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

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Abstract

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)2D, 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)2D 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)2D (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)2D 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.

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Acknowledgements

We thank Uri Alon, MD, for his critical review of the manuscript.

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Authors and Affiliations

  1. Department of Nephrology, Schneider Children’s Medical Center of Israel (SCMCI), 14 Kaplan St, Petach Tikva, 4920235, Israel

    Evgenia Gurevich, Yael Borovitz, Shelli Levi & Daniel Landau

  2. Department of Pediatrics, Barzilai Medical Center, Ashkelon, Ben Gurion University of the Negev, Beer Sheva, Israel

    Evgenia Gurevich

  3. Department of Obstetrics, Schneider Women’s Hospital, Petach Tikva, Israel

    Sharon Perlman

  4. Sackler School of Medicine, Tel Aviv University, Tel Aviv-Yafo, Israel

    Sharon Perlman & Daniel Landau

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  1. Evgenia Gurevich
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Correspondence to Daniel Landau.

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Gurevich, E., Borovitz, Y., Levi, S. et al. Idiopathic infantile hypercalcemia in children with chronic kidney disease due to kidney hypodysplasia. Pediatr Nephrol 38, 1067–1073 (2023). https://doi.org/10.1007/s00467-022-05740-w

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