The Influence of Rosiglitazone on the Diuretic Effect of Furosemide and Amiloride

• Status: Completed
• Trial end date: 2006-11-01
• Target enrollment: 0
• Participant gender: All

Summary

Thiazolidinedione derivates (TZD's) are Peroxisome-Proliferator-Activated-Receptor-γ agonists (PPARγ-agonists) and enhance insulin sensitivity. One of the side effects, however, is the fact that subjects treated with these drugs seem to be more prone to fluid retention. The precise mechanism of rosiglitazone-related fluid retention is unknown, but it is clear that either primary or secondary renal sodium retention is part of the mechanism. Furthermore in observational studies, TZD-related oedema seems to be resistant to loop diuretic therapy. The recent finding that rosiglitazone induces upregulation of the epithelial sodium channel (ENaC) in the kidney could be the explanation for TZD-related fluid retention and the observed resistance to loop diuretics. In the present human in-vivo study the following hypothesis will be tested:

Rosiglitazone treatment stimulates the activity of ENaC in the distal nephron, which enhances the natriuretic effect of amiloride and decreases the natriuretic effect of furosemide in parallel.

• Phase: N/A
• Accepts Healthy Volunteers?: Accepts Healthy Volunteers

Details

• Lead Sponsor: Radboud University
• Treatments: Amiloride; Diuretics; Furosemide; Rosiglitazone

Criteria

Inclusion Criteria:

• Healthy but with 2 features of the metabolic syndrome (AHA/NHLBI) (16)

• Willing and able to provide a signed and dated written informed consent.

• Male or female subject aged between 30 and 70 years

Exclusion Criteria:

• Fasting glucose > 7,0 mmol/L or the use of hypoglycaemic agents. If fasting plasma glucose is between 6.1 and 7,0 mmol/L,an oral 75 g glucose test will be performed to exclude diabetes mellitus.

• Exposure to a PPAR-g agonist during the last 4 months or a documented significant hypersensitivity to a PPAR-g agonist.

• Participant in another study.

• Angina or heart failure (NYHA I-IV).

• Clinically significant liver disease (3 times the upper normal limit of ALAT, ASAT, AF, γGT or LDH)

• Clinically significant anaemia (male Hb < 6,9 mmol/L, female < 6,25 mmol/L)

• Creatinin clearance < 40 mL/min

• Pregnancy, lactation

• Alcohol or drug abuse. Liquorice