Endocrine Abstracts

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Background: Current guidelines recommend avoiding hypercalciuria to minimize the risk of renal complications during treatment of chronic hypoparathyroidism. Measurement of 24-hour urine calcium (24uCa) is the gold standard for diagnosing hypercalciuria; however, this method is inconvenient and susceptible to error. As an alternative, we evaluated calcium excretion per volume of filtrate (E_Ca/C_cr), which is calculated from measurements in simultaneous aliquots of serum and urine and does not require a timed urine collection.

Methods: This was a post-hoc analysis of the PaTH Forward trial (NCT04009291) of palopegteriparatide, in which 59 adults with chronic hypoparathyroidism were enrolled in a phase 2, randomized, double-blind, placebo-controlled 4-week trial followed by an ongoing open-label extension with palopegteriparatide. E_Ca/C_cr was calculated as Ca_u*cr_s/cr_u, where, Ca_u is urine calcium concentration, and cr_u and cr_s are urine and serum creatinine concentrations measured from simultaneous morning non-fasting samples. A 24-hr urine collection was performed 1-7 days (median 3 days) prior to E_Ca/C_cr. Paired 24uCa and E_Ca/C_cr evaluations were matched by visit. Hypercalciuria was defined as 24uCa >300mg/day. Linear associations between E_Ca/C_cr and 24uCa were evaluated with the Pearson correlation (PC) method. Receiver operating characteristic (ROC) analysis was used to assess the diagnostic accuracy of E_Ca/C_cr in detection of hypercalciuria.

Results: There were 247 paired E_Ca/C_cr and 24uCa measurements collected through the 110-week follow-up, including 50 baseline measurements prior to palopegteriparatide initiation. At baseline, median (IQR) 24uCa was 381 (296-602) mg and 72% of individuals had hypercalciuria. Median 24uCa excretion declined to 149, 125, 108, and 150 mg/day during 26, 58, 84, and 110 weeks of open-label period. Baseline mean (SD) E_Ca/C_cr was 0. 25 (0. 13) mg/dL; it fell to 0. 13, 0. 10, 0. 10 and 0. 10 mg/dL during the same time points. E_Ca/C_cr strongly correlated with 24uCa (PC coefficient 0. 61, P < 0. 001). E_Ca/C_cr ≥0. 149 mg/dL had 76% sensitivity, 85% specificity, and 84% accuracy for detecting 24uCa>300mg/day (AUC 0. 837). E_Ca/C_cr of <0. 08 and >0. 21 mg/dL virtually excluded the presence and absence of hypercalciuria.

Conclusions: These results show that E_Ca/C_cr correlates with 24uCa in people with chronic hypoparathyroidism. Given the convenience and the accuracy of E_Ca/C_cr as compared with 24uCa, these findings suggest that E_Ca/C_cr may be useful for the detection of hypercalciuria in individuals treated for chronic hypoparathyroidism.