|
 |
|
|||||||
|
|||||||||
Diabetes 54:2206-2211, 2005
© 2005 by the American Diabetes Association, Inc.
Rosiglitazone Improves Glomerular Hyperfiltration, Renal Endothelial Dysfunction, and Microalbuminuria of Incipient Diabetic Nephropathy in Patients
1 Department of Medicine, Nephrology, University Hospital "Carl Gustav Carus," Dresden, Germany
2 Department of Medicine, Endocrinology and Diabetes, University Hospital "Carl Gustav Carus," Dresden, Germany
Microalbuminuria, an early feature of diabetic nephropathy, indicates intrarenal endothelial damage. In type 2 diabetes, microalbuminuria is strongly related to insulin resistance. We therefore investigated whether rosiglitazone, an insulin-sensitizing drug that is known to improve endothelial dysfunction, was able to improve intrarenal endothelial dysfunction and microalbuminuria. Nineteen type 2 diabetic patients participated in this double-blind cross-over trial. Nine patients with newly diagnosed disease without microalbuminuria were randomized to a treatment with rosiglitazone or nateglinide, each for 12 weeks. Ten patients with microalbuminuria were randomized to rosiglitazone or placebo, each for 12 weeks in addition to their previous antidiabetic medication. After each treatment, glomerular filtration rate (GFR), renal plasma flow, and filtration fraction were measured before and after blockade of nitric oxide (NO) by intravenous administration of N-monomethyl-L-arginine-acetate (L-NMMA). Ten healthy subjects served as control subjects. Type 2 diabetic patients at baseline showed glomerular hyperfiltration compared with healthy control subjects. Rosiglitazone reduced elevated GFR and filtration fraction toward control primarily in patients with microalbuminuria (GFR: 133.4 ± 9.8 vs. 119.6 ± 8.7 ml/min; filtration fraction: 23.2 ± 1.7 vs. 20.5 ± 1.6% before and after rosiglitazone, respectively; control subjects: GFR 111.7 ± 8.6 ml/min, filtration fraction 20.4 ± 1.5%). Rosiglitazone improved intrarenal NO bioavailability in type 2 diabetes toward control as shown by infusion of L-NMMA. Rosiglitazone reduced albumin excretion in type 2 diabetes with microalbuminuria from 116.5 ± 31 to 40.4 ± 12 mg/day. Rosiglitazone ameliorated glomerular hyperfiltration in early type 2 diabetes, improved NO bioavailability, and lessened renal end-organ damage in type 2 diabetes with microalbuminuria.
Address correspondence and reprint requests to Frank Pistrosch, Department of Medicine, Nephrology, University Hospital "Carl Gustav Carus," Fetscherstrasse 74, 01307 Dresden, Germany. E-mail: frankpistrosch{at}hotmail.com
Abbreviations: GFR, glomerular filtration rate; L-NMMA, N-monomethyl-L-arginine-acetate; MAP, mean arterial pressure; PAH, para-aminohippurate; RPF, renal plasma flow
CiteULike 
Del.icio.us 
Digg 
Reddit 
Technorati What's this?
This article has been cited by other articles:
|
|
 |
|
  L. Q. Shen, A. Child, G. M. Weber, J. Folkman, and L. P. Aiello Rosiglitazone and Delayed Onset of Proliferative Diabetic Retinopathy Arch Ophthalmol, June 1, 2008; 126(6): 793 - 799. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 P. Gross and F. Pistrosch PPAR agonists in diabetic nephropathy Nephrol. Dial. Transplant., July 1, 2007; 22(7): 2095 - 2095. [Full Text] [PDF]
|
|
|
|
|
|
H. Boulanger, R. Mansouri, J. F. Gautier, and D. Glotz Reply--PPAR agonists in diabetic nephropathy Nephrol. Dial. Transplant., July 1, 2007; 22(7): 2095 - 2096. [Full Text] [PDF]
|
|
|
|
 |
|
 P. Iglesias and J. J Diez Peroxisome proliferator-activated receptor gamma agonists in renal disease. Eur. J. Endocrinol., May 1, 2006; 154(5): 613 - 621. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 R. E. Gilbert, K. Connelly, D. J. Kelly, C. A. Pollock, and H. Krum Heart Failure and Nephropathy: Catastrophic and Interrelated Complications of Diabetes Clin. J. Am. Soc. Nephrol., March 1, 2006; 1(2): 193 - 208. [Abstract] [Full Text] [PDF]
|
|
| HOME | HELP | FEEDBACK | SUBSCRIPTIONS | ARCHIVE | SEARCH | TABLE OF CONTENTS |
| Diabetes | Diabetes Care | Clinical Diabetes | Diabetes Spectrum |