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BMC Nephrology
Published in: BMC Nephrology 1/2012

Open Access 01-12-2012 | Research article

Relationships between serum MCP-1 and subclinical kidney disease: African American-Diabetes Heart Study

Authors: Mariana Murea, Thomas C Register, Jasmin Divers, Donald W Bowden, J Jeffrey Carr, Caresse R Hightower, Jianzhao Xu, S Carrie Smith, Keith A Hruska, Carl D Langefeld, Barry I Freedman

Published in: BMC Nephrology | Issue 1/2012

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Abstract

Background

Monocyte chemoattractant protein-1 (MCP-1) plays important roles in kidney disease susceptibility and atherogenesis in experimental models. Relationships between serum MCP-1 concentration and early nephropathy and subclinical cardiovascular disease (CVD) were assessed in African Americans (AAs) with type 2 diabetes (T2D).

Methods

Serum MCP-1 concentration, urine albumin:creatinine ratio (ACR), estimated glomerular filtration rate (eGFR), and atherosclerotic calcified plaque (CP) in the coronary and carotid arteries and infrarenal aorta were measured in 479 unrelated AAs with T2D. Generalized linear models were fitted to test for associations between MCP-1 and urine ACR, eGFR, and CP.

Results

Participants were 57% female, with mean ± SD (median) age 55.6±9.5 (55.0) years, diabetes duration 10.3±8.2 (8.0) years, urine ACR 149.7±566.7 (14.0) mg/g, CKD-EPI eGFR 92.4±23.3 (92.0) ml/min/1.73m2, MCP-1 262.9±239.1 (224.4) pg/ml, coronary artery CP 280.1±633.8 (13.5), carotid artery CP 47.1±132.9 (0), and aorta CP 1616.0±2864.0 (319.0). Adjusting for age, sex, smoking, HbA1c, BMI, and LDL, serum MCP-1 was positively associated with albuminuria (parameter estimate 0.0021, P=0.04) and negatively associated with eGFR (parameter estimate −0.0003, P=0.001). MCP-1 remained associated with eGFR after adjustment for urine ACR. MCP-1 levels did not correlate with the extent of CP in any vascular bed, HbA1c or diabetes duration, but were positively associated with BMI. No interaction between BMI and MCP-1 was detected on nephropathy outcomes.

