Pediatric Nephrology

, Volume 21, Issue 4, pp 463–470

Nondiabetic consequences of obesity on kidney

Review

Abstract

There has been a major increase in obesity among children over the past twenty years. Obesity is associated with glomerular hyperperfusion and hyperfiltration from physiological (mal)adaptation resulting from afferent arteriolar vasodilatation. The renal injury from hyperfiltration in obesity is further exacerbated by concomitant presence of dyslipidemia, hyperglycemia and/or insulin resistance, inflammation and hypertension. The renal injury clinically manifests as microalbuminuria, proteinuria and/or poor renal function, and is histologically characterized by glomerulomegaly, mesangial expansion and/or sclerosis, which has been termed “obesity related glomerulopathy”. Obesity portends a poor prognosis in subjects with chronic kidney diseases, IgA nephropathy and nephrectomy. Obese individuals on dialysis and renal transplant have mixed outcomes. The purpose of this review is to highlight the nondiabetic consequences of obesity on kidney for the pediatric nephrology community as we begin to address the obesity epidemic in children.

Keywords

Obesity Leptin Microalbuminuria Glomerulomegaly Hypertension 

References

  1. 1.
    Chen J, Muntner P, Hamm LL, Jones DW, Batuman V, Fonseca V, Whelton PK, He J (2004) The metabolic syndrome and chronic kidney disease in U.S. adults. Ann Intern Med 140:167–174PubMedGoogle Scholar
  2. 2.
    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 65:1870–1876CrossRefPubMedGoogle Scholar
  3. 3.
    Hall JE, Crook ED, Jones DW, Wofford MR, Dubbert PM (2002) Mechanisms of obesity-associated cardiovascular and renal disease. Am J Med Sci 324:127–137CrossRefPubMedGoogle Scholar
  4. 4.
    Reilly JJ, Methven E, McDowell ZC, Hacking B, Alexander D, Stewart L, Kelnar CJ (2003) Health consequences of obesity. Arch Dis Child 88:748–752CrossRefPubMedGoogle Scholar
  5. 5.
    Srinivasan SR, Bao W, Wattigney WA, Berenson GS (1996) Adolescent overweight is associated with adult overweight and related multiple cardiovascular risk factors: the Bogalusa Heart Study. Metabolism 45:235–240CrossRefPubMedGoogle Scholar
  6. 6.
    Hoffmans MD, Kromhout D, de Lezenne Coulander C (1988) The impact of body mass index of 78,612 18-year old Dutch men on 32-year mortality from all causes. J Clin Epidemiol 41:749–756CrossRefPubMedGoogle Scholar
  7. 7.
    Mossberg HO (1989) 40-year follow-up of overweight children. Lancet 2:491–493CrossRefPubMedGoogle Scholar
  8. 8.
    Must A, Jacques PF, Dallal GE, Bajema CJ, Dietz WH (1992) Long-term morbidity and mortality of overweight adolescents. A follow-up of the Harvard Growth Study of 1922 to 1935. N Engl J Med 327:1350–1355PubMedCrossRefGoogle Scholar
  9. 9.
    Speiser PW, Rudolf MC, Anhalt H, Camacho-Hubner C, Chiarelli F, Eliakim A, Freemark M, Gruters A, Hershkovitz E, Iughetti L, Krude H, Latzer Y, Lustig RH, Pescovitz OH, Pinhas-Hamiel O, Rogol AD, Shalitin S, Sultan C, Stein D, Vardi P, Werther GA, Zadik Z, Zuckerman-Levin N, Hochberg Z; Obesity Consensus Working Group (2005) Childhood obesity. J Clin Endocrinol Metab 90:1871–1887CrossRefPubMedGoogle Scholar
  10. 10.
    Ogden CL, Kuczmarski RJ, Flegal KM, Mei Z, Guo S, Wei R, Grummer-Strawn LM, Curtin LR, Roche AF, Johnson CL (2002) Centers for Disease Control and Prevention 2000 growth charts for the United States: improvements to the 1977 National Center for Health Statistics version. Pediatrics 109:45–60CrossRefPubMedGoogle Scholar
