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Article

Urine E-cadherin: A Marker for Early Detection of Kidney Injury in Diabetic Patients

1
Clinic for Nephrology and Rheumatology, University Medical Center Göttingen 1, 37075 Göttingen, Germany
2
Institute for Clinical Chemistry/UMG-Laboratories, University Medical Center Göttingen, 37075 Göttingen, Germany
3
Institute for Animal Breeding and Genetics, University of Veterinary Medicine Hannover, 30559 Hannover, Germany
4
Clinic for Gastroenterology and Gastrointestinal Oncology, University Medical Center Göttingen, 37075 Göttingen, Germany
5
Proteomics Group, Max-Planck-Institute of Experimental Medicine, 37075 Göttingen, Germany
6
Bioanalytical Mass Spectrometry, Max Planck Institute for Biophysical Chemistry, 37075 Göttingen, Germany
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Laboratory of Biotechnology and Molecular Bioengineering, Faculty of Sciences and Techniques Gueliz, Cadi Ayyad University, Marrakech 40000, Morocco
8
Center for Biostructural Imaging of Neurodegeneration (BIN), University Medical Center Göttingen, 37075 Göttingen, Germany
*
Authors to whom correspondence should be addressed.
These authors contributed equally to the work.
J. Clin. Med. 2020, 9(3), 639; https://doi.org/10.3390/jcm9030639
Received: 19 December 2019 / Revised: 11 February 2020 / Accepted: 24 February 2020 / Published: 27 February 2020
(This article belongs to the Special Issue Diabetic Nephropathy: Diagnosis, Prevention and Treatment)
Diabetic nephropathy (DN) is the main reason for end-stage renal disease. Microalbuminuria as the non-invasive available diagnosis marker 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 with microalbuminuria, diabetes with macroalbuminuria 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 DN patients and the other groups. Label-free mass 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 ± 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). View Full-Text
Keywords: Diabetic nephropathy; early diagnosis/prognosis; E-cadherin; early biomarker Diabetic nephropathy; early diagnosis/prognosis; E-cadherin; early biomarker
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MDPI and ACS Style

Koziolek, M.; Mueller, G.A.; Dihazi, G.H.; Jung, K.; Altubar, C.; Wallbach, M.; Markovic, I.; Raddatz, D.; Jahn, O.; Karaköse, H.; Lenz, C.; Urlaub, H.; Dihazi, A.; El Meziane, A.; Dihazi, H. Urine E-cadherin: A Marker for Early Detection of Kidney Injury in Diabetic Patients. J. Clin. Med. 2020, 9, 639. https://doi.org/10.3390/jcm9030639

AMA Style

Koziolek M, Mueller GA, Dihazi GH, Jung K, Altubar C, Wallbach M, Markovic I, Raddatz D, Jahn O, Karaköse H, Lenz C, Urlaub H, Dihazi A, El Meziane A, Dihazi H. Urine E-cadherin: A Marker for Early Detection of Kidney Injury in Diabetic Patients. Journal of Clinical Medicine. 2020; 9(3):639. https://doi.org/10.3390/jcm9030639

Chicago/Turabian Style

Koziolek, Michael, Gerhard A. Mueller, Gry H. Dihazi, Klaus Jung, Constanze Altubar, Manuel Wallbach, Ivana Markovic, Dirk Raddatz, Olaf Jahn, Hülya Karaköse, Christof Lenz, Henning Urlaub, Abdelhi Dihazi, Abdellatif El Meziane, and Hassan Dihazi. 2020. "Urine E-cadherin: A Marker for Early Detection of Kidney Injury in Diabetic Patients" Journal of Clinical Medicine 9, no. 3: 639. https://doi.org/10.3390/jcm9030639

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