The role of obesity in kidney disease: recent findings and potential mechanisms

Nephrology – Review

Abstract

Obesity epidemic is in rise in almost every industrialized country and continues to be a growing problem worldwide. In fact, obesity per se has been recognized as a chronic disease. Consequently, there has been a cascade of metabolic changes initiated by the markedly risen prevalence that contributes to the increased incidence of diabetes, hypertension, and cardiovascular disease. Moreover, obesity is also associated with an increased risk of chronic kidney disease (CKD). The majority of the studies indicate a direct relationship between body mass index (BMI) and CKD risk. Moreover, current evidence emphasized the fact that central obesity measurements, such as waist circumference, could be a better predictor of CKD progression and mortality than BMI. The detrimental effects of obesity on kidney outcome have been recognized in nondialysis-dependent (NDD)-CKD patients. However, survival in overweight or obese CKD patients undergoing maintenance hemodialysis is paradoxically opposed compared with the general population. This “reverse epidemiology,” however, is valid mainly for the inflammated end-stage renal disease (ESRD) patients. In fact, renal transplant recipients with higher BMI have inferior patient and graft survival compared to patients with lower BMI. This review also provides perspectives concerning the mechanisms associated with obesity, such as the renin–angiotensin–aldosterone system (RAAS) activation, and the role of leptin, adiponectin, fetuin-A, and adipose tissue, as factors that contribute to the development of CKD. Prevention strategies for CKD patients are also discussed and should be considered by clinicians.

Keywords

Obesity Kidney Chronic kidney disease 

References

  1. 1.
    Ogden CL, Carroll MD, Curtin LR, McDowell MA, Tabak CJ, Flegal KM (2006) Prevalence of overweight and obesity in the United States, 1999–2004. JAMA 295:1549–1555PubMedCrossRefGoogle Scholar
  2. 2.
    Hall JE, Crook ED, Jones DW, Wofford MR, Dubbert PM (2002) Mechanisms of obesity-associated cardiovascular and renal disease. Am J Med Sci 324:127–137PubMedCrossRefGoogle Scholar
  3. 3.
    Dubbert PM, Carithers T, Sumner AE et al (2002) Obesity, physical inactivity, and risk for cardiovascular disease. Am J Med Sci 324:116–126PubMedCrossRefGoogle Scholar
  4. 4.
    Health implications of obesity (1985) National institutes of health consensus development conference statement. Ann Intern Med 103:147–151Google Scholar
  5. 5.
    Kramer HJ, Saranathan A, Luke A et al (2006) Increasing body mass index and obesity in the incident ESRD population. J Am Soc Nephrol 17:1453–1459PubMedCrossRefGoogle Scholar
  6. 6.
    Bonnet F, Deprele C, Sassolas A et al (2001) Excessive body weight as a new independent risk factor for clinical and pathological progression in primary IgA nephritis. Am J Kidney Dis 37:720–727PubMedCrossRefGoogle Scholar
  7. 7.
    Evans M, Fryzek JP, Elinder CG et al (2005) The natural history of chronic renal failure: results from an unselected, population-based, inception cohort in Sweden. Am J Kidney Dis 46:863–870PubMedCrossRefGoogle Scholar
  8. 8.
    Obermayr RP, Temml C, Gutjahr G et al (2009) Body mass index modifies the risk of cardiovascular death in proteinuric chronic kidney disease. Nephrol Dial Transplant 24:2421–2428PubMedCrossRefGoogle Scholar
  9. 9.
    Kovesdy CP, Anderson JE, Kalantar-Zadeh K (2007) Paradoxical association between body mass index and mortality in men with CKD not yet on dialysis. Am J Kidney Dis 49:581–591PubMedCrossRefGoogle Scholar
  10. 10.
    Kwan BC, Murtaugh MA, Beddhu S (2007) Associations of body size with metabolic syndrome and mortality in moderate chronic kidney disease. Clin J Am Soc Nephrol 2:992–998PubMedCrossRefGoogle Scholar
  11. 11.
    Foster MC, Hwang SJ, Larson MG et al (2008) Overweight, obesity, and the development of stage 3 CKD: the Framingham Heart Study. Am J Kidney Dis 52(1):39–48PubMedCrossRefGoogle Scholar
  12. 12.
    Ryu S, Chang Y, Woo HY et al (2008) Changes in body weight predict CKD in healthy men. J Am Soc Nephrol 21:1798–1805CrossRefGoogle Scholar
  13. 13.
