Skip to main content

Advertisement

Log in

Mineral metabolism and bone abnormalities in children with chronic renal failure

  • Published:
Reviews in Endocrine and Metabolic Disorders Aims and scope Submit manuscript

Abstract

Abnormalities in mineral metabolism and changes in skeletal histology may contribute to growth impairment in children with chronic renal failure. Hyperphosphatemia, hypocalcemia, metabolic acidosis, alterations in vitamin D and IGF synthesis and parathyroid gland dysfunction play significant roles in the development of secondary hyperparathyroidism and subsequently, bone disease in renal failure. The recent KDIGO conference has made recommendations to consider this as a systemic disorder (chronic kidney disease-mineral bone disorder) and to standardize bone histomorphometry to include bone turnover, mineralization and volume (TMV). The use of DXA to assess bone mass is controversial in children with chronic renal failure. Questions arise regarding the accuracy of bone measurements and difficulty in data interpretation especially in children with renal failure who are not only growth retarded but often have pubertal delay and osteosclerosis. The validity and feasibility of new modalities of skeletal imaging which can detect changes in both trabecular and cortical bone are currently being investigated in children. The management of mineral abnormalities and bone disease in chronic renal failure is multifactorial. To manage hyperphosphatemia, dietary phosphate restriction accompanied by intake of calcium-free and metal-free phosphate binding agents are widely utilized. Vitamin D analogs remain the primary therapy for secondary hyperparathyroidism, although the use of the less hypercalcemic agents is preferred due to concerns of calciphylaxis and vascular calcification. Future clinical studies are needed to evaluate the long-term effects of calcimimetic agents and bisphosphonate therapy in children with chronic renal failure.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Fig. 1

Similar content being viewed by others

References

  1. Seikaly M, Salhab N, Gipson D, Yiu V, Stablein D. stature in children with chronic kidney disease: Analysis of NAPRCTS database. Pediatr Nephrol. 2006;21(6):793–9.

    Article  PubMed  Google Scholar 

  2. Lewis M, Shaw J, Reid C, Evans J, Webb N, Verrier-Jones K. Growth in children with established renal failure a registry analysis. Nephrol Dial Transplant. 2007;22(suppl 7):176–80.

    Google Scholar 

  3. Wong C, Gipson D, Gillen D, Emerson S, Koepsell T, Sherrard D, et al. Anthropometric measures and risk of death in children with end-stage renal disease. Am J Kidney Dis. 2000;36(4):811–9.

    Article  PubMed  CAS  Google Scholar 

  4. Furth SL, Hwang W, Yang C, Neu A, Fivush B, Powe N. Growth Failure, Risk of hospitalization and death for children with end-stage renal disease. Pediatr Nephrol. 2002;17(6):450–5.

    Article  PubMed  Google Scholar 

  5. Rosenkranz J, Bonzel K-E, Bulla M, Michalk D, Offner G, Reichwald-Klugger E, et al. Psychosocial adaptation of children and adolescents with chronic renal failure. Pediatr Nephrol. 1992;6:459–63.

    Article  PubMed  CAS  Google Scholar 

  6. Moe S, Cunningham J, Goodman WG, Martin K, Olgaard K, Ott S, et al. Definition, evaluation, and classification of renal osteodystrophy: A position statement from kidney disease: Improving global outcomes (KDIGO). Kidney Int. 2006;69(11):1945–53.

    Article  PubMed  CAS  Google Scholar 

  7. Denda M, Finch J, Slatopolsky E. Phosphorus accelerates the development of parathyroid hyperplasia and secondary hyperparathyroidism in rats with renal failure. Am J Kidney Dis. 1996;28(4):596–602.

    Article  PubMed  CAS  Google Scholar 

  8. Portale AA, Booth BE, Halloran BP, Morris RC. Effect of dietary phosphorus on circulating concentrations of 1,25-dihydroxyvitamin and immunoreactive parathyroid hormone in children with moderate renal insufficiency. J Clin Invest 1984;73:1580–9.

