The effect of calcitriol on fasting urine calcium loss and renal tubular reabsorption of calcium in patients with mild renal failure--actions of a permissive hormone.

AIM: Renal production of 1,25-dihydroxycholecalciferol is attenuated in early renal failure. Renal tubular reabsorption of calcium is diminished in moderate renal failure and we wished to see if this were true in the early stages and whether supplementary calcitriol would bring about correction. We were interested in the idea of 1,25-dihydroxycholecalciferol being a permissive agent, operating indirectly. METHODS: We measured calcium-related variables, including calculated ultrafiltrable serum calcium, before and after calcitriol 0.5 microg daily for six days in 34 subjects with stable mild renal failure. RESULTS: The mean serum creatinine was 0.21 (+/- 0.08) mmol/l. The mean serum Ca++ was normal (1.18 mmol/l) but nine patients had values outside the normal range and in six cases, with low-normal serum Ca++ levels, there was a diminished tubular reabsorption. In five cases, basal serum Ca++ was mildly elevated. The coefficient of variation for serum Ca++ was 4.4%. PTH (1-84) levels were mildly elevated and 1,25-dihydroxycholecalciferol levels low-normal. The urine Ca/Cr, representing net bone resorption, was elevated in six cases. After calcitriol, the mean serum Ca++ level rose slightly and the coefficient of variation decreased to 3.6%. Changes in Ca++ whether upward or downward were accounted for by minor alterations in tubular reabsorption and a tendency to less net bone resorption. The initial Ca++ predicted (negatively) the magnitude of the correction. Neither the prevailing PTH nor the 1,25-dihydroxycholecalciferol levels explained any of the observed changes. CONCLUSION: In early renal failure, there may be impaired regulation of serum Ca++. Despite elevated PTH, mild hypocalcemia may exist in the presence of increased net bone resorption relative to GFR. Hypocalcemia was accounted for by reduced renal tubular reabsorption of calcium which corrected after calcitriol. Net bone resorption tended to fall after calcitriol. Mild hypercalcemia, when present, was corrected by a reduction in tubular reabsorption. Calcitriol did not have a simple unidirectional effect but instead contributed to efficiency of the homeostatic mechanisms controlling the serum Ca++ set-point.

Digestibility, apparent mineral absorption, and voluntary intake by horses fed alfalfa, tall fescue, and caucasian bluestem.

Alfalfa (Medicago sativa L.), low-endophyte (< 5%) tall fescue (Festuca arundinacea Schreb.), and caucasian bluestem (Bothriochloa caucasica [Trin.] C.E. Hubbard) were fed as chopped hay to six Arabian geldings (BW 441 kg; SE 2) in intake and digestibility experiments to determine nutritional value for horses at maintenance. Each experimental design was a replicated Latin square. Alfalfa was higher in DM and CP digestibility, IVDMD, apparent absorption of Ca, K, and S, and voluntary intake than the grasses (P < .05). Caucasian bluestem was higher in Zn but was lower in CP, TNC, Mg, P, K, S, and Cu concentrations than tall fescue. Crude protein digestibility and apparent absorption of Mg, K, and S were higher (P < .05) for tall fescue than for caucasian bluestem. Geldings fed alfalfa for ad libitum intake had higher serum concentrations of vitamin A, blood urea nitrogen, P, S, and Cu than geldings fed grass hays. Serum Zn was higher (P < .05), whole blood Se tended to be higher (P < .06), and BUN was lower (P < .05) in geldings fed caucasian bluestem than in those fed tall fescue. All forages met requirements for CP, Ca, Mg, K, and Fe when fed for ad libitum intake but were deficient in Cu for horses at maintenance. Caucasian bluestem was borderline in CP and was deficient in P but was the only forage that met the Zn requirement for the horses. Based on these results, caucasian bluestem could be a useful hay for horses but may require supplementation of CP and P.

The effect of air abrasion on shear bond strength to dentin with dental adhesives.

