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Implications for kidney disease in obese children and adolescents

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Abstract

Increasing attention has been focused on the implications of obesity in adults on the development of kidney disease, but data on the obese pediatric population are lacking. The aim of this study was to investigate whether changes in various renal function indexes/markers, as expressed by the glomerular filtration rate [GFR, as estimated by the Schwartz formula (eGFR)], serum cystatin C (CysC) level, albumin excretion rate (AER), and modifications in nitric oxide (NO; an important modulator of renal function and morphology), urinary isoprostanes (markers of oxidative stress), and blood pressure (BP), can be detected in obese children and adolescents when compared to normal weight controls. Blood and urinary samples were collected to evaluate markers of renal function, serum and urinary NO, and urinary isoprostanes in 107 obese Caucasian subjects and 50 controls. Ambulatory BP monitoring (ABPM) was performed in all cases. Obesity was expressed by the body mass index standard deviation score (SDS-BMI), and insulin resistance by the homeostasis model assessment of insulin resistance (HOMA-IR). CysC and eGFR did not significantly differ between the two groups; AER was increased in obese children. CysC and GFR were related to HOMA-IR, and AER was related to HOMA-IR and SDS-BMI. Obese subjects had reduced NO levels and increased urinary isoprostanes and BP measurements; all three parameters were related to SDS-BMI and insulin resistance. ABPM showed an increased incidence of hypertension and non-dipping in the obese group. Based on our comparison of obese and nonobese children, we conclude that renal involvement is not an early clinically evident manifestation of adiposity in childhood, since no overt changes in eGFR and only a mild albuminuria were detected. A longer exposure to obesity is probably needed before renal function impairment appears.

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References

  1. Srivastava T (2006) Nondiabetic consequences of obesity on kidney. Pediatr Nephrol 21:463–470

    Article  PubMed  Google Scholar 

  2. Kambham N, Markowitz GS, Valeri AM, Lin J, D’Agati VD (2001) Obesity-related glomerulopathy: an emerging epidemic. Kidney Int 59:1498–1509

    Article  PubMed  CAS  Google Scholar 

  3. Adelman RD (2002) Obesity and renal disease. Curr Opin Nephrol Hypertens 11:331–335

    Article  PubMed  Google Scholar 

  4. Steinberger J, Moran A, Hong CP, Jacobs DR Jr, Sinaiko AR (2001) Adiposity in childhood predicts obesity and insulin resistance in young adulthood. J Pediatr 138:469–473

    Google Scholar 

  5. Csernus K, Lanyi E, Erhardt E, Molnar D (2005) Effect of childhood obesity and obesity-related cardiovascular risk factors on glomerular and tubular protein excretion. Eur J Pediatr 164:44–49

    Article  PubMed  CAS  Google Scholar 

  6. Srivastava T, Alon US, Althahabi R, Garg U (2009) Impact of standardization of creatinine methodology on the assessment of glomerular filtration rate in children. Pediatr Res 65:113–116

    Article  PubMed  CAS  Google Scholar 

  7. Wennmalm A, Benthin G, Edlund A (1993) Metabolism and excretion of nitric oxide in humans. An experimental and clinical study. Circ Res 73:1121–1127

    PubMed  CAS  Google Scholar 

  8. Hogg RJ, Furth S, Lemley KV, Portman R, Schwartz GJ, Coresh J, Balk E, Lau J, Levin A, Kausz AT, Eknoyan G, Levey AS (2003) National Kidney Foundation’s Kidney Disease Outcomes Quality Initiative clinical practice guidelines for chronic kidney disease in children and adolescents: evaluation, classification, and stratification. Pediatrics 111:1416–1421

    Article  PubMed  Google Scholar 

  9. Schwartz GJ, Muñoz A, Schneider MF, Mak RH, Kaskel F, Warady BA, Furth SL (2009) New equations to estimate GFR in children with CKD. J Am Soc Nephrol 20:629–637

    Article  PubMed  Google Scholar 

  10. Zappitelli M, Joseph L, Gupta IR, Bell L, Paradis G (2007) Validation of child serum creatinine-based prediction equations for glomerular filtration rate. Pediatr Nephrol 22:272–281

    Article  PubMed  Google Scholar 

  11. Marcovecchio ML, Patricelli L, Zito M, Capanna R, Ciampani M, Chiarelli F, Mohn A (2006) Ambulatory blood pressure monitoring in obese children: role of insulin resistance. J Hypertension 24:2431–2436

