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Adiponectin and Leptin in Kidney Disease Patients

  • Jerry Zhong Yu
  • Kamyar Kalantar-Zadeh
  • Connie M. Rhee
Chapter

Abstract

Adiponectin is a type of adipokine, namely, a hormonally active molecule secreted by adipose tissue with pervasive effects on multiple organ systems. In the general population, adiponectin has demonstrated anti-inflammatory and cardioprotective properties, and a number of studies have shown that higher levels are associated with favorable cardiovascular outcomes and survival. However, in patients with non-dialysis-dependent (NDD) and dialysis-dependent chronic kidney disease (CKD), higher adiponectin levels have been paradoxically associated with adverse cardiovascular outcomes and higher mortality risk. Similarly, leptin is an adipokine which has been identified as having an important role in the regulation of inflammation and energy metabolism. In the general population, high serum leptin has been associated with adverse cardiovascular outcomes, but these observations are in contradistinction to findings observed in patients with end-stage renal disease (ESRD). The objective of this chapter is to review and discuss the existing body of evidence examining the interrelationships of adiponectin and leptin and outcomes in the general population as well as in those with varying degrees of impaired kidney function.

Keywords

Adiponectin Leptin Adipokines Chronic kidney disease End-stage renal disease 

References

  1. 1.
    Matsuda M, Tamura R, Kishida N, et al. Predictive value of adiponectin in patients with multivessel coronary atherosclerosis detected on computed tomography angiography. J Atheroscler Thromb. 2013;20:767–76.CrossRefGoogle Scholar
  2. 2.
    Kawagoe J, Ishikawa T, Iwakiri H, Date H, Imamura T, Kitamura K. Association between adiponectin production in coronary circulation and future cardiovascular events in patients with coronary artery disease. Int Heart J. 2014;55:239–43.CrossRefGoogle Scholar
  3. 3.
    Yoon JH, Kim SK, Choi HJ, et al. Adiponectin provides additional information to conventional cardiovascular risk factors for assessing the risk of atherosclerosis in both genders. PLoS One. 2013;8:e75535.CrossRefGoogle Scholar
  4. 4.
    Yamashita T, Matsuda M, Nishimoto O, et al. Combination of serum adiponectin level and metabolic syndrome is closely associated with coronary artery disease in Japanese subjects with good glycemic control. Intern Med. 2010;49:721–7.CrossRefGoogle Scholar
  5. 5.
    Komura N, Kihara S, Sonoda M, et al. Clinical significance of high-molecular weight form of adiponectin in male patients with coronary artery disease. Circ J. 2008;72:23–8.CrossRefGoogle Scholar
  6. 6.
    Pischon T, Girman CJ, Hotamisligil GS, Rifai N, Hu FB, Rimm EB. Plasma adiponectin levels and risk of myocardial infarction in men. JAMA. 2004;291:1730–7.CrossRefGoogle Scholar
  7. 7.
    Iwashima Y, Horio T, Kumada M, et al. Adiponectin and renal function, and implication as a risk of cardiovascular disease. Am J Cardiol. 2006;98:1603–8.CrossRefGoogle Scholar
  8. 8.
    Menon V, Li L, Wang X, et al. Adiponectin and mortality in patients with chronic kidney disease. J Am Soc Nephrol. 2006;17:2599–606.CrossRefGoogle Scholar
  9. 9.
    Jorsal A, Tarnow L, Frystyk J, et al. Serum adiponectin predicts all-cause mortality and end stage renal disease in patients with type I diabetes and diabetic nephropathy. Kidney Int. 2008;74:649–54.CrossRefGoogle Scholar
  10. 10.
    Zoccali C, Mallamaci F, Tripepi G, et al. Adiponectin, metabolic risk factors, and cardiovascular events among patients with end-stage renal disease. J Am Soc Nephrol. 2002;13:134–41.CrossRefGoogle Scholar
  11. 11.