Conclusions

Serum MCP-1 levels are associated with eGFR and albuminuria in AAs with T2D. MCP-1 was not associated with subclinical CVD in this population. Inflammation appears to play important roles in development and/or progression of kidney disease in AAs.
Literature
1.
Navarro-Gonzalez JF, Mora-Fernandez C, de Muros FM, Garcia-Perez J: Inflammatory molecules and pathways in the pathogenesis of diabetic nephropathy. Nat Rev Nephrol. 2011, 7: 327-340. 10.1038/nrneph.2011.51.CrossRefPubMed
2.
Galkina E, Ley K: Immune and inflammatory mechanisms of atherosclerosis (*). Annu Rev Immunol. 2009, 27: 165-197. 10.1146/annurev.immunol.021908.132620.CrossRefPubMedPubMedCentral
3.
McNeill E, Channon KM, Greaves DR: Inflammatory cell recruitment in cardiovascular disease: murine models and potential clinical applications. Clin Sci (Lond). 2010, 118: 641-655. 10.1042/CS20090488.CrossRef
4.
Nguyen D, Ping F, Mu W, Hill P, Atkins RC, Chadban SJ: Macrophage accumulation in human progressive diabetic nephropathy. Nephrology (Carlton). 2006, 11: 226-231. 10.1111/j.1440-1797.2006.00576.x.CrossRef
5.
Gosling J, Slaymaker S, Gu L, Tseng S, Zlot CH, Young SG, et al: MCP-1 deficiency reduces susceptibility to atherosclerosis in mice that overexpress human apolipoprotein B. J Clin Invest. 1999, 103: 773-778. 10.1172/JCI5624.CrossRefPubMedPubMedCentral
6.
Young BA, Johnson RJ, Alpers CE, Eng E, Gordon K, Floege J, et al: Cellular events in the evolution of experimental diabetic nephropathy. Kidney Int. 1995, 47: 935-944. 10.1038/ki.1995.139.CrossRefPubMed
7.
Chow FY, Nikolic-Paterson DJ, Ozols E, Atkins RC, Rollin BJ, Tesch GH: Monocyte chemoattractant protein-1 promotes the development of diabetic renal injury in streptozotocin-treated mice. Kidney Int. 2006, 69: 73-80. 10.1038/sj.ki.5000014.CrossRefPubMed
8.
Tesch GH: MCP-1/CCL2: a new diagnostic marker and therapeutic target for progressive renal injury in diabetic nephropathy. Am J Physiol Renal Physiol. 2008, 294: F697-F701. 10.1152/ajprenal.00016.2008.CrossRefPubMed
9.
Gerstein HC, Mann JF, Yi Q, Zinman B, Dinneen SF, Hoogwerf B, et al: Albuminuria and risk of cardiovascular events, death, and heart failure in diabetic and nondiabetic individuals. JAMA. 2001, 286 (4): 421-426. 10.1001/jama.286.4.421.CrossRefPubMed
10.
Arnlov J, Evans JC, Meigs JB, Wang TJ, Fox CS, Levy D, et al: Low-grade albuminuria and incidence of cardiovascular disease events in nonhypertensive and nondiabetic individuals: the Framingham Heart Study. Circulation. 2005, 112 (7): 969-975. 10.1161/CIRCULATIONAHA.105.538132.CrossRefPubMed
11.
Freedman BI, Langefeld CD, Lohman KK, Bowden DW, Carr JJ, Rich SS, et al: Relationship between Albuminuria and Cardiovascular Disease in Type 2 Diabetes. J Am Soc Nephrol. 2005, 16: 2156-2161. 10.1681/ASN.2004100884.CrossRefPubMed
12.
Bild DE, Detrano R, Peterson D, Guerci A, Liu K, Shahar E, et al: Ethnic differences in coronary calcification: the Multi-Ethnic Study of Atherosclerosis (MESA). Circulation. 2005, 111 (10): 1313-1320. 10.1161/01.CIR.0000157730.94423.4B.CrossRefPubMed
13.
Freedman BI, Hsu FC, Langefeld CD, Rich SS, Herrington DM, Carr JJ, et al: The impact of ethnicity and sex on subclinical cardiovascular disease: the Diabetes Heart Study. Diabetologia. 2005, 48 (12): 2511-2518. 10.1007/s00125-005-0017-2.CrossRefPubMed
14.
Hozawa A, Folsom AR, Sharrett AR, Chambless LE: Absolute and attributable risks of cardiovascular disease incidence in relation to optimal and borderline risk factors: comparison of African American with white subjects–Atherosclerosis Risk in Communities Study. Arch Intern Med. 2007, 167: 573-579. 10.1001/archinte.167.6.573.CrossRefPubMed
15.
Young BA, Rudser K, Kestenbaum B, Seliger SL, Andress D, Boyko EJ: Racial and ethnic differences in incident myocardial infarction in end-stage renal disease patients: the USRDS. Kidney Int. 2006, 69: 1691-1698. 10.1038/sj.ki.5000346.CrossRefPubMed
16.
Karter AJ, Ferrara A, Liu JY, Moffet HH, Ackerson LM, Selby JV: Ethnic disparities in diabetic complications in an insured population. JAMA. 2002, 287: 2519-2527. 10.1001/jama.287.19.2519.CrossRefPubMed
17.
