Total & Ionized Hypercalcemia in Cats with Chronic Kidney Disease

Reported prevalence of hypercalcemia in cats with chronic kidney disease (CKD) is highly variable; 13% to 76% of cats with azotemic (ie, International Renal Interest Society [IRIS] stage 2, 3, or 4) CKD have ionized hypercalcemia.^1,2 Total calcium is poorly correlated with ionized calcium levels, particularly in patients with mild ionized hypercalcemia.^3,4  

This study* evaluated ionized and total hypercalcemia in 164 cats with azotemic CKD. At diagnosis, 20% of cats had ionized hypercalcemia and 4% had total hypercalcemia. Ionized hypercalcemia subsequently developed in 42 out of 96 (44%) cats that were normocalcemic at the time of CKD diagnosis. In total, 45.7% of cats had ≥1 instance of hypercalcemia, with transient hypercalcemia noted in 16.7% of cats. Total hypercalcemia was identified in 32% of cats with persistent ionized hypercalcemia. Male cats and cats with higher potassium, higher total calcium, and lower parathyroid hormone concentrations were more likely to have ionized hypercalcemia. 

IRIS stage was not associated with development of ionized hypercalcemia, and severity of ionized hypercalcemia in the study population was generally mild (median, 1.42 mmol/L), which may help exclude non-CKD causes (eg, malignancy) of ionized hypercalcemia in which moderate to marked hypercalcemia is more common.^5,6 Parathyroid hormone concentrations did not have a predictable association with development or persistence of hypercalcemia, and feeding of a therapeutic renal diet did not impact development of ionized hypercalcemia.

Key pearls to put into practice:

Ionized hypercalcemia related to CKD is often mild and can be transient; not all cats with CKD have persistent elevations.

Ionized calcium is considered the physiologically important form of calcium and should be measured in patients at risk for ionized hypercalcemia. Evaluation of total serum calcium alone underestimates ionized hypercalcemia, as total serum calcium is often within the reference interval in patients with mild ionized hypercalcemia.

Neoplasia, idiopathic hypercalcemia, CKD, and parathyroid-dependent hypercalcemia are the most common causes (in descending order) of ionized hypercalcemia in cats and are the primary differentials to consider in cats with total or ionized hypercalcemia.⁵