    Article  CAS  Google Scholar 

  12. Soergel M, Kirschstein M, Busch C, Danne T, Gellermann J, Hall R, Krull F, Reichert H, Reusz GS, Rascher W (1997) Oscillometric twenty-four-hour ambulatory blood pressure values in healthy children and adolescents: a multicenter trial including 1141 subjects. J Pediatr 130:178–184

    Article  PubMed  CAS  Google Scholar 

  13. U.S. Renal Data System (2003) Atlas of end-stage renal disease in the United States. National Institute of Diabetes and Digestive and Kidney Diseases USRD 15th annual data report. National Institutes of Health, Bethesda

  14. Harris MI, Flegal KM, Cowie CC, Goldstein EMS, DE LRR, Wiedmeyer HM, Byrd-Holt DD (1998) Prevalence of diabetes, impaired fasting glucose, and impaired glucose tolerance in US adults. The Third National Health and Nutrition Examination Survey, 1988–1994. Diabetes Care 21:518–524

    Article  PubMed  CAS  Google Scholar 

  15. Ejerblad E, Fored CM, Lindblad P, Fryzek J, McLaughlin JK, Nyrèn O (2006) Obesity and risk for chronic renal failure. J Am Soc Nephrol 17:1695–1702

    Article  PubMed  CAS  Google Scholar 

  16. El-Atat FA, Stas SN, McFarlane SI, Sowers JR (2004) The relationship between hyperinsulinemia, hypertension and progressive renal disease. J Am Soc Nephrol 15:2816–2827

    Article  PubMed  Google Scholar 

  17. Weiss R, Dziura J, Burgert TS, Tamborlane WV, Taksali SE, Yeckel CW, Allen K, Lopes M, Savoye M, Morrison J, Sherwin RS, Caprio S (2004) Obesity and the metabolic syndrome in children and adolescents. N Engl J Med 350:2362–2374

    Article  PubMed  CAS  Google Scholar 

  18. Cruz ML, Huang TT, Johnson MS, Gower BA, Goran MI (2002) Insulin sensitivity and blood pressure in black and white children. Hypertension 40:18–22

    Article  PubMed  CAS  Google Scholar 

  19. Howard BV, Howard WJ (1994) Dyslipidemia in non-insulin-dependent diabetes mellitus. Endocr Rev 15:263–274

    PubMed  CAS  Google Scholar 

  20. Sinha R, Fisch G, Teague B, Tamborlane WV, Banyas B, Allen K, Savoye M, Rieger V, Taksali S, Barbetta G, Sherwin RS, Caprio S (2002) Prevalence of impaired glucose tolerance among children and adolescents with marked obesity. New Engl J Med 346:802–810

    Article  PubMed  CAS  Google Scholar 

  21. D'Adamo E, Marcovecchio ML, Giannini C, Capanna R, Impicciatore M, Chiarelli F, Mohn A (2008) Liver steatosis in obese prepubertal children: a possible role of insulin resistance. Obesity 16:677–683

    Article  PubMed  Google Scholar 

  22. Eckel RH, Grundy SM, Zimmet PZ (2005) The metabolic syndrome. Lancet 365:1415–1428

    Article  PubMed  CAS  Google Scholar 

  23. Tuttle KR (2005) Renal manifestations of the metabolic syndrome. Nephrol Dial Transplant 20:861–864

    Article  PubMed  Google Scholar 

  24. Locatelli F, Pozzoni P, Del Vecchio L (2006) Renal manifestations in the metabolic syndrome. J Am Soc Nephrol 17:S81–S85

    Article  PubMed  Google Scholar 

  25. Sarafidis PA, Ruilopensulin LM (2006) Insulin resistance, hyperinsulinemia, and renal injury: mechanisms and implications. Am J Nephrol 26:232–244

    Article  PubMed  Google Scholar 

  26. 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 73:19–33

    Article  PubMed  CAS  Google Scholar 

  27. Dietz WH (2004) Overweight in childhood and adolescence. New Engl J Med 350:855–857

    Article  PubMed  CAS  Google Scholar 

  28. Chiarelli F, Marcovecchio ML (2008) Insulin resistance and obesity in childhood. Eur J Endocrinol 159:S67–S74

    Article  PubMed  CAS  Google Scholar 

  29. Giannini C, de Giorgis T, Scarinci A, Ciampani M, Marcovecchio ML, Chiarelli F, Mohn A (2008) Obese related effects of inflammatory markers and insulin resistance on increased carotid intima media thickness in pre-pubertal children. Atherosclerosis 197:448–456

