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A Semi-Automated and Reproducible Biological-Based Method to Quantify Calcium Deposition In Vitro
Published on: June 2, 2022
Hypocalcemia and cardiovascular mortality in cinacalcet users
Shunsuke Goto1,2, Takayuki Hamano3,4, Hideki Fujii2
1Committee of Renal Data Registry, Japanese Society for Dialysis Therapy, Tokyo, Japan.
Insights
Hypocalcemia, or low calcium levels, in hemodialysis patients using calcimimetics is linked to increased cardiovascular mortality, especially sudden death. This risk persists regardless of cinacalcet use, highlighting the need for careful monitoring.
Area of Science:
- Nephrology
- Cardiology
- Clinical Pharmacology
Background:
- Calcimimetics are frequently prescribed to hemodialysis patients to manage secondary hyperparathyroidism and influence serum calcium levels.
- While current guidelines suggest low calcium levels induced by calcimimetics may be benign, evidence from large observational studies is limited.
- This study investigates the association between serum calcium levels and cardiovascular mortality in calcimimetic users within a Japanese dialysis registry.
Purpose of the Study:
- To examine the relationship between serum calcium levels and cardiovascular mortality in patients undergoing maintenance hemodialysis or hemodiafiltration.
- To specifically assess this association in patients using calcimimetics, including cinacalcet.
- To determine if hypocalcemia, particularly transiently induced, poses a risk for cardiovascular death.
Main Methods:
- A 9-year prospective cohort study utilizing a nationwide Japanese registry for dialysis patients, with baseline data from end-2009.
- Inclusion criteria encompassed patients on maintenance hemodialysis or hemodiafiltration.
- Cox proportional hazard regression analyses were performed using baseline, time-dependent, and time-averaged models.
Main Results:
- Cinacalcet was used by 12.7% of the 180,136 patients in the cohort.
- In the time-dependent model, the lowest calcium decile (<8.4 mg/dL) was significantly associated with higher cardiovascular mortality in both cinacalcet users (HR 1.32) and the overall cohort (HR 1.15).
- Hypocalcemia was linked to increased risk of sudden death, hemorrhagic stroke, heart failure, and ischemic heart disease, irrespective of cinacalcet use.
Conclusions:
- Transient hypocalcemia is associated with an elevated risk of cardiovascular death, independent of cinacalcet therapy.
- Healthcare providers should be vigilant regarding hypocalcemia, even when transiently induced by calcimimetics like cinacalcet.
- Further attention to managing serum calcium levels in dialysis patients using calcimimetics is warranted to mitigate cardiovascular risks.
Background:
Calcimimetics are widely used in hemodialysis patients and influence serum calcium levels. Although the Kidney Disease: Improving Global Outcomes guidelines argued that low calcium levels induced by calcimimetics may be harmless, large observational studies investigating the association between hypocalcemia and mortality are scarce. We investigated the association between serum calcium levels and cardiovascular mortality in calcimimetics users using the nationwide Japanese registry for dialysis patients.
Methods:
In this 9-year prospective cohort study, the baseline data were collected at the end of 2009. We enrolled patients on maintenance hemodialysis or hemodiafiltration. We employed three models (baseline, time-dependent and time-averaged) to conduct Cox proportional hazard regression analyses.
Results:
Cinacalcet was prescribed to 12.7% (N = 22 853) at baseline. The median observation period was 98 (interquartile range 40-108) months and 108 (interquartile range 59-108) months in the whole cohort (N = 180 136) and in cinacalcet users, respectively. Three-quarters of survivors at the end of 2019 had continued calcimimetic therapy for 10 years, corresponding to a mean annual dropout rate of 2.9%. Hypocalcemia was not associated with cardiovascular mortality in the baseline or time-averaged model. In the time-dependent model, however, the lowest calcium decile (corrected calcium <8.4 mg/dL) was significantly associated with higher cardiovascular mortality than the reference (corrected calcium 8.7-8.9 mg/dL) in both cinacalcet users and all patients [hazard ratio (95% confidence interval) 1.32 (1.00, 1.75) and 1.15 (1.05, 1.26), respectively]. Hypocalcemia was especially associated with sudden death and death due to hemorrhagic stroke, heart failure and ischemic heart disease. Higher rate of fatal and non-fatal cardiovascular events was observed in hypocalcemic patients regardless of cinacalcet usage.
Conclusions:
Our findings suggest that transient hypocalcemia was associated with an increased risk of cardiovascular death independent of cinacalcet usage. We should pay attention to hypocalcemia transiently induced by cinacalcet.
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