Article of the Week


We will be posting commentaries on articles relating to internal medicine and endocrinology that we think are of interest.


October 15th, 2021

Adjusted calcium concentration as a predictor of ionized hypocalcemia in hypoalbuminemic dogs


Formulas to adjust tCa to correct for serum protein concentration have been evaluated in veterinary medicine. Previous studies have shown that, as albumin or total protein concentrations decrease, so does the tCa in a linear fashion. These adjustment formulas were not designed to predict iCa and a subsequent study showed that the use of these formulas to calculate adjusted calcium (aCa) by correcting serum tCa for the total protein or albumin concentration was unreliable surrogates for iCa. This may in part be because such studies consisted of a heterogeneous population, including many patients with renal disease and hyperphosphatemia, and the formulas used do not take into account the complexed fraction of calcium, but assume that iCa and serum albumin concentrations are the sole determinants of tCa concentration.


Although formulas to adjust calcium concentrations are not helpful when applied to a general population, they still might be helpful in patients with hypoalbuminemia. 


Formulas to adjust tCa for decreased albumin (or total protein) concentration are useful to determine if the decrease in tCa is due to changes in serum albumin concentration, but they are not designed for and do not predict the concentration of iCa in the general population. However, perhaps the formulas could be used to predict the presence or absence of decreased iCa in a specific clinical situation in which patients have hypoalbuminemia but not hyperphosphatemia, where the assumption that iCa and serum albumin concentration as the primary determinants of Ca concentration is more valid. 


An important clinical scenario associated with ionized hypocalcemia is patients with protein-losing enteropathies (PLEs).  Hypoalbuminemia and ionized hypocalcemia are common in these patients, but derangements in serum phosphorus concentration are less common. The confounding effect of hypoalbuminemia on the accurate assessment of calcium status is important in dogs with chronic enteropathies, because they have lower serum concentrations of 25-hydroxyvitamin D and it is associated with a negative outcome. Failure to accurately assess ionized calcium homeostasis in such patients might result in suboptimal management of acute or chronic ionized hypocalcemia and additional tools to identify patients at risk for complications of ionized hypocalcemia could be useful to veterinary practitioners who are not able to immediately measure iCa.


Our aim was to determine whether aCa could be predictive of the presence or absence of ionized hypocalcemia in a population of hypoalbuminemic dogs without hyperphosphatemia. Our hypothesis was that aCa could be a clinically useful predictor of ionized hypocalcemia

in hypoalbuminemic, nonhyperphosphatemic dogs.


Background: Ionized calcium (iCa) is the biologically active fraction of total calcium (tCa) with clinical relevance to evaluate calcium homeostasis, but not all primary veterinarians have access to serum iCa. Formulas that adjust tCa to correct for variability in serum protein concentrations were not designed to predict iCa and are considered unreliable surrogates for iCa.


Objectives: To determine whether adjusted calcium concentration (aCa) can predict ionized hypocalcemia in hypoalbuminemic dogs without hyperphosphatemia.


Animals: A total of 262 hypoalbuminemic dogs without hyperphosphatemia.


Methods: Retrospective review of paired tCa and iCa. Patients were included if serum albumin concentration was ≤2.5 g/L and serum phosphorus concentration was ≤5 mg/dL. The aCa was calculated using tCa (mg/dL) serum albumin concentration (g/dL) + 3.5 (g/dL). Sensitivity, specificity, positive (PPVs) and negative (NPVs) predictive values, and accuracy were determined for tCa and aCa at predicting any (<1.13 mmol/L) and moderate (<1.02 mmol/L) ionized hypocalcemia. Patients also were stratified into mild-to-moderate (2.0-2.5 g/dL) and severe hypoalbuminemia (<2.0 g/dL).


Results: A total of 4296 dogs had paired results of which 262 met the inclusion criteria. Of these, 35 (13.4%) dogs had iCa < 1.13 mmol/L and 13 dogs (5.0%) had concentrations <1.02 mmol/L. The sensitivity, specificity, NPVs and PPVs of a decreased tCa and aCa for detecting moderate ionized hypocalcemia were 100% and 92.3%, 57.8% and 94.8%, 100% and 99.6%, and 11.0% and 48.2%, respectively, and accuracy was 60.0% and 94.7%, respectively.


Conclusions: A low aCa was useful to detect ionized hypocalcemia in hypoalbuminemic