Seminars in Nephrology
Volume 29, Issue 4 , Pages 425-434 , July 2009

Current Advances in Chronic Kidney Disease in Children: Growth, Cardiovascular, and Neurocognitive Risk Factors

  • Larry A. Greenbaum, MD, PhD

      Affiliations

    • Division of Pediatric Nephrology, Department of Pediatrics, Emory University and Children's Healthcare of Atlanta, Atlanta, GA
    • Corresponding Author InformationAddress reprint requests to Larry A. Greenbaum, MD, PhD, Division of Pediatric Nephrology, Emory University, 2015 Uppergate Dr, NE, Atlanta, GA 30322
    • ,
  • Bradley A. Warady, MD

      Affiliations

    • Department of Pediatrics, University of Missouri-Kansas City School of Medicine, Kansas City, MO
    • Department of Pediatrics, Pediatric Nephrology, The Children's Mercy Hospital, Kansas City, MO
    • ,
  • Susan L. Furth, MD, PhD

      Affiliations

    • Departments of Pediatrics and Epidemiology, Johns Hopkins Medical Institutions, Baltimore, MD

References 

  1. Hokken-Koelega AC, van Zaal MA, van Bergen W, de Ridder MA, Stijnen T, Wolff ED, et al. Final height and its predictive factors after renal transplantation in childhood. Pediatr Res. 1994;36:323–328
  2. Ho M, Stablein DM. North American Pediatric Renal Transplant Cooperative Study (NAPRTCS) annual report. 2003;Rockville, MD
  3. Schaefer F, Wingen AM, Hennicke M, Rigden S, Mehls O. Growth charts for prepubertal children with chronic renal failure due to congenital renal disorders (European Study Group for Nutritional Treatment of Chronic Renal Failure in Childhood). Pediatr Nephrol. 1996;10:288–293
  4. Schaefer F, Seidel C, Binding A, Gasser T, Largo RH, Prader A, et al. Pubertal growth in chronic renal failure. Pediatr Res. 1990;28:5–10
  5. Mehls O, Ritz E, Hunziker EB, Tonshoff B, Heinrich U. Role of growth hormone in growth failure of uraemia—perspectives for application of recombinant growth hormone. Acta Paediatr Scand Suppl. 1988;343:118–126
  6. Wong CS, Gipson DS, Gillen DL, Emerson S, Koepsell T, Sherrard DJ, et al. Anthropometric measures and risk of death in children with end-stage renal disease. Am J Kidney Dis. 2000;36:811–819
  7. Furth SL, Hwang W, Yang C, Neu AM, Fivush BA, Powe NR. Growth failure, risk of hospitalization and death for children with end-stage renal disease. Pediatr Nephrol. 2002;17:450–455
  8. Furth SL, Stablein D, Fine RN, Powe NR, Fivush BA. Adverse clinical outcomes associated with short stature at dialysis initiation: a report of the North American Pediatric Renal Transplant Cooperative Study. Pediatrics. 2002;109:909–913
  9. Sedman A, Friedman A, Boineau F, Strife CF, Fine R. Nutritional management of the child with mild to moderate chronic renal failure. J Pediatr. 1996;129:13–18
  10. Salusky IB. Bone and mineral metabolism in childhood end-stage renal disease. Pediatr Clin North Am. 1995;42:1531–1550
  11. Goodman WG. Recent developments in the management of secondary hyperparathyroidism. Kidney Int. 2001;59:1187–1201
  12. Chesney RW, Moorthy AV, Eisman JA, Jax DK, Mazess RB, DeLuca HF. Increased growth after long-term oral 1alpha,25-vitamin D3 in childhood renal osteodystrophy. N Engl J Med. 1978;298:238–242
  13. Kuizon BD, Goodman WG, Juppner H, Boechat I, Nelson P, Gales B, et al. Diminished linear growth during intermittent calcitriol therapy in children undergoing CCPD. Kidney Int. 1998;53:205–211
  14. Chantler C, Holliday MA. Growth in children with renal disease with particular reference to the effects of calorie malnutrition: a review. Clin Nephrol. 1973;1:230–242
  15. Roelfsema V, Clark RG. The growth hormone and insulin-like growth factor axis: its manipulation for the benefit of growth disorders in renal failure. J Am Soc Nephrol. 2001;12:1297–1306
