Patients with nephrotic syndrome can lose vitamin D metabolites in the urine, presumably by loss of the vitamin D–binding protein. Such patients may have very low 25(OH)D levels. Some of them develop bone disease. It is not yet clear what value vitamin D therapy has in such patients, because therapeutic trials with vitamin D (or any vitamin D metabolite) have not yet been carried out. Because the problem is not related to vitamin D metabolism, one would not anticipate any advantage in using the more expensive vitamin D metabolites in place of vitamin D.
Individuals with idiopathic hypercalciuria, characterized by hypercalciuria and nephrolithiasis with normal serum calcium and PTH levels, have been divided into three groups: (1) hyperabsorbers, patients with increased intestinal absorption of calcium, resulting in high-normal serum calcium, low-normal PTH, and a secondary increase in urine calcium; (2) renal calcium leakers, patients with a primary decrease in renal reabsorption of filtered calcium, leading to low-normal serum calcium and high-normal serum PTH; and (3) renal phosphate leakers, patients with a primary decrease in renal reabsorption of phosphate, leading to increased 1,25(OH)2D production, increased intestinal calcium absorption, increased ionized serum calcium, low-normal PTH levels, and a secondary increase in urine calcium. There is some disagreement about this classification, and many patients are not readily categorized. Many such patients present with mild hypophosphatemia, and oral phosphate has been used with some success in reducing stone formation. However, a clear role for phosphate in the treatment of this disorder has not been established and is not recommended.
Therapy with hydrochlorothiazide, up to 50 mg twice daily, or chlorthalidone, 50–100 mg daily, is recommended. Loop diuretics such as furosemide and ethacrynic acid should not be used because they increase urinary calcium excretion. The major toxicity of thiazide diuretics, besides hypokalemia, hypomagnesemia, and hyperglycemia, is hypercalcemia. This is seldom more than a biochemical observation unless the patient has a disease such as hyperparathyroidism in which bone turnover is accelerated. Accordingly, one should screen patients for such disorders before starting thiazide therapy and monitor serum and urine calcium when therapy has begun.
An alternative to thiazides is allopurinol. Some studies indicate that hyperuricosuria is associated with idiopathic hypercalcemia and that a small nidus of urate crystals could lead to the calcium oxalate stone formation characteristic of idiopathic hypercalcemia. Allopurinol, 100–300 mg daily, may reduce stone formation by reducing uric acid excretion.
Paget’s disease is a localized bone disorder characterized by uncontrolled osteoclastic bone resorption with secondary increases in poorly organized bone formation. The cause of Paget’s disease is obscure, although some studies suggest that a measles-related virus may be involved. The disease is fairly common, although symptomatic bone disease is less common. Recent studies indicate that this infection may produce a factor that increases the stimulation of bone resorption by 1,25(OH)2D. The biochemical parameters of elevated serum alkaline phosphatase and urinary hydroxyproline are useful for diagnosis. Along with the characteristic radiologic and bone scan findings, these biochemical determinations provide good markers by which to follow therapy.