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

Abstract

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).

Serum integrative omics reveals the landscape of human diabetic kidney disease

“…Cathepsin D is an aspartic endoprotease ubiquitously distributed in lysosomes [ 43 , 44 ] that can regulate extracellular matrix homeostasis, glomerular permeability, endothelial function, and inflammation in kidney diseases [ 45 ]. CD324 (AKA E-cadherin) is a cell–cell adhesion protein increased during microalbuminuria progression after diabetes [ 46 ]. Soluble CD324 fragments in the urine of patients with early-stage DKD is considered to be a sign of kidney deterioration.…”

Potential Role of N-Cadherin in Diagnosis and Prognosis of Diabetic Nephropathy

“…Moreover, a recent study confirmed and validated the use of urine E-cadherin as a marker for early detection of kidney injury in diabetic patients in a longitudinal setting ( 40 ). Their findings indicated not only that E-cadherin levels are elevated in nephropathy patients, but can also differentiate between the different stages of DN.…”

“…analyzed kidney tissues from two biopsy cohorts. They reported a significant upregulation in DN patients in their smaller cohort of 22 samples but no difference in their larger cohort which included 201 biopsies belonging to different diseases groups ( 40 ).…”

Proficient Novel Biomarkers Guide Early Detection of Acute Kidney Injury: A Review

“…According to research, diabetic people who are at risk of developing renal illness may benefit from using the E-cadherin as an early predictive biomarker. Additionally, it appears that the release of E-cadherin in diabetes patients’ urine is an early sign of impaired kidney function and epithelial injury [ 117 ].…”