Idiopathic Infantile Hypercalcemia-Like Phenotype in Infants with Renal Hypodysplasia

Background: Idiopathic infantile hypercalcemia (IIH) has been associated with mutations in CYP24A1 and SLC34A genes, which increase levels of 1,25 (OH)2 vitamin D, leading to mild hypercalcemia and suppressed PTH. IIH-like phenotype has not been previously described in the context of renal hypodysplasia (RHD), the most common etiology for CKD in childhood.

Methods: Retrospective study of children (age 0-18 years) with bilateral RHD and simultaneously tested PTH and 1,25(OH)2D, followed in a tertiary care center between 2015-2021.

Results: We screened 307 patients, 49 fulfilled inclusion criteria and were divided according to PTH, below (study group, n=18) or above 14 pg/dl (controls, n=31). Study and control groups [median (IQR) PTH: 9 (6.3-11) vs 39 (23.8-43) pg/dl, p=0.005] did not differ in their eGFR (65.2± 39 vs 68.4±34.2 ml/min/1.73m2, p=NS) or male proportion (89 Vs 64.5%, p=0.06), or obstructive uropathy rate (19 and 32%, p=NS). Study patients were younger at first detection of low PTH [median (IQR) age: 6.2 (3.8-15.7) Vs 83.5 (25.4-183.6) months, p <0.001]. Study patients had higher 1,25(OH)2D (245±115 vs 159.7±52.7 pmol/l, p<0.001), total Ca (11±0.5 vs 10±0.5 mg/dl, p<0.001) and P (5.3±0.7 vs 4.7±1 mg/dl, p=0.01) Vs controls. PTH increased in the study group at 6 and 12 months of follow up (8.9±2.7, 21.9±11.8 and 28.2±15.6 pg/dl respectively, p<0.001). Serum calcium (11±0.45 vs10.6±0.35 mg/dl , p=0.01) and 1,25(OH)2D (245.3±115 vs 179.9±59 pmol/l, p=0.18) decreased at 6 month follow up. eGFR remained stable along this period. Urine calcium levels were unavailable.

Conclusion: IIH-like phenotype may transiently happen in infants with RHD, but its pathophysiology remains to be elucidated.