The calcimimetic cinacalcet is used to treat secondary hyperparathyroidism in patients
receiving dialysis, and asymptomatic hypocalcemia is often observed following its
initiation. Here we investigated the incidence, predictors and therapeutic consequences
of hypocalcemia by a post hoc analysis of the randomized, double-blind, placebo-controlled
EValuation Of Cinacalcet Hydrochloride Therapy to Lower CardioVascular Events (EVOLVE)
trial. Hypocalcemia was classified as mild (total serum calcium 8.0–8.39 mg/dL), moderate
(7.5–7.99 mg/dL) or severe (under 7.5 mg/dL). At least one episode of hypocalcemia
developed within 16 weeks after the first administered dose among 58.3% of 1938 patients
randomized to cinacalcet versus 14.9% of 1923 patients randomized to placebo. Hypocalcemia
in the cinacalcet group was severe in 18.4% of the patients versus 4.4% in the placebo
group. Severe hypocalcemia following administration of cinacalcet was associated with
higher baseline plasma parathyroid hormone, lower corrected total serum calcium, higher
serum alkaline phosphatase, geographic region (patients from Latin America and Russia
had a higher risk relative to the United States) and higher body mass index. The median
cinacalcet dose immediately prior to the first hypocalcemic episode was 54-58 mg/day
and similar in the three hypocalcemia categories. In the majority of patients, hypocalcemia
resolved spontaneously within 14 days without modification of background therapy.
Among patients who received an intervention, the most common was an increase in the
active vitamin D sterol dose. Thus, the occurrence of hypocalcemia is frequent following
initiation of cinacalcet and the likelihood of developing hypocalcemia was related
to the severity of secondary hyperparathyroidism. Hypocalcemia was generally asymptomatic
and self-limited.
Keywords
To read this article in full you will need to make a payment
ISN Member Login
Login with your ISN username and password.
One-time access price info
- For academic or personal research use, select 'Academic and Personal'
- For corporate R&D use, select 'Corporate R&D Professionals'
Subscribe:
Subscribe to Kidney InternationalPurchase one-time access:
Already a print subscriber? Claim online access
Already an online subscriber? Sign in
Register: Create an account
Institutional Access: Sign in to ScienceDirect
References
- Cinacalcet for secondary hyperparathyroidism in patients receiving hemodialysis.N Engl J Med. 2004; 350: 1516-1525
- Evaluating real-world use of cinacalcet and biochemical response to therapy in US hemodialysis patients.Am J Nephrol. 2013; 37: 389-398
- The OPTIMA study: assessing a new cinacalcet (Sensipar/Mimpara) treatment algorithm for secondary hyperparathyroidism.Clin J Am Soc Nephrol. 2008; 3: 36-45
- Cinacalcet use patterns and effect on laboratory values and other medications in a large dialysis organization, 2004 through 2006.Clin J Am Soc Nephrol. 2009; 4: 354-360
- Cinacalcet and achievement of the NKF/K-DOQI recommended target values for bone and mineral metabolism in real-world clinical practice–the ECHO observational study.Nephrol Dial Transplant. 2009; 24: 2852-2859
- Efficacy of cinacalcet with low-dose vitamin D in incident haemodialysis subjects with secondary hyperparathyroidism.Nephrol Dial Transplant. 2013; 28: 1241-1254
- Biochemical aberrations in a dialysis patient following parathyroidectomy.Am J Kidney Dis. 1997; 29: 759-762
- Executive summary of the 2017 KDIGO Chronic Kidney Disease–Mineral and Bone Disorder (CKD-MBD) Guideline Update: what's changed and why it matters.Kidney Int. 2017; 92: 26-36
- Effect of cinacalcet on cardiovascular disease in patients undergoing dialysis.N Engl J Med. 2012; 367: 2482-2494
- Baseline characteristics of subjects enrolled in the Evaluation of Cinacalcet HCl Therapy to Lower Cardiovascular Events (EVOLVE) trial.Nephrol Dial Transplant. 2012; 27: 2872-2879
- Management of serum calcium reductions among patients on hemodialysis following cinacalcet initiation.Pharmacoepidemiol Drug Saf. 2015; 24: 1058-1067
- Cinacalcet HCl, an oral calcimimetic agent for the treatment of secondary hyperparathyroidism in hemodialysis and peritoneal dialysis: a randomized, double-blind, multicenter study.J Am Soc Nephrol. 2005; 16: 800-807
- A randomized trial of cinacalcet versus vitamin D analogs as monotherapy in secondary hyperparathyroidism (PARADIGM).Clin J Am Soc Nephrol. 2015; 10: 1031-1040
- Cinacalcet-associated severe hypocalcemia resulting in torsades de pointes and cardiac arrest: a case for caution.Eur J Clin Pharmacol. 2016; 72: 373-375
- [Potentialisation of hyperkalemia effects by cinacalcet-induced hypocalcemia on dialysis].Nephrol Ther. 2012; 8: 476-480
- Calcium requirements after parathyroidectomy in patients with refractory secondary hyperparathyroidism.Nephron Clin Pract. 2008; 110: c80-c85
- Importance of low serum intact parathyroid hormone as a predictor of mortality in hemodialysis and peritoneal dialysis patients: 14 years of prospective observation.Am J Kidney Dis. 2001; 38: 1351-1357
- Postoperative calcium requirements in 6,000 patients undergoing outpatient parathyroidectomy: easily avoiding symptomatic hypocalcemia.J Am Coll Surg. 2010; 211: 49-54
- Pitfalls of measuring total blood calcium in patients with CKD.J Am Soc Nephrol. 2008; 19: 1592-1598
- Circadian variation of mineral and bone parameters in end-stage renal disease.J Nephrol. 2015; 28: 351-359
- Cinacalcet, dialysate calcium concentration, and cardiovascular events in the EVOLVE trial.Hemodial Int. 2016; 20: 421-431
- Evaluation of Cinacalcet Therapy to Lower Cardiovascular Events (EVOLVE): rationale and design overview.Clin J Am Soc Nephrol. 2007; 2: 898-905
Article Info
Publication History
Published online: March 07, 2018
Accepted:
December 21,
2017
Received in revised form:
December 14,
2017
Received:
March 31,
2017
Footnotes
see commentary on page 1275
Identification
Copyright
© 2018 International Society of Nephrology. Published by Elsevier Inc. All rights reserved.
ScienceDirect
Access this article on ScienceDirectLinked Article
- Acute pseudogout after cinacalcet treatmentKidney InternationalVol. 94Issue 4
- PreviewThe EVOLVE trial showed that up to 58.3% of patients treated with cinacalcet developed hypocalcemia, albeit mostly asymptomatic and of minor clinical relevance.1 We treated an 80-year-old woman who had hypercalcemic primary hyperparathyroidism with cinacalcet, 30 mg/d. At baseline, her total serum calcium was 2.84 mmol/l. After 14 days of cinacalcet, she developed polyarthralgia and myalgia but no fever. Laboratory studies showed serum calcium of 2.05 mmol/l and C-reactive protein of 138 mg/l, but there was no leukocytosis.
- Full-Text
- Preview
