Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0020438 (hypercalciuria)
 2,502 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Hypercalcemia and hypercalciuria in sarcoidosis are thought to result from the endogenous overproduction of an active vitamin D metabolite. We employed primary cultures of pulmonary alveolar macrophages from two patients with biopsy-proven pulmonary sarcoidosis and a recent or current clinical abnormality in calcium metabolism to synthesize in vitro a 1,25-dihydroxyvitamin D3 [1,25-(OH)2D3]-like metabolite from 25-hydroxyvitamin D3 (25OHD3). The macrophage metabolite cochromatographed with [3H]1,25-(OH)2D3 on normal phase and reverse phase high performance liquid chromatography and was bound with high affinity by the chick intestinal receptor for 1,25-(OH)2D3. On UV spectroscopy, the metabolite possessed the carbon-5,7,10 (19) cis-triene chromophore characteristic of a vitamin D sterol. Electron impact mass spectrometry of trimethylsilyl ether derivatives of the metabolite revealed a mass fragmentation pattern similar to that of the trimethylsilyl ether derivative of authentic 1,25-(OH)2D3. The incubation of cultured macrophages from two patients with idiopathic pulmonary fibrosis and two with scleroderma with [3H]25OHD3 did not result in production of a metabolite with the chromatographic identity of 1,25-(OH)2D3. These data indicate that the metabolite of 25OHD3 synthesized by sarcoid macrophages in vitro is 1,25-(OH)2D3 and that the macrophage is a synthetic source of the sterol metabolite in sarcoidosis.
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PMID:Isolation and structural identification of 1,25-dihydroxyvitamin D3 produced by cultured alveolar macrophages in sarcoidosis. 298 38

Background: Changes in calcium metabolism are quite common in sarcoidosis: hypercalciuria is linked to a persistent clinical phenotype and more active disease. No data is yet available on the specificity of parameters of calcium metabolism as biomarkers for distinguishing different chronic interstitial lung diseases (ILD). Here we assessed calcium metabolism in an Italian population of sarcoidosis patients, which included a group with stage IV fibrotic disease, and compared the results with those of idiopathic pulmonary fibrosis (IPF) and chronic hypersensitivity pneumonitis (cHP) patients. Population and Methods: We recruited sarcoidosis, IPF and cHP patients retrospectively. All patients were diagnosed through multidisciplinary discussion and were monitored at the Regional ILD Referral Centre in Siena. Clinical, radiological, functional, immunological and laboratory parameters were collected and entered in an electronic database for data analysis. Results: A total of 305 patients (237 sarcoidosis, 40 IPF and 28 cHP) were enrolled. Sarcoidosis patients included a predominance of females and were significantly younger than IPF and cHP patients (p < 0.0001 for both). In the sarcoidosis population, 17 patients (7.2%) showed radiological evidence of lung fibrosis, according the Scadding classification; fibrotic disease was also confirmed by CT scan. Concerning calcium metabolism, sarcoidosis patients showed significantly higher serum and urinary concentrations of calcium than IPF and cHP patients (p = 0.0004 and p < 0.0001, respectively). These findings were also confirmed when comparing groups with fibrotic sarcoidosis, IPF and cHP (p = 0.0237 and p = 0.0138). According to receiver operating characteristics (ROC) curve analysis, urinary calcium showed better diagnostic accuracy than serum calcium in discriminating sarcoid and non-sarcoid lung fibrosis (AUC 0.7658 vs. 0.6205; p = 0.0026 vs. p = 0.1820). Discussion: Our results confirmed that changes in calcium metabolism, particularly hypercalciuria, occur in a substantial percentage of patients with sarcoidosis. Higher serum and urinary concentrations of calcium were found than in IPF and cHP; the same results were observed when the comparison was limited to patients with fibrotic sarcoidosis, supporting the hypothesis that dysregulation of calcium metabolism may be a special feature of sarcoid granulomas. Hypercalciuria distinguished fibrotic sarcoidosis from IPF and cHP, suggesting that assessment of calcium metabolism may be useful in the diagnostic pathway of ILDs.
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PMID:Hypercalciuria in Sarcoidosis: A Specific Biomarker With Clinical Utility. 3319 14