    Article  PubMed  CAS  Google Scholar 

  9. Cozzolino M, Lu Y, Finch J, Slatopolsky E, Dusso AS. p21waf1 and TGF-Mediate parathyroid growth arrest by vitamin D and high calcium. Kidney Int. 2001;60(6):2109–17.

    Article  PubMed  CAS  Google Scholar 

  10. Tokumoto M, Tsuruya K, Fukuda K, Kanai H, Kuroki S, Hirakata H. Reduced p21, p27 and vitamin D receptor in the nodular hyperplasia in patients with advanced secondary hyperparathyroidism. Kidney Int. 2002;62(4):1196–207.

    Article  PubMed  CAS  Google Scholar 

  11. Block GA, Hulbert-Shearon TE, Levin NW, Port FK. Association of serum phosphorus and calcium X phosphate product with mortality risk in chronic hemodialysis patients: A national study. Am J Kidney Dis. 1998;31(4):607–17.

    Article  PubMed  CAS  Google Scholar 

  12. 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(9):2796–803.

    Article  PubMed  CAS  Google Scholar 

  13. Naveh-Many T, Rahamimov R, Livni N, Silver J. Parathyroid cell proliferation in normal and chronic renal failure rats. J Clin Invest. 1995;96:1786–93.

    Article  PubMed  CAS  Google Scholar 

  14. Marks KH, Kilav R, Naveh-Many T, Silver J. Calcium, phosphate, vitamin D, and the parathyroid. Pediatr Nephrol. 1996;10:364–7.

    PubMed  CAS  Google Scholar 

  15. Pitts TO, Piraino BH, Mitro R, Chen TC, Segre GV, Greenberg A, et al. Hyperparathyroidism and 1,25-dihydroxyvitamin D deficiency in mild, moderate, and severe renal failure. J Clin Endocrinol Metab. 1988;67(5):876–81.

    Article  PubMed  CAS  Google Scholar 

  16. Portale AA, Booth BE, Tsai HC, Morris RC. Reduced plasma concentration of 1,25-dihydroxyvitamin D in children with moderate renal insufficiency. Kidney Int. 1982;21:627–32.

    Article  PubMed  CAS  Google Scholar 

  17. Al-Aly Z, Qazi R, Gonzalez E, Zeringue A, Martin KJ. Changes in serum 25-hydroxyvitamin D and plasma intact PTH levels following treatment with ergocalciferol in patients with CKD. Am J Kidney Dis. 2007;50(1):59–68.

    Article  PubMed  CAS  Google Scholar 

  18. Ghazali A, Fardellone P, Pruna A, Atik A, Achard J-M, Oprisiu R, et al. Is low plasma 25-(OH) vitamin D a major risk factor for hyperparathyroidism and looser’s zones? J Am Soc Nephrol. 1999;10(6):2169–77.

    Google Scholar 

  19. Elder G, Mackun K. 25-Hydroxyvitamin D deficiency and diabetes predict reduced BMD in patients with chronic kidney disease. J Bone Miner Res. 2006;21(11):1778–84.

    Article  PubMed  CAS  Google Scholar 

  20. NKF. K/DOQI clinical practice guidelines for bone metabolism and disease in children with chronic kidney disease. Am J Kidney Dis. 2005;46(4 Suppl 1):S1–S121.

    Google Scholar 

  21. NKF. K/DOQI clinical practice guidelines for bone metabolism and disease in chronic kidney disease. Am J Kidney Dis. 2003;42(Supplement 3):S1–S201.

    Google Scholar 

  22. Coen G, Mantella D, Manni M, Balducci A, Nofroni I, Sardella D, et al. 25-Hydroxyvitamin D levels and bone histomorphometry in hemodialysis renal osteodystrophy. Kidney Int. 2005;68(4):1840–8.

