Renal osteodystrophy vitamin

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. 

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). 

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). 

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... 

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. 

Renal osteodystrophy Chronic renal failure induces complex metabolic changes resulting in excessive bone resorption Vitamin D, calcium supplements... 

Vitamin D has been used in treating renal osteodystrophy. However, patients with a substantial degree of renal failure who are thus unable to convert vitamin D to its active metabolites usually are refractory to vitamin D. Its use is decreasing as more effective alternatives become available. 

Vitamin D-binding protein and its associated vitamin are lost in nephrotic urine. Biochemical abnormalities in nephrotic patients (children and adults) include hypocalcemia, both total (protein-bound) and ionized hypocalciuria, reduced intestinal calcium absorption and negative calcium balance reduced plasma 25-hydroxycholecalciferol and 24,25-dihydroxycholecalciferol and, surprisingly, also 1,25-dihydroxycholecalciferol and blunted response to parathormon (PTH) administration and increased PTH levels. Clinically, both osteomalacia and hyperparathyroidism have been described in nephrotic patients, more commonly in children than in adults, but bone biopsies are commonly normal, and clinically significant bone disease is very rare in nephrotic subjects. There is, however, evidence that patients with renal failure accompanied by nephrotic range proteinuria may be particularly prone to develop renal osteodystrophy. 

Because the kidney is the only significant source of la-OHase, inadequate formation of l,25-(OH)2D3 occurs in renal failure [168], Not only is the mass of kidney tissue and therefore of enzyme decreased, but also with renal failure, phosphate excretion is reduced and serum phosphate rises. Increased phosphate inhibits la-OHase so that little l,25-(OH)2D3 is formed. Acidosis, a frequent result of renal failure, also impairs la-OHase activity [169, 170]. Deficiency of the active form of vitamin D causes osteomalacia, a prominent feature of renal osteodystrophy. Therapy is directed toward use of l,25-(OH)2D3, reduction of serum phosphate, and correction of acidosis, so that residual la-OHase can be expressed. 

For vitamin D deficiency, 50,000 units once weekly or once monthly dosed dependent on serum cakium 025-0.5 meg orally or 1-2 mc mL intravenously daily for renal osteodystrophy, hypoparalhyroidisnu and refractory rickets... 

Hypercalcemia persists for many months after the cessation of excessive intakes of vitamin D, because of the accumulation of the vitamin in adipose tissue and its slow release into the circulation. The introduction of calcitriol and 1 a -hydroxycalcidiol for the treatment of such conditions as hypoparathyroidism, renal osteodystrophy, hypophosphatemic osteomalacia, and vitamin D-dependent rickets has meant that hypercalcemia is less of a problem than when high doses of vitamin D were used in the treatment of these conditions. Because calcitriol has a short half-life in the circulation, the resultant hypercalcemia is of shorter duration than after cholecalciferol, and adjustment of the dose is easier. 

Renal rickets (renal osteodystrophy) results from chronic renal failure where decreased ability to from active from of vitamin D. 

There is controversy about whether the long-term use of Cl-hydroxylated vitamin D analogues in non-dialysed patients with chronic renal insufficiency is associated with an impairment of glomerular filtration rate (SEDA-9, 639) (49). Treatment with these drugs should be restricted to patients with severe renal osteodystrophy. A proper dose should be administered in order to avoid a deleterious effect on renal function. Serum calcium and creatinine concentrations should be monitored carefully. The treatment should be withdrawn if hypercalcemia develops. 

Contraindications Hypercalcemia, hypervitaminosis D, or renal osteodystrophy with hyperphosphatemia. Use with caution in patients with arteriosclerosis, hyperphosphatemia, hypersensitivity to vitamin D, and renal or cardiac impairment. 

Coburn JW, Slatopolsky E. Vitamin D, parathyroid hormone, and renal osteodystrophy. In Brenner BM, Rector FC Jr, eds. The kidney, 4th ed. Philadelphia WB Saunders, 1991 2213-305. 

Renal osteodystrophy [due to decreased synthesis of 1,25-(0H)2D secondary to kidney failure] is treatable with synthetic l,25-(OH)2D or la-(OH)D. These compounds are also useful in other renal disorders such as hypoparathyroidism and vitamin D-dependent rickets. 

NKF-K/DOQI National Kidney Foundation-Kidney Disease Outcomes Quality Initiative PTH parathyroid hormone ROD renal osteodystrophy sHPT secondary hyperparathyroidism TIBC total iron-binding capacity TSat transferrin saturation VDR vitamin D receptor vWF von Willebrand factor... 

Renal osteodystrophy (ROD)—The condition resulting from sustained metabolic changes that occur with chronic kidney disease including secondary hyperparathyroidism, hyperphosphatemia, hypocalcemia, and vitamin D deficiency. The skeletal complications associated with ROD include osteitis fibrosa cystica (high bone turnover disease), osteomalacia (low bone turnover disease), adynamic bone disease, and mixed bone disorders. 

Dihydrotachysterol, a vitamin-D analog with antihypocalce-mic properties, is indicated in the treatment of familial hypophosphatemia hypocalcemia associated with hypoparathyroidism and pseudohypoparathyroidism and renal osteodystrophy in chronic uremia (see also Figure 66). 

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