Relationship Between Plasma Adiponectin Level With Inflammatory and Metabolic Markers in Patients With Chronic Kidney Disease

How to Cite:Omid SedighiSaeid AbediankenariRelationship Between Plasma Adiponectin Level With Inflammatory and Metabolic Markers in Patients With Chronic Kidney Disease.Nephro-Urol Mon.6(1):e11743.https://doi.org/10.5812/numonthly.11743.

Abstract

Background:

Adiponectin (ADPN) is an important anti-inflammatory marker with anti-atherogenic effects. However, its role in patients with chronic kidney disease (CKD) should be determined.

Objectives:

The aim of this study was to determine the relationship between plasma adiponectin level with some inflammatory and metabolic markers in CKD patients.

Patients and Methods:

In this case-control study, we measured plasma ADPN level in 42 CKD patients and 46 healthy persons with the same age and sex as control group. Then, we investigated the association between plasma ADPN level with some inflammatory and metabolic determinants in CKD patients.

Results:

Plasma ADPN level was significantly higher in CKD patients than control group (P = 0.04). It was directly correlated with HDL-cholesterol (r = 0.599, P < 0.001) and serum creatinine levels (r = 0.675, P < 0.001) and inversely correlated with glomerular filtration rate (GFR) (r = -0.570, P < 0.001), body mass index (BMI) (r = -0.318, P = 0.04), C-reactive protein (CRP) (r = -0.548, P < 0.001) and fasting blood sugar (FBS) (r = -0.640, P < 0.001) in CKD patients.

Conclusions:

These findings suggested that plasma ADPN level is inversely associated with GFR and directly correlate with HDL-cholesterol and inversely with some, but not all metabolic factors of CKD patients who were not undergone dialysis.

Keywords

1. Background

Adiponectin (ADPN) is an important protein that secrete by adipocytes. Plasma level of ADPN is suggested as a predictive marker of metabolic syndrome in patients with chronic kidney disease (CKD) who did not undergo dialysis (1). In some animal studies, ADPN has both anti-inflammatory and anti-oxidative properties. In mice, ADPN deficiency causes foot processes effacement and albuminuria which are reverted after ADPN therapy (2). In human, plasma ADPN level is usually lower in patients with normal renal function and higher in patients with cardiovascular risk factors, such as type 2 diabetes, obesity, and ischemic heart disease (3). However, despite the higher risk of metabolic syndrome in CKD patients (4), plasma level of ADPN is higher in pre-dialysis patients (5) and also patients on hemodialysis (HD) and peritoneal dialysis (PD) (6).

Higher plasma ADPN level in CKD patients depends on low glomerular filtration rate (GFR) (7) because, it significantly decreases after successful kidney transplantation (8). In CKD patients, the role of adiponectin in metabolic syndrome is unclear. In some studies, plasma ADPN level is directly associated with cardiovascular diseases (CVD) and mortality in predialysis CKD patients (9). However, in other studies low plasma ADPN level predicts high cardiovascular events in HD patients (6).

2. Objectives

The aim of our study was to determine the relationship between plasma ADPN level and some inflammatory, and metabolic factors in CKD predialysis patients.

3. Patients and Methods

3.1. Patients

In this case-control study, 42 CKD patients with a GFR level of 15-90 mL/min, referred to the nephrology clinic in Sari in Iran, were selected. GFR estimated by the modified diet in renal disease (MDRD) equation. This group of patients compared with 46 persons in control group with the same age and gender. Exclusions criteria were the presence of active infection, acute myocardial infarction in last 6 weeks, uncontrolled diabetes mellitus, consumption of antioxidant drugs, and presence of active inflammatory diseases. The study was in agreement with the ethics committee guidelines of our institution and all of the participating persons signed an informed consent form.

3.2. Laboratory Studies

Fasting blood specimens were collected from both patients and control groups and then the metabolic and inflammatory markers were measured. Blood urea nitrogen (BUN), creatinine, total cholesterol, high density lipoprotein (HDL) cholesterol, low density lipoprotein (LDL) cholesterol, triglyceride, fasting blood sugar (FBS), calcium, phosphorous, albumin (Alb) (Pars Azmun, Iran), erythrocyte sedimentation rate (ESR), C-reactive protein (CPR), and hemoglobin (Hb) levels were measured by standard kits and using an auto analyzer (prestige 24i, Japan). Body mass index (BMI) was calculated by dividing body weight (kg) to the height (m²). Plasma APDN level (all the isoforms) was measured using an ELISA kit (bender med system, Germany, CV = 2.9) in accordance to manufacture procedure.

