Pediatric Nephrology

, Volume 27, Issue 4, pp 521–527

Adiponectin, cardiovascular disease, chronic kidney disease: emerging data on complex interactions



Over the past decade, adiponectin has been a subject of interest in many fields of medicine. The effect of adiponectin in metabolism and inflammation has been described for cardiovascular disease (CVD) in animal studies and the general population, generally as a protective factor. Extensive literature pertaining to adult studies indicates that low adiponectin levels are associated with increased CVD morbidity and mortality in the general population and patients with obesity and type 2 diabetes. In chronic kidney disease (CKD), however, despite an increased risk of poor cardiovascular outcomes, blood levels of adiponectin are actually higher than typical physiological levels. These unusual relationships question the protective role of elevated adiponectin in the milieu of CKD. This review summarizes the studies of adiponectin in the general pediatric population and its association with CVD risks in children and adults with CKD. Specific adiponectin values are generally avoided in this review, as there are no standardized normative values at this time – different assays with different “normal” cutoffs have been used and hence comparisons between studies would be invalid.


Adiponectin Chronic kidney disease Children Cardiovascular risk 


  1. 1.
    Yamauchi T, Kamon J, Ito Y, Tsuchida A, Yokomizo T, Kita S, Sugiyama T, Miyagishi M, Hara K, Tsunoda M, Murakami K, Ohteki T, Uchida S, Takekawa S, Waki H, Tsuno NH, Shibata Y, Terauchi Y, Froguel P, Tobe K, Koyasu S, Taira K, Kitamura T, Shimizu T, Nagai R, Kadowaki T (2003) Cloning of adiponectin receptors that mediate antidiabetic metabolic effects. Nature 423:762–769PubMedCrossRefGoogle Scholar
  2. 2.
    Yamauchi T, Kamon J, Waki H, Terauchi Y, Kubota N, Hara K, Mori Y, Ide T, Murakami K, Tsuboyama-Kasaoka N, Ezaki O, Akanuma Y, Gavrilova O, Vinson C, Reitman ML, Kagechika H, Shudo K, Yoda M, Nakano Y, Tobe K, Nagai R, Kimura S, Tomita M, Froguel P, Kadowaki T (2001) The fat-derived hormone adiponectin reverses insulin resistance associated with both lipoatrophy and obesity. Nat Med 7:941–946PubMedCrossRefGoogle Scholar
  3. 3.
    Wisse BE (2004) The inflammatory syndrome: the role of adipose tissue cytokines in metabolic disorders linked to obesity. J Am Soc Nephrol 15:2792–2800PubMedCrossRefGoogle Scholar
  4. 4.
    Yokota T, Meka CS, Kouro T, Medina KL, Igarashi H, Takahashi M, Oritani K, Funahashi T, Tomiyama Y, Matsuzawa Y, Kincade PW (2003) Adiponectin, a fat cell product, influences the earliest lymphocyte precursors in bone marrow cultures by activation of the cyclooxygenase-prostaglandin pathway in stromal cells. J Immunol 171:5091–5099PubMedGoogle Scholar
  5. 5.
    Yokota T, Oritani K, Takahashi I, Ishikawa J, Matsuyama A, Ouchi N, Kihara S, Funahashi T, Tenner AJ, Tomiyama Y, Matsuzawa Y (2000) Adiponectin, a new member of the family of soluble defense collagens, negatively regulates the growth of myelomonocytic progenitors and the functions of macrophages. Blood 96:1723–1732PubMedGoogle Scholar
  6. 6.
    Wulster-Radcliffe MC, Ajuwon KM, Wang J, Christian JA, Spurlock ME (2004) Adiponectin differentially regulates cytokines in porcine macrophages. Biochem Biophys Res Commun 316:924–929PubMedCrossRefGoogle Scholar
  7. 7.
    Kumada M, Kihara S, Sumitsuji S, Kawamoto T, Matsumoto S, Ouchi N, Arita Y, Okamoto Y, Shimomura I, Hiraoka H, Nakamura T, Funahashi T, Matsuzawa Y (2003) Association of hypoadiponectinemia with coronary artery disease in men. Arterioscler Thromb Vasc Biol 23:85–89PubMedCrossRefGoogle Scholar