  11. 11.
    Troiano RP, Flegal KM, Kuczmarski RJ, Campbell SM, Johnson CL (1995) Overweight prevalence and trends for children and adolescents. The National Health and Nutrition Examination Surveys, 1963 to 1991. Arch Pediatr Adolesc Med 149:1085–1091PubMedGoogle Scholar
  12. 12.
    Freedman DS, Srinivasan SR, Valdez RA, Williamson DF, Berenson GS (1997) Secular increases in relative weight and adiposity among children over two decades: the Bogalusa Heart Study. Pediatrics 99:420–426CrossRefPubMedGoogle Scholar
  13. 13.
    Whitaker RC, Wright JA, Pepe MS, Seidel KD, Dietz WH (1997) Predicting obesity in young adulthood from childhood and parental obesity. N Engl J Med 337:869–873CrossRefPubMedGoogle Scholar
  14. 14.
    Ogden CL, Flegal KM, Carroll MD, Johnson CL (2002) Prevalence and trends in overweight among US children and adolescents, 1999–2000. JAMA 288:1728–1732CrossRefPubMedGoogle Scholar
  15. 15.
    Ribstein J, du Cailar G, Mimran A (1995) Combined renal effects of overweight and hypertension. Hypertension 26:610–615PubMedGoogle Scholar
  16. 16.
    Chagnac A, Weinstein T, Korzets A, Ramadan E, Hirsch J, Gafter U (2000) Glomerular hemodynamics in severe obesity. Am J Physiol Renal Physiol 278:F817–F822Google Scholar
  17. 17.
    Hopkins PN, Lifton RP, Hollenberg NK, Jeunemaitre X, Hallouin MC, Skuppin J, Williams CS, Dluhy RG, Lalouel JM, Williams RR, Williams GH (1996) Blunted renal vascular response to angiotensin II is associated with a common variant of the angiotensinogen gene and obesity. J Hypertens 14:199–207PubMedCrossRefGoogle Scholar
  18. 18.
    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 65:259–265CrossRefPubMedGoogle Scholar
  19. 19.
    de Jong PE, Verhave JC, Pinto-Sietsma SJ, Hillege HL; PREVEND study group (2002) Obesity and target organ damage: the kidney. Int J Obes Relat Metab Disord 26 Suppl 4:S21–S24CrossRefPubMedGoogle Scholar
  20. 20.
    Praga M, Morales E, Herrero JC, Perez Campos A, Dominguez-Gil B, Alegre R, Vara J, Martinez MA (1999) Absence of hypoalbuminemia despite massive proteinuria in focal segmental glomerulosclerosis secondary to hyperfiltration. Am J Kidney Dis 33:52–58PubMedGoogle Scholar
  21. 21.
    Yoshioka T, Mitarai T, Kon V, Deen WM, Rennke HG, Ichikawa I (1986) Role for angiotensin II in an overt functional proteinuria. Kidney Int 30:538–545PubMedCrossRefGoogle Scholar
  22. 22.
    Cohen AH (1975) Massive obesity and the kidney. A morphologic and statistical study. Am J Pathol 81:117–130PubMedGoogle Scholar
  23. 23.
    Praga M, Hernandez E, Morales E, Campos AP, Valero MA, Martinez MA, Leon M (2001) Clinical features and long-term outcome of obesity-associated focal segmental glomerulosclerosis. Nephrol Dial Transplant 16:1790–1798CrossRefPubMedGoogle Scholar
  24. 24.
    Weisinger JR, Kempson RL, Eldridge FL, Swenson RS (1974) The nephrotic syndrome: a complication of massive obesity. Ann Intern Med 81:440–447PubMedGoogle Scholar
  25. 25.
    Kambham N, Markowitz GS, Valeri AM, Lin J, D’Agati VD (2001) Obesity-related glomerulopathy: an emerging epidemic. Kidney Int 59:1498–1509CrossRefPubMedGoogle Scholar
  26. 26.
    Adelman RD, Restaino IG, Alon US, Blowey DL (2001) Proteinuria and focal segmental glomerulosclerosis in severely obese adolescents. J Pediatr 138:481–485CrossRefPubMedGoogle Scholar
  27. 27.
