Metabolic and histologic investigation of the nature of nephrocalcinosis in children with hypophosphatemic rickets and in the Hyp mouse.
To investigate the biochemical nature of nephrocalcinosis in children with hypophosphatemic rickets treated with orally administered phosphate and vitamin D, we studied five such patients, aged 3.7 to 12.3 years, during treatment and again 3 days after it had been discontinued. Treatment was associated with significant increases in mean serum phosphate concentration and urine phosphate/creatinine ratio, from 0.71 to 1.03 mmol/L and from 3.61 to 9.42 mmol/mmol, respectively. Significant correlation was found between urine phosphate/creatinine and oxalate/creatinine ratios (r = 0.670; p less than 0.01); however, the mean urine oxalate/creatinine ratio of 65.0 mumol/mmol while patients were taking phosphate orally was not significantly different from the ratio of 59.0 mumol/mmol when treatment was discontinued. Kidney biopsy specimens from three of the patients showed that the renal calcifications were located mainly intratubularly and were composed exclusively of calcium phosphate. In a further investigation of the nature of phosphate-induced nephrocalcinosis, six 6-week-old male Hyp mice, the murine analog of the human disease, received oral phosphate therapy with drinking water for 48 days; six others served as control animals. Mice in the experimental group excreted more phosphate (p less than 0.001) and less calcium (p less than 0.01) than control mice did, and medullary nephrocalcinosis, with a high kidney calcium content, developed (p less than 0.001). Histologic sections showed that the renal calcifications were located intratubularly and were composed of calcium phosphate. We conclude that, both in children with hypophosphatemic rickets and in the Hyp mouse, the development of nephrocalcinosis is associated with high oral phosphate intake and subsequent deposition of calcium phosphate precipitates in the kidney.
Alon
U
U
Division of Pediatric Nephrology, Children's Mercy Hospital, University of Missouri, Kansas City 64108.
Donaldson
D L
DL
Hellerstein
S
S
Warady
B A
BA
Harris
D J
DJ
D000818:Animals; D002117:Calcitriol / Q000627:therapeutic use*; D002130:Calcium Phosphates / Q000032:analysis; D002648:Child; D005260:Female; D006801:Humans; D007015:Hypophosphatemia, Familial / Q000150:complications* / Q000188:drug therapy; D007668:Kidney / Q000737:chemistry*; D008297:Male; D051379:Mice; D008815:Mice, Inbred Strains; D009397:Nephrocalcinosis / Q000209:etiology* / Q000378:metabolism / Q000473:pathology; D010710:Phosphates / Q000627:therapeutic use*
D002130:Calcium Phosphates; D010710:Phosphates; C485828:alpha-tricalcium phosphate; C485830:tetracalcium phosphate; C485838:calcium phosphate, monobasic, anhydrous; C020243:calcium phosphate; D002117:Calcitriol; C485829:calcium phosphate, dibasic, anhydrous