    Article  PubMed  CAS  Google Scholar 

  30. Caprio S, Plewe G, Diamond MP, Simonson DC, Boulware SD, Sherwin RS, Tamborlane WV (1989) Increased insulin secretion in puberty: a compensatory response to reductions in insulin sensitivity. J Pediatr 114:963–967

    Article  PubMed  CAS  Google Scholar 

  31. Savino A, Pelliccia P, Chiarelli F, Mohn A (2010) Obesity-related renal injury in childhood. Horm Res Paediatr 73:303–311

    Article  PubMed  CAS  Google Scholar 

  32. Traynor J, Mactier R, Geddes CC, Fox JG (2006) How to measure renal function in clinical practice. Br Med J 333:733–737

    Article  Google Scholar 

  33. Delanghe JR (2009) How to estimate GFR in children. Nephrol Dial Transplant 24:714–716

    Article  PubMed  Google Scholar 

  34. Grubb A, Nyman U, Bjork J, Lindstrom V, Rippe B, Sterner G, Christensson A (2005) Simple cystatin C-based equations for glomerular filtration rate compared with the Modification of Diet in Renal Disease prediction equation for adults and the Schwartz and Counahan–Barratt prediction equation for children. Clin Chem 51:1420–1431

    Article  PubMed  CAS  Google Scholar 

  35. Laterza OF, Price CP, Scott MG (2002) Cystatin C: an improved estimator of glomerular filtration rate. Clin Chem 48:699–707

    PubMed  CAS  Google Scholar 

  36. Narvaez-Sanchez R, Gonzales L, Salamanca A, Silva M, Rios D, Arevalo S, Gastelbondo R, Sanchez J (2008) Cystatin C could be a replacement to serum creatinine for diagnosing and monitoring kidney function in children. Clin Biochem 41:498–503

    Article  PubMed  CAS  Google Scholar 

  37. Bökenkamp A, Domanetzki M, Zinck R, Schumann G, Byrd D, Brodehl J (1998) Cystatin C—a new marker of glomerular filtration rate in children independent of age and height. Pediatrics 101:875–881

    Article  PubMed  Google Scholar 

  38. Burgert TS, Dziura J, Yeckel C, Taksali SE, Weiss R, Tamborlane W, Caprio S (2006) Microalbuminuria in pediatric obesity: prevalence and relation to other cardiovascular risk factors. Int J Obesity 30:273–280

    Article  CAS  Google Scholar 

  39. Bello AK, de Zeeuw D, El Nahas M, Brantsma AH, Bakker SJL, de Jong PE, Gansevoort RT (2007) Impact of weight change on albuminuria in the general population. Nephrol Dial Transplant 22:1619–1627

    Article  PubMed  CAS  Google Scholar 

  40. Cindik N, Baskin E, Agras PI, Kinik ST, Turan M, Saatci U (2005) Effect of obesity on inflammatory markers and renal functions. Acta Paediatr 94(12):1732–1737

    Article  PubMed  Google Scholar 

  41. Amin R, Turner C, Van Aken S, Bahu TK, Watts A, Lindsell DRM, Dalton RN, Dunger DB (2005) The relationship between microalbuminuria and glomerular filtration rate in young type 1 diabetic subjects: The Oxford Regional Prospective Study. Kidney Int 68:1740–1749

    Article  PubMed  Google Scholar 

  42. Chagnac A, Weinstein T, Korzets A, Ramadan E, Hirsch J, Gafter U (2000) Glomerular hemodynamics in severe obesity. Am J Physiol Renal Physiol 278:817–822

    Google Scholar 

  43. Wahba IM, Mak RH (2007) Obesity and obesity-initiated metabolic syndrome: mechanistic links to chronic kidney disease. Clin J Am Soc Nephrol 2:550–562

    Google Scholar 

  44. DeFronzo RA, Cooke CR, Andres R, Faloona GR, Davis PJ (1975) The effect of insulin on renal handling of sodium, potassium, calcium, and phosphate in man. J Clin Invest 55:845–855

    Article  PubMed  CAS  Google Scholar 

  45. Sartori C, Scherrer U (1999) Insulin, nitric oxide and the sympathetic nervous system: at the crossroads of metabolic and cardiovascular regulation. J Hypertens 17:1517–1525

    Article  PubMed  CAS  Google Scholar 

  46. Mogensen CE, Christensen NJ, Gundersen HJ (1980) The acute effect of insulin on heart rate, blood pressure, plasma noradrenaline and urinary albumin excretion: the role of changes in blood glucose. Diabetologia 18:453–457