    Praga M, Hernandez E, Andres A, Leon M, Ruilope LM, Rodicio JL (1995) Effects of body-weight loss and captopril treatment on proteinuria associated with obesity. Nephron 70:35–41PubMedGoogle Scholar
  28. 28.
    Maddox DA, Alavi FK, Santella RN, Zawada ET Jr (2002) Prevention of obesity-linked renal disease: age-dependent effects of dietary food restriction. Kidney Int 62:208–219CrossRefPubMedGoogle Scholar
  29. 29.
    Morales E, Valero MA, Leon M, Hernandez E, Praga M (2003) Beneficial effects of weight loss in overweight patients with chronic proteinuric nephropathies. Am J Kidney Dis 41:319–327CrossRefPubMedGoogle Scholar
  30. 30.
    Kasiske BL, O’Donnell MP, Cleary MP, Keane WF (1988) Treatment of hyperlipidemia reduces glomerular injury in obese Zucker rats. Kidney Int 33:667–672PubMedCrossRefGoogle Scholar
  31. 31.
    Garrison RJ, Kannel WB, Stokes J 3rd, Castelli WP (1987) Incidence and precursors of hypertension in young adults: the Framingham Offspring Study. Prev Med 16:235–251CrossRefPubMedGoogle Scholar
  32. 32.
    Sorof JM, Lai D, Turner J, Poffenbarger T, Portman RJ (2004) Overweight, ethnicity, and the prevalence of hypertension in school-aged children. Pediatrics 113:475–482CrossRefPubMedGoogle Scholar
  33. 33.
    Lurbe E, Alvarez V, Liao Y, Tacons J, Cooper R, Cremades B, Torro I, Redon J (1998) The impact of obesity and body fat distribution on ambulatory blood pressure in children and adolescents. Am J Hypertens 11:418–424CrossRefPubMedGoogle Scholar
  34. 34.
    Hall JE (2003) The kidney, hypertension, and obesity. Hypertension 41:625–633CrossRefPubMedGoogle Scholar
  35. 35.
    Engeli S, Negrel R, Sharma AM (2000) Physiology and pathophysiology of the adipose tissue renin-angiotensin system. Hypertension 35:1270–1277PubMedGoogle Scholar
  36. 36.
    Cooper R, McFarlane-Anderson N, Bennett FI, Wilks R, Puras A, Tewksbury D, Ward R, Forrester TACE (1997) Angiotensinogen and obesity: a potential pathway leading to hypertension. J Hum Hypertens 11:107–111CrossRefPubMedGoogle Scholar
  37. 37.
    Licata G, Scaglione R, Ganguzza A, Corrao S, Donatelli M, Parrinello G, Dichiara MA, Merlino G, Cecala MG (1994) Central obesity and hypertension. Relationship between fasting serum insulin, plasma renin activity, and diastolic blood pressure in young obese subjects. Am J Hypertens 7:314–320PubMedGoogle Scholar
  38. 38.
    Robles RG, Villa E, Santirso R, Martinez J, Ruilope LM, Cuesta C, Sancho JM (1993) Effects of captopril on sympathetic activity, lipid and carbohydrate metabolism in a model of obesity-induced hypertension in dogs. Am J Hypertens 6:1009–1015PubMedGoogle Scholar
  39. 39.
    Reisin E, Weir MR, Falkner B, Hutchinson HG, Anzalone DA, Tuck ML (1997) Lisinopril versus hydrochlorothiazide in obese hypertensive patients: a multicenter placebo-controlled trial. Treatment in Obese Patients with Hypertension (TROPHY) Study Group. Hypertension 30:140–145PubMedGoogle Scholar
  40. 40.
    Kassab S, Kato T, Wilkins FC, Chen R, Hall JE, Granger JP (1995) Renal denervation attenuates the sodium retention and hypertension associated with obesity. Hypertension 25:893–897PubMedGoogle Scholar
  41. 41.
    Wofford MR, Anderson DC Jr, Brown CA, Jones DW, Miller ME, Hall JE (2001) Antihypertensive effect of alpha- and beta-adrenergic blockade in obese and lean hypertensive subjects. Am J Hypertens 14:694–698CrossRefPubMedGoogle Scholar
  42. 42.
    Rumantir MS, Vaz M, Jennings GL, Collier G, Kaye DM, Seals DR, Wiesner GH, Brunner-La Rocca HP, Esler MD (1999) Neural mechanisms in human obesity-related hypertension. J Hypertens 17:1125–1133CrossRefPubMedGoogle Scholar
