Kidney disease, chronic hyperparathyroidism

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. 

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.)... 

Zemplar (paricalcitol) injection is a synthetically manufactured selective vitamin D receptor activator (SVDRA) indicated for the prevention and treatment of secondary hyperparathyroidism associated with chronic kidney disease (CKD) stage 5. The U.S. Food Drug Administration (FDA) approved a capsule form of Zemplar for development to satisfy a need for an oral formulation. The objective of study M04-693 was to assess the bioequivalencies of several dosage strengths of paricalcitol capsules under fasting conditions. 

Paricalcitol is a synthetically manufactured analogue of calcitriol. It is indicated for the prevention and treatment of secondary hyperparathyroidism in chronic kidney disease. Cinacalcet, a drug that acts as a calcimimetic, can be added if the effects on PTH levels are isufficient. 

Cinacalcet is the first representative of a new class of drugs that activates the calcium sensing receptor (CaR). CaR is widely distributed but has its greatest concentration in the parathyroid gland. Cinacalcet blocks PTH secretion by this mechanism and is approved for the treatment of secondary hyperparathyroidism in chronic kidney disease and for the treatment of parathyroid carcinoma. 

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. 

The choice of vitamin D preparation to be used in the setting of chronic kidney disease depends on the type and extent of bone disease and hyperparathyroidism. Individuals with vitamin D deficiency or insufficiency should first have their 25(OH)D levels restored to normal (above 30 ng/mL) with vitamin D. l,25(OH)2D3 (calcitriol) rapidly corrects... 

Two analogs of calcitriol—doxercalciferol and paricalcitol—are approved for the treatment of secondary hyperparathyroidism of chronic kidney disease. Their principal advantage is that they are less likely than calcitriol to induce hypercalcemia for any given reduction in PTH. Their greatest impact is in patients in whom the use of calcitriol may... 

Quarles LD Cinacalcet HCI A novel treatment for secondary hyperparathyroidism in stage 5 chronic kidney disease. Kidney Int Suppl 2005 Jul(96) S24. 

There is epidemiologic evidence to suggest an increased prevalence of duodenal ulcers in patients with certain chronic diseases, but the pathophysiologic mechanisms of these associations are uncertain. A strong association exists in patients with systemic mastocytosis, multiple endocrine neoplasia type 1, chronic pulmonary diseases, chronic renal failure, kidney stones, hepatic cirrhosis, and ai-antitrypsin deficiency. An association may exist in patients with cystic fibrosis, chronic pancreatitis, Crohn s disease, coronary artery disease, polycythemia vera, and hyperparathyroidism. 

Cobum JW, et al. Doxercalcrferol safely suppresses PTH levels in patients with secondary hyperparathyroidism associated with chronic kidney disease stages 3 and 4. Am J Kidney Dis 2004 43 877-890. 

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. 

Tominaga Y, Tsuzuki T, Matsuoka A, et al. Expression of parafibromin in distant metastatic parathyroid tumors in patients with advanced secondary hyperparathyroidism due to chronic kidney disease. World J Surg. 2008 32 815-821. 

Cinacalcet is a calcimimetic agent that lowers parathyroid hormone (PTH) levels by increasing sensing receptor to extracellular calcium. This drug is indicated in the treatment of secondary hyperparathyroidism in patients with chronic kidney disease on dialysis and hypercalcemia in patients with parathyroid carcinoma. 

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. 

Systematic reviews In a meta-analysis of nine trials to evaluate the effectiveness of paricalcitol in the treatment of secondary hyperparathyroidism and proteinuria in chronic kidney disease patients, there was insufficient power to detect adverse events [70 ]. 

Han T, Rong G, Quan D, Shu Y, Liang Z, She N, et al. Meta-analysis the efficacy and safety of paricalcitol for thetreatment of secondary hyperparathyroidism and proteinuria in chronic kidney disease. Biomed Res Int 2013 2013 320560. 

Chronic renal failure. Normal kidney function is needed for the la-hydroxylation reaction that produces 1,25-DHCC. In chronic renal failure a cascade of events is triggered, leading to secondary hyperparathyroidism, which can progress to tertiary hyperparathyroidism and renal bone disease. 

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