    Diez JJ, Estrada P, Bajo MA, et al. High stable serum adiponectin levels are associated with a better outcome in prevalent dialysis patients. Am J Nephrol. 2009;30:244–52.CrossRefGoogle Scholar
  12. 12.
    Takemoto F, Katori H, Sawa N, et al. Plasma adiponectin: a predictor of coronary heart disease in hemodialysis patients--a Japanese prospective eight-year study. Nephron Clin Pract. 2009;111:c12–20.CrossRefGoogle Scholar
  13. 13.
    Abdallah E, Waked E, Nabil M, El-Bendary O. Adiponectin and cardiovascular outcomes among hemodialysis patients. Kidney Blood Press Res. 2012;35:247–53.CrossRefGoogle Scholar
  14. 14.
    Drechsler C, Krane V, Winkler K, Dekker FW, Wanner C. Changes in adiponectin and the risk of sudden death, stroke, myocardial infarction, and mortality in hemodialysis patients. Kidney Int. 2009;76:567–75.CrossRefGoogle Scholar
  15. 15.
    Rao M, Li L, Tighiouart H, et al. Plasma adiponectin levels and clinical outcomes among haemodialysis patients. Nephrol Dial Transplant. 2008;23:2619–28.CrossRefGoogle Scholar
  16. 16.
    Alam A, Molnar MZ, Czira ME, et al. Serum adiponectin levels and mortality after kidney transplantation. Clin J Am Soc Nephrol. 2013;8:460–7.CrossRefGoogle Scholar
  17. 17.
    Maeda K, Okubo K, Shimomura I, Funahashi T, Matsuzawa Y, Matsubara K. cDNA cloning and expression of a novel adipose specific collagen-like factor, apM1 (adipose most abundant gene transcript 1). 1996. Biochem Biophys Res Commun. 2012;425:556–9.CrossRefGoogle Scholar
  18. 18.
    Nigro E, Scudiero O, Monaco ML, et al. New insight into adiponectin role in obesity and obesity-related diseases. Biomed Res Int. 2014;2014:658913.CrossRefGoogle Scholar
  19. 19.
    Pajvani UB, Hawkins M, Combs TP, et al. Complex distribution, not absolute amount of adiponectin, correlates with thiazolidinedione-mediated improvement in insulin sensitivity. J Biol Chem. 2004;279:12152–62.CrossRefGoogle Scholar
  20. 20.
    Arner P. The adipocyte in insulin resistance: key molecules and the impact of the thiazolidinediones. Trends Endocrinol Metab. 2003;14:137–45.CrossRefGoogle Scholar
  21. 21.
    Yamauchi T, Iwabu M, Okada-Iwabu M, Kadowaki T. Adiponectin receptors: a review of their structure, function and how they work. Best Pract Res Clin Endocrinol Metab. 2014;28:15–23.CrossRefGoogle Scholar
  22. 22.
    Cammisotto PG, Bendayan M. Adiponectin stimulates phosphorylation of AMP-activated protein kinase alpha in renal glomeruli. J Mol Histol. 2008;39:579–84.CrossRefGoogle Scholar
  23. 23.
    Ohashi K, Iwatani H, Kihara S, et al. Exacerbation of albuminuria and renal fibrosis in subtotal renal ablation model of adiponectin-knockout mice. Arterioscler Thromb Vasc Biol. 2007;27:1910–7.CrossRefGoogle Scholar
  24. 24.
    Jeon WS, Park JW, Lee N, et al. Urinary adiponectin concentration is positively associated with micro- and macro-vascular complications. Cardiovasc Diabetol. 2013;12:137.CrossRefGoogle Scholar
  25. 25.
    Jorsal A, Petersen EH, Tarnow L, et al. Urinary adiponectin excretion rises with increasing albuminuria in type 1 diabetes. J Diabetes Complicat. 2013;27:604–8.CrossRefGoogle Scholar
  26. 26.
    Kopf S, Oikonomou D, von Eynatten M, et al. Urinary excretion of high molecular weight adiponectin is an independent predictor of decline of renal function in type 2 diabetes. Acta Diabetol. 2014;51:479–89.PubMedGoogle Scholar
  27. 27.
    Arita Y, Kihara S, Ouchi N, et al. Paradoxical decrease of an adipose-specific protein, adiponectin, in obesity. Biochem Biophys Res Commun. 1999;257:79–83.CrossRefGoogle Scholar
  28. 28.
    Weyer C, Funahashi T, Tanaka S, et al. Hypoadiponectinemia in obesity and type 2 diabetes: close association with insulin resistance and hyperinsulinemia. J Clin Endocrinol Metab. 2001;86:1930–5.CrossRefGoogle Scholar
  29. 29.
