Skip to main content
SpringerLink
Log in

Chronic Kidney Disease-Mineral and Bone Disorder, Vitamin D Deficiency, and Secondary Hyperparathyroidism

  • Chapter
  • First Online:
Chronic Kidney Disease

  • 2071 Accesses

Abstract

Chronic kidney disease-mineral and bone disorder (CKD-MBD) encompasses laboratory and bone abnormalities and vascular or other soft tissue calcification and has adverse effects on clinical prognosis. The 2017 KDIGO clinical practice guideline recommends monitoring serum levels of calcium, phosphate, PTH, and alkaline phosphatase activity beginning in CKD G3a. Treatments of CKD-MBD should be based on serial assessments of phosphate, calcium, and PTH levels, considered together. In patients with CKD G3a–G5D with severe hyperparathyroidism who fail to respond to pharmacological therapy, we suggest parathyroidectomy. The ambiguity and lack of unequivocally actionable recommendations highlight potential challenges for implementation and underscore the need for future research in this important area.

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

Access this chapter

Log in via an institution
Chapter
USD 29.95
Price excludes VAT (USA)
  • Available as PDF
  • Read on any device
  • Instant download
  • Own it forever
eBook
USD 79.99
Price excludes VAT (USA)
  • Available as EPUB and PDF
  • Read on any device
  • Instant download
  • Own it forever
Softcover Book
USD 99.99
Price excludes VAT (USA)
  • Compact, lightweight edition
  • Dispatched in 3 to 5 business days
  • Free shipping worldwide - see info
Hardcover Book
USD 129.99
Price excludes VAT (USA)
  • Durable hardcover edition
  • Dispatched in 3 to 5 business days
  • Free shipping worldwide - see info

Tax calculation will be finalised at checkout

Purchases are for personal use only

Institutional subscriptions

References

  1. Moe S, Drueke T, Cunningham J, Goodman W, Martin K, Olgaard K, 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  CAS  PubMed  Google Scholar 

  2. Martin KJ, Olgaard K, Coburn JW, Coen GM, Fukagawa M, Langman C, et al. Diagnosis, assessment and treatment of bone turnover abnormalities in renal osteodystrophy. Am J Kidney Dis. 2004;43(3):558–65.

    Article  PubMed  Google Scholar 

  3. Levin A, Bakris GL, Molitch M, Smulders M, Tian J, Williams LA, Andress DL. Prevalence of abnormal serum vitamin D, PTH, calcium, and phosphorous in patients with chronic kidney disease: results of the study to evaluate early kidney disease. Kidney Int. 2007;71:31–8.

    Article  CAS  PubMed  Google Scholar 

  4. Kidney Disease: Improving Global Outcome (KDIGO) CKD-MBD Work Group. KDIGO clinical practice guidelines for diagnosis, evaluation, prevention, and treatment of chronic kidney disease-mineral and bone disorder (CKD-MBD). Kidney Int Suppl. 2009;113:S1–S130.

    Google Scholar 

  5. Danese MD, Kim J, Doan QV, Dylan M, Griffths R, Chertow GM. PTH and the risks for hip, vertebral and pelvis fractures among patients on dialysis. Am J Kidney Dis. 2008;47(1):149–58.

    Article  Google Scholar 

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

    Article  CAS  PubMed  Google Scholar 

  7. Adeney KL, Siscovick DS, Ix JH, Seliger SL, Shlipak MG, Jenny NS, Kestenbaum BR. Association of serum phosphate with vascular and valvular calcification in moderate CKD. J Am Soc Nephrol. 2009;20(2):381–7.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  8. Uhlig K, Berns J, Kestenbaum B, Kumar R, Leonard MB, Martin KJ, et al. KDOQI US commentary on 2009 KDIGO clinical practice guideline for diagnosis, evaluation, and treatment of CKD-mineral and bone disorder (CKD-MBD). Am J Kidney Dis. 2010;55(5):773–99.

