Strategies to minimize bone disease in renal failure.
The skeletal disorders associated with renal insufficiency result from alterations in calcium, phosphorus, and vitamin D metabolism. Each requires intervention to prevent and control the problem. Hyperparathyroidism and its treatment can also result in extraskeletal complications. To prevent the development of parathyroid hyperplasia and the skeletal complications of chronic kidney disease, it is desirable to initiate interventions early in the course of kidney disease; however, many patients present with established hyperparathyroidism and additional strategies are necessary to suppress hyperparathyroidism. Mainstays of this approach are the control of phosphorus and the use of vitamin D analogs. Phosphorus control requires the use of phosphate binders, preferably non-calcium-containing binders, to prevent intestinal phosphorus absorption. Vitamin D analogs are used to suppress hyperparathyroidism and have the potential to have lesser toxicity than calcitriol. Paricalcitol is the most widely used vitamin D analog in this country and it effectively suppresses hyperparathyroidism with only minimal effects on calcium and phosphorus. A substantial body of data in experimental animals supports the use of paricalcitol as a preferential therapeutic agent. Recently, an additional vitamin D sterol, doxercalciferol, has been introduced, which is metabolized to 1,25-dihydroxyvitamin D(2). Although initially thought to have lesser toxicity than its vitamin D(3) counterpart, recent studies have not provided support for a major difference in this regard. Doxercalciferol is also effective in lowering parathyroid hormone (PTH), though hypercalcemia in hyperphosphatemic episodes occurred relatively frequently during the clinical studies. As these therapeutic strategies are undertaken, it is important not to oversuppress PTH and decrease bone turnover to abnormally low levels because of the risk for adynamic renal bone disease. It is possible that when bone turnover is abnormally low, the extraskeletal deposition of calcium in blood vessels and other tissues is enhanced. Accordingly, constant monitoring is required during treatment, with emphasis on minimizing the calcium load, and, if monitored correctly, a satisfactory control of hyperparathyroidism may be achieved with the agents currently available.
Martin
K J
KJ
Division of Nephrology, Department of Internal Medicine, Saint Louis University School of Medicine, St. Louis, MO 63110, USA. martinkj@slu.edu
González
E A
EA
D000818:Animals; D002118:Calcium / Q000378:metabolism; D012080:Chronic Kidney Disease-Mineral and Bone Disorder / Q000209:etiology / Q000517:prevention & control*; D004872:Ergocalciferols / Q000494:pharmacology / Q000627:therapeutic use; D006801:Humans; D006961:Hyperparathyroidism / Q000150:complications / Q000378:metabolism / Q000517:prevention & control*; D010024:Osteoporosis / Q000517:prevention & control; D010281:Parathyroid Hormone / Q000037:antagonists & inhibitors; D010758:Phosphorus / Q000097:blood; D006435:Renal Dialysis; D051437:Renal Insufficiency / Q000150:complications* / Q000378:metabolism / Q000628:therapy; D014807:Vitamin D / Q000031:analogs & derivatives
D004872:Ergocalciferols; D010281:Parathyroid Hormone; D014807:Vitamin D; D010758:Phosphorus; C084656:paricalcitol; D002118:Calcium