International Urology and Nephrology

, Volume 50, Issue 10, pp 1871–1877 | Cite as

Prevalence and risk factors for hypercalcemia among non-dialysis patients with chronic kidney disease-mineral and bone disorder

  • Jun Jie Benjamin SengEmail author
  • Ying Lin Cheryl Tan
  • Rou Wei Lim
  • Hui Ting Sarah Ng
  • Puay Hoon Lee
  • Jiunn Wong
Nephrology - Original Paper



To examine the prevalence and risk factors for hypercalcemia among non-dialysis chronic kidney disease (CKD) patients with mineral and bone disorder (MBD).


A retrospective cohort study was conducted in Singapore General Hospital, involving all CKD stage 4 and 5 pre-dialysis patients who were on treatment for MBD in June 2016. Each patient was followed up for 1 year and screened for hypercalcemia episodes. Mild, moderate and severe hypercalcemia were defined as corrected calcium of 2.47–3.00, 3.01–3.50 and ≥ 3.51 mmol/l respectively. Patients who were on dialysis, post-renal transplant, post-parathyroidectomy or had no calcium levels taken during the study period were excluded. Details related to patients’ clinical information and hypercalcemia episodes were collected. Multivariate logistic regression analysis was performed to evaluate risk factors for hypercalcemia.


Of 557 patients, 75 (13.4%) patients developed hypercalcemia. There were 120 (97.6%) mild and 3 (2.4%) moderate hypercalcemia episodes. The daily elemental calcium intake from phosphate binders and usage of vitamin D analogues did not differ between patients with and without hypercalcemia (p > 0.05). After adjusting for covariates, lower baseline iPTH level [odds ratio (OR) 0.96, 95% CI 0.93–0.99], history of hypercalcemia in past 1 year (OR 11.11, 95% CI 3.36–36.75) and immobility (OR 3.34, 95% CI 1.34–8.40) were associated with increased hypercalcemia risk.


Hypercalcemia affects a significant proportion of pre-dialysis patients with MBD. More studies should be undertaken to evaluate other risk factors associated with hypercalcemia.


Mineral and bone disorder Hypercalcemia Chronic kidney disease Non-dialysis Pre-dialysis 


