Hidden Hypocalcemia as a Risk Factor for Cardiovascular Events and All-Cause Mortality among Patients Undergoing Incident Hemodialysis

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.

Misclassification of calcium status in end‐stage kidney disease using albumin‐adjusted calcium levels

“…This was true even for those with normal albumin levels (>38 g/L) where albumin‐adjustment was not required in the Dialysis Outcomes and Practice Pattern Study 28 . Recent literature has suggested that hidden hypocalcaemia (that is low ionized calcium, with normal albumin‐adjusted calcium) poses more significant risk than apparent hypocalcaemia (low ionized calcium with low albumin‐adjusted calcium) with increased risk of all‐cause and cardiovascular disease and events 15,29 . Those with hidden hypocalcaemia were less likely to receive interventions to correct hypocalcaemia, increase doses of vitamin D analogues or calcium, and presumably were less likely to have increased monitoring.…”

Cardiovascular risk factors in chronic renal failure patient at Soavinandriana Hospital Antananarivo

“…So, Yamaguchi suggested the importance of measuring ionized calcium. 29 Hyperuricemia is an independent risk factor for cardiovascular disease. 30 This abnormality in uric acid metabolism increases with the worsening of CKD.…”

Phosphate Balance and CKD–Mineral Bone Disease

“… 61 , 62 , 63 Hypocalcemia and low vitamin D (both 25-hydroxy vitamin D and 1,25-dihydroxy vitamin D) concentrations have been associated with increased risk of CVD. 64 , 65 Inhibition of calcitriol (1,25-dihydroxyvitamin D) production due to increased FGF23 66 , 67 is associated with increased cardiac contractility, 68 coronary artery calcification, 69 myocardial fibrosis, 70 and proinflammatory effect. 71 PTH increases the production of calcitriol (1,25-dihydroxyvitamin D), as well as increases bone resorption, which leads to increasing both serum calcium and phosphate concentrations.…”