3.3. Statistical Analysis

Data were expressed as the mean standard deviation and analyzed using SPSS software (version 17.0, SPSS Inc). Comparison between the patientsand the control group was performed by t-test (quantitative variables) and Chi-squared test (qualitative variables). P < 0.05 considered statistically significant.

4. Results

The baseline clinical characteristics of CKD patients (group I, n = 42) and healthy control (group II, n = 46) are shown in Table 1. Mean age of CKD patients and control groups were 65.19 ± 12.69 and 61.04 ± 8.23 years respectively. There were no significant differences between two groups based on the age, sex, and BMI. Mean plasma ADPN levels in group I was 17.84 ± 14.18 mg/L and in group II was 13.26 ± 6.63 mg/L. Plasma ADPN level was significantly higher in CKD patients than control group (P = 0.042).

Table 1.Clinical Characteristics of CKD^a Patients (Group I, n = 42) and Healthy Control (Group II, n = 46)

Parameter	Group I (n = 42)	Group II (n = 46)	P Value
Age, mean ± SD, y	65.19 ± 12.69	61.41 ± 8.23	0.106
Gender, M^a/F^a	22/20	26/20	0.831
BMI^a, mean ± SD, kg/m²	23.85 ± 2.87	23.98 ± 3.24	0.838
GFR^a, mean ± SD, mL/min	42.57 ± 37.72	98.65 ± 18.45	< 0.001
Serum Cr, mean ± SD, mg/dL	2.24 ± 0.81	0.98 ± 0.15	< 0.001
ADPN^a, mean ± SD, mg/L	17.84 ± 14.18	13.26 ± 6.63	0.042
Cholesterol, mean ± SD, mg/dL	202.54 ± 40.91	213.43 ± 45.47	0.243
Triglyceride, mean ± SD, mg/dL	198.54 ± 103.27	181.47 ± 94.10	0.422
LDL^a, mean ± SD, mg/dL	112.74 ± 33.84	121.88 ± 24.28	0.149
HDL^a, mean ± SD, mg/dL	40.30 ± 9.37	45.91 ± 11.94	0.055
Alb^a, mean ± SD, g/dL	4.19 ± 0.71	4.65 ± 0.38	0.02
CRP^a, mean ± SD, mg/dL	5.41 ± 3.67	3.39 ± 4.23	0.02
Hb^a, mean ± SD, g/dL	11.76 ± 1.83	13.59 ± 1.46	0.001
ESR^a, mean ± SD, mm/h	59.54 ± 14.62	22.65 ± 13.3	0.001
FBS^a, mean ± SD, mg/dL	107.54 ± 35.57	95.63 ± 15.56	0.087
Ca, mean ± SD, mg/dL	9.01 ± 1.05	9.55 ± 0.42	0.003
P, mean ± SD, mg/dL	4.25 ± 1.11	3.65 ± 0.40	0.004

Clinical Characteristics of CKD^a Patients (Group I, n = 42) and Healthy Control (Group II, n = 46)

Table 2 shows the correlation between plasma ADPN level and other clinical and biochemical profiles in CKD patients group.

Table 2.Correlation of Plasma ADPN^a Level With Clinical and Biochemical Variables in CKD^a Patients

Parameter	Correlation	P Value
Age, y	-0.152	0.337
BMI^a, kg/m²	-0.318	0.04
GFR^a, mL/min	-0.570	< 0.001
Serum Cr, mg/dL	0.675	< 0.001
Total cholesterol, mg/dL	-0.271	0.083
Triglyceride, mg/dL	-0.182	0.248
LDL^a, mg/dL	-0.189	0.230
HDL^a, mg/dL	0.599	< 0.001
CRP^a, mg/dL	-0.548	< 0.001
ESR^a, mm/h	0.57	0.722
Ca, mg/dL	0.148	0.352
P, mg/dL	0.09	0.569
Alb^a, g/dL	0.101	0.525
Hb^a, g/dL	-0.05	0.751
FBS^a, mg/dL	-0.640	< 0.001

Correlation of Plasma ADPN^a Level With Clinical and Biochemical Variables in CKD^a Patients

There was no significant correlation between plasma ADPN level and age (r = -0.152, P = 0.337), serum total cholesterol (r = -0.271, P = 0.083), triglyceride (r = -0.182, P = 0.248), LDL-cholesterol (r = -0.189, P = 0.230), albumin (r = 0.101, P = 0.525), and hemoglobin (r = -0.05, P = 0.751).

Plasma ADPN level was significantly and directly correlated with serum creatinine (r = 0.675, P < 0.001), and HDL-cholesterol levels (r = 0.599, P < 0.001), while it was significantly and inversely correlated with GFR (r = -0.570, P < 0.001), BMI (r = -0.378, P = 0.04), CRP (r = -0.548, P < 0.001), and FBS (r = -0.640, P < 0.001).