Wagenknecht LE, Divers J, Bertoni AG, Langefeld CD, Carr JJ, Bowden DW, et al: Correlates of coronary artery calcified plaque in blacks and whites with type 2 diabetes. Ann Epidemiol. 2011, 21: 34-41. 10.1016/j.annepidem.2010.10.007.CrossRefPubMedPubMedCentral
18.
Niewczas MA, Ficociello LH, Johnson AC, Walker W, Rosolowsky ET, Roshan B, et al: Serum concentrations of markers of TNFalpha and Fas-mediated pathways and renal function in nonproteinuric patients with type 1 diabetes. Clin J Am Soc Nephrol. 2009, 4: 62-70. 10.2215/CJN.03010608.CrossRefPubMedPubMedCentral
19.
Wolkow PP, Niewczas MA, Perkins B, Ficociello LH, Lipinski B, Warram JH, et al: Association of urinary inflammatory markers and renal decline in microalbuminuric type 1 diabetics. J Am Soc Nephrol. 2008, 19: 789-797. 10.1681/ASN.2007050556.CrossRefPubMedPubMedCentral
20.
Stenvinkel P, Heimburger O, Paultre F, Diczfalusy U, Wang T, Berglund L, et al: Strong association between malnutrition, inflammation, and atherosclerosis in chronic renal failure. Kidney Int. 1999, 55: 1899-1911. 10.1046/j.1523-1755.1999.00422.x.CrossRefPubMed
21.
Stenvinkel P, Lindholm B, Heimburger M, Heimburger O: Elevated serum levels of soluble adhesion molecules predict death in pre-dialysis patients: association with malnutrition, inflammation, and cardiovascular disease. Nephrol Dial Transplant. 2000, 15: 1624-1630. 10.1093/ndt/15.10.1624.CrossRefPubMed
22.
Mourad JJ, Pannier B, Blacher J, Rudnichi A, Benetos A, London GM, et al: Creatinine clearance, pulse wave velocity, carotid compliance and essential hypertension. Kidney Int. 2001, 59: 1834-1841. 10.1046/j.1523-1755.2001.0590051834.x.CrossRefPubMed
23.
Wagenknecht LE, Bowden DW, Carr JJ, Langefeld CD, Freedman BI, Rich SS: Familial aggregation of coronary artery calcium in families with type 2 diabetes. Diabetes. 2001, 50: 861-866. 10.2337/diabetes.50.4.861.CrossRefPubMed
24.
Levey AS, Bosch JP, Lewis JB, Greene T, Rogers N, Roth D: A more accurate method to estimate glomerular filtration rate from serum creatinine: a new prediction equation. modification of diet in renal disease study group. Ann Intern Med. 1999, 130 (6): 461-470.CrossRefPubMed
25.
Levey AS, Stevens LA, Schmid CH, Zhang Y, Castro AF, Feldman HI, et al: A new equation to estimate glomerular filtration rate. Ann Intern Med. 2009, 150: 604-612.CrossRefPubMedPubMedCentral
26.
Coresh J, Astor BC, McQuillan G, Kusek J, Greene T, Van LF, et al: Calibration and random variation of the serum creatinine assay as critical elements of using equations to estimate glomerular filtration rate. Am J Kidney Dis. 2002, 39: 920-929. 10.1053/ajkd.2002.32765.CrossRefPubMed
27.
McCullagh P, Nelder J: Generalized Linear Models. 1989, Boca Raton, Florida: Chapman and Hall/CRC Publishers, SecondCrossRef
28.
Hastings C, Mosteller F, Tukey JW, Winsor CP: Low moments for small samples: a comparative study of order statistics. Ann Math Stat. 1947, 18: 413-426. 10.1214/aoms/1177730388.CrossRef
29.
Box GEP, Cox DR: An analysis of tranformations. J R StatSoc, Series B. 1964, 26: 211-246.
30.
Banba N, Nakamura T, Matsumura M, Kuroda H, Hattori Y, Kasai K: Possible relationship of monocyte chemoattractant protein-1 with diabetic nephropathy. Kidney Int. 2000, 58: 684-690. 10.1046/j.1523-1755.2000.00214.x.CrossRefPubMed
31.
Rovin BH, Doe N, Tan LC: Monocyte chemoattractant protein-1 levels in patients with glomerular disease. Am J Kidney Dis. 1996, 27: 640-646. 10.1016/S0272-6386(96)90097-9.CrossRefPubMed
32.
Wada T, Yokoyama H, Su SB, Mukaida N, Iwano M, Dohi K, et al: Monitoring urinary levels of monocyte chemotactic and activating factor reflects disease activity of lupus nephritis. Kidney Int. 1996, 49: 761-767. 10.1038/ki.1996.105.CrossRefPubMed
33.
Yokoyama H, Wada T, Furuichi K, Segawa C, Shimizu M, Kobayashi K, et al: Urinary levels of chemokines (MCAF/MCP-1, IL-8) reflect distinct disease activities and phases of human IgA nephropathy. J Leukoc Biol. 1998, 63: 493-499.PubMed
34.
Wada T, Furuichi K, Sakai N, Iwata Y, Yoshimoto K, Shimizu M, et al: Up-regulation of monocyte chemoattractant protein-1 in tubulointerstitial lesions of human diabetic nephropathy. Kidney Int. 2000, 58: 1492-1499. 10.1046/j.1523-1755.2000.00311.x.CrossRefPubMed
