Effect of 1α-Hydroxyvitamin D₃ and Dietary Calcium and Phosphate on the Aortic Mineral Content in Rabbits with Mild Azotemia

Abstract

The effect of treatment with 1α-hydroxycholecalciferol (1α-OH-D₃) and different diets on uremic arterial disease was studied. Three groups of rabbits with chronic renal failure (CRF) were kept on three diets with a low, medium or high content of calcium and phosphate. Half the rabbits in each group were treated for 18 weeks with 1α-OH-D₃, 0.02 µg/kg/day, without any significant changes in the serum concentrations of calcium or phosphate compared to placebo treatment. In the thoracic aorta, the content of calcium and phosphate was significantly increased in placebo-treated CRF rabbits on medium and high calcium and phosphate intakes compared to rabbits with normal renal function (p < 0.05). The cholesterol content was unchanged. Treatment with 1α-OH-D₃ caused a further increase in the aortic content of calcium and phosphate in the CRF rabbits on medium and low calcium and phosphate intakes (p < 0.05). No increase in the aortic cholesterol content was observed. The histological changes in the abdominal aorta consisted of medial proliferations with calcifications and intimal proliferations. The severity of these changes paralleled the mineral content of the thoracic aorta. Aggravation of uremic arterial disease may be a hitherto unrecognized side-effect of treatment with 1α-OH-D₃ in CRF.

Effect of Long-Term Administration of 1,25-Dihydroxyvitamin D₃ and 1α-Hydroxyvitamin D₃ on the Calcium Content of the Aorta, Heart and Kidney of Normal and Uremic Rats

“…Our results are in contrast to findings reporting that la-OH-D3 induces histological changes in the abdominal aorta of azotemic rabbits or increases the aortic content of calcium and phosphate [4], The calcium metabolism of the rabbit differs from the conditions in man [7]. As this, to a certain extent, also refers to rats, it cannot be ruled out that the observed differences are merely a reflection of the different spe cies.…”

“…As this, to a certain extent, also refers to rats, it cannot be ruled out that the observed differences are merely a reflection of the different spe cies. Nevertheless, our findings that the long-term appli cation of both l,25-(OH)2D3 or la-OH-D3, in a dosage equivalent which is higher than normally applied in pa tients, is tolerated by uremic rats without any major side effects invalidate to a certain extent the caveat that a therapy with one of the two compounds might be harmful for uremic patients [4,8]. On the other hand, however, our data clearly demonstrate that the administration of 1,25-(OH)2D3 led to a significant increase of the serum cal cium x phosphate product in the uremic rats.…”

“…Tvedegaard et al [4] have recently communicated that a long-term treatment with la-hy droxyvitamin D3 (la-OH-D3) caused an increase of the aortic content of calcium and phosphorus in azotemic rabbits. Furthermore, these workers observed significant histological changes in the aorta after this therapy, which led them to conclude that la-OH-D3 might induce an aggravation of the uremic arterial disease [4], The pur pose of the present study was to investigate whether or not uremic rats would react similarly when exposed to la-OH-D3 and, additionally, whether l,25-(OH)2D3 would exert different effects when applied under the same experimental conditions. Methods 60 male Hanover Wistar rats (5 weeks old, average weight 160 g) were kept for 8 days on a normal diet (Altromin 1320®) containing 0.9% calcium and 0.7% phosphate, and 600 lU/kg vitamin D3.…”

Comparison of 1α-OH-Vitamin D₃ and High Doses of Calcium Carbonate for the Control of Hyperparathyroidism and Hyperaluminemia in Patients on Maintenance Dialysis

“…In our 2 previous studies on la-OH D3 or l,25-(OH): D3 in hemodi alyzed patients without radiological bone disease [3,34], the efficiency of the vitamin D metabolites on histologi cal resorption was quite inconsistent (one third improve ment, one third worsening, one third no change), the improvement appearing dependent upon the quality of the control of plasma concentration of phosphate and of PiPTH. Because of this inconsistent effects of lu-OHD metabolites in infraradiological osteodystrophy and the necessity in patients of increasing doses of Al(OH)3 which maintained higher plasma concentration of alumi nium and because of the fact that la-O H D 3 has been shown to increase the calcium content of the aorta of rats in spite of no increase of their plasma calcium and phos phate [35], we think that high doses of C a C 0 3 alone should be tried first in all patients without radiological bone disease and pursued if they are well tolerated and successful in maintaining a plasma Ca level of 10.0± 0.5 mg/dl and a plasma phosphate of 5.0±0.5 mg/dl.…”

The Approach to the Treatment of Secondary Hyperparathyroidism in Early Renal Failure

“…One should, however, remember that 1.25(OH)2D3 does not only correct malabsorption of calcium but also that of phosphate [7] and that in patients with more advanced renal failure such treatment may lead to marked hyper phosphatemia which when combined with hypercal cemia accelerates the decline of renal function, as pre viously reported [8,9]. Furthermore, such an increase in plasma phosphate limits the beneficial effect of l,25(OH)2D3 on bone resorption [10], Finally, one should keep in mind that in experimental uremia la-OH vitamin D 3 given at doses keeping plasma calcium an phosphate in the normal range may increase the calcium content of the aorta [11] and that in man la-OH vitamin D3 increases plasma aluminum in uremic patients taking Al(OH)3 [12], Therefore, we ask ourself whether another approach for the prevention of hyperparthyroidism in early, as well as more advanced renal failure, would not simply be the use of oral calcium carbonate at the highest doses not inducing hypercalcemia greater than 10.4 mg/dl. The rationale for using these high doses of calcium carbonate is that they not only increase passive calcium absorption making the calcium balance positive but they also act as a phosphate binder, significantly increasing phosphate excretion in the feces [13].…”