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 Table of Contents  
ORIGINAL ARTICLE
Year : 2014  |  Volume : 1  |  Issue : 1  |  Page : 33-37

Level changes of adiponectin and cd146 in serum in type 2 diabetic nephropathy


1 Department of Nephrology, Putuo Hospital, Shanghai University of Traditional Chinese Medicine, Shanghai 200062, China
2 Department of Nephrology, Shanghai First People's Hospital, Shanghai Jiao Tong University, Shanghai 200080, China
3 Department of Nephrology, Lee Wai Lee Hospital, Medical Center of Ningbo, Ningbo 315040, Zhejiang Province, China

Date of Web Publication25-Jul-2014

Correspondence Address:
Jiebo Huang
Department of Nephrology, Putuo Hospital, Shanghai University of Traditional Chinese Medicine, Shanghai 200062
China
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Source of Support: None, Conflict of Interest: None


DOI: 10.4103/2225-1243.137552

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  Abstract 

Objective: The aim was to observe the level changes of adiponectin (ADPN) and CD146 in serum and clarify the properties of these peptides in patients with type 2 diabetic nephropathy (DN). Materials and Methods: Seventy-five patients with type 2 diabetes and 13 control subjects included in this study. Levels of ADPN and CD146 in serum were measured by enzyme-linked immunosorbent assay. Results: The serum level of ADPN was higher in patients with diabetes than that in controls, and it increased significantly in the DN1 group. The serum level of CD146 was considerably higher in the DN1 group than that in the other groups. The serum level of ADPN was positively correlated with the serum level of CD146 and body mass index in diabetics. The serum level of ADPN in 54 patients with diabetes and vascular atherosclerosis was significantly lower than that in 21 patients without vascular atherosclerosis. However, there was a definite relationship between the serum levels of ADPN and CD146. Conclusion: The serum levels of ADPN and CD146 appear to increase in patients with early DN and decrease in the final stage of DN. Serum ADPN and CD146 may protect against vascular endothelial dysfunction and mitigate endothelial dysfunction in DN. Further study is required to elucidate the exact role of ADPN and CD146 in the progression of vascular complication in DN.

Keywords: Adiponectin, CD146, diabetic nephropathy, endothelial dysfunction


How to cite this article:
Huang J, Yu Q, Chen S. Level changes of adiponectin and cd146 in serum in type 2 diabetic nephropathy. J Integr Nephrol Androl 2014;1:33-7

How to cite this URL:
Huang J, Yu Q, Chen S. Level changes of adiponectin and cd146 in serum in type 2 diabetic nephropathy. J Integr Nephrol Androl [serial online] 2014 [cited 2019 May 21];1:33-7. Available from: http://www.journal-ina.com/text.asp?2014/1/1/33/137552


  Introduction Top


Diabetic nephropathy (DN) is a serious microvascular complication associated with diabetes mellitus. The pathogenesis of DN nephropathy is related to glomerular endothelial dysfunction. [1] Damaged endothelial cells release cytokines and growth factors, which causes macrophages and adhesion molecules to gather in the damaged area of the endothelium, resulting in the development of renal disease. [2] Adiponectin (ADPN), a cytokine with a structure similar to collagen, is derived from adipose tissue. It is associated with various kinds of cardiovascular diseases including obesity, type 2 diabetes mellitus, and hypertension. [3] The recently discovered cell adhesion molecule, CD146 (also known as Mel-CAM, MUCl8, S-Endo-1, and P1H12) can mediate adhesive actions among endothelial cells as well between endothelial cells and the matrix. CD146 participates in cell signal transduction, and is closely related to immune processes, cancer, embryo implantation, and trophoblastic disease. [4],[5]

Research on ADPN and CD146 in renal disease has been increasing, [6] but the relationship between serum ADPN, CD146, and renal injury in individuals with DN has not yet been clarified. This study aims at studying the changes of serum ADPN and CD146 in patients with DN and the relationship between the serum levels of ADPN and CD146 in diabetics.