    Iseki K, Ikemiya Y, Kinjo K, Inoue T, Iseki C, Takishita S (2004) Body mass index and the risk of development of end-stage renal disease in a screened cohort. Kidney Int 65:1870–1876PubMedCrossRefGoogle Scholar
  14. 14.
    Hsu CY, McCulloch CE, Iribarren C, Darbinian J, Go AS (2006) Body mass index and risk for end-stage renal disease. Ann Intern Med 144:21–28PubMedGoogle Scholar
  15. 15.
    Ejerblad E, Fored CM, Lindblad P, Fryzek J, McLaughlin JK, Nyren O (2006) Obesity and risk for chronic renal failure. J Am Soc Nephrol 17:1695–1702PubMedCrossRefGoogle Scholar
  16. 16.
    Fox CS, Larson MG, Leip EP, Culleton B, Wilson PW, Levy D (2004) Predictors of new-onset kidney disease in a community-based population. JAMA 291:844–850PubMedCrossRefGoogle Scholar
  17. 17.
    Munkhaugen J, Lydersen S, Wideroe TE, Hallan S (2009) Prehypertension, obesity, and risk of kidney disease: 20-year follow-up of the HUNT I study in Norway. Am J Kidney Dis 54:638–646PubMedCrossRefGoogle Scholar
  18. 18.
    Elsayed EF, Sarnak MJ, Tighiouart H et al (2008) Waist-to-hip ratio, body mass index, and subsequent kidney disease and death. Am J Kidney Dis 52:29–38PubMedCrossRefGoogle Scholar
  19. 19.
    Gelber RP, Kurth T, Kausz AT et al (2005) Association between body mass index and CKD in apparently healthy men. Am J Kidney Dis 46:871–880PubMedCrossRefGoogle Scholar
  20. 20.
    Praga M (2002) Obesity—a neglected culprit in renal disease. Nephrol Dial Transplant 17:1157–1159PubMedCrossRefGoogle Scholar
  21. 21.
    Ogden CL, Yanovski SZ, Carroll MD, Flegal KM (2007) The epidemiology of obesity. Gastroenterology 132:2087–2102PubMedCrossRefGoogle Scholar
  22. 22.
    Coresh J, Selvin E, Stevens LA et al (2007) Prevalence of chronic kidney disease in the United States. JAMA 298:2038–2047PubMedCrossRefGoogle Scholar
  23. 23.
    Flegal KM, Carroll MD, Ogden CL, Johnson CL (2002) Prevalence and trends in obesity among US adults, 1999–2000. JAMA 288:1723–1727PubMedCrossRefGoogle Scholar
  24. 24.
    Flegal KM, Carrol MD, Ogden CL, Curtin LR (2010) Prevalence and trends in obesity among US adults, 1999–2008. J Am Med Assoc 303:235–241CrossRefGoogle Scholar
  25. 25.
    Hallan S, de MR, Carlsen S, Dekker FW, Aasarod K, Holmen J (2006) Obesity, smoking, and physical inactivity as risk factors for CKD: are men more vulnerable? Am J Kidney Dis 47:396–405PubMedCrossRefGoogle Scholar
  26. 26.
    Rennie KL, Jebb SA (2005) Prevalence of obesity in Great Britain. Obes Rev 6:11–12PubMedCrossRefGoogle Scholar
  27. 27.
    Garrison RJ, Kannel WB, Stokes J III, Castelli WP (1987) Incidence and precursors of hypertension in young adults: the Framingham Offspring Study. Prev Med 16:235–251PubMedCrossRefGoogle Scholar
  28. 28.
    Wofford MR, Hall JE (2004) Pathophysiology and treatment of obesity hypertension. Curr Pharm Des 10:3621–3637PubMedCrossRefGoogle Scholar
  29. 29.
    US RDS 2009 Annual Data Report: Atlas of End-Stage Renal Disease in the United States in: National Institutes of Health, National Institutes of Diabetes and Digestive and Kidney Disease. Viewed: 12.8.2010Google Scholar
  30. 30.
    Paeratakul S, Lovejoy JC, Ryan DH, Bray GA (2002) The relation of gender, race and socioeconomic status to obesity and obesity comorbidities in a sample of US adults. Int J Obes Relat Metab Disord 26:1205–1210PubMedCrossRefGoogle Scholar
  31. 31.
