Ignite Creation Date:
2024-05-05 @ 11:59 AM
Last Modification Date:
2024-10-26 @ 9:18 AM
Study NCT ID:
NCT00204334
Status:
COMPLETED
Last Update Posted:
2010-01-13
First Post:
2005-09-12
Brief Title:
Effects of Anemia Correction on Vascular and Monocyte Function in Renal Transplant Recipients
Sponsor:
University Hospital Muenster
Organization:
University Hospital Muenster
Study Overview
Official Title:
Effects of Anemia Correction on Vascular Function Endothelial Cell Markers and Monocyte Apoptosis in Renal Transplant Recipients
Status:
COMPLETED
Status Verified Date:
2008-05
Last Known Status:
None
Delayed Posting:
No
If Stopped, Why?:
Not Stopped
Has Expanded Access:
False
If Expanded Access, NCT#:
N/A
Has Expanded Access, NCT# Status:
N/A
Acronym:
None
Brief Summary:
Correction of anaemia in renal transplant recipients by parenteral application of recombinant erythropoietin and if necessary iron will improve large artery function endothelial function and elasticity as assessed by ultrasound techniques and applanation tonometry
The changes in large artery function will be reflected by changes in serological markers of endothelial function and oxidative stress and by changes in monocyte function and apoptosis
There are gender differences in the responses of vascular function to correction of anemia
Besides improvement of large artery function correction of anemia will also affect parameters of graft function ie glomerular and tubular proteinuria
The changes in large artery function will be reflected by changes in serological markers of endothelial function and oxidative stress and by changes in monocyte function and apoptosis
There are gender differences in the responses of vascular function to correction of anemia
Besides improvement of large artery function correction of anemia will also affect parameters of graft function ie glomerular and tubular proteinuria
Detailed Description:
The value of anaemia therapy with recombinant erythropoietin and iron for improvement of cardiovascular outcome has been clearly demonstrated in dialysis patients and is standard of care In this patient collective one study shows that correction of anaemia together with blood pressure control does improve large artery function After kidney transplantation the situation is not clear Anemia is common in kidney transplant patients despite a functioning graft and is caused by inadequate erythropoietin production inflammatory reactions and toxic bone marrow depression Current guidelines suggest to correct anemia also in kidney transplant recipients in analogy to hemodialysis patients however there is to date no evidence that correction of mild to moderate anemia will improve cardiovascular outcome Since cardiovascular outcome studies are difficult to perform in renal transplant patients we propose to study intermediate endpoints surrogate parameters of cardiovascular endpoints ie large artery distensibility and endothelium-dependent brachial artery dilatation Our group was able to show that the former is a valid marker of cardiovascular morbidity in renal transplant patients 1 and a recent report stated the same prognostic value for brachial artery flow-dependent dilatation in hemodialysis patients Since the causes of anemia in renal transplant patients are complex it is not clear that treatment of at anemia with recombinant erythropoietin and iron will be beneficial Erythropoetin treatment is likely to improve hypoxia and thereby to improve large artery function but also upregulates circulating endothelial progenitor cells already elevated in kidney transplant patients and a marker of vascular stress eg in patients with vasculitis Erythropoietin might therefore be detrimental to endothelial function and as a consequence to vascular elasticity It may be argued that in renal transplant patients vascular damage is profound and irreversible and therefore vascular function does not respond to pharmacological interventions However our group was able to show that although renal transplant patients have severely impaired large artery functional wall properties independent of immunosuppressive treatment regimens 2 they have a preserved large artery vasodilator capacity 3 and that treatment with a statin produces sustained long-term improvements of endothelial function in kidney transplant patients 4 Previous studies showed effects of erythropoietin treatment on serological parameters of endothelial function in hemodialysis patients It is important to relate erythropoietin-induced changes in these parameters to changes in large artery function Particularly in the aimed target population immunological processes are