  Materials and methods Top


Subjects

Seventy-five patients diagnosed with type 2 diabetes mellitus and DN were hospitalized in the Department of Endocrinology and Nephrology, Shanghai First People's Hospital from June 2010 to January 2011. They were matched for body mass index (BMI). They were divided into five groups: DM group (19 subjects; 24-h albuminuria, < 30 mg/day; serum creatinine (SCr) ≤ 120 μmol/L); DN1 group (18 subjects; 24-h albuminuria, 30-300 mg/day; SCr ≤ 120 μmol/L); DN2 group (16 subjects; 24-h albuminuria, > 300 mg/day or 24-h proteinuria ≥3.5 g/day; 120 μmol/L < SCr < 707 μmol/L); DN3 group (12 subjects, maintain continuous hemodialysis group); DN4 group (10 subjects, continuous ambulatory peritoneal dialysis group). Fifty-four patients with diabetes vascular atherosclerosis and 21 diabetics without atherosclerosis were divided into two groups based the results of Doppler ultrasonography.

Thirteen healthy volunteers were enrolled in the healthy control (HC) group. Individuals with the following conditions were excluded from the study: Type 1 diabetes, acute complications of diabetes and other acute or chronic renal disease, hepatic dysfunction, primary hyperuricemia, thyroid dysfunction, cardiac failure, unexplained fever, pulmonary infections, urinary tract infections, cancer, and the recent use of drugs that affect renal function, among others.

Detection and clinical manifestation of high levels of adiponectin, CD146

Fasting morning blood pressure, systolic blood pressure, and diastolic blood pressure (DBP) were measured immediately when the individuals arrived at the hospital. Height (cm) and weight (kg) were measured. BMI was calculated using the formula:

BMI = Weight (kg)/height (m) 2

Blood specimen collection standards: Fasting venous blood samples were obtained on the 2 nd day of admission from patients and volunteers, and some of the blood samples was directly sent for biochemical assays to detect fasting blood glucose (FBG), triglyceride, total cholesterol, high-density lipoprotein, low-density lipoprotein, SCr, glycated hemoglobin (Hb), C-reactive protein, and Hb, etc. The remaining portion of the blood samples was centrifuged for 10 min (centrifugal radius of 14 cm) at 6000 r/min at 25°C. Finally, serum was collected and stored at −20°C to measure the levels of ADPN and CD146. Enzyme-linked immunosorbent assay (ELISA) was performed to determine the levels of ADPN and CD146 according to the protocol; the ELISA kits for these two tests were manufactured by Raybiotech Corporation (USA) and BioCytex (France), respectively.

We used the simplified Modification of Diet in Renal Disease formula (namely, estimated glomerular filtration rate [eGFR] = 186 × SCr − 1.154 × age − 0.203 × [0.742 [female patients]]) to calculate the eGFR. Dialysis adequacy was estimated as follows: (KT/V) =1.18 × (−ln [R]), where ln is the natural logarithm and R (%) = Postdialysis blood urea nitrogen (BUN) (mmol/L)/predialysis BUN (mmol/L).

Statistical analysis

Measurement data were expressed as mean ± standard deviation. The data were analyzed by one-way ANOVA test to compare the differences among various stages of DN. Single regression analysis was performed to evaluate correlations between the parameters. The independence was verified by stepwise regression analysis. Statistical package Stat-View 17.0 by Statistical Product and Service Solutions (SPSS) (IBM, Chicago, USA) was used for the analysis. A P < 0.05 was considered to be statistically significant. Graphics were produced by Sigmaplot from Statistical Product and Service Solutions (SPSS) (IBM, Chicago, USA).


