Vitamin D Deficiency Rickets: Renal Handling of Phosphate and Free Amino Acids

Abstract

ExtractHypophosphatemia, hyperphosphatasemia, and phosphate diabetes in vitamin D deficiency rickets are considered to be due to secondary hyperparathyroidism. It is still questionable whether hyperaminoaciduria in rickets also may be due to hyperparathyroidism. In an attempt to clarify the pathomechanism of tubular transport of phosphate and free amino acids in humans with rickets, clearance studies were performed in three infants (3.5-5 months of age) with mild rickets and in six infants (21 -25 months of age) with severe rickets. In three of the six with severe rickets clearance studies were repeated after 58, 70, and 111 days, respectively, of treatment with vitamin D. Glomerular filtration rate was estimated by use of inulin. Free amino acids in serum and urine were determined by ion exchange column chromatography. It was considered essential to use age-matched control values for comparison.Infants with mild and severe rickets had significantly lowered values of serum phosphate, elevated values for phosphate clearance, and a decrease in percentage tubular reabsorption of phosphate. Comparison of both groups revealed that there were no quantitative differences in the degree of disturbed phosphate metabolism between mildly and severely affected infants if the data of each group were related to agematched control values. The glomerular filtration rate was normal or elevated in both groups, with higher values in the group suffering from severe rickets.Concentrations of free amino acids in serum of infants with rickets were not significantly different from those found in normal subjects. Endogenous clearance rates and excretion levels of amino acids into urine were significantly higher than normal values in both groups. The percentage tubular reabsorption was correspondingly lower. The degree of hyperaminoaciduria was much higher in infants with severe rickets than in those with mild rickets when related to age-matched controls.Individual amino acids show great differences of involvement in vitamin D deficiency rickets; there were, however, no differences found between mild and severe rickets in this respect. The transport of the following amino acids was most severely involved: threonine, serine, glycine, cystine, tyrosine, lysine, and histidine. Some amino acids are either not involved or only to a slight degree: valine, isoleucine, leucine, ornithine, and arginine. The actual values of percentage tubular reabsorption were almost the same in the young and older infants with rickets, which demonstrates the influence of age on the degree of hyperaminoaciduria.There was no correlation evident between urinary excretion rates of free amino acids and hypophosphatemia, between the ratio of amino acid clearance to inulin clearance (C AA /C In ) and the serum phosphate level, and between C AA /Ci n and the ratio of phosphate clearance to inulin clearance (C P /C In ). The only significant correlation found was between inulin clearance and amino acid clearance. Clearance studies were repeated in three infants with sever...