Lieske, John C.

Key Points Fibroblast growth factor 23 and 24,25-dihydroxyvitamin D are positively correlated and are significantly lower in Dent disease than in idiopathic calcium kidney stones patients. Dent patients with low 24,25-dihydroxyvitamin D had greater hypercalciuria and proteinuria, and, among adults, higher 1,25-dihydroxyvitamin D concentrations. Moderate phosphate supplementation mitigates hypercalciuria. 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 with 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 (1 g/d×14 days) with reassessment immediately after 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 9 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-dihydroxyvitamin 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-dihydroxyvitamin 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. Clinical Trial registry name and registration number: ClinicalTrials.gov, NCT02016235.