    Article  PubMed  CAS  Google Scholar 

  23. Gogusev J, Duchambon P, Hory B, Giovannini M, Goureau Y, Sarfati E, et al. Depressed expression of calcium receptor in parathyroid gland tissue of patients with hyperparathyroidism. Kidney Int. 1997;51:328–36.

    Article  PubMed  CAS  Google Scholar 

  24. Fukuda N, Tanaka H, Tominaga Y, Fukagawa M, Kurokawa K, Seino Y. Decreased 1,25-dihydroxyvitamin D3 receptor density is associated with a more severe form of parathyroid hyperplasia in chronic uremic patients. J Clin Invest. 1993;92:1436–43.

    Article  PubMed  CAS  Google Scholar 

  25. 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(3):467–75.

    PubMed  CAS  Google Scholar 

  26. Tonshoff B, Powell DR, Zhao D, Durham SK, Coleman ME, Domene HM, et al. Decreased hepatic insulin-like growth factor (IGF)- I and increased igf binding protein-1 and -2 gene expression in experimental uremia. Endocrinology 1997;128(3):938–46.

    Article  Google Scholar 

  27. Salusky IB, Ramirez JA, Oppenheim W, Gales B, Segre GV, Goodman WG. Biochemical markers of renal osteodystrophy in pediatric patients undergoing CAPD/CCPD. Kidney Int. 1994;45:253–8.

    Article  PubMed  CAS  Google Scholar 

  28. Hodson E, Evans R, Dunstan C, Hills E, Shaw P. Quantitative bone histology in children with chronic renal failure. Kidney Int. 1982;21(6):833–9.

    Article  PubMed  CAS  Google Scholar 

  29. Spasovski GB, Bervoets ARJ, Behets GJS, Ivanovski N, Sikole A, Dams G. Spectrum of renal bone disease in end-stage renal failure patients not yet on dialysis. Nephrol Dial Transplant. 2003;18(6):1159–66.

    Article  PubMed  CAS  Google Scholar 

  30. Avila-Diaz M, Matos M, Garcia-Lopez E, Prado M-d-C, Castro-Vazquez F, Ventura MDJ, et al. Serum markers of low-turnover bone disease in Mexican children with chronic kidney disease undergoing dialysis. Perit Dial Int. 2006;26(1):78–84.

    PubMed  CAS  Google Scholar 

  31. 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;53:205–11.

    Article  PubMed  CAS  Google Scholar 

  32. Slatopolsky E, Finch J, Clay P, Martin D, Sicard G, Singer G, et al. A novel mechanism for skeletal resistance in uremia. Kidney Int. 2000;58(2):753–61.

    Article  PubMed  CAS  Google Scholar 

  33. Quarles LD, Lobaugh B, Murphy G. Intact parathyroid hormone overestimates the presence and severity of parathyroid-mediated osseous abnormalities in uremia. J Clin Endocrinol Metab. 1992;75:145–50.

    Article  PubMed  CAS  Google Scholar 

  34. Salusky IB, Goodman WG, Kuizon BD, Lavigne JR, Zahranik RJ, Gales B, et al. Similar predictive value of bone turnover using the first- and second-generation immunometric Pth assays in pediatric patients treated with peritoneal dialysis. Kidney Int. 2003;63:1801–8.

    Article  PubMed  CAS  Google Scholar 

  35. Hernandez JD, Wesseling K, Boechat M, Gales B, Salusky IB. Osteomalacia in a hemodialysis patient receiving an active vitamin D sterol. Nat Clin Pract Nephrol. 2007;3(4):227–32.

    Article  PubMed  Google Scholar 

  36. Briese S, Wiesner S, Will J, Lembcke A, Opgen-Rhein B, Nissel R, et al. Arterial and cardiac disease in young adults with childhood-onset end-stage renal disease–impact of calcium and vitamin D therapy. Nephrol Dial Transplant. 2006;21(7):1906–14.