    Statnick MA, Beavers LS, Conner LJ, et al. Decreased expression of apM1 in omental and subcutaneous adipose tissue of humans with type 2 diabetes. Int J Exp Diabetes Res. 2000;1:81–8.CrossRefGoogle Scholar
  30. 30.
    Hotta K, Funahashi T, Arita Y, et al. Plasma concentrations of a novel, adipose-specific protein, adiponectin, in type 2 diabetic patients. Arterioscler Thromb Vasc Biol. 2000;20:1595–9.CrossRefGoogle Scholar
  31. 31.
    Yamauchi T, Kamon J, Waki H, et al. The fat-derived hormone adiponectin reverses insulin resistance associated with both lipoatrophy and obesity. Nat Med. 2001;7:941–6.CrossRefGoogle Scholar
  32. 32.
    Li S, Shin HJ, Ding EL, van Dam RM. Adiponectin levels and risk of type 2 diabetes: a systematic review and meta-analysis. JAMA. 2009;302:179–88.CrossRefGoogle Scholar
  33. 33.
    Pereira RI, Snell-Bergeon JK, Erickson C, et al. Adiponectin dysregulation and insulin resistance in type 1 diabetes. J Clin Endocrinol Metab. 2012;97:E642–7.CrossRefGoogle Scholar
  34. 34.
    Hadjadj S, Aubert R, Fumeron F, et al. Increased plasma adiponectin concentrations are associated with microangiopathy in type 1 diabetic subjects. Diabetologia. 2005;48:1088–92.CrossRefGoogle Scholar
  35. 35.
    Saraheimo M, Forsblom C, Thorn L, et al. Serum adiponectin and progression of diabetic nephropathy in patients with type 1 diabetes. Diabetes Care. 2008;31:1165–9.CrossRefGoogle Scholar
  36. 36.
    Okamoto Y, Arita Y, Nishida M, et al. An adipocyte-derived plasma protein, adiponectin, adheres to injured vascular walls. Horm Metab Res. 2000;32:47–50.CrossRefGoogle Scholar
  37. 37.
    Lee FP, Jen CY, Chang CC, et al. Mechanisms of adiponectin-mediated COX-2 induction and protection against iron injury in mouse hepatocytes. J Cell Physiol. 2010;224:837–47.CrossRefGoogle Scholar
  38. 38.
    Ouchi N, Kihara S, Arita Y, et al. Novel modulator for endothelial adhesion molecules: adipocyte-derived plasma protein adiponectin. Circulation. 1999;100:2473–6.CrossRefGoogle Scholar
  39. 39.
    Cheng KK, Lam KS, Wang Y, et al. Erratum. Adiponectin-induced endothelial nitric oxide synthase activation and nitric oxide production are mediated by APPL1 in endothelial cells. Diabetes. 2007;56:1387–94. Diabetes 2016;65:3218.CrossRefGoogle Scholar
  40. 40.
    Wu Z, Cheng Y, Aung LH, Li B. Association between adiponectin concentrations and cardiovascular disease in diabetic patients: a systematic review and meta-analysis. PLoS One. 2013;8:e78485.CrossRefGoogle Scholar
  41. 41.
    Becker B, Kronenberg F, Kielstein JT, 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;16:1091–8.CrossRefGoogle Scholar
  42. 42.
    Zoccali C, Postorino M, Marino C, et al. Waist circumference modifies the relationship between the adipose tissue cytokines leptin and adiponectin and all-cause and cardiovascular mortality in haemodialysis patients. J Intern Med. 2011;269:172–81.CrossRefGoogle Scholar
  43. 43.
    Chudek J, Adamczak M, Karkoszka H, et al. Plasma adiponectin concentration before and after successful kidney transplantation. Transplant Proc. 2003;35:2186–9.CrossRefGoogle Scholar
  44. 44.
    Adamczak M, Szotowska M, Chudek J, Karkoszka H, Cierpka L, Wiecek A. Plasma adiponectin concentration in patients after successful kidney transplantation – a single-center, observational study. Clin Nephrol. 2007;67:381–90.CrossRefGoogle Scholar
  45. 45.
    Mantzoros CS. The role of leptin in human obesity and disease: a review of current evidence. Ann Intern Med. 1999;130:671–80.CrossRefGoogle Scholar
  46. 46.
    Hukshorn CJ, Lindeman JH, Toet KH, et al. Leptin and the proinflammatory state associated with human obesity. J Clin Endocrinol Metab. 2004;89:1773–8.CrossRefGoogle Scholar
  47. 47.
    Dervisoglu E, Eraldemir C, Kalender B, Kir HM, Caglayan C. Adipocytokines leptin and adiponectin, and measures of malnutrition-inflammation in chronic renal failure: is there a relationship? J Ren Nutr. 2008;18:332–7.CrossRefGoogle Scholar
