Dr. Yoshitsugu Obi (YO), from the University of California, Irvine in Orange, California, discusses his abstract for the National Kidney Foundation’s 2016 Spring Clinical Meetings (SCM16), Hidden Hypercalcemia and Mortality in Incident Hemodialysis Patients, with Dr. Kenar Jhaveri, AJKD Blog Editor.

AJKDblog: Why don’t you tell us a little about your research and abstract being presented at the NKF 2016 Spring Meetings?

YO: There is cumulative evidence that neither uncorrected nor albumin-corrected total calcium reliably predict ionized calcium in patients with end-stage renal disease. Although clinical practice guidelines support ionized calcium measurement as the preferred method to evaluate calcium status in patients with advanced kidney diseases, total calcium is typically measured in clinical practice in lieu of ionized calcium, given its lower cost and the less time and effort needed for measurement. However, little is known about the consequences of inaccurate assessment of calcium concentration using total calcium. We hypothesized that hidden hypercalcemia (i.e., elevated ionized calcium with normal total calcium) and apparent hypercalcemia (i.e., elevated ionized calcium with elevated total calcium) are both associated with increased mortality risk.

We identified 869 incident hemodialysis patients with measured serum ionized calcium, total calcium, albumin, phosphorus, intact parathyroid hormone, and bicarbonate using data from a large dialysis organization in the United States. There was only fair inter-index agreement with calcium status between ionized calcium and uncorrected or corrected total calcium (κ=0.32 and 0.27, respectively). Among patients with high ionized calcium (>1.32 mmol/L), 88% and 70% patients were incorrectly categorized as being normocalcemic using uncorrected and corrected total calcium, respectively, and were thus considered to have “hidden hypercalcemia.” Compared to patients with normocalcemia (ionized calcium, 1.16–1.32 mmol/L), those with hidden hypercalcemia by uncorrected and corrected total calcium also had a higher risk for death (adjusted HR, 1.71 [95% CI, 1.08–2.70] and 1.75 [95% CI, 1.07–2.86], respectively). We conclude that hidden hypercalcemia is common in incident hemodialysis patients and associated with higher mortality risk in this population.

AJKDblog: What you speculate is the cause of this hidden hypercalcemia?

YO:  Our preliminary analyses suggest that the risk factors for underestimating calcium status by the conventional equation include high total serum calcium, high serum albumin, low serum phosphorus, and low serum bicarbonate. The coefficient 0.8 for serum albumin in the conventional equation may be higher than the actual value in hemodialysis patients, which is in line with some previous reports. Acidosis decreases the affinity of serum albumin for calcium. In addition to albumin, serum phosphorus also binds to calcium and lowers the proportion of ionized calcium to some extent. Ionized calcium measurement should be considered in patients with such characteristics.

AJKDblog: Where do you and your group go from here?

YO: Our study demonstrated inadequate performance of the conventional correction equation for total serum calcium, which may increase the mortality risk among patients with hidden hypercalcemia. Given the high cost of ionized calcium measurement together with limited medical resources, we are trying to develop a new correction equation that predicts ionized calcium status more precisely and contributes to better risk stratification among hemodialysis patients.

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All Spring Clinical Meeting abstracts are available in the May issue of AJKD.

Check out more AJKDblog coverage of the NKF’s 2016 Spring Clinical Meetings (#SCM16)!