  Results Top


We compared the clinical and biochemical features of diabetics and controls [Table 1]. The average age of the control group was 46.08 ± 10.92 years, which was significantly lower than that of the other groups (P < 0.01). BMI and DBP were not significantly different among these groups. There were no significant differences in the serum levels of lipid among various stages of DN. There were no significant differences between the level of CD146 and the clinical and biochemical features of these groups [Table 1]. The serum level of ADPN was significantly higher in diabetics than that in controls (P < 0.05), and the level in the DN1 group increased significantly. The levels of ADPN were similar between the DN3 and DN4 groups [Figure 1]a. The serum level of CD146 was dramatically higher in the DN1 group than that in the other groups (P < 0.05). The levels of CD146 were not significantly different among the DN2, DN3, and DN4 groups [Figure 1]b. The serum level of ADPN was positively correlated with the serum level of CD146 (r = 0.57, P < 0.01) and BMI (r = 0.34, P < 0.05) in diabetics [Figure 2]a. The former regression by the bivariate regression equation showed that y = 17.64 + 0.013x, whereas the latter regression showed y = 23.00 + 0.001x [Figure 2]b. The incidence of vascular atherosclerosis in diabetics was not related to the progression of diabetes [Table 1]. The level of ADPN in 54 diabetics and vascular atherosclerosis was significantly lower than that in 21 without atherosclerosis. The level of CD146 was not significantly different between the two groups [50.91 ± 26.77 vs. 49.42 ± 30.67, P > 0.05; [Figure 3]].
Figure 1: The level of serum adiponectin (a) CD146 (b) in the diabetic patients (n = 75) and the control subjects (n = 13)

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Figure 2: The relationship of serum adiponectin levels and body mass index (BMI) (a) serum adiponectin levels and CD146 levels (b) in the diabetic patients. Adiponectin = 17.64 + 0.013 × BMI, r = 0.34, P < 0.05; CD146 = 23.00 + 0.001 × adiponectin. r = 0.57, P < 0.001

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Figure 3: The levels of CD146 and ADPN in 54 diabetic patients with vascular atherosclerosis and 21 patients without vascular atherosclerosis. Values are means ± standard error of the mean. *P < 0.05 versus the control subjects

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  Discussion Top


Our study demonstrated that the serum levels of ADPN and CD146 were positively correlated. The results resembled those of Malyszko et al. [7] Among individuals with early DN, a high serum level of ADPN was related to an antiaccommodative response, which could slow the progression of endothelial dysfunction and reduce cardiovascular risk factors. This response is a part of the active protective mechanism, but is limited because of the impact of high renal filtration. [8] Because the levels of ADPN and BMI were positively correlated, ADPN may be related to type 2 diabetes, obesity, hypertension, and other cardiovascular risk factors. Advanced renal failure is generally associated with hypertension and atherosclerosis. Many studies show that hypoadiponectinemia often appears in ischemic cardiac disease, arteriosclerosis obliterans, and other vascular disease. In this study, the level of ADPN in diabetic patients with atherosclerosis was significantly lower than that in those without atherosclerosis. These results are conformed to those of related studies, [2] and indicate that serum ADPN plays an important role in protecting against the progression of vascular lesions. In the 1970s, the mortality of individuals with atherosclerosis undergoing hemodialysis contributed to increased cardiovascular diseases, and endothelial dysfunction accelerated hardening of the arteries. [9] We therefore speculate that serum ADPN may be a predictive factor for vascular atherosclerosis in chronic renal disease.

In this study, we measured the level of CD146 in individuals with varying severities of diabetes. In the diabetic groups, the level of CD146 was significantly higher than that in the control group. In the DN1 group, the level of CD146 was significantly higher (P < 0.05) than the average of 81.06 ± 20.86 ng/mL. In the DN2, DN3, and DN4 groups, the level of CD146 was significantly higher than that in the DM group (P < 0.05). This was consistent with the results of previous studies. [7],[10]

Faure et al. [11] have reported that the level of CD146 was significantly higher in individuals with chronic renal disease than that in HCs. In individuals with end-stage renal disease (ESRD), the level of CD146 markedly increased, regardless of their primary disease. In this study, the level of CD146 in the diabetic groups was significantly higher than that in the controls, especially in the DN1 group (P < 0.05). We speculate that vascular endothelial function was severely impaired in the early stage of DN and that CD146 could modulate cell permeability and promote vascular endothelial growth. CD146 gradually weakened the protection for vascular endothelium, compared with early disease and dialysis treatment. Hence, we conclude that elevated CD146 levels are not related with impaired renal function. This was inconsistent with the results of Saito et al. [2] who observed that the level of CD146 level tended to increase in DN groups and that it was positively correlated with the level of SCr. We would need to increase sample size in order to clarify the difference. Malyszko et al.[12] deduced that CD146 expression could ease vascular endothelial injury and mitigate the influence of cardiovascular risk factors. Our study indicated that CD146 significantly increased in the early stage. A large amount of CD146 was secreted to mitigate vascular endothelial damage. We observed changes in the levels of ADPN and CD146 at different stages of DN-even in ESRD. We found that levels of ADPN and CD146 were similar, regardless of the dialysis process chosen. However, hemodialysis led to more serious atherosclerosis in DN than peritoneal dialysis [Table 1]. We believe that more vascular protective factors were undermined or lost in the course of hemodialysis; hence, more profound research should be conducted.
Table 1: Clinical and biochemical characteristics of 75 patients with DM and 13 health subjects

