Influence of Sirolimus and MMF on Vascular Function and Markers of Cellular Function in Renal Transplant Recipients
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.
|Study Design:||Allocation: Randomized
Endpoint Classification: Efficacy Study
Intervention Model: Parallel Assignment
Masking: Open Label
Primary Purpose: Treatment
|Official Title:||Influence of Sirolimus and MMF on Vascular Function and Markers of Cellular Function in Renal Transplant Recipients - Positive Effects of Calcineurin-free Immunosuppression|
- sympathetic nervous system activity
- endothelial cell marker expression
- monocyte survival
|Study Start Date:||June 2005|
|Study Completion Date:||January 2010|
|Primary Completion Date:||January 2008 (Final data collection date for primary outcome measure)|
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 . 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 .
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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- Hausberg, M., K. Kisters, M. Kosch, K. H. Rahn, and M. Barenbrock. Flow-mediated vasodilation and distensibility of the brachial artery in renal allograft recipients. Kidney Int. 55: 1104-1110, 1999.
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- Hausberg M, Kosch M, Harmelink P, Barenbrock M, Hohage H, Kisters K, Dietl KH, Rahn KH. Sympathetic nerve activity in end-stage renal disease. Circulation. 2002, 106:1974-9.
- Kosch M, Barenbrock M, Kisters K, Rahn KH, Hausberg M. Relationship between muscle sympathetic nerve activity and large artery mechanical vessel wall properties in renal transplant patients. J Hypertens. 2002, 20:501-8.
- Österud, A., Björklid E. Role of monocytes in atherogenesis. Physiological reviews, 2003, 83: 1069-1112.
- Ross R. Atherosclerosis--an inflammatory disease. N Engl J Med. 1999 Jan 14;340(2):115-26.
- Lessner SM, Prado HL, Waller EK, Galis ZS. Atherosclerotic lesions grow through recruitment and proliferation of circulating monocytes in a murine model. Am J Pathol. 2002 Jun;160(6):2145-55.
Please refer to this study by its ClinicalTrials.gov identifier: NCT00204321
|Münster, NRW, Germany, 48149|
|Principal Investigator:||Martin Hausberg, MD||UKM - Medical Department D|