  8. 8.
    Ouchi N, Kihara S, Arita Y, Okamoto Y, Maeda K, Kuriyama H, Hotta K, Nishida M, Takahashi M, Muraguchi M, Ohmoto Y, Nakamura T, Yamashita S, Funahashi T, Matsuzawa Y (2000) Adiponectin, an adipocyte-derived plasma protein, inhibits endothelial NF-kappaB signaling through a cAMP-dependent pathway. Circulation 102:1296–1301PubMedGoogle Scholar
  9. 9.
    Chinetti G, Zawadski C, Fruchart JC, Staels B (2004) Expression of adiponectin receptors in human macrophages and regulation by agonists of the nuclear receptors PPARalpha, PPARgamma, and LXR. Biochem Biophys Res Commun 314:151–158PubMedCrossRefGoogle Scholar
  10. 10.
    Kobayashi H, Ouchi N, Kihara S, Walsh K, Kumada M, Abe Y, Funahashi T, Matsuzawa Y (2004) Selective suppression of endothelial cell apoptosis by the high molecular weight form of adiponectin. Circ Res (Online) 94:e27–e31Google Scholar
  11. 11.
    Fisher FF, Trujillo ME, Hanif W, Barnett AH, McTernan PG, Scherer PE, Kumar S (2005) Serum high molecular weight complex of adiponectin correlates better with glucose tolerance than total serum adiponectin in Indo-Asian males. Diabetologia 48:1084–1087PubMedCrossRefGoogle Scholar
  12. 12.
    Bouskila M, Pajvani UB, Scherer PE (2005) Adiponectin: a relevant player in PPARgamma-agonist-mediated improvements in hepatic insulin sensitivity? Int J Obes (Lond) 29(Suppl 1):S17–S23CrossRefGoogle Scholar
  13. 13.
    Bobbert T, Rochlitz H, Wegewitz U, Akpulat S, Mai K, Weickert MO, Möhlig M, Pfeiffer AF, Spranger J (2005) Changes of adiponectin oligomer composition by moderate weight reduction. Diabetes 54(9):2712–2719PubMedCrossRefGoogle Scholar
  14. 14.
    Woo JG, Dolan LM, Daniels SR, Goodman E, Martin LJ (2005) Adolescent sex differences in adiponectin are conditional on pubertal development and adiposity. Obes Res 13:2095–2101PubMedCrossRefGoogle Scholar
  15. 15.
    Ong KK, Frystyk J, Flyvbjerg A, Petry CJ, Ness A, Dunger DB (2006) Sex-discordant associations with adiponectin levels and lipid profiles in children. Diabetes 55:1337–1341PubMedCrossRefGoogle Scholar
  16. 16.
    Martin LJ, Woo JG, Daniels SR, Goodman E, Dolan LM (2005) The relationships of adiponectin with insulin and lipids are strengthened with increasing adiposity. J Clin Endocrinol Metab 90:4255–4259PubMedCrossRefGoogle Scholar
  17. 17.
    Lee S, Bacha F, Gungor N, Arslanian SA (2006) Racial differences in adiponectin in youth: relationship to visceral fat and insulin sensitivity. Diab Care 29:51–56CrossRefGoogle Scholar
  18. 18.
    Böttner A, Kratzsch J, Müller G, Kapellen TM, Blüher S, Keller E, Blüher M, Kiess W (2004) Gender differences of adiponectin levels develop during the progression of puberty and are related to serum androgen levels. J Clin Endocrinol Metab 89:4053–4061PubMedCrossRefGoogle Scholar
  19. 19.
    Bush NC, Darnell BE, Oster RA, Goran MI, Gower BA (2005) Adiponectin is lower among African Americans and is independently related to insulin sensitivity in children and adolescents. Diabetes 54:2772–2778PubMedCrossRefGoogle Scholar
  20. 20.
    Guebre-Egziabher F, Bernhard J, Funahashi T, Hadj-Aissa A, Fouque D (2005) Adiponectin in chronic kidney disease is related more to metabolic disturbances than to decline in renal function. Nephrol Dial Transplant 20:129–134PubMedCrossRefGoogle Scholar
  21. 21.
    Becker B, Kronenberg F, Kielstein JT, Haller H, Morath C, Ritz E, Fliser D (2005) Renal insulin resistance syndrome, adiponectin and cardiovascular events in patients with kidney disease: the mild and moderate kidney disease study. J Am Soc Nephrol 16:1091–1098PubMedCrossRefGoogle Scholar
