The Role of Urinary Calcium and Chitotriosidase in a Cohort of Chronic Sarcoidosis Patients

Abstract

<b><i>Background:</i></b> Calcium metabolism alterations are quite common in sarcoidosis and have been correlated with disease activity. <b><i>Objectives:</i></b> The aim of the study was to investigate the clinical significance of calcium metabolism alterations in patients with chronic sarcoidosis. We paid particular attention to associations with specific disease phenotypes and chitotriosidase (CTO) expression. <b><i>Methods:</i></b> 212 chronic sarcoidosis patients (mean age 56.07 ± 12 years; 97 males) were retrospectively recruited. Demographic, clinical, functional, and radiological data, and serum-urinary calcium metabolism were entered into an electronical database for analysis. Levels of CTO and angiotensin-converting enzyme (ACE) were measured and bone mineral density and lung function tests were conducted. <b><i>Results:</i></b> Hypercalciuria and hypercalcemia were observed in 18.8 and 1.8% of patients, respectively. Urinary calcium levels correlated with CTO activity (<i>r</i> = 0.33, <i>p</i> = 0.0042). Patients with worsening persistent disease showed the highest levels of urinary calcium. Diffusing capacity of the lung for carbon monoxide (D<sub>LCO</sub>) percentage correlated inversely with urinary calcium (<i>r</i> = 0.1482; <i>p</i> = 0.0397). <b><i>Conclusions:</i></b> Calcium metabolism alteration, particularly hypercalciuria, was observed in a significant percentage of patients of sarcoidosis. Urinary calcium was correlated with clinical status, D<sub>LCO</sub>, and serum CTO activity, suggesting its potential role as a biomarker of the activity and severity of sarcoidosis.

Hypercalciuria in Sarcoidosis: A Specific Biomarker With Clinical Utility

“…Hypercalciuria and hypercalcemia are quite common anomalies in sarcoidosis patients and need to be addressed to prevent severe complications or chronic organ failure (e.g., ventricular arrhythmia, nephrolithiasis, nephrocalcinosis, chronic renal failure). The clinical features of calcium dysregulation in sarcoidosis have been repeatedly described (2,15,25), as well as its underlying pathophysiological processes: however, there are still many concerns about how it should be treated and monitored (26). The guidelines published recently by the ATS endorsed the utility of assessing calcium metabolism in sarcoidosis, recommending serum calcium testing at diagnosis and follow-up to screen for specific alterations (6).…”

“…It has been clearly demonstrated that hypercalciuria and hypercalcemia are reliable negative prognostic factors, being associated with a chronic-persistent disease phenotype, high angiotensin-converting enzyme (ACE) levels, old age, hypergammaglobulinemia, and extrapulmonary sarcoid localizations (particularly in the spleen, bone and kidneys) (12)(13)(14). Our research group recently demonstrated a correlation between hypercalciuria and chitotriosidase concentrations, radiological evidence of severe lung involvement, deterioration of lung function (particularly concerning lung alveolar diffusion) and hepatosplenic disease (15), confirming the potential of this non-invasive and cost-sparing biomarker in routine clinical practice.…”

Systematic Review and Metanalysis of Oncomarkers in IPF Patients and Serial Changes of Oncomarkers in a Prospective Italian Real-Life Case Series

“…In the present study, we evaluated serial changes in chitotriosidase and circulating oncomarkers in a cohort of ILD patients divided into IPF and non-IPF groups. Increased chitotriosidase values have been repeatedly reported in sarcoidosis patients, and may predict clinical course and potential relapse of the disease [ 23 , 24 , 25 , 26 , 27 , 28 ]. As expected, serum chitotriosidase in our non-IPF group was high in relation to the presence of sarcoidosis patients.…”

Toll-like receptors 2 expression in mediastinal lymph node of patients with sarcoidosis

“…The dysregulation of the expression level of TLR2 warrants further investigation of its function on the potential causative agent and pathogenic mechanism of pulmonary sarcoidosis. Altered calcium metabolism, which affects approximately 5% to 25% of sarcoidosis patients, can present as hypercalcemia, hypercalciuria, or kidney stones and have been considered correlating with disease activity (24)(25)(26). Calcium metabolism alteration in sarcoidosis is usually because of increased activity of 1-alpha hydroxylase in macrophages of pulmonary granuloma, resulting in low levels of 25-hydroxyvitamin D and high levels of calcitriol (25).…”