Urinary proteome analysis enables assessment of renoprotective treatment in type 2 diabetic patients with microalbuminuria

BMC Nephrology

Research Article

Harald Mischak¹  Hans-Henrik Parving²  Petra Zürbig³  Sten Andersen⁴  Peter Rossing⁵ 

[1] BHF Glasgow Cardiovascular Research Centre, Glasgow, United Kingdom;Mosaiques diagnostics GmbH, Hannover, Germany;members of EuroKUP, Denmark;Department of Medical Endocrinology Rigshospitalet, University Hospital of Copenhagen, Copenhagen, Denmark;Faculty of Health Sciences, University of Aarhus, Aarhus, Denmark;Mosaiques diagnostics GmbH, Hannover, Germany;members of EuroKUP, Denmark;Steno Diabetes Centre, Gentofte, Denmark;Steno Diabetes Centre, Gentofte, Denmark;members of EuroKUP, Denmark;

关键词: Chronic Kidney Disease;    Diabetic Nephropathy;    Irbesartan;    Urinary Albumin Excretion;    Urinary Proteome;   

DOI  :  10.1186/1471-2369-11-29

 received in 2010-07-01, accepted in 2010-11-01,  发布年份 2010

来源: Springer

【 摘 要 】

BackgroundPreviously the angiotensin II receptor blocker Irbesartan has been demonstrated to reduce the risk for progression from microalbuminuria to macroalbuminuria in type 2 diabetic patients. The purpose of this study was to evaluate the effect of treatment with Irbesartan in type 2 diabetic patients with microalbuminuria on the urinary proteome.MethodsHigh-resolution capillary-electrophoresis coupled to mass-spectrometry (CE-MS) was used to profile the low-molecular-weight proteome in urine of a subgroup of patients from a two year randomized irbesartan versus placebo therapy trial, which included hypertensive type 2 diabetic patients with microalbuminuria on ongoing antihypertensive medication (IRMA2-substudy).ResultsWe demonstrate that the therapy with 300 mg Irbesartan daily over a period of two years results in significant changes of the urinary proteome. Both, a classifier developed previously that consists of urinary peptides indicative of chronic kidney disease, as well as several individual peptides changed significantly after treatment. These changes were not observed in the placebo-treated individuals. Most prominent are changes of urinary collagen fragments associated with progression of diabetic nephropathy, indicating normalization in urinary peptides.ConclusionCE-MS analysis of urine enabled identification of peptides as potential surrogate markers for renoprotection in microalbuminuric type 2 diabetic patients, which show persistent improvement after longterm treatment with Irbesartan. The results suggest that a major benefit of treatment by Irbesartan may be improvement of collagen turnover, reduction of fibrosis. They further suggest that urinary proteome analysis could be utilized to assess potential benefit of therapeutic intervention, providing statistically significant results even on a small population.

【 授权许可】

Unknown   
© Andersen et al; licensee BioMed Central Ltd. 2010. This article is published under license to BioMed Central Ltd. This is an Open Access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/2.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.