Idiopathic infantile hypercalcemia in children with chronic kidney disease due to kidney hypodysplasia

Background Idiopathic infantile hypercalcemia (IIH) etiologies include pathogenic variants in CYP24A1, leading to increased 1,25(OH)(2) D, hypercalciuria and suppressed parathyroid hormone (PTH), and in SLC34A1 and SLC34A3, leading to the same metabolic profile via increased phosphaturia. IIH has not been previously described in CKD due to kidney hypodysplasia (KHD). Methods Retrospective study of children with bilateral KHD and simultaneously tested PTH and 1,25(OH)(2)D, followed in a tertiary care center between 2015 and 2021. Results Of 295 screened patients, 139 had KHD, of them 16 (11.5%) had IIH (study group), 26 with normal PTH and any 1,25(OH)(2)D were controls. There were no differences between groups' gender, obstructive uropathy rate and baseline eGFR. Study patients were younger [median (IQR) age: 5.2 (3.2-11.3) vs. 61 (13.9-158.3) months, p < 0.001], had higher 1,25(OH)(2)D (259.1 +/- 91.7 vs. 156.5 +/- 46.4 pmol/l, p < 0.001), total calcium (11.1 +/- 0.4 vs. 10.7 +/- 0.3 mg/dl, p < 0.001), and lower phosphate standard deviation score (P-SDS) [median (IQR): - 1.4 (- 1.9, - 0.4) vs. - 0.3 (- 0.8, - 0.1), p = 0.03]. During 12 months of follow-up, PTH increased among the study group (8.8 +/- 2.8 to 22.7 +/- 12.4 pg/ml, p < 0.001), calcium decreased (11 +/- 0.5 to 10.3 +/- 0.6 mg/dl, p = 0.004), 1,25(OH)(2)D decreased (259.5 +/- 91.7 to 188.2 +/- 42.6 pmol/l, p = 0.1), P-SDS increased [median (IQR): - 1.4 (- 1.9, - 0.4) vs. - 0.3 (- 0.9, 0.4), p = 0.04], while eGFR increased. Five of 9 study group patients with available urine calcium had hypercalciuria. Five patients had nephrocalcinosis/lithiasis. Genetic analysis for pathogenic variants in CYP24A1, SLC34A1 and SLC34A3 had not been performed. Conclusions Transient IIH was observed in infants with KHD, in association with hypophosphatemia, resembling SLC34A1 and SLC34A3 pathogenic variants' metabolic profile.