    Article  PubMed  Google Scholar 

  9. Ganesh S, Stack AG, Levin NW, Hulbert-Shearon T, Port FK. Association of elevated serum Po 4, Ca × Po 4 product, and parathyroid hormone in cardiac mortality risk in chronic hemodialysis patients. J Am Soc Nephrol. 2001;12(10):2131–8.

    CAS  PubMed  Google Scholar 

  10. Mathew S, Tustison KS, Sugatani T, Chaudhary LR, Rifas L, Hruska KA. The mechanism of phosphorous as a cardiovascular risk factor in CKD. J Am Soc Nephrol. 2008;19(6):1092–105.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  11. Bhuriya R, Li S, Chen S-C, McCullough PA, Bakris GL. Plasma parathyroid hormone level and prevalent cardiovascular disease stage 3 and 4: an analysis from the Keep Early Evaluation Program (KEEP). Am J Kidney Dis. 2009;53(4):S3–S10.

    Article  CAS  PubMed  Google Scholar 

  12. Pierides AM, Edwards WG, Cullum UX, McCall JT, Ellis HA. Hemodialysis encephalopathy with osteomalacia fractures and muscle weakness. Kidney Int. 1980;18:115–24.

    Article  CAS  PubMed  Google Scholar 

  13. Islam MZ. Overview of renal osteodystrophy and current therapeutic approach. J Med. 2011;12:45–9.

    Article  Google Scholar 

  14. Gordon PL, Fresetto LA. Management of osteoporosis in CKD stages 3 to 5. Am J Kidney Dis. 2010;55(5):941–56.

    Article  PubMed  Google Scholar 

  15. Kidney Disease. Improving global outcomes (KDIGO) CKD-MBD update work group. KDIGO 2017 clinical practice guideline update for the diagnosis, evaluation, prevention, and treatment of chronic kidney disease–mineral and bone disorder (CKD-MBD). Kidney Int Suppl. 2017;7:1–59.

    Article  Google Scholar 

  16. Miller PD, Roux C, Boonen S, Barton IP, Dunlap LE, Burgio DE. Safety and efficiency of risedronate in patients with age-related reduced renal function as estimated by Cockcroft and Gault method: a pooled analysis of nine clinical trials. J Bone Miner Res. 2005;20:2015–115.

    Google Scholar 

  17. Miller PD. The role of bone biopsy in patients with chronic renal failure. Clin J Am Soc Nephrol. 2008;3:S140–50.

    Article  PubMed  PubMed Central  Google Scholar 

  18. Danziger J. The bone-renal axis in early chronic kidney disease: an emerging paradigm. Nephrol Dial Transplant. 2008;23(9):2733–7.

    Article  CAS  PubMed  Google Scholar 

  19. Lui S, Quarles LD. How fibroblast growth factor 23 works? J Am Soc Nephrol. 2007;18:1637–47.

    Article  CAS  Google Scholar 

  20. Wesseling-Perry K, Pereira RC, Sahney S, Gales B, Wang H-J, Elashoff R, et al. Calcitriol and doxercalciferol are equivalent in controlling bone turnover, suppressing parathyroid hormone, and increasing fibroblast growth factor-23 in secondary hyperparathyroidism. Kidney Int. 2010;79:112–9.

    Article  PubMed  CAS  Google Scholar 

  21. Isakova T, Wahl P, Vargas GS, Gutierrez OM, Scialla J, Xie H, et al. Fibroblast growth factor 23 is elevated before parathyroid hormone and phosphate in chronic kidney disease. Kidney Int. 2011;79:1370–8.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  22. Wolf M. Update on fibroblast growth factor 23 in chronic kidney disease. Kidney Int. 2012;82:737–47.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  23. Pavik I, Jaeger P, Ebner L, Wagner CA, Petzold K, Spichtig D, et al. Secreted klotho and FGF23 in chronic kidney disease stage 1 to 5: a sequence suggested from a cross-sectional study. Nephrol Dial Transplant. 2013;28:352–9.

