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[维生素D治疗与肾性骨营养不良:适应证与治疗方式]

[Vitamin D treatment and renal osteodystrophy: indications and modalities].

作者信息

Fournier A, Morinière P, Yverneau-Hardy P, Westeel P F, Mazouz H, el Esper N, Ghazali A, Boudailliez B

机构信息

Service de néphrologie, médecine interne, réanimation et transplantation, CHU, Amiens.

出版信息

Nephrologie. 1995;16(2):165-90.

PMID:7753302
Abstract
  1. 1 alpha (OH) vitamin D3 derivatives have an inconstant long term inhibitory effect on PTH secretion. As a matter of fact they act by three mechanisms, one of these being antagonistic: 1) a direct inhibitory action on the prepro-PTH gene; 2) an indirect inhibitory action by increasing plasma calcium; 3) an indirect stimulatory action by increasing plasma phosphate. These two latter phenomena are due to the stimulation of the intestinal absorption of these ions as well as to an intrinsic osteolytic action which may override the inhibition of the bone release of these ions in relation with the decrease of the PTH plasma levels. 2. The use of 1 alpha (OH)D3 derivatives in patients on chronic dialysis is justified in about 30% of the patients on dialysis when in spite of native vitamin D repletion and adequate predialysis control of plasma calcium (2.5 +/- 2 mmol/l) and of plasma phosphate (1.4 - 1.7 mmol/l), the PTH plasma levels are 3 or 5 fold the upper limit of normal whether the patient is on hemodialysis or on CAPD. When hyperphosphatemia is > 1.7 mmol/l it is first necessary to correct it by the use of higher doses of alkaline calcium salts given with the meals as phosphate binder together with a negative perdialytic calcium balance induced by a lower dialysate calcium in order to avoid hypercalcemia. Control of hyperphosphatemia is indeed a necessary prerequisite for the long term PTH suppressive efficacy of 1 alpha OH vitamin D derivatives. 3. The use of 1 alpha(OH)D3 derivatives in the treatment of the predialysis uremic patients is even more limited because there is no additional mean to decrease the risk of hypercalcemia when oral calcium is used as phosphate binder because of the danger of aluminum and magnesium phosphate binders. Fortunately in the adult, oral calcium used as phosphate binder in association with phosphate restriction and correction of possible vitamin D depletion and acidosis is usually efficace to control hyperparathyroïdism without 1 alpha OH vitamin D3. This is not the case in the child to whom protein and phosphate restriction should not be prescribed because of its incompatibility with the Recommended Diet Allowance. Fortunately the high remodeling rate of his growing bones, decreases the risk of hypercalcemia due to the combination of CaCO3 and 1 alpha OH vitamin D3.
摘要
  1. 1α(OH)维生素D3衍生物对甲状旁腺激素(PTH)分泌的长期抑制作用并不稳定。实际上,它们通过三种机制发挥作用,其中一种是拮抗作用:1)对前甲状旁腺素原基因的直接抑制作用;2)通过增加血浆钙产生的间接抑制作用;3)通过增加血浆磷酸盐产生的间接刺激作用。后两种现象是由于这些离子的肠道吸收受到刺激以及一种内在的溶骨作用,这种溶骨作用可能会克服因PTH血浆水平降低而导致的这些离子从骨骼释放的抑制作用。2. 在慢性透析患者中,当尽管补充了天然维生素D且透析前血浆钙(2.5±2 mmol/L)和血浆磷酸盐(1.4 - 1.7 mmol/L)得到充分控制,但无论是血液透析还是持续性非卧床腹膜透析(CAPD)患者的PTH血浆水平是正常上限的3倍或5倍时,约30%的透析患者使用1α(OH)D3衍生物是合理的。当高磷血症>1.7 mmol/L时,首先必须通过餐时使用更高剂量的碱性钙盐作为磷结合剂,并结合较低透析液钙诱导的透析后负钙平衡来纠正,以避免高钙血症。控制高磷血症确实是1α羟维生素D衍生物长期抑制PTH疗效的必要前提。3. 1α(OH)D3衍生物在透析前尿毒症患者治疗中的应用更为有限,因为当口服钙用作磷结合剂时,由于铝和镁磷结合剂的风险,没有其他方法可降低高钙血症的风险。幸运的是,在成年人中,口服钙与磷限制以及纠正可能的维生素D缺乏和酸中毒联合用作磷结合剂时,通常能有效控制甲状旁腺功能亢进,而无需使用1α羟维生素D3。儿童情况并非如此,由于蛋白质和磷限制与推荐膳食摄入量不相容,不应给儿童开此类处方。幸运的是,儿童生长骨骼的高重塑率降低了因碳酸钙和1α羟维生素D3联合使用导致高钙血症的风险。

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