  43. 43.
    Rocchini AP, Key J, Bondie D, Chico R, Moorehead C, Katch V, Martin M (1989) The effect of weight loss on the sensitivity of blood pressure to sodium in obese adolescents. N Engl J Med 321:580–585PubMedCrossRefGoogle Scholar
  44. 44.
    Considine RV, Sinha MK, Heiman ML, Kriauciunas A, Stephens TW, Nyce MR, Ohannesian JP, Marco CC, McKee LJ, Bauer TL, Caro JF (1996) Serum immunoreactive-leptin concentrations in normal-weight and obese humans. N Engl J Med 334:292–295CrossRefPubMedGoogle Scholar
  45. 45.
    Besbas N, Ozaltin F, Coskun T, Ozalp S, Saatci U, Bakkaloglu A, El Nahas AM (2003) Relationship of leptin and insulin-like growth factor I to nutritional status in hemodialyzed children. Pediatr Nephrol 18:1255–1259CrossRefPubMedGoogle Scholar
  46. 46.
    Mak RH, Cheung W, Cone RD, Marks DL (2005) Orexigenic and anorexigenic mechanisms in the control of nutrition in chronic kidney disease. Pediatr Nephrol 20:427–431CrossRefPubMedGoogle Scholar
  47. 47.
    Ziyadeh FN, Hoffman BB, Han DC, Iglesias-De La Cruz MC, Hong SW, Isono M, Chen S, MGowan TA, Sharma K (2000) Long-term prevention of renal insufficiency, excess matrix gene expression, and glomerular mesangial matrix expansion by treatment with monoclonal antitransforming growth factor-beta antibody in db/db diabetic mice. Proc Natl Acad Sci USA 97:8015–8020Google Scholar
  48. 48.
    Aizawa-Abe M, Ogawa Y, Masuzaki H, Ebihara K, Satoh N, Iwai H, Matsuoka N, Hayashi T, Hosoda K, Inoue G, Yoshimasa Y, Nakao K (2000) Pathophysiological role of leptin in obesity-related hypertension. J Clin Invest 105:1243–1252PubMedCrossRefGoogle Scholar
  49. 49.
    Shek EW, Brands MW, Hall JE (1998) Chronic leptin infusion increases arterial pressure. Hypertension 31:409–414PubMedGoogle Scholar
  50. 50.
    Correia ML, Morgan DA, Sivitz WI, Mark AL, Haynes WG (2001) Leptin acts in the central nervous system to produce dose-dependent changes in arterial pressure. Hypertension 37:936–942PubMedGoogle Scholar
  51. 51.
    Wolf G, Hamann A, Han DC, Helmchen U, Thaiss F, Ziyadeh FN, Stahl RA (1999) Leptin stimulates proliferation and TGF-beta expression in renal glomerular endothelial cells: potential role in glomerulosclerosis. Kidney Int 56:860–872CrossRefPubMedGoogle Scholar
  52. 52.
    Festa A, D’Agostino R Jr, Howard G, Mykkanen L, Tracy RP, Haffner SM (2000) Chronic subclinical inflammation as part of the insulin resistance syndrome: the Insulin Resistance Atherosclerosis Study (IRAS). Circulation 102:42–47PubMedGoogle Scholar
  53. 53.
    Honein MA, Moore CA, Watkins ML (2003) Subfertility and prepregnancy overweight/obesity: possible interaction between these risk factors in the etiology of congenital renal anomalies. Birth Defects Res Part A Clin Mol Teratol 67:572–577CrossRefPubMedGoogle Scholar
  54. 54.
    Bonnet F, Deprele C, Sassolas A, Moulin P, Alamartine E, Berthezene F, Berthoux F (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
  55. 55.
    Praga M, Hernandez E, Herrero JC, Morales E, Revilla Y, Diaz-Gonzalez R, Rodicio JL (2000) Influence of obesity on the appearance of proteinuria and renal insufficiency after unilateral nephrectomy. Kidney Int 58:2111–2118CrossRefPubMedGoogle Scholar
  56. 56.
    Friedman AN, Miskulin DC, Rosenberg IH, Levey AS (2003) Demographics and trends in overweight and obesity in patients at time of kidney transplantation. Am J Kidney Dis 41:480–487CrossRefPubMedGoogle Scholar