  48. 48.
    Fantuzzi G. Adipose tissue, adipokines, and inflammation. J Allergy Clin Immunol. 2005;115:911–9. quiz 20CrossRefGoogle Scholar
  49. 49.
    Heimburger O, Lonnqvist F, Danielsson A, Nordenstrom J, Stenvinkel P. Serum immunoreactive leptin concentration and its relation to the body fat content in chronic renal failure. J Am Soc Nephrol. 1997;8:1423–30.PubMedGoogle Scholar
  50. 50.
    Johansen KL, Mulligan K, Tai V, Schambelan M. Leptin, body composition, and indices of malnutrition in patients on dialysis. J Am Soc Nephrol. 1998;9:1080–4.PubMedGoogle Scholar
  51. 51.
    Nishizawa Y, Shoji T, Tanaka S, et al. Plasma leptin level and its relationship with body composition in hemodialysis patients. Am J Kidney Dis. 1998;31:655–61.CrossRefGoogle Scholar
  52. 52.
    Lieb W, Sullivan LM, Harris TB, et al. Plasma leptin levels and incidence of heart failure, cardiovascular disease, and total mortality in elderly individuals. Diabetes Care. 2009;32:612–6.CrossRefGoogle Scholar
  53. 53.
    Vavruch C, Lanne T, Fredrikson M, Lindstrom T, Ostgren CJ, Nystrom FH. Serum leptin levels are independently related to the incidence of ischemic heart disease in a prospective study of patients with type 2 diabetes. Cardiovasc Diabetol. 2015;14:62.CrossRefGoogle Scholar
  54. 54.
    Batsis JA, Sahakyan KR, Singh P, Bartels SJ, Somers VK, Lopez-Jimenez F. Leptin, adiposity, and mortality: results from the National Health and nutrition examination survey III, 1988 to 1994. Mayo Clin Proc. 2015;90:481–91.CrossRefGoogle Scholar
  55. 55.
    Adya R, Tan BK, Randeva HS. Differential effects of leptin and adiponectin in endothelial angiogenesis. J Diabetes Res. 2015;2015:648239.CrossRefGoogle Scholar
  56. 56.
    Merabet E, Dagogo-Jack S, Coyne DW, et al. Increased plasma leptin concentration in end-stage renal disease. J Clin Endocrinol Metab. 1997;82:847–50.PubMedGoogle Scholar
  57. 57.
    Diez JJ, Iglesias P, Fernandez-Reyes MJ, et al. Serum concentrations of leptin, adiponectin and resistin, and their relationship with cardiovascular disease in patients with end-stage renal disease. Clin Endocrinol. 2005;62:242–9.CrossRefGoogle Scholar
  58. 58.
    Diez JJ, Bossola M, Fernandez-Reyes MJ, et al. Relationship between leptin and all-cause and cardiovascular mortality in chronic hemodialysis patients. Nefrologia. 2011;31:206–12.PubMedGoogle Scholar
  59. 59.
    Bian X, Liu N, Bai Y, et al. Association of leptin with mortality in patients on maintenance hemodialysis: a prospective study. Iran J Kidney Dis. 2014;8:314–20.PubMedGoogle Scholar
  60. 60.
    Nasri H. Association of serum leptin with anemia in maintenance hemodialysis patients. Saudi J Kidney Dis Transpl. 2006;17:521–5.PubMedGoogle Scholar
  61. 61.
    Park JT, Yoo TH, Kim JK, et al. Leptin/adiponectin ratio is an independent predictor of mortality in nondiabetic peritoneal dialysis patients. Perit Dial Int. 2013;33:67–74.CrossRefGoogle Scholar
  62. 62.
    Nasri H. Serum leptin concentration and left ventricular hypertrophy and function in maintenance hemodialysis patients. Minerva Urol Nefrol. 2006;58:189–93.PubMedGoogle Scholar

Copyright information

© Springer Nature Switzerland AG 2019

Authors and Affiliations

  • Jerry Zhong Yu
    • 1
  • Kamyar Kalantar-Zadeh
    • 2
  • Connie M. Rhee
    • 3
  1. 1.Nephrology Associates Medical GroupRiversideUSA
  2. 2.Division of Nephrology and Hypertension, Departments of Medicine, Pediatrics, Public Health, and Nursing Sciences, University of California Irvine School of MedicineOrangeUSA
  3. 3.Division of Nephrology and Hypertension, Departments of Medicine and Public Health, University of California Irvine School of MedicineOrangeUSA

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