Suppression of secondary hyperparathyroidism in chronic dialysis patients by single oral weekly dose of 1,25-dihydroxycholecalciferol.

Eleven hemodialysis patients who developed refractory secondary hyperparathyroidism, despite conventional vitamin D therapy, were treated with large oral doses of 1,25-dihydroxycholecalciferol [1,25(OH)2D3]. Therapeutic regimen was a single oral dose of up to 8.0 micrograms administered once weekly following hemodialysis. A maximum serum level of 1,25(OH)2D occurred four hours after the 8.0 micrograms dose. A positive correlation (Y = 84.3X-22.1: P < 0.01) was found between the maximal serum 1,25(OH)2D concentration (Cmax) and the dose of 1,25(OH)2D3 when plotted on a logarithmic scale. Forty-eight hours after the administration of the 8.0 micrograms dose, the parathyroid hormone (PTH) level and the alkaline phosphatase activity (ALP) were markedly decreased without evidence of hypercalcemia. A significant inverse relationship was found between the Cmax of 1,25(OH)2D and the percent change in the PTH level measured after 48 hours, either with carboxy-terminal (C-PTH) or the highly sensitive mid-portion assay (HS-PTH). From these results, the level of serum 1,25(OH)2D required to blunt the rise in serum PTH was 168 pg/ml and 203 pg/ml, respectively; these serum levels were achieved by the oral administration of doses of 6.0-8.0 micrograms or higher. There were no adverse effects of treatment. Following this study, one patient was continuously treated with 8.0 micrograms of 1,25(OH)2D3 orally once a week for 18 months. There was a therapeutic effect (as evidenced by PTH suppression, ALP suppression and the disappearance of subjective complaints) without the development of severe hypercalcemia or hyperphosphatemia. This treatment may help to prevent or treat secondary hyperparathyroidism in patients receiving long-term dialysis.

[Evaluation of nutritional status of patients on continuous ambulatory peritoneal dialysis (CAPD) by dual photon energy X-ray absorptiometry (DEXA)].

Malnutrition is a serious complication in patients on long-term CAPD treatment. Accordingly, quantitative evaluation of nutritional status is a critical issue. This study aimed to assess nutritional status by dual photon energy x-ray absorptiometry (DEXA) in CAPD patients. Total lean body mass (D-TBM), right arm lean mass (D-RAM) and body fat percent (D-% FAT) measured by DEXA were compared with mid-arm muscle circumference (MAMC) and body fat percent (AP-% FAT) measured by anthropometrics (AP) in 51 CAPD patients. The subjects were stratified into groups by gender, age, duration on CAPD, and diabetes mellitus or non-diabetes. There was significant correlation between D-TBM, D-RAM and MAMC (r = 0.519, p = 0.001, r = 0.545, p = 0.001) or D-% FAT and AP-% FAT (r = 0.763, p = 0.0001). However, in the groups of females with over 50 years and over 48 months of dialysis duration, there was no correlation between D-TBM, D-RAM and MAMC. The DEXA method is useful in the quantitative evaluation of nutritional status of dialysis patients serially.

Glutathione may inhibit sodium-dependent phosphate transport by renal brush-border membrane vesicles.

Glutathione, a biological reductant, can affect certain aspects of transport function in renal cortical slices. The influence of glutathione on the rate of sodium-dependent phosphate uptake into renal brush-border membrane (BBM) vesicles was examined. Vesicles were obtained from rat renal cortex by the conventional calcium precipitation method. The amounts of GSH and oxi-glutathione were measured by chromatography. The vesicles were incubated for 15 min with glutathione (10 mM) prior to a 1-min influx of phosphate. The incubation with glutathione reduced the phosphate uptake from 1887 +/- 217 to 1496 +/- 116 pmol/mg (n = 5, p less than 0.05). A kinetic study revealed that the incubation with glutathione resulted in an increase of Km in the sodium-dependent phosphate transporter from 85 +/- 7.9 to 159 +/- 18 microM (n = 5, p less than 0.05). Glutathione was catabolized rapidly by the incubation with BBM, and a concomitant production of oxi-glutathione was recognized. Incubation with oxi-glutathione (10 mM) for 15 min, however, did not affect the phosphate uptake, the present results suggest that incubation with reduced-form glutathione decreases the affinity of the sodium-dependent phosphate transport across the renal brush-border membrane, and that catabolism of glutathione may be linked the inhibitory mechanism.

[A trial of suppressing secondary hyperparathyroidism by oral high dose therapy of 1, 25-dihydroxyvitamin D3].

We reported a successful treatment of secondary hyperparathyroidism by intermittent oral administration of high dose of 1, 25 dihydroxycholecalciferol [1.25-(OH)2D3] in three patients on maintenance hemodialysis. Dialysis durations were 4 months in case 1, 6.5 years in case 2 and 12.5 years in case 3. The levels of c-PTH ranged from 4.7 ng/ml to 94.2 ng/ml. 1, 25-(OH)2D3 in dosages up to 8.0 micrograms was given once a week just after hemodialysis. Before the administration and after 48 hours, serum Ca, serum Pi, serum Mg, c-PTH and highly sensitive PTH were assayed. There was a significant correlation between max. plasma concentration of 1, 25-(OH)2D and logarithm of the dose in all patients. The max. plasma level of 1, 25-(OH)2D reached 25-(OH)2D reached to 200 pg/ml at 4 hours after the oral administration of 8.0 micrograms. Their thresholds of 1, 25-(OH)2D level which could decrease the PTH levels were elevated proportionally to their dialysis durations. Case 1 required 4.0 micrograms to suppress secondary hyperparathyroidism, whereas, case 2 and 3 did 8.0 micrograms of 1, 25-(OH)2D3. Severe hypercalcemia was not observed during a high dose treatment. In conclusion, we have succeeded in treating refractory secondary hyperparathyroidism by intermittent oral administration of high dose 1, 25-(OH)3D3. This therapy is recommended to start in the earlier stage of a long-term dialysis in order to prevent severe secondary hyperparathyroidism and bone disease.