Urine E-cadherin: A Marker for Early Detection of Kidney Injury in Diabetic Patients
Koziolek, Michael ; Mueller, Gerhard A. ; Dihazi, Gry H. ; Jung, Klaus ; Altubar, Constanze ; Wallbach, Manuel ; Markovic, Ivana ; Raddatz, Dirk et al.
Zitierfähiger Link (URL): http://resolver.sub.uni-goettingen.de/purl?gs-1/17408
Diabetic nephropathy (DN) is themain reason for end-stage renal disease. Microalbuminuria as the non-invasive available diagnosismarker lacks specificity and gives high false positive rates. To identify and validate biomarkers for DN, we used in the present study urine samples from four patient groups: diabetes without nephropathy, diabetes withmicroalbuminuria, diabetes withmacroalbuminuria and proteinuria without diabetes. For the longitudinal validation, we recruited 563 diabetic patients and collected 1363 urine samples with the clinical data during a follow-up of 6 years. Comparative urinary proteomics identified four proteins Apolipoprotein A-I (APOA1), Beta-2-microglobulin (B2M), E-cadherin (CDH1) and Lithostathine-1-alpha (REG1A), which differentiated with high statistical strength ($p$ < 0.05) between DNpatients and the other groups. Label-freemass spectrometric quantification of the candidates confirmed the discriminatory value of E-cadherin and Lithostathine-1-alpha ($p$ < 0.05). Immunological validation highlighted E-cadherin as the only marker able to differentiate significantly between the different DN stages with an area under the curve (AUC) of 0.85 (95%-CI: [0.72, 0.97]). The analysis of the samples from the longitudinal study confirmed the prognostic value of E-cadherin, the critical increase in urinary E-cadherin level was measured 20 $\pm $ 12.5 months before the onset of microalbuminuria and correlated significantly ($p$ < 0.05) with the glomerular filtration rate measured by estimated glomerular filtration rate (eGFR).
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