    PubMed  CAS  Google Scholar 

  47. Naour N, Fellahi S, Renucci JF, Poitou C, Rouault C, Basdevant A, Dutour A, Alessi MC, Bastard JP, Clément K, Guerre-Millo M (2009) Potential contribution of adipose tissue to elevated serum cystatin C in human obesity. Obesity 17:2121–2126

    Article  PubMed  CAS  Google Scholar 

  48. Muntner P, Winston J, Uribarri J, Mann D, Fox CS (2008) Overweight, obesity and elevated serum cystatin C levels in adults in the United States. Am J Med 121:341–348

    Article  PubMed  CAS  Google Scholar 

  49. Vupputuri S, Fox CS, Coresh J, Woodward M, Muntner P (2009) Differential estimation of CKD using creatinine- versus cystatin C–based estimating equations by category of body mass index. Am J Kidney Dis 53:993–1001

    Article  PubMed  CAS  Google Scholar 

  50. Retnakaran R, Connelly PW, Harris SB, Zinman B, Hanley AJG (2007) Cystatin C is associated with cardiovascular risk factors and metabolic syndrome in Aboriginal youth. Pediatr Nephrol 22:1007–1013

    Article  PubMed  Google Scholar 

  51. Adelman RD, Restaino IG, Alon US, Blowey BL (2001) Proteinuria and focal segmental glomerulosclerosis in severely obese adolescents. J Pediatr 138:481–485

    Article  PubMed  CAS  Google Scholar 

  52. Praga M, Hernández E, Morales E, Campos AP, Valero MA, Martínez MA, León M (2001) Clinical features and longterm outcome of obesity-associated focal segmental glomerulosclerosis. Nephrol Dial Transplant 16:1790–1798

    Article  PubMed  CAS  Google Scholar 

  53. Verhave JC, Hillege HL, Burgerhof JG, Janssen WM, Gansevoort RT, Navis GJ, de Zeeuw D, de Jong PE for the PREVEND study group (2002) Impact of sodium intake on urinary albumin excretion is enhanced by obesity. J Am Soc Nephrol 13:661–662

    Google Scholar 

  54. Palaniappan L, Carnethon M, Fortmann SP (2003) Association between microalbuminuria and the metabolic syndrome: NANHES III. Am J Hypertens 16:952–958

    Article  PubMed  CAS  Google Scholar 

  55. Catalano C, Muscelli E, Quiñones Galvan A, Baldi S, Masoni A, Gibb I, Torffvit O, Seghieri G, Ferrannini E (1997) Effect of insulin on systemic and renal handling of albumin in nondiabetic and NIDDM subjects. Diabetes 46:868–875

    Article  PubMed  CAS  Google Scholar 

  56. Ferris M, Hogan SL, Chin H, Shoham DA, Gipson DS, Gibson K, Yilmaz S, Falk RJ, Jennette JC (2007) Obesity, albuminuria, and urinalysis findings in US young adults from the Add Health Wave III Study. Clin J Am Soc Nephrol 2:1207–1214

    Article  PubMed  Google Scholar 

  57. Hsu CY, McCulloch CE, Iribarren C, Darbinian J, Go AS (2006) Body mass index and risk for end-stage renal disease. Ann Intern Med 144:21–28

    PubMed  Google Scholar 

  58. Murtaugh MA, Jacobs DR Jr, Yu X, Gross MD, Steffes M (2003) Correlates of urinary albumin excretion in young adult blacks and whites: the Coronary Artery Risk Development in Young Adults Study. Am J Epidemiol 158:676–686

    Article  PubMed  Google Scholar 

  59. Hoq S, Chen W, Srinivasan SR, Berenson GS (2002) Childhood blood pressure predicts adult microalbuminuria in African Americans, but not in whites: the Bogalusa Heart Study. Am J Hypertens 15:1036–1041

    Article  PubMed  CAS  Google Scholar 

  60. Mykkanen L, Zaccaro DJ, Wagenknecht LE, Robbins DC, Gabriel M, Haffner SM (1998) Microalbuminuria is associated with insulin resistance in non diabetic subjects: the Insulin Resistance in Atherosclerosis Study. Diabetes 47:793–800

    Article  PubMed  CAS  Google Scholar 

  61. Castro JP, El-Atat FA, McFarlane SI, Aneja A, Sowers JR (2003) Cardiometabolic syndrome: pathophysiology and treatment. Curr Hypertens Rep 5:393–401

    Article  PubMed  Google Scholar 

  62. Francischetti EA, Genelhu VA (2007) Obesity–hypertension: an ongoing pandemic. Int J Clin Pract 61(2):269–280

    Article  PubMed  CAS  Google Scholar 

  63. Lurbe E, Torro I, Aguilar F, Alvarez J, Alcon J, Pascual JM, Redon J (2008) Added impact of obesity and insulin resistance in nocturnal blood pressure elevation in children and adolescents. Hypertension 51:635–641