  1. 1.
    Jha V, Garcia-Garcia G, Iseki K, Li Z, Naicker S, Plattner B, Saran R, Wang AY, Yang CW (2013) Chronic kidney disease: global dimension and perspectives. Lancet 382(9888):260–272. CrossRefPubMedGoogle Scholar
  2. 2.
    Wee H-L, Seng BJJ, Lee JJ, Chong KJ, Tyagi P, Vathsala A, How P (2016) Association of anemia and mineral and bone disorder with health-related quality of life in Asian pre-dialysis patients. Health Qual Life Outcomes 14:94. CrossRefPubMedPubMedCentralGoogle Scholar
  3. 3.
    Slinin Y, Foley RN, Collins AJ (2005) Calcium, phosphorus, parathyroid hormone, and cardiovascular disease in hemodialysis patients: the USRDS waves 1, 3, and 4 study. J Am Soc Nephrol 16(6):1788–1793. CrossRefPubMedGoogle Scholar
  4. 4.
    Rivara MB, Ravel V, Kalantar-Zadeh K, Streja E, Lau WL, Nissenson AR, Kestenbaum B, de Boer IH, Himmelfarb J, Mehrotra R (2015) Uncorrected and albumin-corrected calcium, phosphorus, and mortality in patients undergoing maintenance dialysis. J Am Soc Nephrol 26(7):1671–1681. CrossRefPubMedPubMedCentralGoogle Scholar
  5. 5.
    Kovesdy CP, Kuchmak O, Lu JL, Kalantar-Zadeh K (2010) Outcomes associated with serum calcium level in men with non-dialysis-dependent chronic kidney disease. Clin J Am Soc Nephrol 5(3):468–476. CrossRefPubMedPubMedCentralGoogle Scholar
  6. 6.
    Meric F, Yap P, Bia MJ (1990) Etiology of hypercalcemia in hemodialysis patients on calcium carbonate therapy. Am J Kidney Dis 16(5):459–464CrossRefPubMedGoogle Scholar
  7. 7.
    Bleyer AJ, Burke SK, Dillon M, Garrett B, Kant KS, Lynch D, Rahman SN, Schoenfeld P, Teitelbaum I, Zeig S, Slatopolsky E (1999) A comparison of the calcium-free phosphate binder sevelamer hydrochloride with calcium acetate in the treatment of hyperphosphatemia in hemodialysis patients. Am J Kidney Dis 33(4):694–701CrossRefPubMedGoogle Scholar
  8. 8.
    Moe S, Drueke T, Cunningham J, Goodman W, Martin K, Olgaard K, Ott S, Sprague S, Lameire N, Eknoyan G (2006) Definition, evaluation, and classification of renal osteodystrophy: a position statement from kidney disease: improving global outcomes (KDIGO). Kidney Int 69(11):1945–1953. CrossRefPubMedGoogle Scholar
  9. 9.
    WHO Expert Consultation (2004) Appropriate body-mass index for Asian populations and its implications for policy and intervention strategies. Lancet 363(9403):157–163. CrossRefGoogle Scholar
  10. 10.
    Pai M, Lloyd NS, Cheng J, Thabane L, Spencer FA, Cook DJ, Haynes RB, Schunemann HJ, Douketis JD (2013) Strategies to enhance venous thromboprophylaxis in hospitalized medical patients (SENTRY): a pilot cluster randomized trial. Implement Sci 8:1. CrossRefPubMedPubMedCentralGoogle Scholar
  11. 11.
    Payne RB, Little AJ, Williams RB, Milner JR (1973) Interpretation of serum calcium in patients with abnormal serum proteins. BMJ 4(5893):643–646CrossRefPubMedGoogle Scholar
  12. 12.
    Carroll MF, Schade DS (2003) A practical approach to hypercalcemia. Am Fam Physician 67(9):1959–1966PubMedGoogle Scholar
  13. 13.
    Kong X, Zhang L, Zhang L, Chen N, Gu Y, Yu X, Liu W, Chen J, Peng L, Yuan W, Wu H, Chen W, Fan M, He L, Ding F, Chen X, Xiong Z, Zhang J, Jia Q, Shi W, Xing C, Tang X, Hou F, Shu G, Mei C, Wang L, Xu D, Ni Z, Zuo L, Wang M, Wang H (2012) Mineral and bone disorder in Chinese dialysis patients: a multicenter study. BMC Nephrol 13:116. CrossRefPubMedPubMedCentralGoogle Scholar
  14. 14.
    Vikrant S, Parashar A (2016) Prevalence and severity of disordered mineral metabolism in patients with chronic kidney disease: a study from a tertiary care hospital in India. Indian J Endocrinol Metab 20(4):460–467. CrossRefPubMedPubMedCentralGoogle Scholar
  15. 15.
    Cheng CJ, Chou CH, Lin SH (2006) An unrecognized cause of recurrent hypercalcemia: immobilization. South Med J 99(4):371–374. CrossRefPubMedGoogle Scholar
  16. 16.
    Teo HK, Wong J (2017) Unusual cause of hypercalcaemia in end stage renal failure patients. Hemodial Int 21(2):E40–E44. CrossRefPubMedGoogle Scholar
  17. 17.
    Spatz JM, Wein MN, Gooi JH, Qu Y, Garr JL, Liu S, Barry KJ, Uda Y, Lai F, Dedic C, Balcells-Camps M, Kronenberg HM, Babij P, Pajevic PD (2015) The Wnt inhibitor sclerostin is up-regulated by mechanical unloading in osteocytes in vitro. J Biol Chem 290(27):16744–16758. CrossRefPubMedPubMedCentralGoogle Scholar
  18. 18.
    Palmer SC, McGregor DO, Macaskill P, Craig JC, Elder GJ, Strippoli GF (2007) Meta-analysis: vitamin D compounds in chronic kidney disease. Ann Intern Med 147(12):840–853CrossRefPubMedGoogle Scholar
  19. 19.
    Thadhani R, Appelbaum E, Pritchett Y, Chang Y, Wenger J, Tamez H, Bhan I, Agarwal R, Zoccali C, Wanner C, Lloyd-Jones D, Cannata J, Thompson BT, Andress D, Zhang W, Packham D, Singh B, Zehnder D, Shah A, Pachika A, Manning WJ, Solomon SD (2012) Vitamin D therapy and cardiac structure and function in patients with chronic kidney disease: the PRIMO randomized controlled trial. Jama 307(7):674–684. CrossRefPubMedGoogle Scholar
  20. 20.
    Wang AY, Fang F, Chan J, Wen YY, Qing S, Chan IH, Lo G, Lai KN, Lo WK, Lam CW, Yu CM (2014) Effect of paricalcitol on left ventricular mass and function in CKD—the OPERA trial. J Am Soc Nephrol 25(1):175–186. CrossRefPubMedGoogle Scholar
  21. 21.
    Wilson RJ, Copley JB (2017) Elemental calcium intake associated with calcium acetate/calcium carbonate in the treatment of hyperphosphatemia. Drugs Context 6:212302. CrossRefPubMedPubMedCentralGoogle Scholar
  22. 22.
    Ghimire S, Castelino RL, Lioufas NM, Peterson GM, Zaidi STR (2015) Nonadherence to medication therapy in haemodialysis patients: a systematic review. PLoS ONE 10(12):e0144119. CrossRefPubMedPubMedCentralGoogle Scholar

Copyright information

© Springer Nature B.V. 2018

Authors and Affiliations

  1. 1.Duke-NUS Medical SchoolSingaporeSingapore
  2. 2.Department of PharmacySingapore General HospitalSingaporeSingapore
  3. 3.Department of Renal MedicineSingapore General HospitalSingaporeSingapore

Personalised recommendations