Ignite Creation Date:
2024-05-05 @ 5:28 PM
Last Modification Date:
2024-10-26 @ 9:32 AM
Study NCT ID:
NCT00464503
Status:
COMPLETED
Last Update Posted:
2008-04-08
First Post:
2007-04-20
Brief Title:
Statins and the Urinary Proteome
Sponsor:
Universiteit Antwerpen
Organization:
Universiteit Antwerpen
Study Overview
Official Title:
The Effect of Statins on the Urinary Proteome
Status:
COMPLETED
Status Verified Date:
2008-04
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:
This study aims to investigate whether statines rosuva- and pravastatin induce tubular proteinuria
Detailed Description:
The proximal tubular cells of the kidney are responsible for reabsorption of proteins from the tubular lumen In a study using Opossum kidney OK cells receptor-mediated protein endocytosis was reduced by statins inhibitors of 3-hydroxy-3-methylglutaryl CoA HMG-CoA reductase which are widely used for therapeutic reduction of plasma cholesterol levels 1 In a subsequent in vitro study protein endocytosis in human mixed proximaldistal kidney tubular cells was investigated in the presence and absence of statins to explore the possible clinical relevance of the observations in OK cells 2 The uptake of FITC-labeled albumin in these cultures occurred selectively into proximal tubular cells while it was absent in distal tubularcollecting duct cells Three statins simvastatin pravastatin and rosuvastatin significantly inhibited the uptake of protein in a concentration-dependent way This inhibitory effect of statins could be prevented by the co-addition of mevalonate the product of HMG-CoA reductase This effect was not the result of a statin-induced cytotoxicity since cell-viability was unaffected
These data suggest that statins have the potential to inhibit albumin uptake by the human proximal nephron as a result of inhibition of HMG-CoA reductase in the proximal tubule cells A reduced prenylation of some proteins critically involved in endocytosis has been put forward as the underlying mechanism
Knowing these data it has been suggested that the occurrence of proteinuria in some patients treated with high statin doses is the result of a reduced tubular reabsorptionendocytosis of normally filtered proteins To further explore the clinical relevance of such a mechanism the composition of the urinary proteome under statin treatment will be investigated in normal healthy volunteers by two-dimensional gel electrophoresis based proteomics analysis
These data suggest that statins have the potential to inhibit albumin uptake by the human proximal nephron as a result of inhibition of HMG-CoA reductase in the proximal tubule cells A reduced prenylation of some proteins critically involved in endocytosis has been put forward as the underlying mechanism
Knowing these data it has been suggested that the occurrence of proteinuria in some patients treated with high statin doses is the result of a reduced tubular reabsorptionendocytosis of normally filtered proteins To further explore the clinical relevance of such a mechanism the composition of the urinary proteome under statin treatment will be investigated in normal healthy volunteers by two-dimensional gel electrophoresis based proteomics analysis
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