  22. 22.
    Zoccali C, Mallamaci F, Tripepi G, Benedetto FA, Cutrupi S, Parlongo S, Malatino LS, Bonanno G, Seminara G, Rapisarda F, Fatuzzo P, Buemi M, Nicocia G, Tanaka S, Ouchi N, Kihara S, Funahashi T, Matsuzawa Y (2002) Adiponectin, metabolic risk factors, and cardiovascular events among patients with end-stage renal disease. J Am Soc Nephrol 13:134–141PubMedCrossRefGoogle Scholar
  23. 23.
    Stenvinkel P, Marchlewska A, Pecoits-Filho R, Heimbürger O, Zhang Z, Hoff C, Holmes C, Axelsson J, Arvidsson S, Schalling M, Barany P, Lindholm B, Nordfors L (2004) Adiponectin in renal disease: relationship to phenotype and genetic variation in the gene encoding adiponectin. Kidney Int 65:274–281PubMedCrossRefGoogle Scholar
  24. 24.
    Bakkaloglu SA, Buyan N, Funahashi T, Pasaoglu H, Elhan AH, Hasanoglu E, Soylemezoglu O (2005) Adiponectin levels and atherosclerotic risk factors in pediatric chronic peritoneal dialysis patients. Perit Dial Int 25:357–361PubMedGoogle Scholar
  25. 25.
    Díez JJ, Iglesias P, Fernández-Reyes MJ, Aguilera A, Bajo MA, Alvarez-Fidalgo P, Codoceo R, Selgas R (2005) Serum concentrations of leptin, adiponectin and resistin, and their relationship with cardiovascular disease in patients with end-stage renal disease. Clin Endocrinol (Oxf) 62:242–249CrossRefGoogle Scholar
  26. 26.
    Chudek J, Adamczak M, Karkoszka H, Budziński G, Ignacy W, Funahashi T, Matsuzawa Y, Cierpka L, Kokot F, Wiecek A (2003) Plasma adiponectin concentration before and after successful kidney transplantation. Transplant Proc 35:2186–2189PubMedCrossRefGoogle Scholar
  27. 27.
    Adamczak M, Szotowska M, Chudek J, Karkoszka H, Cierpka L, Wieçek A (2007) Plasma adiponectin concentration in patients after successful kidney transplantation–a single-center, observational study. Clin Nephrol 67:381–390PubMedGoogle Scholar
  28. 28.
    Büscher AK, Büscher R, Hauffa BP, Hoyer PF (2010) Alterations in appetite-regulating hormones influence protein-energy wasting in pediatric patients with chronic kidney disease. Pediatr Nephrol 25:2295–2301PubMedCrossRefGoogle Scholar
  29. 29.
    Halberg N, Schraw TD, Wang ZV, Kim JY, Yi J, Hamilton MP, Luby-Phelps K, Scherer PE (2009) Systemic fate of the adipocyte-derived factor adiponectin. Diabetes 58:1961–1970PubMedCrossRefGoogle Scholar
  30. 30.
    Marchlewska A, Stenvinkel P, Lindholm B, Danielsson A, Pecoits-Filho R, Lönnqvist F, Schalling M, Heimbürger O, Nordfors L (2004) Reduced gene expression of adiponectin in fat tissue from patients with end-stage renal disease. Kidney Int 66(1):46–50PubMedCrossRefGoogle Scholar
  31. 31.
    Mitsnefes MM, KJ KPR, Daniels SR (2007) Adiponectin in children with chronic kidney disease: role of adiposity and kidney dysfunction. Clin J Am Soc Nephrol 2:46–50PubMedCrossRefGoogle Scholar
  32. 32.
    Kollerits B, Fliser D, Heid IM, Reitz E, Kronenberg F (2007) Gender-specific association of adiponectin as a predictor of progression of chronic kidney disease: the mild to moderate kidney disease study. Kidney Int 71:1279–1286PubMedCrossRefGoogle Scholar
  33. 33.
    Norata GD, Baragetti I, Raselli S, Stucchi A, Garlaschelli K, Vettoretti S, Piloni G, Buccianti G, Catapano AL (2010) Plasma adiponectin levels in chronic kidney disease patients: relation with molecular inflammatory profile and metabolic status. Nutr Metab Cardiovasc Dis 20:56–63PubMedCrossRefGoogle Scholar
  34. 34.
    Tamei N, Ogawa T, Ishida H, Ando Y, Nitta K (2010) Relationship of high-molecular-weight adiponectin levels to visceral fat accumulation in hemodialysis patients. Intern Med 49:299–305PubMedCrossRefGoogle Scholar
