatabstoßung (Index-Biopsie im Median 3 Jahre nach Transplantation) inkludiert. Auf Basis des Biopsiebefundes wurde von Cyclosporin A auf Tacrolimus umgestellt. Weiters erfolgte, sofern nicht bereits Bestandteil der immunsuppressiven Basistherapie, eine Umstellung auf Mycophenolat Mofetil. Wir untersuchten den Effekt dieser Intervention auf den klinischen sowie, unter Einsatz durchflusszytometrischer Methodik (FlowPRA), den serologischen Verlauf humoraler Alloreaktivität. ERGEBNISSE: Die Ergebnisse unserer Fallserie zeigen, dass eine Therapieumstellung auf Tacrolimus und Mycophenolat Mofetil eine progrediente Verschlechterung der Nierenfunktion nicht aufhalten kann. So entwickelten 4 Patienten innerhalb von 4–18 Monaten eine terminale Niereninsuffizienz. Serielle serologische Analysen zeigten bei 7 Patienten den Nachweis von Alloantikörpern gegen HLA Klasse I und/oder Klasse II Antigene. Tacrolimus/Mycophenolat Mofetil hatte keinen Effekt auf den Verlauf dieser FlowPRA-Reaktivitäten. Bei einem Patienten mit C4d-positiver Transplantat-Glomerulopathie wurde nach fehlendem Ansprechen auf Tacrolimus/Mycophenolat Mofetil eine Immunadsorptionstherapie begonnen. Es konnte zwar ein Rückgang der FlowPRA-Reaktivität sowie eine Reduktion der C4d Ablagerungen erreicht werden, dennoch entwickelte der Patient unter dieser Therapie ein dialysepflichtiges Nierenversagen. SCHLUSSFOLGERUNG: Unsere Ergebnisse sprechen gegen eine Effizienz von Tacrolimus/Mycophenolat Mofetil in der Therapie der C4d-positiven chronischen Transplantatdysfunktion. Allerdings kann nur eine prospektive kontrollierte Studie den tatsächlichen Benefit dieser oder alternativer, vorzugsweise frühzeitig eingesetzter antihumoraler Strategien klären.
Summary
BACKGROUND: Humoral alloresponses may contribute to chronic allograft nephropathy (CAN) in a subset of kidney transplant recipients. For chronic humoral rejection, the efficacy of rescue therapy with tacrolimus and mycophenolate mofetil has been suggested. METHODS: Eleven recipients with C4d-positive CAN (index biopsy performed after a median of 3 years posttransplantation), who had been on cyclosporine A-based immunosuppression, were converted to tacrolimus, and if not part of basal therapy, to mycophenolate mofetil. We evaluated the effect of this tacrolimus/mycophenolate mofetil rescue therapy on clinical outcomes and on alloantibody formation detected with flow cytometric testing of panel-reactive antibody. RESULTS: Tacrolimus/mycophenolate mofetil rescue therapy (plus anti-rejection treatment in six recipients with additional signs of acute cellular rejection) failed to prevent progressive deterioration of graft function. Four patients returned to dialysis after 4 to 18 months. Serial post-transplant serology detected HLA class I and/or II reactivity in seven recipients. Tacrolimus/mycophenolate mofetil therapy did not affect the time course of alloantibody levels. One patient with C4d-positive transplant glomerulopathy, who did not respond to tacrolimus/mycophenolate mofetil rescue therapy, developed nephroticrange proteinuria associated with a rapid decline of allograft function. Despite considerable reduction in alloantibody levels and nearly complete clearance of C4d deposits, immunoadsorption failed to prevent graft failure in this patient. CONCLUSION: Our data argue against the efficacy of tacrolimus/mycophenolate mofetil rescue therapy in established C4d-positive chronic allograft dysfunction. Prospective trials are needed to evaluate whether early initiation of this or other antihumoral strategies are capable of effectively preventing alloantibody-mediated chronic graft injury.
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Schwarz, C., Regele, H., Huttary, N. et al. Rescue therapy with tacrolimus and mycophenolate mofetil does not prevent deterioration of graft function in C4d-positive chronic allograft nephropathy. Wien Klin Wochenschr 118, 397–404 (2006). https://doi.org/10.1007/s00508-006-0531-3
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DOI: https://doi.org/10.1007/s00508-006-0531-3