A Novel Method for the Evaluation of Hypercalciuria in Individuals With Chronic Hypoparathyroidism

Guidelines recommend avoiding hypercalciuria during treatment of chronic hypoparathyroidism, but measurements of 24-hour calcium excretion (24-hour urine calcium [24uCa]) have limitations. We evaluated calcium excretion per volume of filtrate (E_Ca/C_cr), which does not require timed collections, as an alternative to 24uCa to detect hypercalciuria.

This was a post-hoc analysis of the PaTH Forward trial (NCT04009291). Fifty-nine adults with chronic hypoparathyroidism managed with conventional therapy were enrolled in a randomized, double-blind, placebo-controlled 4-week period followed by an open-label extension (OLE), in which all participants received palopegteriparatide (TransConPTH). E_Ca/C_cr was calculated as (Ca_u×cr_s)/cr_u from morning non-fasting samples (Ca_u-urine calcium, cr_u-urine creatinine, and cr_s-serum creatinine). The diagnostic accuracy of E_Ca/C_cr was assessed using receiver operating characteristic analysis.

Median (interquartile range) 24uCa was 381 (296-602) mg/d at baseline and declined by 61% to 72% during OLE. Mean (SD) E_Ca/C_cr was 0.249 (0.131) mg/dL at baseline and fell by 47% to 62% during OLE. Area under the curve for E_Ca/C_cr as a test for hypercalciuria (24uCa >300 mg/d) was 0.837. Hypercalciuria was invariably absent at E_Ca/C_cr <0.083 mg/dL and almost uniformly present at E_Ca/C_cr > 0.212 mg/dL. Positive predictive value of E_Ca/C_cr ≥ 0.149 mg/dL was ≥92% when pretest probability of hypercalciuria was high. Negative predictive value of E_Ca/C_cr was ≥97% at all cutoffs when pretest probability was low.

E_Ca/C_cr correlates with 24uCa in patients with chronic hypoparathyroidism. The lowest E_Ca/C_cr cutoff values ensure that hypercalciuria is not missed. Sufficiently high E_Ca/C_cr supports presence of hypercalciuria. In these scenarios, 24uCa collections can be avoided. Intermediate E_Ca/C_cr must be followed by 24uCa.