    Article  PubMed  CAS  Google Scholar 

  37. Goodman WG, Goldin J, Kuizon B, Yoon C, Gales B, Sider D, et al. Coronary artery calcification in young adults with end-stage renal disease who are undergoing dialysis. N Eng J Med. 2000;342(20):1478–83.

    Article  CAS  Google Scholar 

  38. Stenvinkel P, Wang K, Qureshi A, Axelsson J, Pecoits-Filho R, Gao P, et al. Low fetuin-a levels are associated with cardiovascular death: Impact of variations in the gene encoding fetuin. Kidney Int. 2005;67(6):2383–92.

    Article  PubMed  CAS  Google Scholar 

  39. Davies MR, Lund RJ, Hruska KA. Bmp-7 is an efficacious treatment of vascular calcification in a murine model of atherosclerosis and chronic renal failure. J Am Soc Nephrol. 2003;14(6):1559–67.

    Article  PubMed  Google Scholar 

  40. Moe SM, O, Neill KD, Duan D, Ahmed S, Chen NX, et al. Medial artery calcification in ESRD patients is associated with deposition of bone matrix proteins. Kidney Int 2002;61(2):638–48.

    Article  PubMed  Google Scholar 

  41. Mitsnefes MM, Daniels SR, Schwartz SM, Khoury P, Strife CF. Changes in left ventricular mass in children and adolescents during chronic dialysis. Pediatr Nephrol. 2001;16:318–23.

    Article  PubMed  CAS  Google Scholar 

  42. Litwin M, Wuhl E, Jourdan C, Trelewicz J, Niemirska A, Fahr K, et al. Altered morphologic properties of large arteries in children with chronic renal failure and after renal transplantation. J Am Soc Nephrol. 2005;16(5):1494–500.

    Article  PubMed  Google Scholar 

  43. Lobao R, Carvalho A, Cuppari L, Ventura R, Lazaretti-Castro M, Jorgetti V, et al. High prevalence of low bone mineral density in pre-dialysis chronic kidney disease patients: Bone histomorphometric analysis. Clin Nephrol. 2004;62(6):432–9.

    PubMed  CAS  Google Scholar 

  44. Andrade M, Carvalhaes L, Carvalho A, Lazaretti-Castro M, Brandao C. Bone mineral density and bone histomorphometry in children on long-term dialysis. Pediatr Nephrol. 2007;22(10):1767–72.

    Article  PubMed  Google Scholar 

  45. Rix M, Andreassen H, Eskildsen P, Lagdahl B, Olgaard K. Bone mineral density and biochemical markers of bone turnover in patients with predialysis chronic renal failure. Kidney Int. 1999;56(3):1084–93.

    Article  PubMed  CAS  Google Scholar 

  46. Jadoul M, Albert J, Akiba T, Akizawa T, Arab L, Bragg-Gresham J, et al. Incidence and risk factors for hip or other bone fractures among hemodialysis patients in the dialysis outcomes and practice patterns study. Kidney Int. 2006;70:1358–66.

    Article  PubMed  CAS  Google Scholar 

  47. Coco M, Rush H. Increased incidence of hip fractures in dialysis patients with low serum parathyroid hormone. Am J Kidney Dis. 2000;36(6):1115–21.

    Article  PubMed  CAS  Google Scholar 

  48. Lima EM, Goodman WG, Kuizon BD, Gales B, Emerick A, Goldin J, et al. Bone density measurements in pediatric patients with renal osteodystrophy. Pediatr Nephrol. 2003;18:554–9.

    PubMed  Google Scholar 

  49. Wehrli F, Leonard M, Saha P, Gomberg B. Quantitative high-resolution magnetic resonance imaging reveals structural implications of renal osteodystrophy on trabecular and cortical bone. J Magn Reson Imag. 2004;20(1):83–89.