This study compared the effects of different dentin surface treatments on the shear bond strengths of three adhesive systems. The adhesive systems included a resin-modified glass ionomer, Fuji II LC, and two dentin bonding systems, One Step and Scotchbond Multi-Purpose Plus. The surface treatments compared for each adhesive system were as follows: 1) the controls, which were conditioned, 2) air abrasion at 120 psi without conditioning, 3) air abrasion at 160 psi without conditioning, 4) air abrasion at 120 psi with conditioning, and 5) air abrasion at 160 psi with conditioning. The KCP 1000 Whisperjet was used for all air-abrasive specimens. Controls for each adhesive material (Fuji II LC, One Step, Scotchbond Multi-Purpose Plus) were bonded using manufacturers' recommendations. Results showed that air abrasion significantly lowered bond strength of the resin-modified glass ionomer, conditioned or nonconditioned (P < 0.01). Air abrasion alone significantly lowered bond strengths of the dentin bonding agent systems (P < 0.01). However, air abrasion plus conditioning of the dentin surface resulted in bond strengths that were similar to the conditioned-only specimens (P < 0.01).

Effects of hydrated sodium calcium aluminosilicate on fescue toxicosis and mineral absorption.

The possibility of supplementing livestock diets with an aluminosilicate to protect them from fescue toxicosis was investigated. An in vitro study showed that hydrated sodium calcium aluminosilicate (HSCAS) removed greater than 90% of the ergotamine from aqueous solutions at pH 7.8 or lower, indicating a high affinity of ergotamine for HSCAS in vitro. Rats fed diets containing tall fescue seed infested (E+) with the endophytic fungus Acremonium coenophialum had lower (P less than .05) feed intakes and weight gains than did rats fed diets containing uninfested (E-) tall fescue seed. When feed intake by rats fed the E- seed diet was limited to that of rats fed the E+ seed diet, weight gains did not differ, but testes weights and serum prolactin (PRL) concentrations were lower (P less than .05 and .10, respectively) in rats receiving E+ seed. Supplementing E+ seed diets with HSCAS did not eliminate effects of E+ seed on intake, PRL, or testes weights. Sheep fed E+ tall fescue hay had higher (P less than .05) rectal temperatures than did sheep fed an equal amount of E- tall fescue hay, but OM and N digestion coefficients did not differ between the two hays. Supplementing E+ hay diets with HSCAS did not eliminate the effect of E+ hay on rectal temperatures. Addition of 2% HSCAS to tall fescue hay diets did not affect apparent absorption by sheep of OM, N, Ca, P, Na, K, or Cu, but it reduced (P less than .05) the apparent absorption of Mg, Mn, and Zn.(ABSTRACT TRUNCATED AT 250 WORDS)

Nutrient utilization by sheep fed forage grown on soil treated with fluidized-bed combustion residue.

A mineral balance trial was conducted with 18 wether lambs fed sun-cured hay harvested from pastures located on a reclaimed strip-mined site. The following soil applications were made during each of 3 yr: 1) none, 2) dolomitic limestone and 3) fluidized-bed combustion residue (FBCR). Because FBCR had half the buffering capacity of limestone, it was applied at twice the rate of limestone. Apparent digestibility of hemicellulose was higher (P less than .05) for limestone-amended forage than for FBCR-amended forage (70.2 vs 67.0%), and apparent digestibility of cellulose was higher (P less than .05) for amended forages (66.7%) than for the control (63.9%). Apparent absorption and retention of N were similar among treatments, when expressed as a percentage of intake. Lambs fed control forage were in negative Ca balance, lower (P less than .01) than with amended forages. Apparent absorption and retention of Mg and Fe (g/d basis) were higher (P less than .05) for lambs on the limestone treatment than for lambs on the FBCR treatment. Apparent absorption of S was higher (P less than .01) for lambs on the FBCR treatment than for those on the limestone treatment. These differences were related to differences in mineral concentrations of the forages. Serum P was lower (P less than .05) for lambs fed FBCR-treated forage than for lambs fed limestone-treated forage (10.1 vs 12.9 mg/dl). Soil amendment with FBCR did not have deleterious effects on digestibility or mineral metabolism; in fact, it may have enhanced utilization of Ca and S and improved digestibility of some fiber components by lambs.