5. Discussion

We investigated the association between plasma ADPN level with some inflammatory and metabolic determinants in CKD patients. Several studies have shown that plasma ADPN level is inversely correlated with some metabolic syndrome factors such as BMI and type 2 diabetic mellitus in the general population (10). Other studies showed that plasma ADPN level is higher in CKD patients compared with healthy persons (11). The major mechanisms, can decrease the renal ADPN clearance (12), dysregulation in the ligand/receptor activity (13), or a response to metabolic disorders in renal dysfunction (14). Moreover, higher plasma ADPN level may be the predictor of disease progression in CKD patients (15).

Our study found that plasma ADPN level inversely correlates with GFR, some metabolic and inflammatory factors such as BMI, CRP, FBS, and HDL-cholesterol levels in CKD patients not in dialysis patients, but it was not associated with other important metabolic syndrome determinants such as total cholesterol, triglyceride, LDL-cholesterol, and other inflammatory markers such as ESR, albumin, and hemoglobin levels in these patients.

Adiponectin, an adipokine secreted by adipocyte, has many systemic effects and important roles in vascular protection. Hypoadiponectinemia is a risk factor for ischemic heart disease, hypertension and endothelial dysfunction in some studies (16). However, other studies had not found any association between low plasma ADPN level and cardiovascular mortality in the general population (17).

The role of ADPN in CKD patients is unclear. High plasma ADPN level was significantly correlated with a low risk of cardiovascular events in some studies (1, 11). Moreover, plasma ADPN level was inversely correlated with other metabolic syndrome determinants such as BMI, FBS, and Triglyceride. It also directly correlated with HDL in CKD patients did not undergo dialysis (5).

Anti-inflammatory effects of ADPN in CKD patients may be due to inhibition of oxidative stress or induction of macrophage tolerance stimulated by new inflammatory stimuli (18). Our study had some limitation. First, we measured the total plasma ADPN level while, APDN has at the least three different oligomeric complexes with multiple functions (19). However, analysis of total ADPN or a specific oligomeric complex in plasma has provided similar results (20). Second, we analyzed a small number of patients in a single center, so other multicenter studies with large number of patients are required to evaluate the role of ADPN in CKD patients, precisely.

In summary, the results of this study showed that the plasma ADPN was inversely correlated with some determinants of the metabolic syndrome. In addition, plasma total ADPN level was inversely associated with GFR in these patients. Thus, it is concluded that ADPN can be known as an important marker for CKD patients.