very likely to affect vascular function It has been shown that endothelial cell proliferation is induced by angiogenetic factors released by activated monocytes Besides monocyte adhesion to endothelial cells is triggered eg by endothelial cells themselves when they are exposed to shear stress5 During the adhesion process different costimulatory factors become important in the early and critical atherogenetic event Monocyte survival and activation do have a key role in this process leading to arteriosclerosis and endothelial damage6 Changes in monocyte survival in dependence of immunosuppression or erythropoietin treatment may be responsible for increasing circulating endothelial cells7 Therefore we aim to relate erythropoietin-induced changes in vascular function to changes in monocyte function and apoptosis In many disease states changes in endothelial function are reflected by changes in urinary protein excretion Therefore erythropoietin therapy could alter urinary protein excretion in parallel to the changes observed in large artery function Finally anemia is more common in female renal transplant recipients than in male renal transplant recipients and female dialysis patients tend to require more erythropoietin for anemia treatment that male patients Therefore it is conceivable that gender differences exist with respect to the effects of anemia correction on vascular function
1 Barenbrock M M Kosch E Joster K Kisters K H Rahn and M Hausberg Reduced arterial distensibility is a predictor of cardiovascular disease in patients after renal transplantation JHypertens 2002 20 79-84
2 Kosch M Hausberg M Suwelack B Studies on effects of calcineurin inhibitor withdrawal on arterial distensibility and endothelial function in renal transplant recipient Transplantation 2003 761516-9
3 Hausberg M Kisters K Kosch M Rahn KH Barenbrock M Flow-mediated vasodilation and distensibility of the brachial artery in renal allograft recipients Kidney Int 1999 55 1104-1110
4 Kosch M Barenbrock M Suwelack B Schaefer RM Rahn KH Hausberg M Effect of a 3-year therapy with the 3-hydroxy-3-methylglutaryl coenzyme a reductase-inhibitor fluvastatin on endothelial function and distensibility of large arteries in hypercholesterolemic renal transplant recipient Am J Kidney Dis 2003 411088-96
5 Hwang J Saha A Boo YC Sorescu GP McNally JS Holland SM Dikalov S Giddens DP Griendling KK Harrison DG Jo H Oscillatory shear stress stimulates endothelial production of O2- from p47phox-dependent NADPH oxidases leading to monocyte adhesion J Biol Chem 200327847 47291-47298
6 Österud A Björklid E Role of monocytes in atherogenesis Physiological reviews 2003 83 1069-1112
7 Bahlmann FH DeGroot K Duckert T Niemczyk E Bahlmann E Boehm SM Haller H Fliser D Endothelial progenitor cell proliferation and differentiation is regulated by erythropoietin Kidney Int 2003 641648-1652
1 Barenbrock M M Kosch E Joster K Kisters K H Rahn and M Hausberg Reduced arterial distensibility is a predictor of cardiovascular disease in patients after renal transplantation JHypertens 2002 20 79-84
2 Kosch M Hausberg M Suwelack B Studies on effects of calcineurin inhibitor withdrawal on arterial distensibility and endothelial function in renal transplant recipient Transplantation 2003 761516-9
3 Hausberg M Kisters K Kosch M Rahn KH Barenbrock M Flow-mediated vasodilation and distensibility of the brachial artery in renal allograft recipients Kidney Int 1999 55 1104-1110
4 Kosch M Barenbrock M Suwelack B Schaefer RM Rahn KH Hausberg M Effect of a 3-year therapy with the 3-hydroxy-3-methylglutaryl coenzyme a reductase-inhibitor fluvastatin on endothelial function and distensibility of large arteries in hypercholesterolemic renal transplant recipient Am J Kidney Dis 2003 411088-96
5 Hwang J Saha A Boo YC Sorescu GP McNally JS Holland SM Dikalov S Giddens DP Griendling KK Harrison DG Jo H Oscillatory shear stress stimulates endothelial production of O2- from p47phox-dependent NADPH oxidases leading to monocyte adhesion J Biol Chem 200327847 47291-47298
6 Österud A Björklid E Role of monocytes in atherogenesis Physiological reviews 2003 83 1069-1112
7 Bahlmann FH DeGroot K Duckert T Niemczyk E Bahlmann E Boehm SM Haller H Fliser D Endothelial progenitor cell proliferation and differentiation is regulated by erythropoietin Kidney Int 2003 641648-1652
Study Oversight
Has Oversight DMC:
None
Is a FDA Regulated Drug?:
None
Is a FDA Regulated Device?:
None
Is an Unapproved Device?:
None
Is a PPSD?:
None
Is a US Export?:
None
Is an FDA AA801 Violation?:
None
Secondary IDs
| Secondary ID | Type | Domain | Link |
|---|---|---|---|
| DE-2004-4077 | None | None | None |