    Article  Google Scholar 

  50. Hopper T, Wehrli FW, Saha P, Andre J, Wright A, Sanchez C, et al. Quantitative microcomputed tomography assessment of intratrabecular, intertrabecular, and cortical bone architecture in a rat model of severe renal osteodystrophy. J Comput Assist Tomography 2007;31(2):320–8.

    Article  Google Scholar 

  51. Hothi D, Harvey E, Piva E, Keating L, Secker D, Geary D. Calcium and phosphate balance in adolescents on home nocturnal haemodialysis. Pediatr Nephrol. 2006;21(6):835–41.

    Article  PubMed  Google Scholar 

  52. Goodman WG, Veldhuis JD, Belin TR, Juppner H, Salusky IB. Suppressive effect of calcium on parathyroid hormone release in adynamic renal osteodystrophy and secondary hyperparathyroidism. Kidney Int. 1997;51:1590–5.

    Article  PubMed  CAS  Google Scholar 

  53. Pieper A, Haffner D, Hoppe B, Dittrich K, Offner G, Bonzel K-E, et al. A randomized crossover trial comparing sevelamer with calcium acetate in children with Ckd. Am J Kidney Dis. 2006;47(4):625–35.

    Article  PubMed  CAS  Google Scholar 

  54. Mahdavi H, Kuizon B, Gales B, Wang H, Elashoff R, Salusky IB. Sevelamer hydrochloride: An effective phosphate binder in dialyzed children. Pediatr Nephrol. 2003;18(12):1260–4.

    Article  PubMed  Google Scholar 

  55. Mathew S, Lund RJ, Strebeck F, Tustison KS, Geurs T, Hruska KA. Reversal of the adynamic bone disorder and decreased vascular calcification in chronic kidney disease by sevelamer carbonate therapy. J Am Soc Nephrol. 2007;18(1):122–30.

    Article  PubMed  CAS  Google Scholar 

  56. Brezina B, Qunibi WY, Nolan CR. Acid loading during treatment with sevelamer hydrochloride: Mechanisms and clinical implications. Kidney Int. 2004;66(S90):S39–S45.

    Article  Google Scholar 

  57. Bervoets AR, Oste L, Behets GJ, Dams G, Blust R, Marynissen R, et al. Development and reversibility of impaired mineralization associated with lanthanum carbonate treatment in chronic renal failure rats. Bone 2006;38(6):803–10.

    Article  PubMed  CAS  Google Scholar 

  58. Slatopolsky E, Liapis H, Finch J. Progressive accumulation of lanthanum in the liver of normal and uremic rats. Kidney Int. 2005;68(6):2809–13.

    Article  PubMed  CAS  Google Scholar 

  59. Sanchez C, He Y. Bone growth during daily or intermittent calcitriol treatment during renal failure with advanced secondary hyperparathyroidism. Kidney Int. 2007;72(5):582–91.

    Article  PubMed  CAS  Google Scholar 

  60. Scharla S, Strong D, Rosen C, Mohan S, Holick M, Baylink D, et al. 1,25-Dihydroxyvitamin D3 increases Secretion of insulin-like growth factor binding protein-4 (IGFBP-4) by human osteoblast-like cells in vitro and elevates IGFBP-4 serum levels in Vivo. J Clin Endocrinol Metab. 1993;77(5):1190–7.

    Article  PubMed  CAS  Google Scholar 

  61. Mizobuchi M, Finch JL, Martin DR, Slatopolsky E. Differential effects of vitamin d receptor activators on vascular calcification in uremic rats. Kidney Int. 2007;72(6):709–15.

    Article  PubMed  CAS  Google Scholar 

  62. Joist H, Ahya S, Giles K, Norwood K, Slatopolsky E, Coyne D. Differential effects of very high doses of doxercalciferol and paricalcitol on serum phosphorus in hemodialysis patients. Clin Nephrol. 2006;65(5):335–41.

    PubMed  CAS  Google Scholar 

  63. Sprague SM, Lerma E, McCormmick D, Abraham M, Batlle D. Suppression of parathyroid hormone secretion in hemodialysis patients: Comparison of paricalcitol with calcitriol. Am J Kidney Dis. 2001;38(5 Suppl 5):S51–S56.