    Cossrow N, Falkner B (2004) Race/ethnic issues in obesity and obesity-related comorbidities. J Clin Endocrinol Metab 89:2590–2594PubMedCrossRefGoogle Scholar
  32. 32.
    Perneger TV, Whelton PK, Klag MJ (1995) Race and end-stage renal disease. Socioeconomic status and access to health care as mediating factors. Arch Intern Med 155:1201–1208PubMedCrossRefGoogle Scholar
  33. 33.
    Perneger TV, Klag MJ, Whelton PK (1995) Race and socioeconomic status in hypertension and renal disease. Curr Opin Nephrol Hypertens 4:235–239PubMedCrossRefGoogle Scholar
  34. 34.
    Klag MJ, Whelton PK, Randall BL, Neaton JD, Brancati FL, Stamler J (1997) End-stage renal disease in African–American and white men. 16-year MRFIT findings. JAMA 277:1293–1298PubMedCrossRefGoogle Scholar
  35. 35.
    Chang VW, Asch DA, Werner RM (2010) Quality of care among obese patients. JAMA 303:1274–1281PubMedCrossRefGoogle Scholar
  36. 36.
    Drewnowski A, Specter SE (2004) Poverty and obesity: the role of energy density and energy costs. Am J Clin Nutr 79:6–16PubMedGoogle Scholar
  37. 37.
    Xue JL, Ma JZ, Louis TA, Collins AJ (2001) Forecast of the number of patients with end-stage renal disease in the United States to the year 2010. J Am Soc Nephrol 12:2753–2758PubMedGoogle Scholar
  38. 38.
    Schoolwerth AC, Engelgau MM, Hostetter TH et al (2006) Chronic kidney disease: a public health problem that needs a public health action plan. Prev Chronic Dis 3:A57PubMedGoogle Scholar
  39. 39.
    USRD 2008 ADR/reference tables. Available: http://www.usrds.org-2008.htm.Viewed 12/11/09
  40. 40.
    Dirks JH, de ZD, Agarwal SK et al (2005) Prevention of chronic kidney and vascular disease: toward global health equity—the Bellagio 2004 declaration. Kidney Int Suppl 98:S1–S6PubMedCrossRefGoogle Scholar
  41. 41.
    Coresh J, Astor BC, Greene T, Eknoyan G, Levey AS (2003) Prevalence of chronic kidney disease and decreased kidney function in the adult US population: Third National Health and Nutrition Examination Survey. Am J Kidney Dis 41:1–12PubMedCrossRefGoogle Scholar
  42. 42.
    Wilson PW, D’Agostino RB, Sullivan L, Parise H, Kannel WB (2002) Overweight and obesity as determinants of cardiovascular risk: the Framingham experience. Arch Intern Med 162:1867–1872PubMedCrossRefGoogle Scholar
  43. 43.
    Liu K, Ruth KJ, Flack JM, Jones-Webb R, Burke G, Savage PJ et al (1996) Blood pressure in young blacks and whites: relevance of obesity and lifestyle factors in determining differences. The CARDIA study. Coronary artery risk development in young adults. Circulation 93:60–66PubMedGoogle Scholar
  44. 44.
    Chan JM, Rimm EB, Colditz GA, Stampfer MJ, Willett WC (1994) Obesity, fat distribution, and weight gain as risk factors for clinical diabetes in men. Diabetes Care 17:961–969PubMedCrossRefGoogle Scholar
  45. 45.
    Burrows NR, Wang J, Geiss LS, Venkat Narayan KM, Engelgau MM (2005) Incidence of end-stage renal disease among persons with diabetes—United States, 1990–2002 MMWR. Morb Mortal Wkly Rep 54:1097–1100Google Scholar
  46. 46.
    Wang Y, Chen X, Song Y, Caballero B, Cheskin LJ (2008) Association between obesity and kidney disease: a systematic review and meta-analysis. Kidney Int 73:19–33PubMedCrossRefGoogle Scholar
  47. 47.
    Ritz E (2008) Obesity and CKD: how to assess the risk? Am J Kidney Dis 52:1–6PubMedCrossRefGoogle Scholar
  48. 48.
    Fesler P, Safar ME, du CG, Ribstein J, Mimran A (2007) Pulse pressure is an independent determinant of renal function decline during treatment of essential hypertension. J Hypertens 25:1915–1920PubMedCrossRefGoogle Scholar
  49. 49.
