Effects of the PPAR-gamma agonist rosiglitazone on renal haemodynamics and the renin-angiotensin system in diabetes.
BACKGROUND
Thiazolidinediones (TZD) have been reported to improve early stages of diabetic nephropathy independent of glycaemic control. Since blockade of the renin-angiotensin system (RAS) is known to reduce the risk of nephropathy, we hypothesised that the renal effect of TZDs might be related to a favourable effect on the intrarenal RAS. We aimed to determine if the TZD rosiglitazone could reduce RAS activation.


METHODS
We studied adult type 2 diabetic patients and placed them on rosiglitazone for three months. We have previously used the renal haemodynamic response to angiotensin-converting enzyme (ACE) inhibition to demonstrate the state of RAS activation, and thus measured renal plasma flow (RPF) and glomerular filtration rate (GFR) before and after administration of captopril at 0 month and at three months. Plasma renin activity (PRA), active renin, aldosterone and natriuretic peptides were analysed.


RESULTS
The RPF response to ACE inhibition was not altered. There was no change in GFR, PRA, active renin and aldosterone levels. Two patients developed oedema one had an elevated baseline active renin and another had an elevated baseline aldosterone level.


CONCLUSIONS
The favourable effects of TZDs on diabetic nephropathy is likely not related to an influence on the RAS.
Lansang
M Cecilia
MC
Department of Medicine, University of Florida, Gainesville, Florida, FL 32610-0226, USA. lansamc@medicine.ufl.edu
Coletti
Caroline
C
Ahmed
Sofia
S
Gordon
Michael S
MS
Hollenberg
Norman K
NK
D000328:Adult; D000368:Aged; D003924:Diabetes Mellitus, Type 2 / Q000503:physiopathology*; D005260:Female; D005919:Glomerular Filtration Rate / Q000187:drug effects; D006801:Humans; D007004:Hypoglycemic Agents / Q000008:administration & dosage*; D008297:Male; D008875:Middle Aged; D047495:PPAR gamma / Q000819:agonists*; D012079:Renal Circulation / Q000187:drug effects*; D012084:Renin-Angiotensin System / Q000187:drug effects*; D000077154:Rosiglitazone; D045162:Thiazolidinediones / Q000008:administration & dosage*
D007004:Hypoglycemic Agents; D047495:PPAR gamma; D045162:Thiazolidinediones; D000077154:Rosiglitazone