Statins and the Urinary Proteome

April 3, 2008 updated by: Universiteit Antwerpen

The Effect of Statins on the Urinary Proteome

This study aims to investigate whether statines (rosuva- and pravastatin) induce tubular proteinuria.

Study Overview

Status

Completed

Conditions

Intervention / Treatment

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 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.

Study Type

Interventional

Enrollment (Actual)

7

Phase

  • Not Applicable

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Locations

  • Belgium
      • Antwerp, Belgium, 2610
        • University of Antwerp

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Ages Eligible for Study

25 years to 65 years (Adult, Older Adult)

Accepts Healthy Volunteers

No

Genders Eligible for Study

Male

Description

Inclusion Criteria:

  • Male, age range: 25 - 65 years
  • Non-smoker
  • Proteinuria: < 60 mg/24 hours
  • Dipstick negative hematuria
  • Bloodpressure: < 135 mm systolic, < 85 mm dyastolic
  • Waist circumference: < 94 cm

Exclusion Criteria:

  • Treatment with lipid-lowering drugs <1 year prior to the study
  • Known history of diabetes or fasting glucose level: < 110 mg/dl
  • Anti-hypertensive medication
  • Life-expectancy < 1 year
  • Pharmacological treatment with inotropes
  • Acute or chronic inflammatory process, use if anti-inflammatory drugs or immunosuppression
  • Clinically active malignant disease
  • Administration of any investigational drug within 30 days preceding study start and during the study
  • Known intolerance to rosuvastatin or other statins
  • Acute or chronic liver disease or ALAT>2.0 x upper limit of normal (ULN) at enrolment visit.
  • Chronic muscle disease such as dermatomyositis or polymyositis or unexplained creatinine kinase (CK) above 3 x ULN at enrolment.
  • Uncontrolled hypothyroidism as indicated by a thyroid stimulating hormone (TSH) > 2 x ULN at enrolment.
  • Renal insufficiency: creatinine > 2.0mg/dl
  • Known or suspect alcohol or drug abuse.

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Primary Purpose: Diagnostic
  • Allocation: Randomized
  • Interventional Model: Crossover Assignment
  • Masking: Double

What is the study measuring?

Primary Outcome Measures

Outcome Measure
The urinary protein pattern observed by difference gel electrophoresis based proteomics analysis in healthy subjects before and after the administration of rosuvastatin (Crestor®).

Secondary Outcome Measures

Outcome Measure
The urinary protein pattern observed by difference gel electrophoresis based proteomics analysis in healthy subjects before and during the administration of pravastatin (Pravasine®).
The urinary protein pattern observed by difference gel electrophoresis based proteomics analysis in healthy subjects during the administration of rosuvastatin (Crestor®) vs pravastatin (Pravasine®).
The urinary protein pattern observed by difference gel electrophoresis based proteomics analysis in healthy subjects during the administration of rosuvastatin (Crestor®) or pravastatin (Pravasine®) and after wash-out of these compounds.
The urinary albumin and retinol binding protein concentration before in healthy subjects, during and after administration of rosuvastatin (Crestor®) or pravastatin (Pravasine®).

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

Universiteit Antwerpen

Investigators

  • Study Director: Patrick C D'Haese, Prof, Universiteit Antwerpen

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start

September 1, 2007

Primary Completion (Actual)

October 1, 2007

Study Completion (Actual)

October 1, 2007

Study Registration Dates

First Submitted

April 20, 2007

First Submitted That Met QC Criteria

April 20, 2007

First Posted (Estimate)

April 23, 2007

Study Record Updates

Last Update Posted (Estimate)

April 8, 2008

Last Update Submitted That Met QC Criteria

April 3, 2008

Last Verified

April 1, 2008

More Information

Terms related to this study

Keywords

Additional Relevant MeSH Terms

Other Study ID Numbers

  • STAT-AZ-01

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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