James C.M. Chan

Renal hypophosphatemic rickets

Renal hyponhosphatemic rickets is a renal tubular disorder which has fascinated workers in the field for a long time (1–7). The condition is concurrently known as sex-linked dominant hypophosphatemic rickets, vitamin D resistant rickets and familial hypophosphatemia. Recent advances in phosphate metabolism, pathophysiology, and treatment will be reviewed here.

Effects of oral furosemide and salt loading on parathyroid function in normal subjects. Physiological basis for renal hypercalciuria.

With oral furosemide administration and salt loading, urinary calcium was significantly increased in 8 normal subjects, accompanied by parallel natriuresis. In spite of the excessive calcium loss in the urine, total and ionized serum calcium remained unchanged. All subjects had significant increases in nephrogenous cyclic AMP, suggesting that parathyroid activity is elevated in subjects with furosemide-induced hypercalciuria. With furosemide, fecal calcium was significantly decreased, and resultantly, there was no significant change in the cumulative calcium balance. It is suggested that urinary calcium loss with furosemide is compensated for by secondary hyperparathyroidism via increased intestinal calcium absorption in order to maintain serum calcium at a normal level. The experimental model thus mimics the condition of the renal type of idiopathic hypercalciuria.

Renal Osteodystrophy in Children Progress in Its Management

The original research of the investigator was supported in part by grants RR-00284 from the National Institutes of Health, Department of Health, Education, and Welfare; the Ruth and Arnold Orlean’s Kidney Research Funds. * Associate Professor of Child Health and Development, George Washington University School of Medicine; Chief, Department of Nephrology, Children’s Hospital National Medical Center. Washington. D.C. Presented at the Annual Meeting of the American Academy of Pediatrics, Washington, D.C., October 18-23, 1975. THE CLASSICAL RADIOLOGIC FEATURES of renal osteodystrophy, by conventional x-ray techniques, are shown in Figure I -demineralization of the forearm bones and a pathologic fracture of the left radius; subperiosteal resorption in the skeleton of the hands, demineralization of the phalanges with acroosteolysis of the terminal phalanx; severe demineralization of the pelvis and femurs. The hips show widened and ragged epiphyseal plates with bilateral slipped femoral epiphysis. Renal osteodystrophy may appear after several years of chronic uremia, but occasionally may be the presenting symptom.’ Renal diseases such as oligomegalonephrenia, nephronophthisis, and chronic pyelonephritis that are associated with a high incidence of renal osteodystrophy are perhaps related to damage affecting other parts of the kidney in addition to the

Control of Aldosterone Secretion

This paper reviews the control of aldosterone secretion, including the role played by hepatic metabolic clearance, ACTH, and the renin-angiotensin system, and the interrelationships of aldosterone sec

Urinary sulfate excretion in children with classic renal tubular acidosis.

These studies quantitat the significantly elevated sulfate excretion in the urine of children with classic renal tubular acidosis as compared to six weight-matched controls (1.4 +/-0.5 vs. 0.7 +/- 0.2 mEq/kg/day;p less than 0.05). This sulfate loss may result in a subclinical sulfate deficiency which may contribute to a chondroitin sulfate metabolic disorder.,and thus contribute to the growth failure in children with real tubular acidosis. Futhermore, elevated urinary sulfate excretion may be an early diagnostic finding in infancy prior to the manifestation of renal acidification defects. It is not known whether the sulfate loss is related to a primary renal tubular defect or secondary to metabolic acidosis, although the increased sulfate excretion persisting after correction of metabolic acidosis would tend to suggest a primary defect. However, the normal plasma sulfate concentration and the relatively short period of study permit no definitive answer at this time.

Hydrogen Ion Production Secondary to Metabolism of Sulfur-Amino Acids and Organic Acids

The rate of acid production in infants and young children was quoted to be 1-2 mEq/kg/day but in fact, the sole reference used in all these instances did not permit such quantitation. In order to evaluate the rate of endogenous acid production, we applied the quantitative technique of Lennon et al. in the following normal subjects, where column A represents hydrogen ion released from metabolism of sulfur-containing amion acids; column B represents hydrogen ion released from incomplete oxidation of organic acids; the sum A and B gives an estimation of endogenous net acid production (NAP).

Lack of Evidence for a Role for Prostaglandins in the Mediation of Impaired Urinary Concentrating Ability in Bartter’s Syndrome

Imparied urinary concentrating ability in Bartters syndrome may result in part from overproduction of prostaglandins and from the defect in chloride reabsorption by the loop of Henle, or both. To assess the role of prostaglandins, concentration of the urine before and after treatment with prostaglandin inhibitors was studied in 3 patients with this syndrome, taking a constant metabolic diet. Maximal urinary osmolality was determined after overnight fluid deprivation and during infusion of Pitressin. The studies were repeated after 4 days of treatment with the prostaglandin inhibitors, indomethacin and ibuprofen. The maximal urinary osmolality was 694 +/- 39 and 717 +/- 78 mosm/kg, and solute clearance was 1.3 +/- 0.3 and 1.2 +/- 0.5 ml/min for the control and treatment periods, respectively. Prostaglandin inhibitors failed to increase the maximal urinary osmolality or solute clearance. The data thus suggest that factors other than prostaglandin overproduction cause the impairment in urinary concentration in Bartters syndrome. The defective chloride transport with a loss of interstitial hyperosmolality may be one such factor.

Effect of Metabolic Acidosis and Alkalosis on the Renal Response to Parathyroid Hormone Infusion in Normal Man

Six normal volunteers were observed for 24 days on a constant metabolic diet in a study designed to test the hypothesis that the action of parathyroid hormone may be altered by renal acidosis.

Anorexia nervosa with Acute Tubular Necrosis Treated with Parenteral Nutrition

A patient with nonoliguric acute renal failure secondary to acute tubular necrosis in conjunction with anorexia nervosa is described. Parenteral feeding at a critical time has salutory effects on the biosynthesis of new protein and thereby reduces many of the hazards of azotemia. The technique of estimating endogenous acid production is applied for the first time in a severely malnourished subject and documents the retention of dietary sulfur which presumably is retained in the formation of new tissue in the recovery phase.

Nephrocalcinosis and Nephrolithiasis in Children

From the Section on Steroid and Mineral Metabolism, Hypertension-Endocrine Branch, National Heart Lung and Blood Institute; the Artificial Kidney/Chronic Uremia Section, National Institute of Arthritis Metabolism and Digestive Diseases, National Institutes of Health, Bethesda, Md. * Visiting Scientist, Section on Steroid and Mineral Metabolism, NHLBI, NIH, Bethesda, Md. t Staff physician, Artificial Kidney/Chronic Uremia Section, NIAMDD, NIH, Bethesda, Md. Correspondence to: James C. M. Chan, M.D., Bg 10 Rm8N214, National Institutes of Health, Bethesda, Md. 20014 CLINICAL DISORDER of calcium metabolism, nephrocalcinosis consists of calcium deposition in the renal tubular cells and the interstitium, with a predisposition to the renal medulla and the cortical medul-