  16. Powell DR, Liu F, Baker BK, Hinzt RL, Kale A, Suwanichkul A, et al. Effect of chronic renal failure and growth hormone therapy on the insulin-like growth factors and their binding proteins. Pediatr Nephrol. 2000;14:579–583
  17. Schaefer F, Chen Y, Tsao T, Nouri P, Rabkin R. Impaired JAK-STAT signal transduction contributes to growth hormone resistance in chronic uremia. J Clin Invest. 2001;108:467–475
  18. Fine RN, Kohaut EC, Brown D, Perlman AJ. Growth after recombinant human growth hormone treatment in children with chronic renal failure: report of a multicenter randomized double-blind placebo-controlled study. J Pediatr. 1994;124:374–382
  19. Hokken-Koelega AC, Stijnen T, de Muinck Keizer-Schrama SM, Wit JM, Wolff ED, de Jong MC, et al. Placebo-controlled, double-blind, cross-over trial of growth hormone treatment in prepubertal children with chronic renal failure. Lancet. 1991;338:585–590
  20. Berard E, Crosnier H, Six-Beneton A, Chevallier T, Cochat P, Broyer M. Recombinant human growth hormone treatment of children on hemodialysis (French Society of Pediatric Nephrology). Pediatr Nephrol. 1998;12:304–310
  21. Haffner D, Schaefer F, Nissel R, Wuhl E, Tonshoff B, Mehls O. Effect of growth hormone treatment on the adult height of children with chronic renal failure (German Study Group for Growth Hormone Treatment in Chronic Renal Failure). N Engl J Med. 2000;343:923–930
  22. Broyer M. Results and side-effects of treating children with growth hormone after kidney transplantation—a preliminary report (Pharmacia & Upjohn Study Group). Acta Paediatr Suppl. 1996;417:76–79
  23. Tonshoff B, Haffner D, Mehls O, Dietz M, Ruder H, Blum WF, et al. Efficacy and safety of growth hormone treatment in short children with renal allografts: three year experience (Members of the German Study Group for Growth Hormone Treatment in Children with Renal Allografts). Kidney Int. 1993;44:199–207
  24. National Kidney Foundation. K/DOQI clinical practice guidelines for bone metabolism and disease in children with chronic kidney disease. Am J Kidney Dis. 2005;46:S1–S122
  25. Fine RN, Ho M, Tejani A, Blethen S. Adverse events with rhGH treatment of patients with chronic renal insufficiency and end-stage renal disease. J Pediatr. 2003;142:539–545
  26. Seikaly MG, Salhab N, Warady BA, Stablein D. Use of rhGH in children with chronic kidney disease: lessons from NAPRTCS. Pediatr Nephrol. 2007;22:1195–1204
  27. Greenbaum LA, Hidalgo G, Chand D, Chiang M, Dell K, Kump T, et al. Obstacles to the prescribing of growth hormone in children with chronic kidney disease. Pediatr Nephrol. 2008;23:1531–1535
  28. US Renal Data System. USRDS 2007 annual report: atlas of chronic kidney disease and end-stage renal disease in the United States. Bethesda, MD: National Institutes of Health, National Institute of Diabetes and Digestive and Kidney Diseases; 2007;
  29. North American Pediatric Renal Trials and Collaborative Studies (NAPRTCS) (2007 annual report). Rockville, MD 2007;
  30. Chavers BM, Li S, Collins AJ, Herzog CA. Cardiovascular disease in pediatric chronic dialysis patients. Kidney Int. 2002;62:648–653
  31. Mitsnefes MM. Cardiovascular complications of pediatric chronic kidney disease. Pediatr Nephrol. 2008;23:27–39
  32. Grundy SM. Atherogenic dyslipidemia: lipoprotein abnormalities and implications for therapy. Am J Cardiol. 1995;75:45B–52B
  33. Third report of the National Cholesterol Education Program (NCEP) Expert Panel on Detection, Evaluation, and Treatment of High Blood Cholesterol in Adults (Adult Treatment Panel III) final report. Circulation. 2002;106:3143–3421
