Should total calcium be adjusted for albumin? A retrospective observational study of laboratory data from central Norway

Abstract

ObjectivesAlbumin-adjusted total calcium is often used as a surrogate marker for free calcium to evaluate hypocalcaemia or hypercalcaemia. Many adjustment formulas based on simple linear regression models have been published, and continue to be used in spite of questionable diagnostic accuracy. In the hope of finding a more pure albumin effect on total calcium, we used multiple linear regression models to adjust for other relevant variables. The regression coefficients of albumin were used to construct local adjustment formulas, and we tested whether the diagnostic accuracy was improved compared with previously published formulas and unadjusted calcium.DesignA retrospective hospital laboratory data study.Data sourcesThe local hospital laboratory data system.SettingNorway, 2006–2015.Participants6549 patients above 2 years of age, where free calcium standardised at pH 7.40, total calcium, creatinine, albumin and phosphate had been analysed in a single blood draw, including hospitalised patients and patients from outpatient clinics and general practice.Main outcome measuresDiagnostic accuracy by Harrell’s c and receiver operating characteristic curve analysis, using free calcium standardised at pH 7.40 as a gold standard, in subgroups with estimated glomerular filtration rate (eGFR) ≥60 or <60 mL/min/1.73 m2.ResultsIn the subgroup with eGFR <60 mL/min/1.73 m2, the Harrell’s c of unadjusted total calcium (0.801) was significantly larger than those of the local formulas (0.790, p=0.002) and the best formula taken from literature (0.791, p=0.004). In the subgroup with eGFR ≥60 mL/min/1.73 m2, no significant differences were found between these three formulas.ConclusionsOur study shows that the diagnostic accuracy of unadjusted total calcium is superior to several commonly used adjustment formulas, and we suggest that the use of such formulas should be abandoned in clinical practice. If the clinician does not trust total calcium to reflect the calcium status of the patient, free calcium should be measured.

Prospective study comparing the outcome of a population-specific adjusted calcium equation to ionized calcium

“…On the contrary, another research group presented a similar concept but could not confirm that the addition of phosphate improved the adjusted calcium equation in renal failure patients. 27…”

Cinacalcet-induced hypocalcemia in a cohort of European haemodialysis patients: predictors, therapeutic approaches and outcomes

“…Second, our diagnosis of hypocalcemia was based on total rather than ionized serum calcium. While albumin-concentrations were available in 97% of the patients, albumin-corrected total calcium only correlates moderately with ionized serum calcium in advanced CKD [ 26 ] and others have concluded that uncorrected calcium is not inferior to corrected calcium in HD patients [ 15 , 16 ]. Third, whereas short-term adjustments of dialysate calcium might not have been captured in severely hypocalcemic patients, data shown in Table 6 provides little evidence for any systematic trend towards higher dialysate calcium in those with hypocalcemia which is similar to our observations in EVOLVE [ 11 ].…”

“…The main cohort for analysis was restricted to patients with normal uncorrected total serum calcium levels ≥ 2.1 mmol/L at time of cinacalcet initiation. In clinical practice, physicians use uncorrected or albumin-corrected calcium to evaluate hypocalcemia although data suggest that uncorrected is not inferior to corrected calcium [ 15 , 16 ]; therefore, sensitivity analyses were also carried out based with albumin-corrected calcium. Similar to previous studies, hypocalcemia was defined as mild (calcium 2.0− < 2.1 mmol/L), moderate (calcium 1.87− < 2.0 mmol/L), and severe (calcium < 1.87 mmol/L).…”

Plasma total calcium concentration is associated with blood pressure and systemic vascular resistance in normotensive and never-treated hypertensive subjects

“…Plasma total calcium concentration is influenced by the plasma albumin level. Numerous algorithms have been developed to allow correction of plasma total calcium concentration with the plasma albumin level, but their reliability remains questionable [54][55][56]. In the present study, we excluded participants with potential causes for abnormal plasma albumin concentration, like patients with renal disease, diabetes, liver disease, or any severe acute or chronic illness, and did not use albumin correction for the plasma total calcium values.…”