TY - JOUR
T1 - ALCAM a novel biomarker in patients with type 2 diabetes mellitus complicated with diabetic nephropathy
AU - Sulaj, Alba
AU - Kopf, Stefan
AU - Gröne, Elisabeth
AU - Gröne, Hermann Josef
AU - Hoffmann, Sigrid
AU - Schleicher, Erwin
AU - Häring, Hans Ulrich
AU - Schwenger, Vedat
AU - Herzig, Stephan
AU - Fleming, Thomas
AU - Nawroth, Peter P.
AU - von Bauer, Rüdiger
N1 - Publisher Copyright:
© 2017
PY - 2017/6
Y1 - 2017/6
N2 - 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 ± 14.99 ng/ml vs. 126.88 ± 66.45 ng/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 ± 66.45 ng/ml vs. 197.50 ± 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 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.
AB - 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 ± 14.99 ng/ml vs. 126.88 ± 66.45 ng/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 ± 66.45 ng/ml vs. 197.50 ± 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 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.
KW - ALCAM
KW - Cell adhesion molecule
KW - Diabetes mellitus type 2
KW - Diabetic nephropathy
KW - Soluble form of ALCAM
UR - http://www.scopus.com/inward/record.url?scp=85015680525&partnerID=8YFLogxK
U2 - 10.1016/j.jdiacomp.2017.01.002
DO - 10.1016/j.jdiacomp.2017.01.002
M3 - Article
C2 - 28325697
AN - SCOPUS:85015680525
SN - 1056-8727
VL - 31
SP - 1058
EP - 1065
JO - Journal of Diabetes and its Complications
JF - Journal of Diabetes and its Complications
IS - 6
ER -