  34. Mitsnefes MM, Ho PL, McEnery PT, Schurman S. Hypertension and progression of chronic renal failure in children: the North American Pediatric Renal Transplant Cooperative Study report. J Am Soc Nephrol. 2002;13:426A
  35. Flynn JT, Mitsnefes M, Pierce C, Cole SR, Parekh RS, Furth SL, et al. Blood pressure in children with chronic kidney disease: a report from the Chronic Kidney Disease in Children study. Hypertension. 2008;52:631–637
  36. Sorof JM, Cardwell G, Franco K, Portman RJ. Ambulatory blood pressure and left ventricular mass index in hypertensive children. Hypertension. 2002;39:903–908
  37. Lande MB, Carson NL, Roy J, Meagher CC. Effects of childhood primary hypertension on carotid intima media thickness: a matched controlled study. Hypertension. 2006;48:40–44
  38. Blacher J, Guerin AP, Pannier B, Marchais SJ, Safar ME, London GM. Impact of aortic stiffness on survival in end-stage renal disease. Circulation. 1999;99:2434–2439
  39. Sorof JM, Alexandrov AV, Cardwell G, Portman RJ. Carotid artery intimal-medial thickness and left ventricular hypertrophy in children with elevated blood pressure. Pediatrics. 2003;111:61–66
  40. Mitsnefes MM, Kimball TR, Kartal J, Witt SA, Glascock BJ, Khoury PR, et al. Progression of left ventricular hypertrophy in children with early chronic kidney disease: 2-year follow-up study. J Pediatr. 2006;149:671–675
  41. Mitsnefes MM, Kimball TR, Border WL, Witt SA, Glascock BJ, Khoury PR, et al. Impaired left ventricular diastolic function in children with chronic renal failure. Kidney Int. 2004;65:1461–1466
  42. Mitsnefes MM, Kimball TR, Border WL, Witt SA, Glascock BJ, Khoury PR, et al. Abnormal cardiac function in children after renal transplantation. Am J Kidney Dis. 2004;43:721–726
  43. Kasiske BL. Hyperlipidemia in patients with chronic renal disease. Am J Kidney Dis. 1998;32:S142–S156
  44. National Kidney Foundation. K/DOQI clinical practice guidelines for management of dyslipidemias in patients with kidney disease. Am J Kidney Dis. 2003;41:S1–S91
  45. Fried LF, Orchard TJ, Kasiske BL. Effect of lipid reduction on the progression of renal disease: a meta-analysis. Kidney Int. 2001;59:260–269
  46. Levin A, Djurdjev O, Thompson C, Barrett B, Ethier J, Carlisle E, et al. Canadian randomized trial of hemoglobin maintenance to prevent or delay left ventricular mass growth in patients with CKD. Am J Kidney Dis. 2005;46:799–811
  47. Matteucci MC, Wuhl E, Picca S, Mastrostefano A, Rinelli G, Romano C, et al. Left ventricular geometry in children with mild to moderate chronic renal insufficiency. J Am Soc Nephrol. 2006;17:218–226
  48. El-Husseini AA, Sheashaa HA, Hassan NA, El-Demerdash FM, Sobh MA, Ghoneim MA. Echocardiographic changes and risk factors for left ventricular hypertrophy in children and adolescents after renal transplantation. Pediatr Transplant. 2004;8:249–254
  49. Morris KP, Sharp J, Watson S, Coulthard MG. Non-cardiac benefits of human recombinant erythropoietin in end-stage renal failure and anaemia. Arch Dis Child. 1993;69:580–586
  50. Stenvinkel P, Carrero JJ, Axelsson J, Lindholm B, Heimburger O, Massy Z. Emerging biomarkers for evaluating cardiovascular risk in the chronic kidney disease patient: how do new pieces fit into the uremic puzzle?. Clin J Am Soc Nephrol. 2008;3:505–521
  51. Mitsnefes MM, Kimball TR, Kartal J, Witt SA, Glascock BJ, Khoury PR, et al. Cardiac and vascular adaptation in pediatric patients with chronic kidney disease: role of calcium-phosphorus metabolism. J Am Soc Nephrol. 2005;16:2796–2803
  52. Goldstein SL, Leung JC, Silverstein DM. Pro- and anti-inflammatory cytokines in chronic pediatric dialysis patients: effect of aspirin. Clin J Am Soc Nephrol. 2006;1:979–986
