Endothelial dysfunction and inflammation predict development of diabetic nephropathy in the Irbesartan in Patients with Type 2 Diabetes and Microalbuminuria (IRMA 2) study. Export

@article{citeulike:4096687, abstract = {OBJECTIVE: To evaluate risk factors for progression from persistent microalbuminuria to diabetic nephropathy in the Irbesartan in Patients with Type 2 diabetes and Microalbuminuria (IRMA 2) study, including biomarkers of endothelial dysfunction, chronic low-grade inflammation, growth factors and advanced glycation end products (AGE peptides). METHODS: IRMA 2 was a 2-year multicentre, randomized, double-blind trial comparing irbesartan (150 and 300 mg once daily) versus placebo. The primary end-point was time to onset of diabetic nephropathy. Samples from a subgroup from the placebo and the 300 mg irbesartan treatment group were used in this post-hoc analysis (n = 269, 68 \%). Nine biomarkers were analysed: high sensitivity C-reactive protein (hs-CRP), interleukin 6 (IL-6), fibrinogen, von Willebrand Factor (vWf), soluble vascular cell adhesion molecule-1 (sVCAM-1), soluble intercellular cell adhesion molecule-1 (sICAM-1), sE-selectin, transforming growth factor-beta (TGF-beta) and AGE peptides. Mean standard deviation scores (Z-scores) were used to combine biomarker information. RESULTS: In a Cox enter model with combined Z-scores for biomarkers of endothelial dysfunction (vWf, sVCAM-1, sICAM-1, sE-selectin) and for biomarkers of inflammation (hs-CRP, IL-6, fibrinogen), endothelial dysfunction (hazard ratio for a 28 \% increase ( = 1 SD) in Z-score) 3.20 (1.56 to 6.56), p = 0.001) and UAER (HR for a 75 \% increase ( = 1 SD) in UAER) 2.61 (1.30 to 5.23), p = 0.007) were found as independent predictors. Independently, IL-6 and vWf predicted the end-point. In addition, endothelial Z-score was associated with progression of albuminuria (p = 0.038). CONCLUSION: Endothelial dysfunction and possibly inflammation are novel predictors of progression to diabetic nephropathy in patients with type 2 diabetes and microalbuminuria independently of traditional risk factors. ClinicalTrials.gov ID: NCT00317915.}, author = {Persson, F. and Rossing, P. and Hovind, P. and Stehouwer, C. D. and Schalkwijk, C. G. and Tarnow, L. and Parving, H. H.}, citeulike-article-id = {4096687}, citeulike-linkout-0 = {http://dx.doi.org/10.1080/00365510802187226}, citeulike-linkout-1 = {http://view.ncbi.nlm.nih.gov/pubmed/18609080}, citeulike-linkout-2 = {http://www.hubmed.org/display.cgi?uids=18609080}, doi = {10.1080/00365510802187226}, issn = {1502-7686}, journal = {Scandinavian journal of clinical and laboratory investigation}, keywords = {arb, dm, enddysf, inflammation, rct, uae}, number = {8}, pages = {731--738}, posted-at = {2009-02-25 07:09:24}, priority = {2}, title = {Endothelial dysfunction and inflammation predict development of diabetic nephropathy in the Irbesartan in Patients with Type 2 Diabetes and Microalbuminuria (IRMA 2) study.}, url = {http://dx.doi.org/10.1080/00365510802187226}, volume = {68}, year = {2008} }

TY - JOUR ID - citeulike:4096687 L3 - citeulike-article-id:4096687 N2 - OBJECTIVE: To evaluate risk factors for progression from persistent microalbuminuria to diabetic nephropathy in the Irbesartan in Patients with Type 2 diabetes and Microalbuminuria (IRMA 2) study, including biomarkers of endothelial dysfunction, chronic low-grade inflammation, growth factors and advanced glycation end products (AGE peptides). METHODS: IRMA 2 was a 2-year multicentre, randomized, double-blind trial comparing irbesartan (150 and 300 mg once daily) versus placebo. The primary end-point was time to onset of diabetic nephropathy. Samples from a subgroup from the placebo and the 300 mg irbesartan treatment group were used in this post-hoc analysis (n = 269, 68 %). Nine biomarkers were analysed: high sensitivity C-reactive protein (hs-CRP), interleukin 6 (IL-6), fibrinogen, von Willebrand Factor (vWf), soluble vascular cell adhesion molecule-1 (sVCAM-1), soluble intercellular cell adhesion molecule-1 (sICAM-1), sE-selectin, transforming growth factor-beta (TGF-beta) and AGE peptides. Mean standard deviation scores (Z-scores) were used to combine biomarker information. RESULTS: In a Cox enter model with combined Z-scores for biomarkers of endothelial dysfunction (vWf, sVCAM-1, sICAM-1, sE-selectin) and for biomarkers of inflammation (hs-CRP, IL-6, fibrinogen), endothelial dysfunction (hazard ratio for a 28 % increase ( = 1 SD) in Z-score) 3.20 (1.56 to 6.56), p = 0.001) and UAER (HR for a 75 % increase ( = 1 SD) in UAER) 2.61 (1.30 to 5.23), p = 0.007) were found as independent predictors. Independently, IL-6 and vWf predicted the end-point. In addition, endothelial Z-score was associated with progression of albuminuria (p = 0.038). CONCLUSION: Endothelial dysfunction and possibly inflammation are novel predictors of progression to diabetic nephropathy in patients with type 2 diabetes and microalbuminuria independently of traditional risk factors. ClinicalTrials.gov ID: NCT00317915. IS - 8 JF - Scandinavian journal of clinical and laboratory investigation SN - 1502-7686 EP - 738 TI - Endothelial dysfunction and inflammation predict development of diabetic nephropathy in the Irbesartan in Patients with Type 2 Diabetes and Microalbuminuria (IRMA 2) study. VL - 68 SP - 731 KW - arb KW - dm KW - enddysf KW - inflammation KW - rct KW - uae AU - Persson, F AU - Rossing, P AU - Hovind, P AU - Stehouwer, CD AU - Schalkwijk, CG AU - Tarnow, L AU - Parving, HH PY - 2008/// UR - http://dx.doi.org/10.1080/00365510802187226 ER -