0021-972X/78/4701-0138$02.00/0 Journal of Clinical Endocrinology and Metabolism Copyright © 1978 by The Endocrine Society
Vol. 47, No. 1 Printed in U.S.A.
Effect of Oral Glucose Ingestion on Renal Phosphate Reabsorption and Clearance in Vitamin D-Resistant Rickets* DANIEL T. BARAN, THEODORE J. HAHN, AND LOUIS V. AVIOLI Department of Medicine, Washington University School of Medicine, The Jewish Hospital of St. Louis, St. Louis, Missouri 63178 ABSTRACT. The effect of oral glucose ingestion on renal phosphate reabsorption was studied in 13 patients with the inherited form of vitamin D-resistant rickets (VDRR) and 5 normal subjects. In contrast to the normal subjects, glycosuria developed in six VDRR patients after glucose ingestion and resulted in a further 43% decrease in renal phosphate reabsorption. This was
phosphate reabsorption was less and baseline phosphate clearance was greater in those VDRR subjects who developed glycosuria. The accumulated data suggest that excessive glucose ingestion by some patients with VDRR may add an additional insult to the phosphaturia characteristic of this disorder. This, in turn, would further compromise the response of circulating phosphate to therapeutic attempts at oral phosphate supplementation, thereby reducing the efficacy of oral phosphate therapy on skeletal growth and development in this disorder. (J Clin Endocrinol Metab 47: 138, 1978)
accompanied by a 33% increase in phosphate clearance.
This was not attended by differences in fasting glucose or phosphorus levels between groups, or in their respective values 1 h after glucose ingestion. Baseline renal
V
ITAMIN D-resistant rickets or osteomalacia (VDRR) is a disorder characterized by hypophosphatemia, increased renal clearance of phosphate, decreased intestinal absorption of calcium and phosphate, and skeletal lesions which are resistant to physiological replacement doses of vitamin D (1-3). The nature of the increased phosphate clearance in VDRR is not well understood. The renal phosphate wasting has been variously reported to be secondary to: 1) loss of a parathyroid hormone (PTH)-independent component of renal phosphate transport with normal responsiveness to elevated serum PTH levels (4, 5); 2) an exaggerated phosphaturic response to PTH (6); or 3) loss of a PTH-sensitive component of renal phosphate transport (7). Renal phosphate wasting has been shown to be independent of PTH in the mutant hypophosphatemic mouse model of VDRR (8). Pending further elucidation of this renal defect in phosphate handling in VDRR, successReceived November 7,1977. Address requests for repints to: Dr. Daniel T. Baran, Department of Medicine, Washington University School of Medicine, The Jewish Hospital of St. Louis, P.O. Box 14109, St. Louis, Missouri 63178. * This work was supported in part by NIH Grants AM11674, AM-07033, and AM-20521.
ful therapy depends upon correction of the hypophosphatemia by treatment with oral phosphorus plus supplemental vitamin D (3, 9-13) and by minimizing renal phosphate loss. It has been known for some time that glucose can alter renal phosphate handling, suggesting that glucose and phosphate either share a common transport mechanism or a common energy source. Furthermore, mild glycosuria has been previously reported to occur in some patients with VDRR (14). Pitts and Alexander demonstrated in the dog that the maximum ability to reabsorb phosphate was reduced when the reabsorption of glucose was increased by the induction of hyperglycemia (15). In normal subjects, the tubular reabsorption of phosphate was depressed when glucose was given iv to measure maximal glucose reabsorption (16-17). Intravenous glucose infusion has been demonstrated to both increase (18-19) and to have no effect (20) on the clearance of phosphate in VDRR, but the presence or absence of glycosuria was not commented upon in these studies. Although oral glucose tolerance tests in patients with VDRR have been reported to be normal, no mention was made of their effect on phosphate clearance (20).
138
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GLYCOSURIA IN VITAMIN D-RESISTANT RICKETS (,
Recent studies indicate that hypophosphatemia is associated with decreased tubular reabsorption of glucose in the dog (21). Based upon these observations, we postulated that the hypophosphatemia of patients with VDRR would result in glycosuria which could enhance renal phosphate wasting. Data herein reported are consistent with the hypothesis * that oral ingestion of carbohydrate by some patients with VDRR results in glycosuria at relatively low serum levels of blood glucose with resulting decreases in tubular reabsorp
Vol. 47, No. 1 Printed in U.S.A.