  57. 57.
    Hanevold CD, Ho PL, Talley L, Mitsnefes MM (2005) Obesity and renal transplant outcome: a report of the North American Pediatric Renal Transplant Cooperative Study. Pediatrics 115:352–356CrossRefPubMedGoogle Scholar
  58. 58.
    Holley JL, Monaghan J, Byer B, Bronsther O (1998) An examination of the renal transplant evaluation process focusing on cost and the reasons for patient exclusion. Am J Kidney Dis 32:567–574PubMedGoogle Scholar
  59. 59.
    Marks WH, Florence LS, Chapman PH, Precht AF, Perkinson DT (2004) Morbid obesity is not a contraindication to kidney transplantation. Am J Surg 187:635–638CrossRefPubMedGoogle Scholar
  60. 60.
    Bennett WM, McEvoy KM, Henell KR, Valente JF, Douzdjian V (2004) Morbid obesity does not preclude successful renal transplantation. Clin Transplant 18:89–93CrossRefPubMedGoogle Scholar
  61. 61.
    Johnson DW, Isbel NM, Brown AM, Kay TD, Franzen K, Hawley CM, Campbell SB, Wall D, Griffin A, Nicol DL (2002) The effect of obesity on renal transplant outcomes. Transplantation 74:675–681CrossRefPubMedGoogle Scholar
  62. 62.
    Howard RJ, Thai VB, Patton PR, Hemming AW, Reed AI, Van der Werf WJ, Fujita S, Karlix JL, Scornik JC (2002) Obesity does not portend a bad outcome for kidney transplant recipients. Transplantation 73:53–55CrossRefPubMedGoogle Scholar
  63. 63.
    Mitsnefes MM, Khoury P, McEnery PT (2002) Body mass index and allograft function in pediatric renal transplantation. Pediatr Nephrol 17:535–539CrossRefPubMedGoogle Scholar
  64. 64.
    Snyder JJ, Foley RN, Gilbertson DT, Vonesh EF, Collins AJ (2003) Body size and outcomes on peritoneal dialysis in the United States. Kidney Int 64:1838–1844CrossRefPubMedGoogle Scholar
  65. 65.
    Stack AG, Murthy BV, Molony DA (2004) Survival differences between peritoneal dialysis and hemodialysis among “large” ESRD patients in the United States. Kidney Int 65:2398–2408CrossRefPubMedGoogle Scholar
  66. 66.
    Abbott KC, Glanton CW, Trespalacios FC, Oliver DK, Ortiz MI, Agodoa LY, Cruess DF, Kimmel PL (2004) Body mass index, dialysis modality, and survival: analysis of the United States Renal Data System Dialysis Morbidity and Mortality Wave II Study. Kidney Int 65:597–605CrossRefPubMedGoogle Scholar
  67. 67.
    McDonald SP, Collins JF, Rumpsfeld M, Johnson DW (2004) Obesity is a risk factor for peritonitis in the Australian and New Zealand peritoneal dialysis patient populations. Perit Dial Int 24:340–346PubMedGoogle Scholar
  68. 68.
    McDonald SP, Collins JF, Johnson DW (2003) Obesity is associated with worse peritoneal dialysis outcomes in the Australia and New Zealand patient populations. J Am Soc Nephrol 14:2894–2901CrossRefPubMedGoogle Scholar
  69. 69.
    Salahudeen AK (2003) Obesity and survival on dialysis. Am J Kidney Dis 41:925–932CrossRefPubMedGoogle Scholar
  70. 70.
    Wiesholzer M, Harm F, Schuster K, Putz D, Neuhauser C, Fiedler F, Balcke P (2003) Initial body mass indexes have contrary effects on change in body weight and mortality of patients on maintenance hemodialysis treatment. J Ren Nutr 13:174–185CrossRefPubMedGoogle Scholar

Copyright information

© IPNA 2006

Authors and Affiliations

  1. 1.Section of Pediatric NephrologyChildren’s Mercy Hospitals and Clinics and University of MissouriKansas CityUSA
  2. 2.Section of NephrologyThe Children’s Mercy HospitalKansas CityUSA

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