Effect of High-Dose Glucocorticoids on Markers of Inflammation and Bone Metabolism in Patients with Primary Glomerular Disease.

Background: Glucocorticoids are one of the most commonly used drugs for treatment of inflammatory and autoimmune diseases. Sirtuin-1 (SIRT-1) belongs to the family of proteins involved in protection against inflammation and oxidative stress. A role of SIRT-1 in regulation of bone metabolism during high-dose steroid therapy is unknown. Objectives: The study assessed influence of high doses of intravenous corticosteroids on plasma inflammation and bone markers in patients with primary glomerular disease. Methods: The study included 40 patients (25 M, 15 F; mean age 53.1 ± 14 years) with chronic kidney disease (mean estimated glomerular filtration rate, 58.9 ± 31.3 mL/min). The main inclusion criterion was clinical and histopathological diagnosis of primary glomerular disease and urine protein excretion >2.0 g/24 h. The patients received intravenous pulses of methylprednisolone 20–30 mg/kg/day for three consecutive days followed by oral prednisone 0.8–1.0 mg/kg/day. The blood was taken before administration of methylprednisolone to assess plasma SIRT-1, sclerostin, calcium, phosphate, and parathormone; and first-morning urine sample was taken for measurement of calcium, phosphate, and albumin to creatinine ratio. The same laboratory tests were repeated after 4, 7, and 30 days during steroid therapy. Results: Plasma SIRT-1 increased significantly during steroid administration. Plasma sclerostin did not change significantly. There was a significant linear negative correlation between changes in SIRT-1 levels and sclerostin throughout the study. In a multiple regression model, changes of plasma sclerostin induced by steroid therapy explained the largest part of variance of respective changes of plasma SIRT-1. Conclusions: Plasma SIRT-1 increase during high-dose corticosteroid therapy is negatively related to the change of plasma sclerostin that may suggest a protective role of SIRT-1 against the negative effects of steroid therapy on bone. [ABSTRACT FROM AUTHOR]