Acknowledgments

Footnotes

References

1.
Iwashima Y, Horio T, Kumada M, Suzuki Y, Kihara S, Rakugi H, et al. Adiponectin and renal function, and implication as a risk of cardiovascular disease. Am J Cardiol. 2006;98(12):1603-8. [PubMed ID: 17145218]. https://doi.org/10.1016/j.amjcard.2006.07.039.
2.
Sharma K, Ramachandrarao S, Qiu G, Usui HK, Zhu Y, Dunn SR, et al. Adiponectin regulates albuminuria and podocyte function in mice. J Clin Invest. 2008;118(5):1645-56. [PubMed ID: 18431508]. https://doi.org/10.1172/JCI32691.
3.
Chudek J, Adamczak M, Nieszporek T, Wiecek A. The adipose tissue as an endocrine organ-a nephrologists' perspective. Contrib Nephrol. 2006;151:70-90. [PubMed ID: 16929134]. https://doi.org/10.1159/000095320.
4.
Zoccali C. Cardiovascular risk in uraemic patients-is it fully explained by classical risk factors? Nephrol Dial Transplant. 2000;15(4):454-7. [PubMed ID: 10727537].
5.
Norata GD, Baragetti I, Raselli S, Stucchi A, Garlaschelli K, Vettoretti S, et al. Plasma adiponectin levels in chronic kidney disease patients: relation with molecular inflammatory profile and metabolic status. Nutr Metab Cardiovasc Dis. 2010;20(1):56-63. [PubMed ID: 19359150]. https://doi.org/10.1016/j.numecd.2009.01.011.
6.
Zoccali C, Mallamaci F, Tripepi G, Benedetto FA, Cutrupi S, Parlongo S, et al. Adiponectin, metabolic risk factors, and cardiovascular events among patients with end-stage renal disease. J Am Soc Nephrol. 2002;13(1):134-41. [PubMed ID: 11752030].
7.
Stenvinkel P, Marchlewska A, Pecoits-Filho R, Heimburger O, Zhang Z, Hoff C, et al. Adiponectin in renal disease: relationship to phenotype and genetic variation in the gene encoding adiponectin. Kidney Int. 2004;65(1):274-81. [PubMed ID: 14675060]. https://doi.org/10.1111/j.1523-1755.2004.00370.x.
8.
Chudek J, Adamczak M, Karkoszka H, Budzinski G, Ignacy W, Funahashi T, et al. Plasma adiponectin concentration before and after successful kidney transplantation. Transplant Proc. 2003;35(6):2186-9. [PubMed ID: 14529883].
9.
Menon V, Li L, Wang X, Greene T, Balakrishnan V, Madero M, et al. Adiponectin and mortality in patients with chronic kidney disease. J Am Soc Nephrol. 2006;17(9):2599-606. [PubMed ID: 16885405]. https://doi.org/10.1681/ASN.2006040331.
10.
Yatagai T, Nagasaka S, Taniguchi A, Fukushima M, Nakamura T, Kuroe A, et al. Hypoadiponectinemia is associated with visceral fat accumulation and insulin resistance in Japanese men with type 2 diabetes mellitus. Metabolism. 2003;52(10):1274-8. [PubMed ID: 14564678].
11.
Becker B, Kronenberg F, Kielstein JT, Haller H, Morath C, Ritz E, et al. Renal insulin resistance syndrome, adiponectin and cardiovascular events in patients with kidney disease: the mild and moderate kidney disease study. J Am Soc Nephrol. 2005;16(4):1091-8. [PubMed ID: 15743998]. https://doi.org/10.1681/ASN.2004090742.
12.
Isobe T, Saitoh S, Takagi S, Takeuchi H, Chiba Y, Katoh N, et al. Influence of gender, age and renal function on plasma adiponectin level: the Tanno and Sobetsu study. Eur J Endocrinol. 2005;153(1):91-8. [PubMed ID: 15994750]. https://doi.org/10.1530/eje.1.01930.
13.
Shen Y, Peake PW, Kelly JJ. Should we quantify insulin resistance in patients with renal disease? Nephrology (Carlton). 2005;10(6):599-605. [PubMed ID: 16354245]. https://doi.org/10.1111/j.1440-1797.2005.00490.x.
14.
Zoccali C, Mallamaci F, Panuccio V, Tripepi G, Cutrupi S, Parlongo S, et al. Adiponectin is markedly increased in patients with nephrotic syndrome and is related to metabolic risk factors. Kidney Int Suppl. 2003;(84):S98-102. [PubMed ID: 12694320].
15.
Kollerits B, Fliser D, Heid IM, Ritz E, Kronenberg F. Gender-specific association of adiponectin as a predictor of progression of chronic kidney disease: the Mild to Moderate Kidney Disease Study. Kidney Int. 2007;71(12):1279-86. [PubMed ID: 17457380]. https://doi.org/10.1038/sj.ki.5002191.
16.
Zhu W, Cheng KK, Vanhoutte PM, Lam KS, Xu A. Vascular effects of adiponectin: molecular mechanisms and potential therapeutic intervention. Clin Sci (Lond). 2008;114(5):361-74. [PubMed ID: 18230060]. https://doi.org/10.1042/CS20070347.
17.
Laughlin GA, Barrett-Connor E, May S, Langenberg C. Association of adiponectin with coronary heart disease and mortality: the Rancho Bernardo study. Am J Epidemiol. 2007;165(2):164-74. [PubMed ID: 17101706]. https://doi.org/10.1093/aje/kwk001.
18.
Tsatsanis C, Zacharioudaki V, Androulidaki A, Dermitzaki E, Charalampopoulos I, Minas V, et al. Adiponectin induces TNF-alpha and IL-6 in macrophages and promotes tolerance to itself and other pro-inflammatory stimuli. Biochem Biophys Res Commun. 2005;335(4):1254-63. [PubMed ID: 16115611]. https://doi.org/10.1016/j.bbrc.2005.07.197.
19.
Wang Y, Lam KS, Yau MH, Xu A. Post-translational modifications of adiponectin: mechanisms and functional implications. Biochem J. 2008;409(3):623-33. [PubMed ID: 18177270]. https://doi.org/10.1042/BJ20071492.
20.
Devaraj S, Swarbrick MM, Singh U, Adams-Huet B, Havel PJ, Jialal I. CRP and adiponectin and its oligomers in the metabolic syndrome: evaluation of new laboratory-based biomarkers. Am J Clin Pathol. 2008;129(5):815-22. [PubMed ID: 18426744]. https://doi.org/10.1309/RN84K51B2JJY1Y0B.

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Author(s):

Omid Sedighi:[PubMed][Scholar]
Saeid Abediankenari:[PubMed][Scholar]