The Influence of Rosiglitazone on the Diuretic Effect of Furosemide and Amiloride
Status:
Completed
Trial end date:
2006-11-01
Target enrollment:
Participant gender:
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.