    Kambham N, Markowitz GS, Valeri AM, Lin J, D’Agati VD (2001) Obesity-related glomerulopathy: an emerging epidemic. Kidney Int 59:1498–1509PubMedCrossRefGoogle Scholar
  50. 50.
    Kramer H, Reboussin D, Bertoni AG et al (2009) Obesity and albuminuria among adults with type 2 diabetes: the look AHEAD (Action for Health in Diabetes) study. Diabetes Care 32:851–853PubMedCrossRefGoogle Scholar
  51. 51.
    Afshinnia F, Wilt TJ, Duval S, Esmaeili A, Ibrahim HN (2010) Weight loss and proteinuria: systematic review of clinical trials and comparative cohorts. Nephrol Dial Transplant 25:1173–1183PubMedCrossRefGoogle Scholar
  52. 52.
    Kramer H, Luke A, Bidani A, Cao G, Cooper R, McGee D (2005) Obesity and prevalent and incident CKD: the hypertension detection and follow-up program. Am J Kidney Dis 46:587–594PubMedCrossRefGoogle Scholar
  53. 53.
    Goodkin DA, Bragg-Gresham JL, Koenig KG et al (2003) Association of comorbid conditions and mortality in hemodialysis patients in Europe, Japan, and the United States: the dialysis outcomes and practice patterns study (DOPPS). J Am Soc Nephrol 14:3270–3277PubMedCrossRefGoogle Scholar
  54. 54.
    Leavey SF, McCullough K, Hecking E, Goodkin D, Port FK, Young EW (2001) Body mass index and mortality in ‘healthier’ as compared with ‘sicker’ haemodialysis patients: results from the dialysis outcomes and practice patterns study (DOPPS). Nephrol Dial Transplant 16:2386–2394PubMedCrossRefGoogle Scholar
  55. 55.
    Chazot C, Gassia JP, Di BA, Cesare S, Ponce P, Marcelli D (2009) Is there any survival advantage of obesity in Southern European haemodialysis patients? Nephrol Dial Transplant 24:2871–2876PubMedCrossRefGoogle Scholar
  56. 56.
    Degoulet P, Legrain M, Reach I et al (1982) Mortality risk factors in patients treated by chronic hemodialysis. Report of the diaphane collaborative study. Nephron 31:103–110PubMedCrossRefGoogle Scholar
  57. 57.
    Johansen KL, Young B, Kaysen GA, Chertow GM (2004) Association of body size with outcomes among patients beginning dialysis. Am J Clin Nutr 80:324–332PubMedGoogle Scholar
  58. 58.
    Kaizu Y, Tsunega Y, Yoneyama T et al (1998) Overweight as another nutritional risk factor for the long-term survival of non-diabetic hemodialysis patients. Clin Nephrol 50:44–50PubMedGoogle Scholar
  59. 59.
    Port FK, Ashby VB, Dhingra RK, Roys EC, Wolfe RA (2002) Dialysis dose and body mass index are strongly associated with survival in hemodialysis patients. J Am Soc Nephrol 13:1061–1066PubMedGoogle Scholar
  60. 60.
    Kopple JD (1997) Nutritional status as a predictor of morbidity and mortality in maintenance dialysis patients. ASAIO J 43:246–250PubMedGoogle Scholar
  61. 61.
    Churchill D, Wayne Teylor D, Keshaviah P (1996) Adequacy of dialysis and nutrition in continuous peritoneal dialysis: association with clinical outcomes. Canada-USA (CANUSA) peritoneal dialysis study group. J Am Soc Nephrol 7:198–207Google Scholar
  62. 62.
    Johnson DW, Herzig KA, Purdie DM et al (2000) Is obesity a favorable prognostic factor in peritoneal dialysis patients? Perit Dial Int 20:715–721PubMedGoogle Scholar
  63. 63.
    Kalantar-Zadeh K, Block G, Humphreys MH, Kopple JD (2003) Reverse epidemiology of cardiovascular risk factors in maintenance dialysis patients. Kidney Int 63:793–808PubMedCrossRefGoogle Scholar
  64. 64.
    Ducloux D, Kazory A, Simula-Faivre D, Chalopin JM (2005) One-year post-transplant weight gain is a risk factor for graft loss. Am J Transplant 5:2922–2928PubMedCrossRefGoogle Scholar
  65. 65.
