Phosphorus is a well-known modulator of renal 1 alpha-hydroxylase activity. In early and moderate renal failure it is proposed that dietary Pi reduction ameliorates secondary hyperparathyroidism through increased circulating levels of calcitriol (i.e, 1 alpha, 25-dihydroxycholecalciferol). To gain further insight into the mechanisms by which a low-Pi diet ameliorates secondary hyperparathyroidism in advanced renal insufficiency, studies were performed in five dogs before and 6 mo after the induction of uremia by 5/6 nephrectomy. Glomerular filtration rate decreased from 69.0 +/- 2.3 to 10.5 +/- 0.5 ml/min, immunoreactive parathyroid hormone (irPTH) increased from 66.0 +/- 8.8 to 321.0 +/- 46 pg/ml, and calcitriol decreased from 39.0 +/- 10.4 to 27.0 +/- 6.2 pg/ml. Thereafter, dietary Pi was decreased gradually every 2 wk from 0.95% to 0.6, 0.45, and 0.3%, respectively. Dietary Ca was reduced from 1.6 to 0.6% to prevent development of hypercalcemia. Ionized Ca (ICa) decreased from 5.4 +/- 0.04 to 5.2 +/- 0.05 mg/dl (P less than 0.02), and plasma Pi decreased from 6.3 +/- 0.7 to 4.7 +/- 0.2 mg/dl (P less than 0.05). Calcitriol remained low (23.3 +/- 4.7 pg/ml). However, irPTH gradually decreased from 321.0 +/- 46.0 to 94.7 +/- 22.9 pg/ml (P less than 0.005). These studies indicate that a decrease in dietary Pi from 0.95 to 0.3% suppressed irPTH by approximately 70%. Reduction of irPTH was observed in the absence of a concomitant increase in levels of ICa or calcitriol. These studies suggest that reduction in dietary Pi in advanced renal insufficiency improves secondary hyperparathyroidism by a mechanism that is independent of the levels of calcitriol or plasma ICa.

Renal 1-alpha-hydroxylase activity is tightly regulated in normal humans and intact animals. No significant changes in serum 1,25(OH)2D levels occur in response to vitamin D challenge. However, conflicting reports have appeared in the literature with regard to stimulation of 1,25(OH)2D production after 25(OH)D administration in uremia. To provide further insight into this issue, 25(OH)D at a dose of 100 micrograms every other day for two weeks followed by 50 micrograms every other day for the next two weeks was given orally to seven uremic mongrel dogs. After two weeks of 25(OH)D therapy, 1,25(OH)2D levels increased from 16.4 +/- 0.9 to 28.0 +/- 1.9 pg/ml (P less than 0.001) in parallel with a fourfold increase in 25(OH)D concentrations from a basal of 50.1 +/- 6.5 to 203.2 +/- 18.1 ng/ml. No significant changes in serum i-PTH, ICa or P were observed. Linear regression analysis of the relationship between serum concentrations of 1,25(OH)2D versus 25(OH)D, for each dog during this period, showed highly significant correlation coefficients. To evaluate the possibility that extra-renal sites contribute to the described enhanced 1,25(OH)2D net synthesis after 25(OH)D treatment, similar studies were performed in four anephric patients undergoing hemodialysis. Basal serum 1,25(OH)2D levels were 5.5 +/- 2.4 pg/ml and increased to 19.6 +/- 5.0 pg/ml after 25(OH)D administration. A significant correlation was also found for the relationship between serum levels of 1,25(OH)2D and 25(OH)D in anephrics (r = 0.72, P less than 0.001). The same therapy in four normal volunteers showed no significant changes in serum 1,25(OH)2D concentrations.(ABSTRACT TRUNCATED AT 250 WORDS)