  53. Sylvestre LC, Fonseca KP, Stinghen AE, Pereira AM, Meneses RP, Pecoits-Filho R. The malnutrition and inflammation axis in pediatric patients with chronic kidney disease. Pediatr Nephrol. 2007;22:864–873
  54. Balakrishnan VS, Guo D, Rao M, Jaber BL, Tighiouart H, Freeman RL, et al. Cytokine gene polymorphisms in hemodialysis patients: association with comorbidity, functionality, and serum albumin. Kidney Int. 2004;65:1449–1460
  55. Rao M, Wong C, Kanetsky P, Girndt M, Stenvinkel P, Reilly M, et al. Cytokine gene polymorphism and progression of renal and cardiovascular diseases. Kidney Int. 2007;72:549–556
  56. Badiou S, Cristol JP, Jaussent I, Terrier N, Morena M, Maurice F, et al. Fine-tuning of the prediction of mortality in hemodialysis patients by use of cytokine proteomic determination. Clin J Am Soc Nephrol. 2008;3:423–430
  57. Oh J, Wunsch R, Turzer M, Bahner M, Raggi P, Querfeld U, et al. Advanced coronary and carotid arteriopathy in young adults with childhood-onset chronic renal failure. Circulation. 2002;106:100–105
  58. Goodman WG, Goldin J, Kuizon BD, Yoon C, Gales B, Sider D, et al. Coronary-artery calcification in young adults with end-stage renal disease who are undergoing dialysis. N Engl J Med. 2000;342:1478–1483
  59. Barker DJ. The developmental origins of insulin resistance. Horm Res. 2005;64:2–7
  60. Luyckx VA, Brenner BM. Low birth weight, nephron number, and kidney disease. Kidney Int. 2005;97:S68–S77
  61. Bayrakci US, Schaefer F, Duzova A, Yigit S, Bakkaloglu A. Abnormal circadian blood pressure regulation in children born preterm. J Pediatr. 2007;151:399–403
  62. Hemachandra AH, Klebanoff MA, Furth SL. Racial disparities in the association between birth weight in the term infant and blood pressure at age 7 years: results from the Collaborative Perinatal Project. J Am Soc Nephrol. 2006;17:2576–2581
  63. Chiu KC, Chu A, Go VL, Saad MF. Hypovitaminosis D is associated with insulin resistance and beta cell dysfunction. Am J Clin Nutr. 2004;79:820–825
  64. Shroff R, Egerton M, Bridel M, Shah V, Hiorns M, Donald A, et al. Vitamin D, inflammation and vascular calcification in children on dialysis. Pediatr Nephrol. 2007;22:1448
  65. Li YC, Kong J, Wei M, Chen ZF, Liu SQ, Cao LP. 1,25-dihydroxyvitamin D(3) is a negative endocrine regulator of the renin-angiotensin system. J Clin Invest. 2002;110:229–238
  66. Levin A, Li YC. Vitamin D and its analogues: do they protect against cardiovascular disease in patients with kidney disease?. Kidney Int. 2005;68:1973–1981
  67. Chesney RW, Brewer E, Moxey-Mims M, Watkins S, Furth SL, Harmon WE, et al. Report of an NIH task force on research priorities in chronic kidney disease in children. Pediatr Nephrol. 2006;21:14–25
  68. Rotundo A, Nevins TE, Lipton M, Lockman LA, Mauer SM, Michael AF. Progressive encephalopathy in children with chronic renal insufficiency in infancy. Kidney Int. 1982;21:486–491
  69. McGraw ME, Haka-Ikse K. Neurologic-developmental sequelae of chronic renal failure in infancy. J Pediatr. 1985;106:579–583
  70. Polinsky MS, Kaiser BA, Stover JB, Frankenfield M, Baluarte HJ. Neurologic development of children with severe chronic renal failure from infancy. Pediatr Nephrol. 1987;1:157–165
  71. Bock GH, Conners CK, Ruley J, Samango-Sprouse CA, Conry JA, Weiss I, et al. Disturbances of brain maturation and neurodevelopment during chronic renal failure in infancy. J Pediatr. 1989;114:231–238
  72. Qvist E, Pihko H, Fagerudd P, et al. Neurodevelopmental outcome in high-risk patients after renal transplantation in early childhood. Pediatr Transplantation. 2002;6:53–62
  73. Valanne L, Qvist E, Jalanko H, Holmberg C, Pihko H. Neuroradiologic findings in children with renal transplantation under 5 years of age. Pediatr Transplantation. 2004;8:44–51