    Meier-Kriesche HU, Arndorfer JA, Kaplan B (2002) The impact of body mass index on renal transplant outcomes: a significant independent risk factor for graft failure and patient death. Transplantation 15(73):70–74CrossRefGoogle Scholar
  66. 66.
    Massarweh NN, Clayton JL, Mangum CA, Florman SS, Slakey DP (2005) High body mass index and short- and long-term renal allograft survival in adults. Transplantation 80:1430–1434PubMedCrossRefGoogle Scholar
  67. 67.
    Lentine KL, Rocca-Rey LA, Bacchi G et al (2008) Obesity and cardiac risk after kidney transplantation: experience at one center and comprehensive literature review. Transplantation 86:303–312PubMedCrossRefGoogle Scholar
  68. 68.
    Kovesdy CP, Czira ME, Rudas A et al (2010) Body mass index, waist circumference and mortality in kidney transplant recipients. Am J Transplant 10:2644–2651PubMedCrossRefGoogle Scholar
  69. 69.
    Bosma RJ, van der Heide JJ, Oosterop EJ, de Jong PE, Navis G (2004) Body mass index is associated with altered renal hemodynamics in non-obese healthy subjects. Kidney Int 65:259–265PubMedCrossRefGoogle Scholar
  70. 70.
    Tomaszewski M, Charchar FJ, Maric C et al (2007) Glomerular hyperfiltration: a new marker of metabolic risk. Kidney Int 71:816–821PubMedCrossRefGoogle Scholar
  71. 71.
    Pinto-Sietsma SJ, Navis G, Janssen WM, de ZD, Gans RO, de Jong PE (2003) A central body fat distribution is related to renal function impairment, even in lean subjects. Am J Kidney Dis 41:733–741PubMedCrossRefGoogle Scholar
  72. 72.
    Haffner SM, Stern MP, Hazuda HP, Pugh J, Patterson JK (1987) Do upper-body and centralized adiposity measure different aspects of regional body-fat distribution? Relationship to non-insulin-dependent diabetes mellitus, lipids, and lipoproteins. Diabetes 36:43–51PubMedCrossRefGoogle Scholar
  73. 73.
    Postorino M, Marino C, Tripepi G, Zoccali C (2009) Abdominal obesity and all-cause and cardiovascular mortality in end-stage renal disease. J Am Coll Cardiol 14(53):1265–1272CrossRefGoogle Scholar
  74. 74.
    Huang CX, Tighiouart H, Beddhu S et al (2010) Both low muscle mass and low fat are associated with higher all-cause mortality in hemodialysis patients. Kidney Int 77:624–629PubMedCrossRefGoogle Scholar
  75. 75.
    Chen HM, Li SJ, Chen HP, Wang QW, Li LS, Liu ZH (2008) Obesity-related glomerulopathy in China: a case series of 90 patients. Am J Kidney Dis 52:58–65PubMedCrossRefGoogle Scholar
  76. 76.
    Weisinger JR, Kempson RL, Eldridge FL, Swenson RS (1974) The nephrotic syndrome: a complication of massive obesity. Ann Intern Med 81:440–447PubMedGoogle Scholar
  77. 77.
    Serra A, Romero R, Lopez D et al (2008) Renal injury in the extremely obese patients with normal renal function. Kidney Int 73:947–955PubMedCrossRefGoogle Scholar
  78. 78.
    Griffin KA, Kramer H, Bidani AK (2008) Adverse renal consequences of obesity. Am J Physiol Renal Physiol 294:F685–F696PubMedCrossRefGoogle Scholar
  79. 79.
    Goumenos DS, Kawar B, El NM et al (2009) Early histological changes in the kidney of people with morbid obesity. Nephrol Dial Transplant 24:3732–3738PubMedCrossRefGoogle Scholar
  80. 80.
    Carey RM, Siragy HM (2003) Newly recognized components of the renin-angiotensin system: potential roles in cardiovascular and renal regulation. Endocr Rev 24:261–271PubMedCrossRefGoogle Scholar
  81. 81.
    Tuck ML, Sowers J, Dornfeld L, Kledzik G, Maxwell M (1981) The effect of weight reduction on blood pressure, plasma renin activity, and plasma aldosterone levels in obese patients. N Engl J Med 304:930–933PubMedCrossRefGoogle Scholar
  82. 82.
    Engeli S, Bohnke J, Gorzelniak K et al (2005) Weight loss and the renin-angiotensin-aldosterone system. Hypertension 45:356–362PubMedCrossRefGoogle Scholar
  83. 83.