    Article  CAS  PubMed  Google Scholar 

  24. Magyar CE, Friedman PA. Chapter 25. Renal regulation of calcium, phosphate, and magnesium. In: Dubose TD, Hamm LL, editors. Acid-base and electrolyte disorders. Philadelphia: Elsevier Saunders; 2002. p. 435–52.

    Google Scholar 

  25. Peacock M. Calcium metabolism in health and disease. Clin J Am Soc Nephrol. 2010;5(1):S23–30.

    Article  CAS  PubMed  Google Scholar 

  26. Foutounas C. Phosphorous metabolism in chronic kidney disease. Hippokratia. 2011;15:S50–2.

    Google Scholar 

  27. Juppner H, Wolf M, Salusky IB. FGF-23: more than a regulator of renal phosphate handling? J Bone Miner Res. 2010;25(10):2091–7.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  28. Neves KR, Graciolli FG, dos Reis LM, Pasqalucci CA, Moysés RM, Jorgetti V. Adverse effects of hyperphosphatemia on myocardial hypertrophy, renal function, and bone in rats with renal failure. Kidney Int. 2004;66:2237–44.

    Article  CAS  PubMed  Google Scholar 

  29. Souberbielle JC, Roth H, Fouque DP. Parathyroid hormone measurement in CKD. Kidney Int. 2010;77:93–100.

    Article  CAS  PubMed  Google Scholar 

  30. Cozzolino M, Gallieni M, Brancaccio D, Arcidiacono T, Bianchi G, Vezzoli G. Vitamin D retains an important role in the pathogenesis and management of secondary hyperparathyroidism. J Nephrol. 2006;19(5):566–77.

    CAS  PubMed  Google Scholar 

  31. Messa P, Macário F, Yaqoob M, Bowman K, Braun J, Von Albertini B, et al. The OPTIMA study: assessing a new cinacalcet (sensipar/mimpara) treatment algorithm for secondary hyperparathyroidism. Clin J Am Soc Nephrol. 2008;3(1):36–45.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  32. Martin KJ, Gonzalez EA. Vitamin D analogs: action and role in the treatment of secondary hyperparathyroidism. Semin Nephrol. 2004;24(5):456–9.

    Article  CAS  PubMed  Google Scholar 

  33. Vervloet MC, Ittersum FJ, Büttler RM, Heijboer AC, Blankenstein MA, Ter Wee PM. Effects of dietary phosphate and calcium intake on fibroblast growth factor-23. Clin J Am Soc Nephrol. 2011;6(2):383–9.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  34. Li D, Zhang L, Zuo L, Jin CG, Li WG, Chen J-B. Association of CKD-MBD markers with all-cause mortality in prevalent hemodialysis patients: a cohort study in Beijing. PLoS One. 2017;12(1):e0168537.

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  35. Ben Dov IZ, et al. The parathyroid is a target organ for FGF23 in rats. J Clin Invest. 2007;117:4003–8.

    CAS  PubMed  PubMed Central  Google Scholar 

  36. Lavi-Moshayoff V, Silver J, Naveh-Many T. Human PTH gene regulation in vivo using transgenic mice. Am J Physiol Renal Physiol. 2009;297:F713–9.

    Article  CAS  PubMed  Google Scholar 

  37. Galitzer H, Ben Dov IZ, Silver J, Naveh- Many T. Parathyroid cell resistance to fibroblast growth factor 23 in secondary hyperparathyroidism of chronic kidney disease. Kidney Int. 2010;77:211–8.

    Article  CAS  PubMed  Google Scholar 

  38. Komaba H, et al. Depressed expression of Klotho and FGF receptor 1 in hyperplastic parathyroid glands from uremic patients. Kidney Int. 2010;77:232–8.