Hypocalcemia is the main factor responsible for the genesis of secondary hyperparathyroidism in chronic renal disease. Studies with parathyroid cells obtained from uremic patients indicate that there is a shift in the set point for calcium-regulated hormone (parathyroid hormone [PIH) secretion. Studies were performed in dogs to further clarify this new potential mechanism. Hypocalcemia was prevented in uremic dogs by the administration of a high calcium diet. Initially, ionized calcium was 4.79±0.09 mg/dl and gradually increased up to 5.30±0.05 mg/dl. Despite a moderate increase in ionized calcium, immunoreactive PTH (iPTH) increased from 64±7.7 to 118±21 pg/ml. Serum 1,25(0H-)D3 decreased from 25.4±3.8 to 12.2±3.6 pg/ml. Further studies were performed in two other groups of dogs. One group received 150-200 ng and the second group 75-100 ng of 1,25(OH)2D3 twice daily. The levels of 1,25(OH)2D3 increased from 32.8±3.5 to a maximum of 69.6±4A pg/ml. In the second group the levels of serum 1,25(0H)D3 after nephrectomy remained normal during the study. Amino-terminal iPTH did not increase in either of the two groups treated with 1,25(OH)2D3.In summary, the dogs at no time developed hypocalcemia however, there was an 84% increase in iPTH levels, suggesting that hypocalcemia, per se, may not be the only factor responsible for the genesis of secondary hyperparathyroidism.

Parathyroid suppression by intraperitoneal calcitriol (1,25(OH)2D3) during peritoneal dialysis. The purpose of this study was to determine if parathyroid hormone (PTH) suppression could be achieved by increasing calcium mass transfer (Ca MT) with high dialysate Ca (4 mEq/liter) or via intraperitoneal (i.p.) 1,25(OH)2D3 in patients undergoing continuous ambulatory peritoneal dialysis. Eleven patients were dialyzed for two months with standard Ca dialysate (3.5 mEq/liter) followed by two months with 4.0 mEq/liter Ca, then by three months of i.p. 1,25(OH)2D3. During the latter period, patients were randomized to groups whose dialysate contained either 3.5 mEq/liter or 4.0 mEq/liter Ca. We found that 4.0 mEq/liter Ca dialysate more than doubled Ca MT (37 +/- 17 mg/day to 84 +/- 6 mg/day) leading to a modest fall (P less than 0.05) in PTH levels (84 +/- 5.5% of controls). Ionized calcium levels did not change. With i.p. 1,25(OH)2D3, however, ionized calcium rose significantly (P less than 0.001) leading to a decline in PTH levels to 53.9 +/- 7.9% of control values. Serum 1,25(OH)2D3 levels rose from undetectable to 47.7 +/- 7.2 pg/dl (normal range 20 to 35). These studies indicate that increasing Ca MT using a 4.0 mEq/liter Ca dialysate leads to a small reduction in PTH concentrations. On the other hand, i.p. 1,25(OH)2D3 is well absorbed into the systemic circulation, raises ionized calcium levels, and leads to a marked suppression of PTH. Thus, i.p. 1,25(OH)2D3 may be a simple and effective means to suppress secondary hyperparathyroidism in patients undergoing CAPD.

synopsisFurther studies on the thermal degradation of POPG-TDI polymer have been carried out. It has been shown that at temperatures of -2OO0C., the predominant degradation process involves random scission of the urethane linkages to give substantial amounts of isocyanate and hydroxyl. Kinetic data suggests that the weakest links in POPG-TDI polymer are spaced a t intervals of -10,000 in molecular weight and that they may be eliminated by pretreatment of the POPG with ethylene oxide to form a block COpolyether which is used to prepare the polyurethane. At temperatures exceeding 250°C. and a greater conversion to volatile fragments (>lo%) the kinetics of degradation of POPG-TDI are similar to results for POPG and indicate scission of the polyether bonds by a combination of intramolecular proton abstraction and free radical unzipping reactions, in agreement with previous studies of POPG of much higher molecular weight.

Korean hemorrhagic fever (KHF) is an epidemic viral disease characterized by high fever, hemorrhagic tendency and renal failure, and by hemorrhages of right atrium and renal medulla as well as necrosis of anterior hypophysis. Plasma immunoreactive atrial natriuretic peptide (irANP) levels of 15 patients in the oliguric phase was 94.8 ± 8.4 pg/ml (mean ± SEM), 80% higher than of the normal control group (53.0 ± 4.7 pg/ml; n = 28). In the diuretic phase it declined to 63.7 ± 5.3 pg/ml (n = 26). Plasma renin activity (PRA) in the oliguric phase was 19.0 ± 1.3 ng Al/ml/h, and in the diuretic phase 5.3 ± 0.9 ng Al/ml/h, significantly higher than the control value (2.5 ± 0.1 ng Al/ml/h). Elevations of irANP and PRA were not correlated in each group. Also systemic blood pressure as well as heart beats were significantly increased in the oliguric phase. These findings suggest that the increased irANP may have resulted from increased circulatory volume and that the ANP secretory process may not be affected by the disease.

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