Ligia Petrica1, Adrian Vlad2, Gheorghe Gluhovschi1, Alina Zamfir3, Cristina Popescu4, Florica Gadalean1, Victor Dumitrascu5, Daliborca Vlad5, Roxana Popescu6, Silvia Velciov1, Cristina Gluhovschi1, Flaviu Bob1, Oana Milas7, Sorin Ursoniu8. 1. Department of Nephrology, "Victor Babes" University of Medicine and Pharmacy Timisoara, Romania. 2. Department of Diabetes and Metabolic Diseases, "Victor Babes" University of Medicine and Pharmacy Timisoara, Romania. 3. National Institute for Research and Development of Electrochemistry and Condensed Matter Timisoara, Romania. 4. Department of Experimental and Applied Biology, Institute of Life Sciences, "Vasile Goldis" Western University Arad, Romania. 5. Department of Pharmacology, "Victor Babes" University of Medicine and Pharmacy Timisoara, Romania. 6. Department of Cellular Biology, "Victor Babes" University of Medicine and Pharmacy Timisoara, Romania. 7. Department of Nephrology, County Emergency Hospital Timisoara, Romania. 8. Department of Public Health Medicine, "Victor Babes" University of Medicine and Pharmacy Timisoara, Romania.
Abstract
BACKGROUND: Advanced glycation end-products have been involved in the pathogenesis of proximal tubule dysfunction which characterizes diabetic tubulopathy. METHODS: A total of 76 Type 2 diabetes mellitus patients and 28 healthy controls were evaluated concerning a potential association of glycated peptides with proximal tubule dysfunction by assessing urine albumin:creatinine ratio, urinary alpha1-microglobulin, urinary neutrophil gelatinase-associated lipocalin, plasma and urinary advanced glycation end-products, plasma asymmetric dimethyl-arginine, serum cystatin C. Fully automated chip-nanoelectrospray ionization and high-capacity ion trap multistage mass spectrometry characterized the urinary proteomic profile. RESULTS: The urinary glycated proteins displayed a molecular weight of 15,121.4 Da in normoalbuminuric patients and of 30,180.4 Da in microalbuminuric patients. Urinary alpha1-microglobulin and neutrophil gelatinase-associated lipocalin correlated with urinary advanced glycation end-products (R(2)=0.586; R(2)=0.415), urine albumin: creatinine ratio (R(2)=0.292; R(2)=0.116), estimated glomerular filtration rate (R(2)=0.172; R(2)=0.135), serum cystatin C (R(2)=0.146; R(2)=0.129), but not with asymmetric dimethyl-arginine. In multivariable regression analysis models, the correlations for urinary alpha1-microglobulin and neutrophil gelatinase-associated lipocalin remained significant with urine albumin: creatinine ratio, urinary advanced glycation end-products, estimated glomerular filtration rate (P<0.0001, R(2)=0.674; P<0.0001, R(2)=0.551; P<0.0001, R(2)=0.482). CONCLUSIONS: In patients with Type 2 diabetes mellitus urinary glycated peptides are associated with proximal tubule dysfunction. The proteomic patterns of urinary glycated peptides could differentiate normo- from microalbuminuric patients and may explain a potential relation between the size and the glycation status of glycated peptides, and the extent of proximal tubule dysfunction. The lack of correlation between parameters of endothelial dysfunction and proximal tubule dysfunction cannot exclude glomerular involvement in early diabetic nephropathy.
BACKGROUND: Advanced glycation end-products have been involved in the pathogenesis of proximal tubule dysfunction which characterizes diabetic tubulopathy. METHODS: A total of 76 Type 2 diabetes mellituspatients and 28 healthy controls were evaluated concerning a potential association of glycated peptides with proximal tubule dysfunction by assessing urine albumin:creatinine ratio, urinary alpha1-microglobulin, urinary neutrophil gelatinase-associated lipocalin, plasma and urinary advanced glycation end-products, plasma asymmetric dimethyl-arginine, serum cystatin C. Fully automated chip-nanoelectrospray ionization and high-capacity ion trap multistage mass spectrometry characterized the urinary proteomic profile. RESULTS: The urinary glycated proteins displayed a molecular weight of 15,121.4 Da in normoalbuminuric patients and of 30,180.4 Da in microalbuminuric patients. Urinary alpha1-microglobulin and neutrophil gelatinase-associated lipocalin correlated with urinary advanced glycation end-products (R(2)=0.586; R(2)=0.415), urine albumin: creatinine ratio (R(2)=0.292; R(2)=0.116), estimated glomerular filtration rate (R(2)=0.172; R(2)=0.135), serum cystatin C (R(2)=0.146; R(2)=0.129), but not with asymmetric dimethyl-arginine. In multivariable regression analysis models, the correlations for urinary alpha1-microglobulin and neutrophil gelatinase-associated lipocalin remained significant with urine albumin: creatinine ratio, urinary advanced glycation end-products, estimated glomerular filtration rate (P<0.0001, R(2)=0.674; P<0.0001, R(2)=0.551; P<0.0001, R(2)=0.482). CONCLUSIONS: In patients with Type 2 diabetes mellitus urinary glycated peptides are associated with proximal tubule dysfunction. The proteomic patterns of urinary glycated peptides could differentiate normo- from microalbuminuric patients and may explain a potential relation between the size and the glycation status of glycated peptides, and the extent of proximal tubule dysfunction. The lack of correlation between parameters of endothelial dysfunction and proximal tubule dysfunction cannot exclude glomerular involvement in early diabetic nephropathy.
Entities:
Keywords:
Glycated peptides; Type 2 diabetes mellitus; normoalbuminuria; proximal tubule
Authors: Michael Morcos; Ahmed A R Sayed; Angelika Bierhaus; Benito Yard; Rüdiger Waldherr; Wolfgang Merz; Ingrid Kloeting; Erwin Schleicher; Stefani Mentz; Randa F Abd el Baki; Hans Tritschler; Michael Kasper; Vedat Schwenger; Andreas Hamann; Klaus A Dugi; Anne-Marie Schmidt; David Stern; Reinhard Ziegler; Hans U Haering; Martin Andrassy; Fokko van der Woude; Peter P Nawroth Journal: Diabetes Date: 2002-12 Impact factor: 9.461
Authors: E Ritz; G C Viberti; L M Ruilope; A J Rabelink; J L Izzo; S Katayama; S Ito; A Mimran; J Menne; L C Rump; A Januszewicz; H Haller Journal: Diabetologia Date: 2009-10-30 Impact factor: 10.122