    Article  CAS  PubMed  Google Scholar 

  39. Thadhani R. Is calcitriol life-protective for patients with chronic kidney disease? J Am Soc Nephrol. 2009;20(11):2285–90.

    Article  CAS  PubMed  Google Scholar 

  40. Kandula P, Dobre M, Schold JD, Schrieber MJ Jr, Mehrotra R, Navaneethan SD. Vitamin D supplementation in chronic kidney disease: systemic review and meta-analysis of observational studies and randomized controlled trials. Clin J Am Soc Nephrol. 2011;6(6):50–62.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  41. Ravani P, Malberti F, Tripepi G, Pecchini P, Cutrupi S, Pizzini P, et al. Vitamin D levels and patient outcome in chronic kidney disease. Kidney Int. 2007;75:88–95.

    Article  CAS  Google Scholar 

  42. Iimori S, Mori Y, Akita W, et al. Diagnostic usefulness of bone mineral density and biochemical markers of bone turnover in predicting fracture in CKD stage 5D patients—a single-center cohort study. Nephrol Dial Transplant. 2012;27(1):345–51.

    Article  CAS  PubMed  Google Scholar 

  43. Naylor KL, Garg AX, Zou G, et al. Comparison of fracture risk prediction among individuals with reduced and normal kidney function. Clin J Am Soc Nephrol. 2015;10(4):646–53.

    Article  PubMed  PubMed Central  Google Scholar 

  44. West SL, Lok CE, Langsetmo L, et al. Bone mineral density predicts fractures in chronic kidney disease. J Bone Miner Res. 2015;30(5):913–9.

    Article  PubMed  Google Scholar 

  45. Yenchek RH, Ix JH, Shlipak MG, et al. Bone mineral density and fracture risk in older individuals with CKD. Clin J Am Soc Nephrol. 2012;7(7):1130–6.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  46. Moe SM. Vascular calcification and renal osteodystrophy relationship in chronic kidney disease. Eur J Clin Invest. 2006;36:51–62.

    Article  CAS  PubMed  Google Scholar 

  47. Massy ZA, Maziere C, Kamel S, Brazier M, Choukroun G, Tribouilloy C, et al. Impact of inflammation and oxidative stress on vascular calcifications in chronic kidney disease. Pediatr Nephrol. 2005;20:380–2.

    Article  CAS  PubMed  Google Scholar 

  48. Goodman WG, London G, Amann K, Block GA, Giachelli C, Hruska KA, et al. Vascular calcification in chronic kidney disease. Am J Kidney Dis. 2004;43:572–9.

    Article  PubMed  Google Scholar 

  49. London GM, Guerin AP, Marchais SJ, Metivier F, Pannier B, Adda H. Arterial media calcification in end-stage renal disease: impact on all-cause and cardiovascular mortality. Nephrol Dial Transplant. 2003;18:1731–40.

    Article  PubMed  Google Scholar 

  50. Lau WL, Linnes M, Chu EY, Foster BL, Bartley BA, Somerman MJ, et al. High phosphate feeding promotes mineral and bone abnormalities in mice with chronic kidney disease. Nephrol Dial Transplant. 2013;28:62–9.

    Article  CAS  PubMed  Google Scholar 

  51. Slatopolsky E, Caglar S, Gradowska L, Canterbury J, Reiss E, Bricker NS. On prevention of secondary hyperparathyroidism in experimental chronic renal disease using ‘proportional reduction’ of dietary phosphorous intake. Kidney Int. 1972;2:147–51.

    Article  CAS  PubMed  Google Scholar 

  52. Tonelli M, Pannu N, Manns B. Oral phosphate binders in patients with kidney failure. N Engl J Med. 2010;362:1312–24.

    Article  CAS  PubMed  Google Scholar 

  53. Navaneethan SD, Palmer SC, Craig JC, Elder GJ, Strippoli GFM. Bene fi ts and harms of phosphate binders in CKD: a systemic review of randomized controlled trial. Am J Kidney Dis. 2009;54(4):619–37.