Effect of Oral Glucose Ingestion on Renal Phosphate Reabsorption and Clearance in Vitamin D-Resistant Rickets* DANIEL T. BARAN, THEODORE J. HAHN, AND LOUIS V. AVIOLI Department of Medicine, Washington University School of Medicine, The Jewish Hospital of St. Louis, St. Louis, Missouri 63178 ABSTRACT. The effect of oral glucose ingestion on renal phosphate reabsorption was studied in 13 patients with the inherited form of vitamin D-resistant rickets (VDRR) and 5 normal subjects. In contrast to the normal subjects, glycosuria developed in six VDRR patients after glucose ingestion and resulted in a further 43% decrease in renal phosphate reabsorption. This was
phosphate reabsorption was less and baseline phosphate clearance was greater in those VDRR subjects who developed glycosuria. The accumulated data suggest that excessive glucose ingestion by some patients with VDRR may add an additional insult to the phosphaturia characteristic of this disorder. This, in turn, would further compromise the response of circulating phosphate to therapeutic attempts at oral phosphate supplementation, thereby reducing the efficacy of oral phosphate therapy on skeletal growth and development in this disorder. (J Clin Endocrinol Metab 47: 138, 1978)
accompanied by a 33% increase in phosphate clearance.
This was not attended by differences in fasting glucose or phosphorus levels between groups, or in their respective values 1 h after glucose ingestion. Baseline renal
V
ITAMIN D-resistant rickets or osteomalacia (VDRR) is a disorder characterized by hypophosphatemia, increased renal clearance of phosphate, decreased intestinal absorption of calcium and phosphate, and skeletal lesions which are resistant to physiological replacement doses of vitamin D (1-3). The nature of the increased phosphate clearance in VDRR is not well understood. The renal phosphate wasting has been variously reported to be secondary to: 1) loss of a parathyroid hormone (PTH)-independent component of renal phosphate transport with normal responsiveness to elevated serum PTH levels (4, 5); 2) an exaggerated phosphaturic response to PTH (6); or 3) loss of a PTH-sensitive component of renal phosphate transport (7). Renal phosphate wasting has been shown to be independent of PTH in the mutant hypophosphatemic mouse model of VDRR (8). Pending further elucidation of this renal defect in phosphate handling in VDRR, successReceived November 7,1977. Address requests for repints to: Dr. Daniel T. Baran, Department of Medicine, Washington University School of Medicine, The Jewish Hospital of St. Louis, P.O. Box 14109, St. Louis, Missouri 63178. * This work was supported in part by NIH Grants AM11674, AM-07033, and AM-20521.
ful therapy depends upon correction of the hypophosphatemia by treatment with oral phosphorus plus supplemental vitamin D (3, 9-13) and by minimizing renal phosphate loss. It has been known for some time that glucose can alter renal phosphate handling, suggesting that glucose and phosphate either share a common transport mechanism or a common energy source. Furthermore, mild glycosuria has been previously reported to occur in some patients with VDRR (14). Pitts and Alexander demonstrated in the dog that the maximum ability to reabsorb phosphate was reduced when the reabsorption of glucose was increased by the induction of hyperglycemia (15). In normal subjects, the tubular reabsorption of phosphate was depressed when glucose was given iv to measure maximal glucose reabsorption (16-17). Intravenous glucose infusion has been demonstrated to both increase (18-19) and to have no effect (20) on the clearance of phosphate in VDRR, but the presence or absence of glycosuria was not commented upon in these studies. Although oral glucose tolerance tests in patients with VDRR have been reported to be normal, no mention was made of their effect on phosphate clearance (20).
138
The Endocrine Society. Downloaded from press.endocrine.org by [${individualUser.displayName}] on 20 November 2015. at 07:10 For personal use only. No other uses without permission. . All rights reserved.
GLYCOSURIA IN VITAMIN D-RESISTANT RICKETS (,
Recent studies indicate that hypophosphatemia is associated with decreased tubular reabsorption of glucose in the dog (21). Based upon these observations, we postulated that the hypophosphatemia of patients with VDRR would result in glycosuria which could enhance renal phosphate wasting. Data herein reported are consistent with the hypothesis * that oral ingestion of carbohydrate by some patients with VDRR results in glycosuria at relatively low serum levels of blood glucose with resulting decreases in tubular reabsorp
