ALCAM a novel biomarker in patients with type 2 diabetes mellitus complicated with diabetic nephropathy

Alba Sulaj; Stefan Kopf; Elisabeth Gröne; Hermann-Josef Gröne; Sigrid Hoffmann; Erwin Schleicher; Hans-Ulrich Häring; Vedat Schwenger; Stephan Herzig; Thomas Fleming; Peter P Nawroth; Rüdiger von Bauer

doi:10.1016/j.jdiacomp.2017.01.002

ALCAM a novel biomarker in patients with type 2 diabetes mellitus complicated with diabetic nephropathy

J Diabetes Complications. 2017 Jun;31(6):1058-1065. doi: 10.1016/j.jdiacomp.2017.01.002. Epub 2017 Jan 21.

Authors

Affiliations

¹ Department of Medicine I and Clinical Chemistry, University of Heidelberg, INF 410, 69120 Heidelberg, Germany. Electronic address: Sulaj.Alba@med.uni-heidelberg.de.
² Department of Medicine I and Clinical Chemistry, University of Heidelberg, INF 410, 69120 Heidelberg, Germany.
³ Division of Cellular and Molecular Pathology, German Cancer Research Center, INF 280, 69120 Heidelberg, Germany.
⁴ Medical Research Center, Medical Faculty Mannheim, University of Heidelberg, Theodor-Kutzer Ufer 1-3, 68135 Mannheim, Germany.
⁵ Department of Internal Medicine, University of Tübingen, 72074 Tübingen, Germany.
⁶ Department of Internal Medicine, University of Tübingen, 72074 Tübingen, Germany; German Center for Diabetes Research, 85764 Neuherberg, Germany.
⁷ Department of Nephrology, University of Heidelberg, INF 410, 69120 Heidelberg, Germany.
⁸ Institute for Diabetes and Cancer IDC, Helmholtz Center Munich and Joint Heidelberg-IDC Translational, Diabetes Program, University of Heidelberg, INF 410, 69120 Heidelberg, Germany.
⁹ Department of Medicine I and Clinical Chemistry, University of Heidelberg, INF 410, 69120 Heidelberg, Germany; German Center for Diabetes Research, 85764 Neuherberg, Germany.
¹⁰ Department of Medicine I and Clinical Chemistry, University of Heidelberg, INF 410, 69120 Heidelberg, Germany; German Center for Diabetes Research, 85764 Neuherberg, Germany; Institute for Diabetes and Cancer IDC, Helmholtz Center Munich and Joint Heidelberg-IDC Translational, Diabetes Program, University of Heidelberg, INF 410, 69120 Heidelberg, Germany.

PMID: 28325697
DOI: 10.1016/j.jdiacomp.2017.01.002

Abstract

Background & aim: Activated leukocyte cell adhesion molecule (ALCAM/CD166) functions analogue to the receptor of advanced glycation end products, which has been implicated in the development of diabetic nephropathy (DN). We investigated the expression of ALCAM and its ligand S100B in patients with DN.

Methods: A total of 34 non-diabetic patients, 29 patients with type 2 diabetes and normal albuminuria and 107 patients with type 2 diabetes complicated with DN were assessed for serum concentration of soluble ALCAM (sALCAM) by ELISA. Expression of ALCAM and S100B in kidney histology from patients with DN was determined by immunohistochemistry. Cell expression of ALCAM and S100B was analyzed through confocal immunofluorescence microscopy.

Results: Serum concentration of sALCAM was increased in diabetic patients with DN compared to non-diabetic (59.85±14.99ng/ml vs. 126.88±66.45ng/ml, P<0.0001). Moreover sALCAM correlated positively with HbA1c (R=0.31, P<0.0001), as well as with the stages of chronic kidney disease and negatively correlated with eGFR (R=-0.20, P<0.05). In diabetic patients with normal albuminuria sALCAM was increased compared to patients with DN (126.88±66.45ng/ml vs. 197.50±37.17ng/ml, P<0.0001). In diabetic patients, ALCAM expression was significantly upregulated in both the glomeruli and tubules (P<0.001). ALCAM expression in the glomeruli correlated with presence of sclerosis (R=0.25, P<0.001) and localized mainly in the podocytes supporting the hypothesis that membrane bound ALCAM drives diabetic nephropathy and thus explaining sALCAM decrease in diabetic patients with DN. The expression of S100B was increased significantly in the glomeruli of diabetic patients (P<0.001), but not in the tubules. S100B was as well localized in the podocytes.

Conclusions: This study identifies for the first time ALCAM as a potential mediator in the late complications of diabetes in the kidney.

Keywords: ALCAM; Cell adhesion molecule; Diabetes mellitus type 2; Diabetic nephropathy; Soluble form of ALCAM.

Publication types

Randomized Controlled Trial

MeSH terms

Adult
Aged
Antigens, CD / analysis
Antigens, CD / blood*
Antigens, CD / physiology
Biomarkers / blood*
Case-Control Studies
Cell Adhesion Molecules, Neuronal / analysis
Cell Adhesion Molecules, Neuronal / blood*
Cell Adhesion Molecules, Neuronal / physiology
Diabetes Mellitus, Type 2 / blood*
Diabetes Mellitus, Type 2 / complications*
Diabetes Mellitus, Type 2 / diagnosis
Diabetic Nephropathies / blood
Diabetic Nephropathies / diagnosis*
Diabetic Nephropathies / etiology
Disease Progression
Female
Fetal Proteins / analysis
Fetal Proteins / blood*
Fetal Proteins / physiology
Humans
Kidney / physiopathology
Male
Middle Aged
Prognosis

Substances

ALCAM protein, human
Antigens, CD
Biomarkers
Cell Adhesion Molecules, Neuronal
Fetal Proteins