    Article  CAS  PubMed  Google Scholar 

  54. Hutchison A. Oral phosphate binders. Kidney Int. 2009;75:906–14.

    Article  CAS  PubMed  Google Scholar 

  55. Nolan CR, Califano JR, Butzin CA. Influence of calcium acetate or calcium citrate on intestinal aluminum absorption. Kidney Int. 1990;38:937–41.

    Article  CAS  PubMed  Google Scholar 

  56. Froment DPH, Molitoris BA, Buddington B, Miller N, Alfrey AC. Site and mechanism of enhanced gastrointestinal absorption of aluminum by citrate. Kidney Int. 1989;36:978–84.

    Article  CAS  PubMed  Google Scholar 

  57. Alfrey AC. Dialysis encephalopathy. Kidney Int. 1986;29:S53–7.

    Google Scholar 

  58. Hodsman AB, Sherrard DJ, Alfrey AC, Ott S, Brickman AS, Miller NL, et al. Bone aluminum and histomorphometric features of renal osteodystrophy. Clin Endocrinol Metab. 1982;54(3):539–46.

    Article  CAS  Google Scholar 

  59. Cozzolino M, Mazzaferro S, Brandenburg V. The treatment of hyperphosphatemia in CKD: calcium based or calcium-free phosphate binders? Nephrol Dial Transplant. 2011;26:402–7.

    Article  CAS  PubMed  Google Scholar 

  60. Chertow GM, Raggi P, McCarthy JT, Schulman G, Silberzweig J, Kuhlik A, et al. Effect of sevelamer and calcium acetate on proxies of atherosclerotic and atherosclerotic vascular disease in hemodialysis patients. J Nephrol. 2003;23(5):307–14.

    Article  CAS  Google Scholar 

  61. Chertow GM, Burke SK, Lazarus JM, Stenzel KH, Wombolt D, Goldberg D, et al. Poly [allylamine hydrochloride] (RenaGel): a non-calcemic phosphate binder for the treatment of hyperphosphatemia in chronic renal failure. Am J Kidney Dis. 1997;29(1):66–71.

    Article  CAS  PubMed  Google Scholar 

  62. Qunibi W, Moustafa M, Muenz LR, He DY, Kessler PD. Diaz-buxo JA, et al. 1-year randomized trial of calcium acetate versus sevelamer on progression of coronary artery calcification in hemodialysis patients with comparable lipid control: the calcium acetate Renagel Evaluation-2 (CARE-2) study. Am J Kidney Dis. 2008;51(6):952–65.

    Article  CAS  PubMed  Google Scholar 

  63. Navaneethan SD, Palmer SC, Vecchio M, Craig JC, Elder GJ, Strippoli GF. Phosphate binders for preventing and treating bone disease in chronic kidney disease patients. Cochrane Database Syst Rev. 2011;(2):CD006023.

    Google Scholar 

  64. Isakova T, Xie H, Barchi-Chung A, et al. Daily variability in mineral metabolites in CKD and effects of dietary calcium and calcitriol. Clin J Am Soc Nephrol. 2012;7(5):820–8.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  65. Kakajiwala A, Jemielita TO, Copelovitch L, et al. Variability in measures of mineral metabolism in children on hemodialysis: impact on clinical decision-making. Pediatr Nephrol. 2017;32:2311–8. https://doi.org/10.1007/s00467-017-3730-4.

    Article  PubMed  Google Scholar 

  66. Gutierrez OM, Isakova T, Andress DL, Levin A, Wolf M. Prevalence and severity of disordered mineral metabolism in blacks with chronic kidney disease. Kidney Int. 2008;73(8):956–62.

    Article  CAS  PubMed  Google Scholar 

  67. Ennis J, Worcester E, Coe F. Contribution of calcium, phosphorus and 25-hydroxyvitamin D to the excessive severity of secondary hyperparathyroidism in African-Americans with CKD. Nephrol Dial Transplant. 2012;27(7):2847–53.

