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

作者：Sulaj Alba^*; Kopf Stefan; Grone Elisabeth; Grone Hermann Josef; Hoffmann Sigrid; Schleicher Erwin; Haring Hans Ulrich; Schwenger Vedat; Herzig Stephan; Fleming Thomas; Nawroth Peter P; von Bauer Rudiger

来源：Journal of Diabetes and Its Complications, 2017, 31(6): 1058-1065.

DOI：10.1016/j.jdiacomp.2017.01.002

• Diabetes mellitus type 2
• Diabetic nephropathy
• Cell adhesion molecule
• ALCAM
• Soluble form of ALCAM

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 SlOOB 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 SlOOB was analyzed through confocal immunofluorescence microscopy.
Results: Serum concentration of sALCAM was increased in diabetic patients with DN compared to non-diabetic (59.85 +/- 14.99 ng/ml vs. 126.88 +/- 66.45 ng/ml, P < 0.0001). Moreover sALCAM correlated positively with HbA1c (R = 031, 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 66.45 ng/ml vs. 19750 37.17 ng/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 SlOOB was increased significantly in the glomeruli of diabetic patients (P < 0.001), but not in the tubules. SlOOB 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.

• 出版日期2017-6