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Hidden Hypocalcemia as a Risk Factor for Cardiovascular Events and All-Cause Mortality among Patients Undergoing
Satoshi Yamaguchi1, Takayuki Hamano2,3, Yohei Doi1
1Department of Nephrology, Osaka University Graduate School of Medicine, Suita, Japan.
Insights
True hypocalcemia, indicated by low ionized calcium (iCa), is a significant risk factor for death and cardiovascular events in dialysis patients. Hidden hypocalcemia, where iCa is low but corrected calcium (cCa) is normal, poses a greater risk than apparent hypocalcemia.
Area of Science:
- Nephrology
- Clinical Chemistry
- Cardiovascular Medicine
Background:
- Lower corrected calcium (cCa) levels correlate with better prognosis in incident dialysis patients.
- Corrected calcium (cCa) may overestimate true calcium status, as ionized calcium (iCa) is the biologically active form.
- The prognostic significance of iCa in dialysis patients is not well-established.
Purpose of the Study:
- To investigate the prognostic importance of true calcium status, defined by iCa, in incident hemodialysis patients.
- To differentiate between apparent and hidden hypocalcemia and their respective associations with clinical outcomes.
Main Methods:
- Retrospective cohort study of 332 incident hemodialysis patients.
- Collected iCa levels immediately before the first dialysis.
- Categorized patients into apparent hypocalcemia, hidden hypocalcemia, and normocalcemia based on iCa and cCa levels.
- Primary outcome: composite of all-cause death and cardiovascular diseases.
Main Results:
- 75% of patients exhibited true hypocalcemia (iCa <1.15 mmol/L), with 61% of these having hidden hypocalcemia.
- True hypocalcemia was a significant risk factor (HR 2.34), while hypocalcemia defined by cCa was not.
- Hidden hypocalcemia significantly increased the risk of adverse outcomes (HR 2.56) compared to normocalcemia, unlike apparent hypocalcemia.
- Patients with hidden hypocalcemia received fewer interventions to correct calcium levels.
Conclusions:
- True hypocalcemia, particularly hidden hypocalcemia, is a strong predictor of mortality and cardiovascular events in incident dialysis patients.
- Measuring iCa is crucial for accurately assessing calcium status and prognosis in this population.
- Hidden hypocalcemia may be under-treated, contributing to worse outcomes.
Abstract:
Lower corrected calcium (cCa) levels are associated with a better prognosis among incident dialysis patients. However, cCa frequently overestimates ionized calcium (iCa) levels. The prognostic importance of the true calcium status defined by iCa remains to be revealed. We conducted a retrospective cohort study of incident hemodialysis patients. We collected data of iCa levels immediately before the first dialysis. We divided patients into three categories: apparent hypocalcemia (low iCa; <1.15 mmol/L and low cCa; <8.4 mg/dL), hidden hypocalcemia (low iCa despite normal or high cCa), and normocalcemia (normal iCa). The primary outcome was the composite of all-cause death and cardiovascular diseases after hospital discharge. Among the enrolled 332 patients, 75% of the patients showed true hypocalcemia, defined as iCa <1.15 mmol/L, 61% of whom showed hidden hypocalcemia. In multivariate Cox models including other potential risk factors, true hypocalcemia was a significant risk factor (hazard ratio [HR], 2.34; 95% confidence interval [CI], 1.03-5.34), whereas hypocalcemia defined as corrected calcium <8.4 mg/dL was not. Furthermore, hidden hypocalcemia was significantly associated with an increased risk of the outcome compared with normocalcemia (HR, 2.56; 95% CI, 1.11-5.94), while apparent hypocalcemia was not. Patients with hidden hypocalcemia were less likely to receive interventions to correct hypocalcemia, such as increased doses of active vitamin D or administration of calcium carbonate, than patients with apparent hypocalcemia (odds ratio, 0.45; 95% CI, 0.23-0.89). Hidden hypocalcemia was a strong predictor of death and cardiovascular events, suggesting the importance of measuring iCa.
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