Renal Hemodynamic Effects of the HMG-CoA Reductase Inhibitors in Normal Volunteers and in Patients With Chronic Renal Failure

This study was done to determine whether Simvastatin (a medication commonly used to treat patients with high cholesterol levels in the blood increases blood flow to the kidneys and improves renal function in normal volunteers and patients with impaired renal function secondary to polycystic kidney diseases.

Study Overview

• Status: Completed
• Conditions: Hypertension; Hyperlipidemia; Chronic Renal Failure
• Intervention / Treatment: Drug: Simvastatin

• Study Type: Interventional
• Phase: Not Applicable

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: Yes
• Genders Eligible for Study: All

Description

Patients with chronic renal failure:

1. Age 18 or older
2. Chronic renal failure secondary to Autosomal Dominant Polycystic Kidney Disease
3. Serum creatinine ≥ 1.4 but ≤ 2.0 mg/dl
4. Creatinine or iothalamate clearance between 35-70 ml/min per 1.73m2
5. Stable renal function for the three preceding months
6. Blood pressure needs to be adequately controlled (< 140/90 mm Hg), with or without the use of antihypertensive agents. However, ACE inhibitors or AT1 receptor blockers must not be initiated, or have their dose increased during the study period.

Patients with normal renal function:

1. Age 18 or older
2. Normal renal function and diagnosed with Autosomal Dominant Polycystic Kidney Disease
3. Serum creatinine ≤ 1.4
4. Creatinine or iothalamate clearance ≥70 ml/min per 1.73m2
5. Renal function has to be stable for the three preceding months
6. Blood pressure needs to be adequately controlled (< 140/90 mm Hg), with or without the use of antihypertensive agents. However, ACE inhibitors or AT1 receptor blockers must not be initiated, or have their dose increased during the study period.

Exclusion criteria include:

1. Patients using corticosteroids, cytotoxic drugs (alkylating agents, chlorambucil, cyclophosphamide), CellCept, or cyclosporin A therapy
2. Positive hepatitis B surface antigen (HBsAg) or hepatitis C antibody (HCV-Ab)
3. Serum transaminase levels (AST, ALT) 2 times the upper limit of normal
4. Clinically significant medical conditions
5. Pregnant patients, patients who are breast-feeding, or women intending to conceive during the course of the study
6. Presence or suspicion of active infection, recent serious infection or chronic/recurrent viral or bacterial infection
7. Presence of concomitant renal artery stenosis.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Effect of short term HMG-CoA reductase treatment	Differences between mean values for RPF, GFR and FF at baseline versus mean values obtained for these same parameters after 4 weeks of treatment will be analyzed using two-tailed Student's paired t-test. A similar analysis will be performed regarding patient's profiles for creatinine clearance, serum creatinine, urinary protein excretion and serum lipids. All results will be expressed as mean ± standard deviations. Differences will be considered significant at P <0.05.	4 weeks

Collaborators and Investigators

• Sponsor: Mayo Clinic

Publications and helpful links

General Publications

• Zand L, Torres VE, Larson TS, King BF, Sethi S, Bergstralh EJ, Angioi A, Fervenza FC. Renal hemodynamic effects of the HMG-CoA reductase inhibitors in autosomal dominant polycystic kidney disease. Nephrol Dial Transplant. 2016 Aug;31(8):1290-5. doi: 10.1093/ndt/gfv394. Epub 2015 Nov 27.

Study record dates

Study Major Dates

• Primary Completion (Actual): January 1, 2007

Study Registration Dates

• First Submitted: July 24, 2015
• First Submitted That Met QC Criteria: July 27, 2015
• First Posted (Estimate): July 30, 2015

Study Record Updates

• Last Update Posted (Actual): March 16, 2023
• Last Update Submitted That Met QC Criteria: March 15, 2023
• Last Verified: March 1, 2023

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Metabolic Diseases; Kidney Diseases; Urologic Diseases; Lipid Metabolism Disorders; Dyslipidemias; Renal Insufficiency, Chronic; Kidney Failure, Chronic; Renal Insufficiency; Hyperlipidemias; Molecular Mechanisms of Pharmacological Action; Enzyme Inhibitors; Antimetabolites; Anticholesteremic Agents; Hypolipidemic Agents; Lipid Regulating Agents; Hydroxymethylglutaryl-CoA Reductase Inhibitors; Simvastatin
• Other Study ID Numbers: 475-01