  74. Warady BA. Neurodevelopment of infants with end-stage renal disease: is it improving?. Pediatr Transplantation. 2002;6:5–7
  75. Hulstijn-Dirkmaat GM, Damhuis IH, Jetten ML, Koster AM, Schroder CH. The cognitive development of pre-school children treated for chronic renal failure. Pediatr Nephrol. 1995;9:464–469
  76. Honda M, Kamiyama Y, Kawamura K, Kawahara K, Shishido S, Nakai H, et al. Growth, development and nutritional status in Japanese children under 2 years on continuous ambulatory peritoneal dialysis. Pediatr Nephrol. 1995;9:543–548
  77. Warady BA, Belden B, Kohaut E. Neurodevelopmental outcome of children initiating peritoneal dialysis in early infancy. Pediatr Nephrol. 1999;13:759–765
  78. Ledermann SE, Scanes ME, Fernando ON, Duffy PG, Madden SJ, Trompeter RS. Long-term outcome of peritoneal dialysis in infants. J Pediatr. 2000;136:24–29
  79. Madden SJ, Ledermann SE, Guerrero-Blanco M, Bruce M, Trompeter RS. Cognitive and psychosocial outcome of infants dialysed in infancy. Child Care Health Dev. 2003;29:55–61
  80. Mendley SR, Zelko FA. Improvement in specific aspects of neurocognitive performance in children after renal transplantation. Kidney Int. 1999;56:318–323
  81. Brouhard BH, Donaldson LA, Lawry KW, McGowan KR, Drotar D, Davis I, et al. Cognitive functioning in children on dialysis and post-transplantation. Pediatr Transplantation. 2000;4:261–267
  82. Lawry KW, Brouhard BH, Cunningham RJ. Cognitive functioning and school performance in children with renal failure. Pediatr Nephrol. 1994;8:326–329
  83. Gerson AC, Butler R, Moxey-Mims M, et al. Neurocognitive outcomes in children with chronic kidney disease: current findings and contemporary endeavors. Ment Retard Dev Disabil Res. 2006;12:208–215
  84. Slickers J, Duquette P, Hooper S, Gipson D. Clinical predictors of neurocognitive deficits in children with chronic kidney disease. Pediatr Nephrol. 2007;22:565–572
  85. Fennell RS, Fennell EB, Carter RL, Mings EL, Klausner AB, Hurst JR. Association between renal function and cognition in childhood chronic renal failure. Pediatr Nephrol. 1990;4:16–20
  86. Fennell RS, Fennell EB, Carter RL, Mings EL, Klausner AB, Hurst JR. A longitudinal study of the cognitive function of children with renal failure. Pediatr Nephrol. 1990;4:11–15
  87. Gipson DS, Hooper SR, Duquette PJ, Wetherington CE, Stellwagen KK, Jenkins TL, et al. Memory and executive functions in pediatric chronic kidney disease. Child Neuropsychol. 2006;12:391–405
  88. Lande MB, Kaczorowski JM, Auinger P, et al. Elevated blood pressure and decreased cognitive function among school-age children and adolescents in the United States. J Pediatr. 2003;143:720–724
  89. Duquette PJ, Hooper SR, Wetherington CE, Icard PF, Gipson DS. Brief report: intellectual and academic functioning in pediatric chronic kidney disease. J Pediatr Psychol. 2007;32:1011–1017
  90. Icard PF, Hower SJ, Kuchenreuther AR, Hooper SR, Gipson DS. The transition from childhood to adulthood with ESRD: educational and social challenges. Clin Nephrol. 2007;68:1–7
  91. Groothoff JW, Grootenhius M, Dommerholt A, Gruppen MP, Offringa M, Heymans HS. Impaired cognition and schooling in adults with end stage renal disease since childhood. Arch Dis Child. 2002;87:380–385
  92. Furth S, Cole S, Moxey-Mims M, Kaskel F, Mak R, Schwartz G, et al. Design and Methods of the Chronic Kidney Disease in Children (CKiD) prospective cohort study. Clin J Am Soc Nephrol. 2006;1:1006–1015

PII: S0270-9295(09)00054-0

doi: 10.1016/j.semnephrol.2009.03.017

Seminars in Nephrology
Volume 29, Issue 4 , Pages 425-434 , July 2009

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