    Montani JP, Antic V, Yang Z, Dulloo A (2002) Pathways from obesity to hypertension: from the perspective of a vicious triangle. Int J Obes Relat Metab Disord 26(Suppl 2):S28–S38PubMedCrossRefGoogle Scholar
  84. 84.
    Faloia E, Gatti C, Camilloni MA et al (2002) Comparison of circulating and local adipose tissue renin-angiotensin system in normotensive and hypertensive obese subjects. J Endocrinol Invest 25:309–314PubMedGoogle Scholar
  85. 85.
    Giacchetti G, Faloia E, Mariniello B et al (2002) Overexpression of the renin-angiotensin system in human visceral adipose tissue in normal and overweight subjects. Am J Hypertens 15:381–388PubMedCrossRefGoogle Scholar
  86. 86.
    Faloia E, Camilloni MA, Giacchetti G, Mantero F (2000) Adipose tissue as an endocrine organ? A review of some recent data. Eat Weight Disord 5:116–123PubMedGoogle Scholar
  87. 87.
    Giacchetti G, Faloia E, Sardu C et al (2000) Gene expression of angiotensinogen in adipose tissue of obese patients. Int J Obes Relat Metab Disord 24(Suppl 2):S142–S143PubMedGoogle Scholar
  88. 88.
    Hajer GR, van Haeften TW, Visseren FL (2008) Adipose tissue dysfunction in obesity, diabetes, and vascular diseases. Eur Heart J 29:2959–2971PubMedCrossRefGoogle Scholar
  89. 89.
    Hutley L, Prins JB (2005) Fat as an endocrine organ: relationship to the metabolic syndrome. Am J Med Sci 330:280–289PubMedCrossRefGoogle Scholar
  90. 90.
    Guha PK, Villarreal D, Reams GP, Freeman RH (2003) Role of leptin in the regulation of body fluid volume and pressures. Am J Ther 10:211–218PubMedCrossRefGoogle Scholar
  91. 91.
    Sharma V, McNeill JH (2005) The emerging roles of leptin and ghrelin in cardiovascular physiology and pathophysiology. Curr Vasc Pharmacol 3:169–180PubMedCrossRefGoogle Scholar
  92. 92.
    Wolf G, Ziyadeh FN (2006) Leptin and renal fibrosis. Contrib Nephrol 151:175–183PubMedCrossRefGoogle Scholar
  93. 93.
    Wolf G, Chen S, Han DC, Ziyadeh FN (2002) Leptin and renal disease. Am J Kidney Dis 39:1–11PubMedCrossRefGoogle Scholar
  94. 94.
    Stenvinkel P, Lonnqvist F, Schalling M (1999) Molecular studies of leptin: implications for renal disease. Nephrol Dial Transplant 14:1103–1112PubMedCrossRefGoogle Scholar
  95. 95.
    Sharma K, Considine RV, Michael B et al (1997) Plasma leptin is partly cleared by the kidney and is elevated in hemodialysis patients. Kidney Int 51:1980–1985PubMedCrossRefGoogle Scholar
  96. 96.
    Johansen KL, Mulligan K, Tai V, Schambelan M (1998) Leptin, body composition, and indices of malnutrition in patients on dialysis. J Am Soc Nephrol 9:1080–1084PubMedGoogle Scholar
  97. 97.
    Locatelli F, Pozzoni P, Del Vecchio L (2006) Renal manifestations in the metabolic syndrome. J Am Soc Nephrol 17(4 Suppl 2):S81–S85PubMedCrossRefGoogle Scholar
  98. 98.
    Kadowaki T, Yamauchi T, Kubota N, Hara K, Ueki K, Tobe K (2006) Adiponectin and adiponectin receptors in insulin resistance, diabetes, and the metabolic syndrome. J Clin Invest 116:1784–1792PubMedCrossRefGoogle Scholar
  99. 99.
    Sharma K, Ramachandrarao S, Qiu G et al (2008) Adiponectin regulates albuminuria and podocyte function in mice. J Clin Invest 118:1645–1656PubMedGoogle Scholar
  100. 100.
    Ouedraogo R, Gong Y, Berzins B et al (2007) Adiponectin deficiency increases leukocyte-endothelium interactions via upregulation of endothelial cell adhesion molecules in vivo. J Clin Invest 117:1718–1726PubMedCrossRefGoogle Scholar
  101. 101.