    Article  PubMed  CAS  Google Scholar 

  64. Whaley-Connell A, Sowers JR (2008) Obesity, insulin resistance, and nocturnal systolic blood pressure. Hypertension 51:620–621

    Article  PubMed  CAS  Google Scholar 

  65. Lurbe E, Redon J, Kesani A, Pascual JM, Tacons J, Alvarez V, Batlle D (2002) Increase in nocturnal blood pressure and progression to microalbuminuria in type 1 diabetes. N Engl J Med 347:797–805

    Article  PubMed  CAS  Google Scholar 

  66. Williams IL, Wheatcroft SB, Shah AM, Kearney MT (2002) Obesity, atherosclerosis and the vascular endothelium: mechanisms of reduced nitric oxide bioavailability in obese humans. Int J Obes Relat Metab Disord 26:754–764

    Article  PubMed  CAS  Google Scholar 

  67. Gruber HJ, Mayer C, Mangge H, Fauler G, Grandits N, Wilder-Truschnig M (2008) Obesity reduces the bioavailability of nitric oxide in juveniles. Int J Obesity 32:826–831

    Article  CAS  Google Scholar 

  68. Scherrer U, Sartori C (2000) Defective nitric oxide synthesis: a link between metabolic insulin resistance, sympathetic overactivity and cardiovascular morbidity. Eur J Endocrinology 142:315–323

    Article  CAS  Google Scholar 

  69. Kim JA, Montagnani M, Koh KK, Quon MJ (2006) Reciprocal relationships between insulin resistance and endothelial dysfunction: molecular and pathophysiological mechanisms. Circulation 113:1888–1904

    Article  PubMed  Google Scholar 

  70. Komers R, Anderson S (2003) Paradoxes of nitric oxide in the diabetic kidney. Am J Physiol Renal Physiol 284:F1121–F1137

    Google Scholar 

  71. Prabhakar SS (2004) Role of nitric oxide in diabetic nephropathy. Semin Nephrol 24:333–344

    Article  PubMed  CAS  Google Scholar 

  72. Mather KJ, Lteif A, Steinberg HO, Baron AD (2004) Interactions between endothelin and nitric oxide in the regulation of vascular tone in obesity and diabetes. Diabetes 53:2060–2066

    Article  PubMed  CAS  Google Scholar 

  73. Maniscalco M, de Laurentiis G, Zedda A, Faraone S, Giardiello C, Cristiano S (2007) Exhaled nitric oxide in severe obesity: effect of weight loss. Respir Physiol Neurobiol 156:370–373

    Article  PubMed  CAS  Google Scholar 

  74. Shea S, Aymong E, Zynbert P (2003) Obesity, fasting plasma insulin and C-reactive protein levels in healthy children. Obes Res 11:95–103

    Article  PubMed  CAS  Google Scholar 

  75. Ceriello A (2000) Oxidative stress and glycemic regulation. Metabolism 49:27–29

    Article  PubMed  CAS  Google Scholar 

  76. Yaqoob M, McClelland P, Patrick AW, Stevenson A, Mason H, White MC, Bell GM (1994) Evidence of oxidant injury and tubular damage in early diabetic nephropathy. Q J Med 87:601–607

    CAS  Google Scholar 

  77. Oberg BP, McMenamin E, Lucas FL, Mc-Monagle E, Morrow J, Ikizler TA, Himmelfarb J (2004) Increased prevalence of oxidant stress and inflammation in patients with moderate to severe chronic kidney disease. Kidney Int 65:1009–1016

    Article  PubMed  Google Scholar 

  78. Roberts II, Morrow JD (2000) Measurement of F2-isoprostanes as an index of oxidative stress in vivo. Free Radic Biol Med 28:505–513

    Article  PubMed  CAS  Google Scholar 

  79. Keaney JF Jr, Larson MG, Vasan RS, Wilson PW, Lipinska I, Corey D, Massaro JM, Sutherland P, Vita JA, Benjamin EJ; Framingham Study (2003) Obesity and systemic oxidative stress: clinical correlates of oxidative stress. Arterioscler Thromb Vasc Biol 23:434–439

    Article  PubMed  CAS  Google Scholar 

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Savino, A., Pelliccia, P., Giannini, C. et al. Implications for kidney disease in obese children and adolescents. Pediatr Nephrol 26, 749–758 (2011). https://doi.org/10.1007/s00467-010-1659-y

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