Parathyroid hormone suppression by intravenous 1,25-dihydroxyvitamin D. A role for increased sensitivity to calcium.

Numerous in vitro studies in experimental animals have demonstrated a direct suppressive effect of 1,25-dihydroxyvitamin D (1,25(OH)2D) on parathyroid hormone (PTH) synthesis. We therefore sought to determine whether such an effect could be demonstrated in uremic patients undergoing maneuvers designed to avoid changes in serum calcium concentrations. In addition, the response of the parathyroid gland in patients undergoing hypercalcemic suppression (protocol I) and hypocalcemic stimulation (protocol II) before and after 2 wk of intravenous 1,25(OH)2D was evaluated. In those enlisted in protocol I, PTH values fell from 375 +/- 66 to 294 +/- 50 pg (P less than 0.01) after 1,25(OH)2D administration. During hypercalcemic suppression, the "set point" (PTH max + PTH min/2) for PTH suppression by calcium fell from 5.24 +/- 0.14 to 5.06 +/- 0.15 mg/dl (P less than 0.05) with 1,25(OH)2D. A similar decline in PTH levels after giving intravenous 1,25(OH)2D was noted in protocol II patients. During hypocalcemic stimulation, the parathyroid response was attenuated by 1,25(OH)2D. We conclude that intravenous 1,25(OH)2D directly suppresses PTH secretion in uremic patients. This suppression, in part, appears to be due to increased sensitivity of the gland to ambient calcium levels.

Comparison of the effects of prazosin versus propranolol on plasma lipoprotein lipids in patients receiving hemodialysis.

A prospective, crossover study was used to evaluate the effects of prazosin and propranolol on lipid metabolism in 10 hypertensive patients receiving long-term hemodialysis therapy. Adequate blood pressure control was achieved with either agent (mean predialysis blood pressure was 144/77 mm Hg). Total triglyceride levels increased by 27 +/- 4 percent during propranolol therapy but decreased during prazosin therapy by 8 +/- 2 percent (p less than 0.05). These changes were accounted for by a 21 +/- 1.5 percent increase in very-low-density lipoprotein triglyceride during propranolol therapy and a 6 +/- 2 percent decrease in very-low-density lipoprotein triglyceride during prazosin therapy (p less than 0.05). Although no change in total cholesterol occurred with either agent, a significant decrease (19 +/- 1 percent, p less than 0.01) in high-density lipoprotein cholesterol occurred with propranolol therapy and an increase of 16 +/- 4 percent occurred during treatment with prazosin (not significant). The high-density lipoprotein2 cholesterol levels decreased by 22 +/- 4 percent after treatment with propranolol and increased by 4 percent after prazosin therapy. Propranolol reduced high-density lipoprotein3 cholesterol levels by 18 +/- 2 percent, whereas prazosin increased these values by 19 +/- 2 percent (p less than 0.01). These changes were associated with a reduction in tissue lipoprotein lipase activity after propranolol therapy (2.4 +/- 0.3 percent) and an increase after prazosin therapy (2.5 +/- 1 percent, p less than 0.05). These data suggest that treatment with propranolol may be associated with unfavorable changes in the lipid profile that are not observed after treatment with prazosin.

Effects of prazosin and propranolol on blood pressure and plasma lipids in patients undergoing chronic hemodialysis.

Twenty patients receiving hemodialysis who had mild to moderate hypertension were treated with prazosin or propranolol to control predialysis hypertension. Effective blood pressure control was achieved with prazosin (mean dose 8.3 +/- 2.2 mg [+/- standard error of the mean], n = 10) and propranolol (mean dose 123 +/- 39 mg, n = 10). Therapy with prazosin did not significantly affect total plasma triglyceride or total cholesterol levels. The level of high-density lipoprotein (HDL) cholesterol tended to increase, but not significantly. However, the HDL3 subfraction did increase significantly, from 16.3 +/- 1.5 to 20.6 +/- 1.5 mg/dl (p = 0.05). Propranolol therapy increased plasma triglyceride levels, primarily of the very low density lipoprotein class. HDL cholesterol levels decreased from 44.2 +/- 6.7 to 34.7 +/- 4.2 mg/dl (p less than 0.03). The reduction in the HDL cholesterol levels was attributable to a decrease in HDL2 cholesterol levels (from 21.3 +/- 3.8 to 16.3 +/-3.0 mg/dl, p less than 0.04) and HDL3 cholesterol levels (from 23.0 +/- 3.1 to 19.5 +/- 2.1 mg/dl, difference not significant). Thus, both prazosin and propranolol are effective in controlling hypertension in patients undergoing hemodialysis. HDL3 cholesterol levels increased in patients treated with prazosin, but no other significant changes in the plasma lipids occurred. Patients treated with propranolol had a significant decrease in plasma HDL2 and HDL3 cholesterol levels.

Intestinal alkaline phosphatase in patients with chronic renal failure.

Because of the suggestion that intestinal alkaline phosphatase was elevated in the serum of patients with chronic renal failure, we studied the serum of 42 patients undergoing hemodialysis with elevated enzyme activity. Using a sensitive and specific electroimmunoassay for the intestinal isoenzyme, 26 of 42 serum samples were positive, compared with 3 of 25 samples obtained from hospitalized patients with elevated phosphatase activity. The fractional amount of this isoenzyme was also higher, ranging from 1.5% to 41% of the total serum phosphatase, compared with 0.1%-1.2% in control sera. Kidneys removed during transplantation or postmortem contained a membranous phosphatase with immunologic activity identical to the intestinal isoenzyme in 5 of 6 patients. This enzyme accounted for 8%-21% of the total kidney phosphatase activity. By morphology the immunoreaction was localized to the apical membranes of the collecting tubules. Thus, the kidney is the likely source of the observed increase in serum intestinal-type phosphatase activity noted in patients with chronic renal failure. An elevation in the intestinal isoenzyme rather than the presence of early metabolic bone disease or hepatic disease should be considered in renal failure patients with mildly elevated (up to 50% over normal) total serum alkaline phosphatase.

Calcium acetate as a phosphorus binder in hemodialysis patients.

Much interest is currently centered on the use of calcium acetate as a phosphorus binder in patients with renal failure. Therefore, this compound in subjects previously stable on calcium carbonate and undergoing high-efficiency hemodialysis with a dialysate calcium of 2.5 mEq/L was evaluated. Twenty subjects were switched from generic calcium carbonate to a single calcium carbonate preparation for a period of 2 months. This was followed by a phase (1 month) in which calcium acetate was substituted for calcium carbonate at a dose containing half the amount of elemental calcium. Subjects then continued calcium acetate for 6 months. It was found that calcium acetate allowed comparable control of immunoreactive parathyroid hormone, calcium, and phosphorus levels compared with calcium carbonate. This occurred with half the amount of elemental calcium ingested in the form of calcium acetate (349 +/- 25 versus 699 +/- 75 mmol/day; P less than 0.001). With this lower dose, the overall incidence of hypercalcemia was the same with each formulation. In the eight subjects concurrently receiving i.v. calcitriol, the incidence of hypercalcemia was significantly higher during the first month of calcium acetate compared with that in those not receiving this compound (P less than 0.05). Of those four subjects receiving the high dose of calcitriol (2 micrograms thrice weekly), all required either reduction in the dose or discontinuation of the drug. Thus, mineral metabolism could be controlled adequately with calcium acetate despite using half as much elemental calcium compared with calcium carbonate. This, however, did not result in a lower incidence of hypercalcemia, particularly in those receiving i.v. calcitriol.