Bone modulating factors in nephrotic children with normal glomerular filtration rate.

Factors influencing bone and mineral metabolism were evaluated in 16 children with active nephrotic syndrome and normal glomerular filtration rate. All patients were proteinuric and/or hypoalbuminemic and had elevated serum triglyceride and cholesterol levels. Seven patients had never received or had discontinued glucocorticoid treatment at least 6 months before the study; six patients were receiving prednisone at the time of study. Although all patients were hypocalcemic (serum total or ionized calcium), none was hypomagnesemic. Despite the low serum calcium levels, circulating immunoreactive parathyroid hormone was elevated in only nine of 16. Plasma 25-hydroxyvitamin D was low in all 16 patients, averaging 7.6 +/- 1.2 ng/mL for the group. In contrast, levels of 1,25-dihydroxyvitamin D were normal in 12 of 14 patients. Bone mineral content measured by photon absorptiometry averaged 83% and was less than 90% of normal in six of nine patients tested. The findings were not influenced by the recent or concurrent administration of glucocorticoid. The data demonstrate abnormalities of mineral and bone modulation in nephrotic children even in the absence of impaired glomerular filtration rate and irrespective of glucocorticoid therapy. The decrease in serum ionized calcium may be related to an absolute deficiency in 25-hydroxyvitamin D and/or a relative deficiency in 1,25-dihydroxyvitamin D. Undermineralization of bone may result from the low levels of vitamin D metabolites and, in some patients, from an increase in immunoreactive parathyroid hormone. Whether treatment with vitamin D metabolites and/or calcium supplementation will prevent the abnormalities remains to be demonstrated.

Plasma parathyroid hormone and divalent cation response to induction of acute metabolic acidosis.

Since the effect of acute administration of acid upon blood magnesium and parathyroid hormone (PTH) is unclear we infused anesthetized dogs with saline (controls), HCl, lactic, and methylmalonic acids for 3 h. In all groups but lactic acid, plasma magnesium decreased; ionized calcium levels were increased by all three acids. Nevertheless, PTH increased in each of six dogs following methylmalonic acid and decreased in four of six animals after lactic acid. The decrease in plasma magnesium concentration after methylmalonic acid appeared to be an important factor in explaining the disparate PTH changes in these two groups because concomitant magnesium administration obviated the increases in PTH in four of six additional methylmalonic acid-infused dogs.

Acute actions of 1,25-dihydroxy-vitamin D3 in normal man: effect on calcium and parathyroid status.

The present study was undertaken to evaluate the acute effect of 1,25-dihydroxy-vitamin D3 (1,25 (OH)2D3) on serum Ca, P and immunoreactive parathyroid (iPTH) and urinary Ca, P. and cyclic AMP. In 8 normal subjects, samples were collected over intervals of 30 to 60 min during a control day and on a treatment day following oral ingestion of 1,25(OH)2D3, 2.7 microgram. For the entire group there were no significant changes in serum Ca. P, iPTH or urinary P. Urinary Ca increased significantly 7 h after administration of 1,25(OH)2D3, and urinary cAMP decreased at 12 h. In 4 patients (group A). showing an increase in serum Ca by 0;2 to 0.4 mg/dl, serum iPTH decreased in 3, and the decrease in urinary cAMP appeared sooner. Among 4 patients showing no change in serum Ca after 1,25(HO)2D3 (group B), 3 showed an increase in iPTH. These data document the early onset of action of 1,25(OH)2D3 following its administration to normal man; increments in urinary Ca provide the most sensitive index of its action. The data provide no support for the view that 1,25(OH)2D3 exerts any direct inhibitory effect on the secretion of parathyroid hormone.

Evidence for secondary hyperparathyroidism in idiopathic hypercalciuria.

Circulating levels of immunoreactive parathyroid hormone (PTH) were measured in 40 patients with idiopathic hypercalciuria (IH) before and during reversal of hypercalciuria with thiazide, and in four normal subjects before and during induction of hypercalciuria with furosemide. 26 patients with IH had elevated serum PTH levels. The remaining patients had normal levels. Although the correlation was not complete, high PTH levels were generally found in patients who had more severe average urinary calcium losses. When initially elevated. PTH levels fell to normal or nearly normal values during periods of thiazide administration lasting up to 22 months. When initially normal, PTH levels were not altered by thiazide. Reversal of hyperparathyroidism by thiazide could not be ascribed to the induction of hypercalcemia, since serum calcium concentration failed to rise in a majority of patients. Renal hypercalciuria produced by furosemide administration elevated serum PTH to levels equivalent to those observed in patients with IH. The findings in this study help to distinguish between several current alternative views of IH and its relationship to hyperparathyroidism. Alimentary calcium hyperabsorption cannot be the major cause of IH with high PTH levels, because this mechanism could not elevate PTH. Idiopathic hypercalciuria cannot be a variety of primary hyperparathyroidism, as this disease is usually defined, because PTH levels are not elevated in all patients and, when high, are lowered by reversal of hypercalciuria. Primary renal loss of calcium could explain the variable occurrence of reversible hyperparathyroidism in IH, since renal hypercalciuria from furosemide elevates serum PTH in normal subjects. Consequently, a reasonable working hypothesis is that IH is often due to a primary renal defect of calcium handling that leads, by unknown pathways, to secondary hyperparathyroidism.

The role of phosphate in the secretion of parathyroid hormone in man.

In man, oral administration of 1 g of phosphorus resulted in a 60-125% increase in serum immunoassayable parathyroid hormone (PTH) concentration. Peak PTH levels were attained in 1 hr, and PTH returned to base line levels in 2 hr. This increase in PTH appeared to be initiated by a very small decrease of total and ionized calcium and was abolished by a calcium infusion. There was no correlation between serum phosphorus and PTH. The experiments show that oral phosphorus administration initiates a calcium-mediated control system for PTH secretion and that this system operates very sensitively in man.