Renal osteodystrophy

Osteitis fibrosa cystica Renal osteodystrophy Osteosclerosis Anticonvulsant treatment... 

In the treatment of diseases where the metaboUtes are not being deUvered to the system, synthetic metaboUtes or active analogues have been successfully adrninistered. Vitamin metaboUtes have been successfully used for treatment of milk fever ia catde, turkey leg weakness, plaque psoriasis, and osteoporosis and renal osteodystrophy ia humans. Many of these clinical studies are outlined ia References 6, 16, 40, 51, and 141. The vitamin D receptor complex is a member of the gene superfamily of transcriptional activators, and 1,25 dihydroxy vitamin D is thus supportive of selective cell differentiation. In addition to mineral homeostasis mediated ia the iatestiae, kidney, and bone, the metaboUte acts on the immune system, P-ceUs of the pancreas (iasulin secretion), cerebellum, and hypothalamus. 

Renal osteodystrophy stems from disruptions in calcium, phosphorus, and vitamin D homeostasis through the interaction with the parathyroid hormone. 

What information would you request to determine if the patient has renal osteodystrophy ... 

FIGURE 23-5. Pathogenesis of secondary hyperparathyroidism and renal osteodystrophy in patients with CKD. 

Clinical Presentation of Secondary Hyperparathyroidism and Renal Osteodystrophy ... 

Renal osteodystrophy Altered bone turnover that results from sustained metabolic conditions that occur in chronic kidney disease, including secondary hyperparathyroidism, hyperphosphatemia, hypocalcemia, and vitamin D deficiency. 

Secondary hyperparathyroidism Increased secretion of parathyroid hormone from the parathyroid glands caused by hyperphosphatemia, hypocalcemia, and vitamin D deficiency that result from decreased kidney function. It can lead to bone disease (renal osteodystrophy). 

Patients with end-stage renal disease hyperphosphatemia ineffectively filter excess phosphate that enters the body in the normal diet.278 Elevated phosphate produces the bone disorder renal osteodystrophy. Skeletal deformity may occur, possibly associated with cardiovascular disease. Calcium deposits may further build up around the body and in blood vessels creating further health risks. The use of lanthanum carbonate is being promoted as an alternative to aluminum-based therapies.279,280 Systemic absorption, and cost have produced a clinical candidate, Fosrenol (AnorMED), an intriguing use of a lanthanide compound in therapy. 

Calcium-phosphorus balance is mediated through a complex interplay of hormones and their effects on bone, GI tract, kidney, and parathyroid gland. As kidney disease progresses, renal activation of vitamin D is impaired, which reduces gut absorption of calcium. Low blood calcium concentration stimulates secretion of parathyroid hormone (PTH). As renal function declines, serum calcium balance can be maintained only at the expense of increased bone resorption, ultimately resulting in renal osteodystrophy (ROD) (Fig. 76-7). 

FIGURE 76-7. Pathogenesis of secondary hyperparathyroidism and renal osteodystrophy in patients with chronic kidney disease. These adaptations are lost as renal failure progresses. (Ca, calcium, P04 phosphate PTH, parathyroid hormone.)... 

Patients with advanced renal insufficiency (Ccr less than 30 mL/min) exhibit phosphate retention and some degree of hyperphosphatemia. The retention of phosphate plays a role in causing secondary hyperparathyroidism associated with osteodystrophy and soft-tissue calcification. Calcium acetate, when taken with meals, combines with dietary phosphate to form insoluble calcium phosphate, which is excreted in the feces. 

The pharmacotherapeutic uses of vitamin D include vitamin D deficiencies, rickets in children and osteomalacia in adults, and renal osteodystrophy in patients with chronic renal failure. For metabolic rickets in patients with a deficiency of... 

The treatment of the complications of CRF may occur before or during dialysis. They include pericarditis, congestive heart failure, hypertension, hemopoietic abnormalities and renal osteodystrophy. 

Renal osteodystrophy is a complex disorder with several pathogenic factors. Histological evidence of bone disease is common in early renal failure and deficits in calcitriol synthesis seems to be an important factor in the pathogenesis of secondary hyperparathyroidism in early CRF. The most common component is osteitis fibrosa manifested as subperiosteal resorption of bone. This is due to decreased excretion as well as increased secretion of parathyroid hormone. In CRF small increments of serum phosphorus cause small decreases in serum calcium. 

Patients with chronic renal failure develop hyperphosphatemia, hypocalcemia, secondary hyperparathyroidism, and severe metabolic bone disease. The secondary hyperparathyroidism is thought to be due to hyperphosphatemia and decreased 1, 25-(OH)2 formation. Oral or intravenous l,25-(OH)2D3 (calcitriol) therapy along with oral phosphate-binding agents and calcium supplementation is effective in reducing the effects of renal osteodystrophy. 

Nutritional rickets PO 0.5 mg as a single dose or 13-50 mcg/day until healing occurs. Renal osteodystrophy PO 0.25-0.6 mg/24 hr adjusted as necessary to achieve normal serum calcium levels and promote bone healing. 

Vitamin D analog of choice for prevention and treatment of renal osteodystrophy less expensive than calcitriol... 

It is indicated in osteoporosis, hypoparathyroidism, hyperparathyroidism (with bone disease), renal osteodystrophy, nutritional and malabsorptive rickets, hypophosphataemic vitamin D resistant rickets and osteomalacia. 

Osteitis fibrosa does not occur, as in renal osteodystrophy. The common features that appear to be important in this group of diseases are malabsorption of calcium and malabsorption of vitamin D. Liver disease may, in addition, reduce the production of 25(OH)D from vitamin D, although its importance in all but patients with terminal liver failure remains in dispute. The malabsorption of vitamin D is probably not limited to exogenous vitamin D. The liver secretes into bile a substantial number of vitamin D metabolites and conjugates that are reabsorbed in (presumably) the distal jejunum and ileum. Interference with this process could deplete the body of endogenous vitamin D metabolites as well as limit absorption of dietary vitamin D. 

In mild forms of malabsorption, vitamin D (25,000-50,000 units three times per week) should suffice to raise serum levels of 25(OH)D into the normal range. Many patients with severe disease do not respond to vitamin D. Clinical experience with the other metabolites is limited, but both calcitriol and calcifediol have been used successfully in doses similar to those recommended for treatment of renal osteodystrophy. Theoretically, calcifediol should be the drug of choice under these conditions, because no impairment of the renal metabolism of 25(OH)D to l,25(OH)2D and 24,25(OH)2D exists in these patients. Both calcitriol and 24,25(OH)2D may be of importance in reversing the bone disease. However, calcifediol is no longer available. 

Renal rickets (renal osteodystrophy) This disorder results from chronic renal failure and, thus, the decreased ability to form the active form of the vitamin. 1,25-diOH cholecalciferol (calcitriol) administration is effective replacement therapy. 

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