MO084THE INFLUENCE OF INTRAVENOUS CORTICOSTEROIDS ON PLASMA SIRTUIN-1 AND SCLEROSTIN LEVELS IN PATIENTS WITH PRIMARY GLOMERULAR DISEASE

Abstract

Abstract Background and Aims SIRT-1 is member of seven protein family that are involved in the cellular response to inflammatory, metabolic, and oxidative stress. The sirtuin family is a group of class III histone deacetylases. The best known of the family is SIRT-1. It may induce organ protection through inactivation of apoptosis and anti-inflammatory action. Sclerostin is a glycoprotein produced by the osteocytes and an inhibitor of Wnt signaling. Increased activity of sclerostin increases the resorption of bone tissue and inhibits osteogenesis. It has been hypothesized that by deacetylating histones SIRT-1 could negatively regulate sclerostin gene. That mechanism requires a confirmation in clinical setting. This exploratory study was designed to assess the influence of high doses of intravenous methylprednisolone on plasma SIRT-1 and sclerostin levels in patients with primary glomerular disease. Method The study included 40 patients (25 M, 15 F; mean age 53.1±14 years, mean eGFR 58.9±31.3 ml/min) in different stages of chronic kidney disease. 20 patients had eGFR below the median value of 46 ml/min. The main inclusion criterion was the clinical and histopathological diagnosis of primary glomerular disease and urine protein excretion >2.0 g/24h. The main biopsy-proven diagnoses were IgA nephropathy (13 patients) and focal segmental glomerulonephritis (FSGS) (13 patients). The patients were hospitalized to receive scheduled 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 the administration of methylprednisolone to assess SIRT-1, sclerostin, calcium, phosphate and PTH and urine for was taken for the measurement of calcium, phosphate and albumin to creatinine ratio. The same laboratory tests were repeated after 4, 7 and 30 days of steroid therapy. Results Plasma SIRT-1 during increased significantly during steroid administration (Fig.1). Plasma sclerostin did not change significantly during the study however a statistically significant correlation between the changes of SIRT-1 levels and sclerostin was found. In a multiple regression model the changes of plasma sclerotin induced by steroid therapy explained the largest part of the variance of the respective changes of plasma SIRT-1. Conclusion Plasma SIRT-1 increases during high-dose corticosteroids therapy. The negative relation between the changes of plasma SIRT-1 and plasma sclerostin may suggest a protective role of SIRT-1 against the rapid bone loss induced by corticosteroids.