    Article  PubMed  CAS  Google Scholar 

  64. Greenbaum L, Benador N, Goldstein S, Paredes A, Melnick J, Mattingly S, et al. Intravenous paricalcitol for treatment of secondary hyperparathyroidism in children on hemodialysis. Am J Kidney Dis. 2007;49(6):814–23.

    Article  PubMed  CAS  Google Scholar 

  65. Seeherunvong W, Nwobi O, Abitbol C, Chandar J, Strauss J, Zilleruelo G. Paricalcitol versus calcitriol treatment for hyperparathyroidism in pediatric hemodialysis patients. Pediatr Nephrol. 2006;21(10):1434–9.

    Article  PubMed  Google Scholar 

  66. Shah N, Bernardini J, Piraino B. Prevalence and correction of 25(OH) vitamin D deficiency in peritoneal dialysis patients. Perit Dial Int. 2005;25(4):362–6.

    PubMed  CAS  Google Scholar 

  67. Tylavsky F, Ryder K, Li R, Park V, Womack C, Norwood J, et al. Preliminary findings: 25(OH)D levels and PTH are indicators of rapid bone accrual in pubertal children. J Am Coll Nutr. 2007;26(5):462–70.

    PubMed  CAS  Google Scholar 

  68. Cheng S, Tylavsky F, Kroger H, Karkkainen M, Lyytikainen A, Koistinen A, et al. Association of low 25-hydroxyvitamin D concentrations with elevated parathyroid hormone concentrations and low cortical bone density in early pubertal and prepubertal Finnish girls. Am J Clin Nutr. 2003;78(3):485–92.

    PubMed  CAS  Google Scholar 

  69. Block GA, Martin KJ, de Francisco ALM, Turner SA, Avram MM, Suranyi MG, et al. Cinacalcet for secondary hyperparathyroidism in patients receiving hemodialysis. N Engl J Med. 2004;350(15):1516–25.

    Article  PubMed  CAS  Google Scholar 

  70. Cunningham J, Danese M, Olson K, Klassen P, Chertow GM. Effects of the calcimimetic cinacalcet HCl on cardiovascular disease, fracture, and health-related quality of life in secondary hyperparathyroidism. Kidney Int. 2005;68(4):1793–800.

    Article  PubMed  CAS  Google Scholar 

  71. Wu S, Palese T, Mishra O, Delivoria-Papadopoulos M, Luca FD. Effects of Ca2+-sensing receptor activation in the growth plate. FASEB J. 2004;18(1):143–5.

    PubMed  CAS  Google Scholar 

  72. Zeitlin L, Rauch F, Plotkin H, Glorieux FH. Height and weight development during four years of therapy with cyclical intravenous pamidronate in children and adolescents with osteogenesis imperfecta types I, III, and IV. Pediatr. 2003;111:1030–6.

    Article  Google Scholar 

  73. Rauch F, Travers R, Glorieux FH. Pamidronate in children with osteogenesis imperfecta: Histomorphometric effects of long-term therapy. J Clin Endocrinol Metab. 2006;91(2):511–6.

    Article  PubMed  CAS  Google Scholar 

Download references

Acknowledgement

This work was supported in part by the Research & Development Grant from the Department of Pediatrics, University of Wisconsin School of Medicine & Public Health, Madison, WI.

Author information

Authors and Affiliations

Authors

Corresponding author

Correspondence to Cheryl P. Sanchez.

Rights and permissions

Reprints and permissions

About this article

Cite this article

Sanchez, C.P. Mineral metabolism and bone abnormalities in children with chronic renal failure. Rev Endocr Metab Disord 9, 131–137 (2008). https://doi.org/10.1007/s11154-007-9071-z

Download citation

  • Received:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s11154-007-9071-z

Keywords

Navigation