  35. 35.
    Halleux CM, Takahashi M, Delporte ML, Detry R, Funahashi T, Matsuzawa Y, Brichard SM (2001) Biochem Biophys Res Commun 288:1102–1107PubMedCrossRefGoogle Scholar
  36. 36.
    Axelsson J, Heimburger O, Lindholm B, Stenvinkel P (2005) Adipose tissue and its relation to inflammation: the role of adipokines. J Ren Nutr 15:131–136PubMedCrossRefGoogle Scholar
  37. 37.
    Sethna CB, Leonard MB, Gallagher PR, Meyers KE (2009) Serum adiponectin levels and ambulatory blood pressure monitoring in pediatric renal transplant recipients. Transplantation 88:1030–1037PubMedCrossRefGoogle Scholar
  38. 38.
    Bakkaloglu SA, Soylemezoglu O, Buyan N, Oktar SO, Funahashi T, Pasaoglu H, Elhan AH, Peru H, Hasanoglu E (2006) Adiponectin levels and arteriosclerotic risk factors in pediatric renal transplant recipients. Pediatr Transplant 10:187–192PubMedCrossRefGoogle Scholar
  39. 39.
    Dunajska K, Milewicz A, Jedrzejuk D, Szymczak J, Kuliczkowski W, Salomon P, Bialy D, Poczatek K, Nowicki P (2004) Plasma adiponectin concentration in relation to severity of coronary atherosclerosis and cardiovascular risk factors in middle-aged men. Endocr 25:215–221CrossRefGoogle Scholar
  40. 40.
    Iwashima Y, Katsuya T, Ishikawa K, Ouchi N, Ohishi M, Sugimoto K, Fu Y, Motone M, Yamamoto K, Matsuo A, Ohashi K, Kihara S, Funahashi T, Rakugi H, Matsuzawa Y, Ogihara T (2004) Hypoadiponectinemia is an independent risk factor for hypertension. Hypertension 43:1318–1323PubMedCrossRefGoogle Scholar
  41. 41.
    Shioji K, Moriguchi A, Moriwaki S, Manabe K, Takeuchi Y, Uegaito T, Mutsuo S, Matsuda M (2005) Hypoadiponectinemia implies the development of atherosclerosis in carotid and coronary arteries. J Cardiol 46:105–112PubMedGoogle Scholar
  42. 42.
    Maahs DM, Ogden LG, Kinney GL, Wadwa P, Snell-Bergeon JK, Dabelea D, Hokanson JE, Ehrlich J, Eckel RH, Rewers M (2005) Low plasma adiponectin levels predict progression of coronary artery calcification. Circulation 111:747–753PubMedCrossRefGoogle Scholar
  43. 43.
    Menon V, Li L, Wang X, Greene T, Balakrishnan V, Madero M, Pereira AA, Beck GJ, Kusek JW, Collins AJ, Levey AS, Sarnak MJ (2006) Adiponectin and mortality in patients with chronic kidney disease. J Am Soc Nephrol 17:2599–2606PubMedCrossRefGoogle Scholar
  44. 44.
    Park SH, Carrero JJ, Lindholm B, Stenvinkel P (2009) Adiponectin in chronic kidney disease has an opposite impact on protein-energy wasting and cardiovascular risk: two sides of the same coin. Clin Nephrol 72:87–96PubMedGoogle Scholar
  45. 45.
    Ouchi N, Kobayashi H, Kihara S, Kumada M, Sato K, Inoue T, Funahashi T, Walsh K (2004) Adiponectin stimulates angiogenesis by promoting cross-talk between AMP-activated protein kinase and Akt signaling in endothelial cells. J Biol Chem 279:1304–1309PubMedCrossRefGoogle Scholar
  46. 46.
    Okamoto Y, Kihara S, Ouchi N, Nishida M, Arita Y, Kumada M, Ohashi K, Sakai N, Shimomura I, Kobayashi H, Terasaka N, Inaba T, Funahashi T, Matsuzawa Y (2002) Adiponectin reduces atherosclerosis in apolipoprotein E-deficient mice. Circulation 106:2767–2770PubMedCrossRefGoogle Scholar
  47. 47.
    Matsuda M, Shimomura I, Sata M, Arita Y, Nishida M, Maeda N, Kumada M, Okamoto Y, Nagaretani H, Nishizawa H, Kishida K, Komuro R, Ouchi N, Kihara S, Nagai R, Funahashi T, Matsuzawa Y (2002) Role of adiponectin in preventing vascular stenosis. The missing link of adipo-vascular axis. J Biol Chem 277:37487–37491PubMedCrossRefGoogle Scholar
  48. 48.
