Kidney disease, chronic hypocalcemia

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. 

The main features of hypocalcemia are neuromuscular—tetany, paresthesias, laryngospasm, muscle cramps, and convulsions. The major causes of hypocalcemia in the adult are hypoparathyroidism, vitamin D deficiency, chronic kidney disease, and malabsorption. Neonatal hypocalcemia is a common disorder that usually resolves without therapy. The roles of PTH, vitamin D, and calcitonin in the neonatal syndrome are under active investigation. Large infusions of citrated blood can produce hypocalcemia by the formation of citrate-calcium complexes. Calcium and vitamin D (or its metabolites) form the mainstay of treatment of hypocalcemia. 

In contrast to the hypocalcemia that is more often associated with chronic kidney disease, some patients may become hypercalcemic from two other possible causes (in addition to overzealous treatment with calcium). The most common cause of hypercalcemia is the development of severe secondary (sometimes referred to as tertiary) hyperparathyroidism. In such cases, the PTH level in blood is very high. Serum alkaline phosphatase levels also tend to be high. Treatment often requires parathyroidectomy. 

Acute renal failure due to cisplatin therapy is usually partially reversible with time and supportive care, including dialysis. Serummag-nesium concentrations should be monitored frequently and hypomagnesemia corrected (see Chap. 50). Hypocalcemia and hypokalemia may be difficult to reverse until hypomagnesemia is corrected. Progressive chronic kidney disease due to cumulative toxicity may not be reversible and in some cases may require chronic dialysis support. 

The most common cause of hyperphosphatemia is a decrease in urinary phosphorus excretion secondary to decreased glomerular filtration rate. ° Retention of phosphorus decreases vitamin D synthesis and induces hypocalcemia, which leads to an increase in PTH. This physiologic response inhibits further tubular reabsorption of phosphorus to correct hyperphosphatemia and normalize serum calcium concentrations. Patients with excessive exogenous phosphorus administration or endogenous intracellular phosphorus release in the setting of acute renal failure may develop profound hyperphosphatemia. Severe hyperphosphatemia is commonly encountered in patients with chronic kidney disease, especially those with GFRs less than 15 mL/ min per 1.73 m (see Chap. 44). 

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. 

Cinacalcet is available in 30-, 60-, and 90-mg tablets. Optimal doses have not been defined. The recommended starting dose for treatment of secondary hyperparathyroidism in patients with chronic kidney disease on dialysis is 30 mg once daily, with a maximum of 180 mg/day. For treatment of parathyroid carcinoma, a starting dose of 30 mg twice daily is recommended, with a maximum of 90 mg four times daily. The starting dose is titrated upward every 2 to 4 weeks to maintain the PTH level between 150 and 300 pg/mL (secondary hyperparathyroidism) or to normalize serum calcium (parathyroid carcinoma). The principal adverse event with cinacalcet is hypocalcemia. Thus, the drug should not be used if the initial serum calcium concentration is less than 8.4 mg/dL serum calcium and phosphorus concentrations should be measured within 1 week, and PTH should be measured within 4 weeks after initiating therapy or after changing dosage. 

A 40-year-old man with chronic kidney disease on phenytoin for seizme prophylaxis after an intracranial hemorrhage developed severe hypocalcemia associated with profound vitamin D deficiency. Phenytoin affects the cytochrome P450 system and can accelerate the breakdown of 25-hydroxyvitamin D3 and la,25-dihydroxyvitamin D3. Therefore, patients with chronic kidney disease may be more likely to develop hypocalcemia on phenytoin due to its effects on vitamin D metabolism [135 ]. 

The major effects of hyperphosphatemia are related to the development of hypocalcemia (caused by phosphate inhibition of renal la-hydroxylase) and its related consequences, as well as vascular and organ damage resulting from the deposition of calcium-phosphate crystals. Extravascular calcification can result in band keratopathy, red eye, pruritus, and periarticular calcification, especially in renal failure patients (see Chap. 44). In addition, soft-tissue calcifications in the conjunctiva, skin, heart, cornea, lung, gastric mucosa, and kidney have been observed, primarily in chronic renal failure patients." Hyperphosphatemia associated with chronic renal disease may result in renal osteodystrophy because of overproduction of parathyroid hormone. This condition is discussed in detail in Chap. 44. 

In addition to an increase in serum urea and creatinine levels, uric acid and inorganic phosphate levels also increase in chronic renal failure. The increase in serum inorganic phosphate leads to deposition of calcium phosphate in bones, causing hypocalcemia. In the early stages of chronic renal failure, calcium levels are restored by the stimulation of parathyroid hormone. However, as the renal disease progresses, the ability of the kidney to hydroxylate vitamin D and thus convert it to the active form decreases, thereby affecting the uptake of calcium by the gut and thus perpetuating hypocalcemia. Serum alkaline phosphatase levels increase due to disordered bone metabolism. Loss of bicarbonate is seen in some patients with increased parathyroid hormone activity. 

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