Influence of Sirolimus and MMF on Vascular Function and Markers of Cellular Function in Renal Transplant Recipients
Condition: Renal Transplantation
Study type: Interventional
Phase: Phase 4

Summary: 
      Chronic transplant nephropathy and cardiovascular death are the main reasons for loss of
      transplanted organs after kidney transplantation.

      Vascular changes, induced by hypertension and/or immunological processes, determine long time
      transplant survival.

      It will be tested whether the withdrawal of calcineurininhibitors will improve the vessel
      wall function in renal transplant patients. It is supposed that this immunosuppressive
      regimen reduces the activation of endothelial cells with important impact on arteriosclerosis
      and therefore on patient and transplant survival.
    

Detailed description: 
      Cardiovascular complications and chronic rejection are chief causes of transplant loss[1,2].
      After renal transplantation patients are still characterized by their pre-existing
      arteriosclerotic changes [3]. Endothelial dysfunction and disturbed distensibility of great
      arteries are independent predictors of cardiovascular morbidity [4,5]. Additionally the
      activation of sympathetic nervous system leads to dysfunction of vessel wall[6,7]. There are
      important therapeutic options in improvement of endothelial function [8].

      In addition monocytes of the recipient will contribute to vessel wall changes. [9-11]. Aim of
      therapy - especially of immunosuppressive therapy- have to prevent these fatal vessel wall
      changes.

      Therefore in this study the following topics will be addressed.

      1. Discontinuing of calcineurininhibitors will lead to improvement of vessel wall function 2.
      Sirolimus and Mycophenolat Mofetil affect vessel wall properties in a different way.

      3. There are risk factors, e.g. activity of sympathetic nervous system, which may determine
      the efficacy of discontinuing the calcineurininhibitor concerning the vessel wall function.

      4. Calcineurininhibitorfree immunosuppression reduces the activity of endothelial cells.

      5. Survival of monocytes and release of procoagulatory activity will be changed by the
      immunosuppressive regimen.

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        8. Kosch M, Barenbrock M, Kisters K, Rahn KH, Hausberg M. Relationship between muscle
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        9. Österud, A., Björklid E. Role of monocytes in atherogenesis. Physiological reviews,
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Intervention name(s): sirolimus (drug), mmf (drug)
Intervention type(s): Drug
Intervention MeSH terms: Sirolimus
Allocation: Randomized
Intervention model: Parallel Assignment
Masking: None (Open Label)
Primary purpose: Treatment
Keywords: rejection; vesselwall function; endothelial cell function; monocytes