    Ix JH, Shlipak MG, Brandenburg VM, Ali S, Ketteler M, Whooley MA (2006) Association between human fetuin-A and the metabolic syndrome: data from the heart and soul study. Circulation 11(113):1760–1767CrossRefGoogle Scholar
  102. 102.
    Stefan N, Hennige AM, Staiger H et al (2006) Alpha2-Heremans-Schmid glycoprotein/fetuin-A is associated with insulin resistance and fat accumulation in the liver in humans. Diabetes Care 29:853–857PubMedCrossRefGoogle Scholar
  103. 103.
    Axelsson J, Wang X, Ketteler M et al (2008) Is fetuin-A/alpha2-Heremans-Schmid glycoprotein associated with the metabolic syndrome in patients with chronic kidney disease? Am J Nephrol 28:669–676PubMedCrossRefGoogle Scholar
  104. 104.
    Rauth G, Poschke O, Fink E et al (1992) The nucleotide and partial amino acid sequences of rat fetuin. Identity with the natural tyrosine kinase inhibitor of the rat insulin receptor. Eur J Biochem 204:523–529PubMedCrossRefGoogle Scholar
  105. 105.
    Srinivas PR, Wagner AS, Reddy LV et al (1993) Serum alpha 2-HS-glycoprotein is an inhibitor of the human insulin receptor at the tyrosine kinase level. Mol Endocrinol 7:1445–1455PubMedCrossRefGoogle Scholar
  106. 106.
    Ix JH, Sharma K (2010) Mechanisms linking obesity, chronic kidney disease, and fatty liver disease: the roles of fetuin-A, adiponectin, and AMPK. J Am Soc Nephrol 21:406–412PubMedCrossRefGoogle Scholar
  107. 107.
    Hennige AM, Staiger H, Wicke C et al (2008) Fetuin-A induces cytokine expression and suppresses adiponectin production. PLoS One 3:e1765PubMedCrossRefGoogle Scholar
  108. 108.
    Shen WW, Chen HM, Chen H, Xu F, Li LS, Liu ZH (2010) Obesity-related glomerulopathy: body mass index and proteinuria. Clin J Am Soc Nephrol 5:1401–1409PubMedCrossRefGoogle Scholar
  109. 109.
    Chagnac A, Weinstein T, Herman M, Hirsh J, Gafter U, Ori Y (2003) The effects of weight loss on renal function in patients with severe obesity. J Am Soc Nephrol 14:1480–1486PubMedCrossRefGoogle Scholar
  110. 110.
    Deen WM, Robertson CR, Brenner BM (1972) A model of glomerular ultrafiltration in the rat. Am J Physiol 223:1178–1183PubMedGoogle Scholar
  111. 111.
    Hirakata M, Kaname S, Chung UG et al (1997) Tyrosine kinase dependent expression of TGF-beta induced by stretch in mesangial cells. Kidney Int 51:1028–1036PubMedCrossRefGoogle Scholar
  112. 112.
    Li Q, Muragaki Y, Hatamura I, Ueno H, Ooshima A (1998) Stretch-induced collagen synthesis in cultured smooth muscle cells from rabbit aortic media and a possible involvement of angiotensin II and transforming growth factor-beta. J Vasc Res 35:93–103PubMedCrossRefGoogle Scholar
  113. 113.
    Russo LM, Osicka TM, Bonnet F, Jerums G, Comper WD (2002) Albuminuria in hypertension is linked to altered lysosomal activity and TGF-beta1 expression. Hypertension 39:281–286PubMedCrossRefGoogle Scholar
  114. 114.
    Jacobs DB, Sowers JR, Hmeidan A, Niyogi T, Simpson L, Standley PR (1993) Effects of weight reduction on cellular cation metabolism and vascular resistance. Hypertension 21:308–314PubMedGoogle Scholar
  115. 115.
    Kurata A, Nishizawa H, Kihara S et al (2006) Blockade of Angiotensin II type-1 receptor reduces oxidative stress in adipose tissue and ameliorates adipocytokine dysregulation. Kidney Int 70:1717–1724PubMedCrossRefGoogle Scholar

Copyright information

© Springer Science+Business Media, B.V. 2011

Authors and Affiliations

  1. 1.Department of Internal Medicine, Medical SchoolUniversity of IoanninaIoanninaGreece

Personalised recommendations