#1096 Improving the diagnostic accuracy of absorptive hypercalciuria: a comparative analysis of calcium load tests at 2-hour and 4-hour intervals
Authors: Cabezas Lara , Letourneau Pierre , De Mul Aurelie , Chardon Laurence , Derain-Dubourg Laurence , Lemoine Sandrine 
Published: May 2024

Abstract

Background and Aims
A calcium load test (CLT) has been developed by Pak et al in 1974 to better discriminate absorptive, resorptive and renal hypercalciuria, leading to a tailored treatment approaches for patients. Originally, Calcium load was a 4-hours (4 h) test with a timepoint at 2-hours (2 h) defining an absorptive hypercalciuria (AH) by an increase of the difference between urinary calcium on creatininuria ratio (ΔUCa/Cr) of more than 0.5 mmol/mmol. In clinical practice and in more recent studies, CLT is only a 2 h test using this 0.5 or sometime 0.6 mmol/mmol cut-off. We hypothesized that a 2-hours timepoint is not sufficient to diagnose all AH and that the 4-hours timepoint as initially described is more efficient to improve accuracy of AH diagnosis.

Method
We report a single-centre, retrospective study including all patients who underwent CLT between January 2015 and September 2020. These tests were carried out in patients with hypercalciuria or in patients with elevated parathyroid hormone (PTH, standard 15-65 ng/L, Elecsys PTH) with normocalcemia, with or without kidney stones history. After a low-calcium diet for 3 days and a 12-hours fast, 24-hours urine were collected and blood and urinary samples were done at arrival. Two hours and 4 h after ingestion of one gram of calcium per os, blood and urinary samples were collected. AH was diagnosed by a ΔUCa/Cr at baseline and 2 h or 4 h timepoints of more than 0.5 mmol/mmol. We compared the number of AH diagnosed after 2 h and 4 h of testing using a 0.5 mmol/mmol delta at each timepoint. We also analysed clinical and biological profile of early and late AH.

Results
A total of 328 patients were included, 48 ± 14.8 years old, mean glomerular filtration rate of 92.8 ± 22.1 mL/min/1.73 m², 52.8% of women. At baseline, ionized calcemia (iCa2+) was 1.2 ± 0.1 mmol/L with a significant increase at 2 h (1.3 ± 0.1 mmol/L, p &lt; 0.001) and a stabilisation at 4 h (1.3 ± 0.1 mmol/L, p = ns). Simultaneously, PTH showed a significant drop between baseline and 2-hours (60 ± 26.1 ng/L versus 35.3 ± 19.7 ng/L, p &lt; 0.001) follows by a significant increase between 2 and 4 h (35.3 ± 19.7 ng/L versus 39.5 ± 21.4 ng/L, p &lt; 0.01). Mean 25-Hydroxyvitamin D and 1,25-Dihydroxyvitamin D3 were respectively 67.4 ± 24.7 ng/mL and 154.6 ± 54pg/mL. Baseline UCa/Cr ratio was 0.3 ± 0.2 mmol/mmol and increased significantly after 2 h (0.6 ± 0.3 mmol/mmol, p &lt; 0.001) and 4 h (0.8 ± 0.4 mmol/mmol, p &lt; 0.001) (Fig. 1a). ΔUCa/Cr was significantly different between baseline and 2 h and between baseline and 4 h (0.2 ± 0.2 versus 0.5 ± 0.4, p &lt; 0.001) (Fig. 1b). AH was diagnosed in 35 (10.7%) patients after 2 h, 84 (25.6%) more were diagnosed at 4 h (p &lt; 0.001) for a total of 119 (36.3%) AH diagnosed. Between early and late AH, we found no significant differences in 1,25-Dihydroxyvitamin D3, phosphatemia or phosphaturia, but 25-Hydroxyvitamin D which (67.3 ± 21 ng/mL in late AH versus 59.2 ± 18.3 ng/mL, p = 0.039). In comparison to the rest of the cohort, AH have a higher 1,25-Dihydroxyvitamin D3 level, a lower PTH at 2 h and 4 h, a lower phosphaturia at 2 h and 4 h and a higher magnesiuria at 4 h.

Conclusion
This study shows that performing the 4 h CLT improves the diagnosis of AH with more than fifty percent of AH diagnosed within 4 h of calcium ingestion. It seems that there are AH of later diagnosis with a similar clinical and biological profile depending of enteral absorption.