35.
Morii T, Fujita H, Narita T, Shimotomai T, Fujishima H, Yoshioka N, et al: Association of monocyte chemoattractant protein-1 with renal tubular damage in diabetic nephropathy. J Diabetes Complications. 2003, 17 (1): 11-15. 10.1016/S1056-8727(02)00176-9.CrossRefPubMed
36.
Munshi R, Johnson A, Siew ED, Ikizler TA, Ware LB, Wurfel MM, et al: MCP-1 Gene Activation Marks Acute Kidney Injury. J Am Soc Nephrol. 2011, 22: 165-175. 10.1681/ASN.2010060641.CrossRefPubMedPubMedCentral
37.
Ruggenenti P, Remuzzi G: Nephropathy of type 1 and type 2 diabetes: diverse pathophysiology, same treatment?. Nephrol Dial Transplant. 2000, 15: 1900-1902. 10.1093/ndt/15.12.1900.CrossRefPubMed
38.
Paalani M, Lee JW, Haddad E, Tonstad S: Determinants of inflammatory markers in a bi-ethnic population. Ethn Dis. 2011, 21: 142-149.PubMedPubMedCentral
39.
Feairheller DL, Park JY, Sturgeon KM, Williamson ST, Diaz KM, Veerabhadrappa P, et al: Racial differences in oxidative stress and inflammation: in vitro and in vivo. Clin Transl Sci. 2011, 4: 32-37. 10.1111/j.1752-8062.2011.00264.x.CrossRefPubMedPubMedCentral
40.
Gonzalez-Quesada C, Frangogiannis NG: Monocyte chemoattractant protein-1/CCL2 as a biomarker in acute coronary syndromes. Curr Atheroscler Rep. 2009, 11: 131-138. 10.1007/s11883-009-0021-y.CrossRefPubMedPubMedCentral
41.
Deo R, Khera A, McGuire DK, Murphy SA, Meo Neto JP, Morrow DA, et al: Association among plasma levels of monocyte chemoattractant protein-1, traditional cardiovascular risk factors, and subclinical atherosclerosis. J Am Coll Cardiol. 2004, 44: 1812-1818. 10.1016/j.jacc.2004.07.047.CrossRefPubMed
42.
Wong CK, Ho AW, Tong PC, Yeung CY, Kong AP, Lun SW, et al: Aberrant activation profile of cytokines and mitogen-activated protein kinases in type 2 diabetic patients with nephropathy. Clin Exp Immunol. 2007, 149: 123-131. 10.1111/j.1365-2249.2007.03389.x.CrossRefPubMedPubMedCentral
43.
Sartipy P, Loskutoff DJ: Monocyte chemoattractant protein 1 in obesity and insulin resistance. Proc Natl Acad Sci USA. 2003, 100: 7265-7270. 10.1073/pnas.1133870100.CrossRefPubMedPubMedCentral
44.
Sell H, Eckel J: Monocyte chemotactic protein-1 and its role in insulin resistance. Curr Opin Lipidol. 2007, 18: 258-262. 10.1097/MOL.0b013e3281338546.CrossRefPubMed
45.
Matsumori A, Furukawa Y, Hashimoto T, Yoshida A, Ono K, Shioi T, et al: Plasma levels of the monocyte chemotactic and activating factor/monocyte chemoattractant protein-1 are elevated in patients with acute myocardial infarction. J Mol Cell Cardiol. 1997, 29: 419-423. 10.1006/jmcc.1996.0285.CrossRefPubMed
46.
de Lemos JA, Morrow DA, Sabatine MS, Murphy SA, Gibson CM, Antman EM, et al: Association between plasma levels of monocyte chemoattractant protein-1 and long-term clinical outcomes in patients with acute coronary syndromes. Circulation. 2003, 107: 690-695. 10.1161/01.CIR.0000049742.68848.99.CrossRefPubMed
47.
Register TC, Cann JA, Kaplan JR, Williams JK, Adams MR, Morgan TM, et al: Effects of soy isoflavones and conjugated equine estrogens on inflammatory markers in atherosclerotic, ovariectomized monkeys. J Clin Endocrinol Metab. 2005, 90: 1734-1740.CrossRefPubMed
48.
Xia M, Sui Z: Recent developments in CCR2 antagonists. Expert Opin Ther Pat. 2009, 19: 295-303. 10.1517/13543770902755129.CrossRefPubMed
49.
Kang YS, Lee MH, Song HK, Ko GJ, Kwon OS, Lim TK, et al: CCR2 antagonism improves insulin resistance, lipid metabolism, and diabetic nephropathy in type 2 diabetic mice. Kidney Int. 2010, 78: 883-894. 10.1038/ki.2010.263.CrossRefPubMed
Metadata
Title
Relationships between serum MCP-1 and subclinical kidney disease: African American-Diabetes Heart Study
Authors
Mariana Murea
Thomas C Register
Jasmin Divers
Donald W Bowden
J Jeffrey Carr
Caresse R Hightower
Jianzhao Xu
S Carrie Smith
Keith A Hruska
Carl D Langefeld
Barry I Freedman
Publication date
01-12-2012
Publisher
BioMed Central
Published in
BMC Nephrology / Issue 1/2012
Electronic ISSN: 1471-2369
DOI
https://doi.org/10.1186/1471-2369-13-148

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