The Significance of FGF23 and 24,25-Dihydroxyvitamin D in Dent Disease Type 1

Background: Hypercalciuria is a prominent characteristic in Dent disease type 1 (DD1) and is associated with kidney stones and nephrocalcinosis. The objectives of this study were to assess fibroblast growth factor 23 (FGF23) and 24,25-dihydroxyvitamin D (24,25(OH) 2 D) in DD1 patients and investigate the effects of phosphate supplementation on urinary calcium excretion. Methods: Serum and 24-hour urine assessments from adult and pediatric DD1 patients ( n =10 adults; n =9 pediatrics) were compared to adult control subjects with a history of idiopathic calcium kidney stones and hypercalciuria ( n =9). Adult DD1 patients and control participants completed an oral phosphate supplementation intervention (1g/day x 14 days) with reassessment immediately following intervention. Results: FGF23 was significantly lower in DD1 than in the control cohort (adults, p =0.006) and positively correlated with 24,25(OH) 2 D across all study cohorts. The concentrations of 24,25(OH) 2 D were low with conversion ratios (25-hydroxyvitamin D:24,25(OH) 2 D) exceeding the clinical reference limit for five of 10 adults and six of nine pediatric DD1 patients. The DD1 cohorts were then stratified by the 24,25(OH) 2 D ratio into “normal” and “low” 24,25(OH) 2 D. Adult DD1 patients with low 24,25(OH) 2 D (n=5) had lower FGF23, higher 1,25(OH) 2 D, greater urine calcium, and greater urine protein. Pediatric stratified data mirrored that in adults with the exception of no difference in serum 1,25(OH) 2 D. Phosphate supplementation was effective in decreasing urine calcium in both adult DD1 and control adult cohorts. Conclusions: Clinical measurement of 24,25(OH) 2 D is a novel and useful analysis for evaluating the severity of calcium and protein dysregulation in DD1. In addition, moderate phosphate supplementation effectively mitigates urine calcium excretion in DD1 adult patients.