Nephrocalcinosis in X-linked hypophosphatemia: effect of treatment versus disease

While the literature has suggested that vitamin D and phosphate therapy benefits children, and possibly adults, with X-linked hypophosphatemia (XLH), there have been increasing reports of nephrocalcinosis by renal ultrasound examination in treated patients. Although it has been assumed that nephrocalcinosis is the result of treatment, there has been no systematic comparison of treated and untreated XLH patients with long-term follow-up. Therefore, we studied 10 adults and 4 children by renal ultrasound examination with no history of medical therapy and 10 adults and 8 children with a history of medical therapy. None of the untreated patients had nephrocalcinosis; 5 treated adults and 5 treated children had nephrocalcinosis. In 3 of 4 treated children, serial renal ultrasounds did not show progression of the nephrocalcinosis. One patient progressed from baseline to year 1 only. Comparisons of means between treated patients without and with nephrocalcinosis showed statistically significant differences for urine calcium/creatinine ratios and urine phosphorus/creatinine ratios, differences not seen between untreated patients and treated patients without nephrocalcinosis. Phosphate dose, but not vitamin D dose, was statistically significantly different between the two treated groups. Our studies point to a convincing role for the association between nephrocalcinosis, as diagnosed by renal ultrasound examination, and medical therapy.