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Horm Metab Res 2012; 44(12): 914-918
DOI: 10.1055/s-0032-1314836
Humans, Clinical
© Georg Thieme Verlag KG Stuttgart · New York

Effect of Thiazolidinedione Treatment on Proteinuria and Renal Hemodynamic in Type 2 Diabetic Patients with Overt Nephropathy

F. Pistrosch
1   Medical Clinic III, Department of Internal Medicine, University Hospital “Carl Gustav Carus”, Dresden, Germany
,
J. Passauer
1   Medical Clinic III, Department of Internal Medicine, University Hospital “Carl Gustav Carus”, Dresden, Germany
,
K. Herbrig
1   Medical Clinic III, Department of Internal Medicine, University Hospital “Carl Gustav Carus”, Dresden, Germany
,
U. Schwanebeck
2   Koordinationszentrum für klinische Studien, Technical University Dresden, Dresden, Germany
,
P. Gross
1   Medical Clinic III, Department of Internal Medicine, University Hospital “Carl Gustav Carus”, Dresden, Germany
,
S. R. Bornstein
1   Medical Clinic III, Department of Internal Medicine, University Hospital “Carl Gustav Carus”, Dresden, Germany
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Publikationsverlauf

received 20. Februar 2012

accepted 07. Mai 2012

Publikationsdatum:
21. Juni 2012 (online)

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Abstract

Proteinuria in diabetic nephropathy predicts the progressive loss of glomerular filtration rate (GFR) and serves as independent predictor for mortality. We performed the present study (ClinicalTrials.gov identifier: NCT 00324675) to clarify whether the activation of PPARγ receptor by thiazolidinediones was able to improve proteinuria and preserve renal function in advanced diabetic nephropathy. A total of 28 type 2 diabetic patients (4 women and 24 men, mean age 66.1±9.1 years) with urinary albumin excretion >300 mg/24 h and an estimated GFR <60 ml/min were included into this prospective double blind trial to receive either rosiglitazone (RSG) 4 mg b.i.d or matching placebo (PLC) for 52 weeks in addition to their concomitant antidiabetic background therapy. At baseline and after 26 and 52 weeks, renal plasma flow (RPF) and GFR were determined before and after blockade of nitric oxide (NO) by intravenous administration of N-monomethyl-l-arginine acetate. RSG treatment resulted in a significant reduction of proteinuria (2.4±1.1; 1.2±0.6; 1.5±0.7 g/d at baseline, 26 weeks and 52 weeks; respectively, p<0.05) whereas PLC did not influence proteinuria (1.6±0.6; 1.6±0.8; 1.7±0.8 g/d). GFR and RPF did not change significantly during the study, however, RSG improved the intrarenal NO bioavailability. RSG treatment was generally well tolerated and the major adverse event – development of edema – could be controlled by dose adjustment of the study drug and diuretic agents. In conclusion, we demonstrated a possible renoprotective effect of RSG in patients with advanced diabetic nephropathy.

Key words

diabetic nephropathy - nitric oxide - proteinuria - type 2 diabetes - thiazolidinedione
 

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