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[Vitamin D treatment and renal osteodystrophy: indications and modalities]
A Fournier1, P Morinière, P Yverneau-Hardy
1Service de néphrologie, médecine interne, réanimation et transplantation, CHU, Amiens.
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.
Insights
1 alpha (OH) vitamin D3 derivatives offer limited long-term control of parathyroid hormone (PTH) secretion due to complex actions on calcium and phosphate. Effective use in dialysis patients requires strict hyperphosphatemia control before initiating treatment.
Area of Science:
- Nephrology
- Endocrinology
- Mineral and Bone Disorders
Background:
- 1 alpha (OH) vitamin D3 derivatives have multifaceted effects on parathyroid hormone (PTH) secretion, including direct and indirect mechanisms.
- These derivatives can directly inhibit the prepro-PTH gene and indirectly influence PTH by altering plasma calcium and phosphate levels.
- An intrinsic osteolytic action may counteract the bone-protective effects of these vitamin D derivatives, complicating their long-term efficacy.
Purpose of the Study:
- To evaluate the clinical utility and efficacy of 1 alpha (OH) vitamin D3 derivatives in managing secondary hyperparathyroidism in chronic kidney disease patients.
- To determine the conditions and patient subgroups where 1 alpha (OH) vitamin D3 derivatives provide a justifiable therapeutic benefit.
- To assess the prerequisites for successful long-term PTH suppression using 1 alpha (OH) vitamin D3 derivatives, particularly concerning mineral balance.
Main Methods:
- Analysis of the mechanisms of action of 1 alpha (OH) vitamin D3 derivatives on PTH secretion.
- Review of patient data to identify subgroups of chronic dialysis patients (hemodialysis and CAPD) benefiting from 1 alpha (OH) vitamin D3 therapy.
- Evaluation of treatment strategies for hyperphosphatemia and hypercalcemia in predialysis and dialysis patients.
Main Results:
- Approximately 30% of chronic dialysis patients may benefit from 1 alpha (OH) vitamin D3 derivatives when PTH levels remain elevated despite adequate vitamin D repletion and mineral control.
- Effective control of hyperphosphatemia (plasma phosphate < 1.7 mmol/l) is crucial for the long-term PTH-suppressive efficacy of 1 alpha (OH) vitamin D3 derivatives.
- The use of 1 alpha (OH) vitamin D3 derivatives in predialysis uremic patients is more limited due to the risk of hypercalcemia, especially when using oral calcium binders.
Conclusions:
- 1 alpha (OH) vitamin D3 derivatives have an inconsistent long-term inhibitory effect on PTH secretion.
- Careful management of hyperphosphatemia is a prerequisite for the successful application of 1 alpha (OH) vitamin D3 derivatives in dialysis patients.
- Alternative strategies, including phosphate restriction and calcium-based binders, are often sufficient for managing hyperparathyroidism in adult predialysis patients without 1 alpha (OH) vitamin D3.