Physiological and pharmacological aspects of 24,25-dihydroxycholecalciferol in man.

The present study describes the response to small oral doses (1--10 microgram/day) of 24,25-DHCC in man. Contrary to expectation, 24,25-DHCC was as potent as 1,25-DHCC in increasing intestinal absorption of calcium both in normal persons and in patients with a variety of disorders of calcium metabolism. Despite this increase in intestinal absorption, plasma and urine calcium did not increase after 24,25-DHCC as they did after 1,25-DHCC. Metabolic balance studies showed calcium balances to increase by 1.6 to 11.5 mmoles/day in 5 of the 6 patients studied. 24,25-DHCC increased intestinal absorption of calcium equally well in anephric patients, suggesting that conversion of 24,25-DHCC to 1,24,25-trihydroxycholecalciferol by the kidney cannot be the sole mechanism by which 24,25-DHCC expresses biological activity, even though in vitamin D deficient rats nephrectomy does abolish the ability of large doses of 24,25-DHCC to increase calcium absorption. It is concluded that 24,25-DHCC may be a calcium-regulating hormone in man. In view of the effects demonstrated here and its relatively high concentration in plasma and slow turnover rate, 24,25-DHCC has the properties that might be ideal for a long-acting stimulator of bone mineralisation. Further work is needed to explain why 24,25-DHCC has effects in man which are not readily seen in other species.

Acute responsiveness to calcitonin in chronic renal failure.

The acute effect of porcine calcitonin was tested in 17 patients undergoing chronic haemodialysis. In normal adults calcitonin has no effect on plasma calcium or phosphate levels, but in nine patients both concentrations were substantially reduced after calcitonin. This hypocalcaemic and hypophosphataemic effect was a function of the initial plasma phosphate level but was unrelated to the initial plasma calcium level. Plasma hydroxyproline levels were not significantly different in the two groups an were unaffected by calcitonin. In 11 patients fasting plasma calcitonin levels were undetectable with an assay sensitive to 0-1 mug/1. Calcitonin seems to have an acute effect in chronic renal failure which may not operate by arresting bone resorption but is dependent on the plasma phosphate concentration.

Effect of correction of metabolic acidosis on bone mineralisation rates in patients with renal osteomalacia.

The role of metabolic acidosis in the genesis of renal osteomalacia was investigated by studying bone mineralisation and resorption rates with a combined isotope and balance technique in six patients, before and after the administration of alkali. Correction of blood pH was achieved in five cases and was associated with a significant rise in the bone mineralisation rates and a significant positive trend in the calcium balances. It is suggested that acidosis contributes to the pathogenesis of osteomalacia in renal failure by slowing skeletal mineralisation, possibly by inhibiting bone alkaline phosphatase.

Renal effects of calcitonin.

Porcine calcitonin in a slow-release gelatin vehicle was given by intramuscular injection to 10 patients-four with primary hyperparathyroidism, four with Paget's disease, and two with carcinoma of the breast and hypercalcaemia. All cases showed a fall in serum calcium with an immediate rise in urine calcium. All except three patients with primary hyperparathyroidism showed a fall in serum phosphorus, but an immediate rise in urine phosphorus occurred in all cases. Urine hydroxyproline output fell in three patients with severe Paget's disease. Urine sodium rose in all cases, but the effects on potassium, magnesium, water, and pH were not appreciably different from results obtained in four control subjects who were given the gelatin vehicle alone.The data suggest that calcitonin caused a decrease in the tubular resorption of calcium and phosphorus. The hypocalcaemic effect appeared to be due to a decrease in bone resorption in the patients with Paget's disease but in the remaining cases could be accounted for in part or entirely by the rise in urine calcium.