    Pilz S, Horejsi R, Moller R, Almer G, Scharnagl H, Stojakovic T, Dimitrova R, Weihrauch G, Borkenstein M, Maerz W, Schauenstein K, Mangge H (2005) Early atherosclerosis in obese juveniles is associated with low serum levels of adiponectin. J Clin Endocrinol Metab 90(8):4792–4796PubMedCrossRefGoogle Scholar
  49. 49.
    Pilz S, Horejsi R, Möller R, Almer G, Scharnagl H, Stojakovic T, Dimitrova R, Weihrauch G, Borkenstein M, Maerz W, Schauenstein K, Mangge H (2004) Associations among plasma adiponectin, hypertension, left ventricular diastolic function and left ventricular mass index. Blood Press 13:236–242CrossRefGoogle Scholar
  50. 50.
    Shibata R, Ouchi N, Ito M, Kihara S, Shiojima I, Pimentel DR, Kumada M, Sato K, Schiekofer S, Ohashi K, Funahashi T, Colucci WS, Walsh K (2004) Adiponectin-mediated modulation of hypertrophic signals in the heart. Nat Med 10:1384–1389PubMedCrossRefGoogle Scholar
  51. 51.
    Piñeiro R, Iglesias MJ, Gallego R, Raghay K, Eiras S, Rubio J, Diéguez C, Gualillo O, González-Juanatey JR, Lago F (2005) Adiponectin is synthesized and secreted by human and murine cardiomyocytes. FEBS Lett 579:5163–5169PubMedCrossRefGoogle Scholar
  52. 52.
    Sharma K, RamachandraRao S, Qiu G, Kataoka Usui H, Zhu Y, Dunn SR, Ouedraogo R, Hough K, McCue P, Chan L, Falkner B, Goldstein BJ (2008) Adiponectin regulates albuminuria and podocyte function in mice. J Clin Invest 118:1645–1656PubMedGoogle Scholar
  53. 53.
    Ohashi K, Iwatani H, Kihara S, Nakagawa Y, Komura N, Fujita K, Maeda N, Nishida M, Katsube F, Shimomura I, Ito T, Funahashi T (2007) Exacerbation of albuminuria and renal fibrosis in subtotal renal ablation model of adiponectin-knockout mice. Arterioscler Thromb Vasc Biol 27:1910–1917PubMedCrossRefGoogle Scholar
  54. 54.
    Oguz Y, Yilmaz MI, Acikel C, Eyileten T, Caglar K, Oktenli C, Yenicesu M, Vural A (2009) The relationship between adiponectin levels and degree of proteinuria in patients with nephrotic and non-nephrotic proteinuria. Ren Fail 31:29–35PubMedCrossRefGoogle Scholar
  55. 55.
    Hayakawa K, Ohashi H, Yokoyama H, Yoshida G, Okada M, Minatoguchi S (2009) Adiponectin is increased and correlated with the degree of proteinuria, but plasma leptin is not changed in patients with chronic glomerulonephritis. Nephrology (Carlton Print) 14:327–331CrossRefGoogle Scholar
  56. 56.
    Teplan V Jr, Vyhnánek F, Gürlich R, Haluzík M, Racek J, Vyhnankova I, Stollová M, Teplan V (2010) Increased proinflammatory cytokine production in adipose tissue of obese patients with chronic kidney disease. Wien Klin Wochenschr 122:466–473PubMedCrossRefGoogle Scholar
  57. 57.
    Zoccali C, Mallamaci F, Panuccio V, Tripepi G, Cutrupi S, Parlongo S, Catalano F, Tanaka S, Ouchi N, Kihara S, Funahashi T, Matsuzawa Y (2003) Adiponectin is markedly increased in patients with nephrotic syndrome and is related to metabolic risk factors. Kidney Int Suppl 84:S98–S102PubMedCrossRefGoogle Scholar
  58. 58.
    Bakkaloglu SA, Soylemezoglu O, Buyan N, Funahashi T, Elhan AH, Peru H, Fidan K, Yilmaz S, Hasanoglu E (2005) High serum adiponectin levels during steroid-responsive nephrotic syndrome relapse. Pediatr Nephrol 20:474–477PubMedCrossRefGoogle Scholar
  59. 59.
    Shen YY, Hughes JT, Charlesworth JA, Kelly JJ, Peake PW (2008) Adiponectin is present in the urine in its native conformation, and specifically reduces the secretion of MCP-1 by proximal tubular cells. Nephrology (Carlton Print) 13:405–410CrossRefGoogle Scholar

Copyright information

© IPNA 2011

Authors and Affiliations

  1. 1.Division of Nephrology and HypertensionCincinnati Children’s Hospital and Medical CenterCincinnatiUSA

Personalised recommendations