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Sponsored by: |
Universiteit Antwerpen |
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Information provided by: | Universiteit Antwerpen |
ClinicalTrials.gov Identifier: | NCT00464503 |
This study aims to investigate whether statines (rosuva- and pravastatin) induce tubular proteinuria.
Condition | Intervention |
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Statin Induced Proteinuria |
Drug: Rosuvastatin-Crestor Drug: Pravastatin-Pravasine |
Study Type: | Interventional |
Study Design: | Diagnostic, Randomized, Double-Blind, Uncontrolled, Crossover Assignment, Safety Study |
Official Title: | The Effect of Statins on the Urinary Proteome |
Enrollment: | 7 |
Study Start Date: | September 2007 |
Study Completion Date: | October 2007 |
Primary Completion Date: | October 2007 (Final data collection date for primary outcome measure) |
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 proximal/distal 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 tubular/collecting 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 reabsorption/endocytosis 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.
Ages Eligible for Study: | 25 Years to 65 Years |
Genders Eligible for Study: | Male |
Accepts Healthy Volunteers: | Yes |
Inclusion Criteria:
Exclusion Criteria:
Study ID Numbers: | STAT-AZ-01 |
Study First Received: | April 20, 2007 |
Last Updated: | April 3, 2008 |
ClinicalTrials.gov Identifier: | NCT00464503 |
Health Authority: | Belgium: The Federal Public Service (FPS) Health, Food Chain Safety and Environment; Belgium: Directorate general for the protection of Public health: Medicines |
statins proteinuria proteomic analysis healthy volunteers |
Pravastatin Signs and Symptoms Proteinuria Rosuvastatin |
Urologic Diseases Urination Disorders Healthy |
Antimetabolites Urological Manifestations Molecular Mechanisms of Pharmacological Action Therapeutic Uses Antilipemic Agents |
Enzyme Inhibitors Anticholesteremic Agents Hydroxymethylglutaryl-CoA Reductase Inhibitors Pharmacologic Actions |