    Article  CAS  PubMed  Google Scholar 

  68. Wang AY, Fang F, Chan J, et al. Effect of paricalcitol on left ventricular mass and function in CKD–the OPERA trial. J Am Soc Nephrol. 2014;25(1):175–86.

    Article  CAS  PubMed  Google Scholar 

  69. Thadhani R, Appelbaum E, Pritchett Y, et al. Vitamin D therapy and cardiac structure and function in patients with chronic kidney disease: the PRIMO randomized controlled trial. JAMA. 2012;307(7):674–84.

    Article  CAS  PubMed  Google Scholar 

  70. EVOLVETrialInvestigators CGM, Block GA, Correa Rotter R, et al. Effect of cinacalcet on cardiovascular disease in patients undergoing dialysis. N Engl J Med. 2012;367(26):2482–94.

    Article  Google Scholar 

  71. Baker LR, Muir JW, Sharman VL, et al. Controlled trial of calcitriol in hemodialysis patients. Clin Nephrol. 1986;26(4):185–91.

    CAS  PubMed  Google Scholar 

  72. Sprague SM, Llach F, Amdahl M, Taccetta C, Batlle D. Paricalcitol versus calcitriol in the treatment of secondary hyperparathyroidism. Kidney Int. 2003;63(4):1483–90.

    Article  CAS  PubMed  Google Scholar 

  73. Moe SM, Abdalla S, Chertow GM, et al. Effects of cinacalcet on fracture events in patients receiving hemodialysis: the EVOLVE trial. J Am Soc Nephrol. 2015;26(6):1466–75.

    Article  CAS  PubMed  Google Scholar 

  74. Apetrii M, Goldsmith D, Nistor I, Siriopol D, Voroneanu L, Scripcariu D, et al. Impact of surgical parathyroidectomy on chronic kidney disease-mineral and bone disorder (CKD-MBD)—a systematic review and meta-analysis. PLoS One. 2017;12(11):e0187025.

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  75. Fang L, Wu J, Luo J, Wen P, Xiong M, Cao J, Chen X, Yang J. Changes in bone mineral density after total parathyroidectomy without auto transplantation in the end-stage renal disease patients with secondary hyperparathyroidism. BMC Nephrol. 2018;19:142.

    Article  PubMed  PubMed Central  CAS  Google Scholar 

Download references

Author information

Authors and Affiliations

  1. Centre for Kidney Disease, Second Affiliated Hospital, Nanjing Medical University, Nanjing, Jiangsu, China

    Mingxia Xiong

Authors
  1. Mingxia Xiong
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to Mingxia Xiong .

Editor information

Editors and Affiliations

  1. Centre for Kidney Disease, Second Affiliated Hospital, Nanjing Medical University, Nanjing, Jiangsu, China

    Junwei Yang

  2. Centre for Kidney Disease, Second Affiliated Hospital, Nanjing Medical University, Nanjing, Jiangsu, China

    Weichun He

Rights and permissions

Reprints and permissions

Copyright information

© 2020 Springer Nature Singapore Pte Ltd.

About this chapter

Check for updates. Verify currency and authenticity via CrossMark

Cite this chapter

Xiong, M. (2020). Chronic Kidney Disease-Mineral and Bone Disorder, Vitamin D Deficiency, and Secondary Hyperparathyroidism. In: Yang, J., He, W. (eds) Chronic Kidney Disease. Springer, Singapore. https://doi.org/10.1007/978-981-32-9131-7_11

Download citation

  • DOI: https://doi.org/10.1007/978-981-32-9131-7_11

  • Published:

  • Publisher Name: Springer, Singapore

  • Print ISBN: 978-981-32-9130-0

  • Online ISBN: 978-981-32-9131-7

  • eBook Packages: MedicineMedicine (R0)

Publish with us

Policies and ethics

Search

Navigation