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In summary, we suggest that ADPN is an important marker of endothelial cell injury in individuals with DN. The low level of serum ADPN may affect endothelial dysfunction. We speculate that the levels of serum ADPN and CD146 may protect vascular endothelial cells. Further study is required to clarify the specific roles and mechanism of ADPN and CD146 in the progression of DN and other complications related to diabetes mellitus.

 
  References Top

1.Cai K, Yan L, Sun ZL, Li L, Zhang XL, Liu BC, et al. Significance of serum adiponectin in type 2 diabetic patients with nephropathy. Nephrol Dial Transplant 2009;18:39-43.  Back to cited text no. 1
    
2.Saito T, Saito O, Kawano T, Tamemoto H, Kusano E, Kawakami M, et al. Elevation of serum adiponectin and CD146 levels in diabetic nephropathy. Diabetes Res Clin Pract 2007;78:85-92.  Back to cited text no. 2
    
3.Peer M, Mashavi M, Matas Z, Harpaz D, Shargorodsky M. Adiponectin as an Independent Predictor of Left Ventricular Hypertrophy in Nondiabetic Patients With Hypertension. Angiology 2014. (Published online before print February 26, 2014, doi: 10.1177/0003319714523332).  Back to cited text no. 3
    
4.Pires FR, Shihle M, da Crus Perez DE, et al. Mel-CAM (CDI46) expression in parotid mucoepidermoid carcinoma. Oral Oncol 2003;39:277-81.  Back to cited text no. 4
    
5.Daniel L, Bardin N, Moal V, Dignat-George F, Berland Y, Figarella-Branger D. Tubular CD146 expression in nephropathies is related to chronic renal failure. Nephron Exp Nephrol 2005;99:e105-11.  Back to cited text no. 5
    
6.Saito O, Saito T, Okuda K, Okuda K, Kotoda A, Akimoto T, et al. Serum adiponectin and markers of endothelial injury in hemodialysis patients with arteriosclerosis obliterans. Clin Exp Nephrol 2008;12:58-64.  Back to cited text no. 6
    
7.Malyszko J, Malyszko JS, Kozminski P, Pawlak K, Mysliwiec M. Adipokines, linking adipocytes and vascular function in hemodialyzed patients, may also be possibly related to CD146, a novel adhesion molecule. Clin Appl Thromb Hemost 2008;14:338-45.  Back to cited text no. 7
    
8.Zhou XL, Chen MH. Interrelationship among urinary albumin elimination rate, serum adiponectin and blood glucose level in patients with type 2 diabetic nephropathy. Chin J Nephrol 2010;5:339-42.  Back to cited text no. 8
    
9.Lindner A, Charra B, Sherrard DJ, Scribner BH. Accelerated atherosclerosis in prolonged maintenance hemodialysis. N Engl J Med 1974;290:697-701.  Back to cited text no. 9
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10.Ma³yszko J, Ma³yszko JS, My?liwiec M. Is there a link between CD146, a novel adhesion molecule and other markers of endothelial dysfunction in nephrotic syndrome and continuous ambulatory peritoneal dialysis? Thromb Res 2005;115:19-24.  Back to cited text no. 10
    
11.Faure V, Dou L, Sabatier F, Cerini C, Sampol J, Berland Y, et al. Elevation of circulating endothelial microparticles in patients with chronic renal failure. J Thromb Haemost 2006;4:566-73.  Back to cited text no. 11
    
12.Malyszko J, Malyszko JS, Brzosko S, Wolczynski S, Mysliwiec M. Adiponectin is related to CD146, a novel marker of endothelial cell activation/injury in chronic renal failure and peritoneally dialyzed patients. J Clin Endocrinol Metab 2004;89:4620-7.  Back to cited text no. 12
    


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