Pęczek Katarzyna, Nowicki Michał
Department of Nephrology, Hypertension and Kidney Transplantation, Medical University of Lodz, Lodz, Poland,
Department of Nephrology, Hypertension and Kidney Transplantation, Medical University of Lodz, Lodz, Poland.
Kidney Blood Press Res. 2022;47(8):534-544. doi: 10.1159/000524091. Epub 2022 May 24.
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.
The study assessed influence of high doses of intravenous corticosteroids on plasma inflammation and bone markers in patients with primary glomerular disease.
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.
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.
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.
糖皮质激素是治疗炎症和自身免疫性疾病最常用的药物之一。沉默调节蛋白1（SIRT-1）属于参与抗炎和抗氧化应激保护的蛋白质家族。SIRT-1在大剂量类固醇治疗期间对骨代谢调节中的作用尚不清楚。
本研究评估大剂量静脉注射糖皮质激素对原发性肾小球疾病患者血浆炎症和骨标志物的影响。
本研究纳入40例慢性肾脏病患者（男性25例，女性15例；平均年龄53.1±14岁）（平均估计肾小球滤过率为58.9±31.3 mL/min）。主要纳入标准为原发性肾小球疾病的临床和组织病理学诊断以及尿蛋白排泄>2.0 g/24 h。患者连续三天接受20-30 mg/kg/天的静脉注射甲泼尼龙脉冲治疗，随后口服0.8-1.0 mg/kg/天的泼尼松。在给予甲泼尼龙之前采集血液以评估血浆SIRT-1、硬化素、钙、磷和甲状旁腺激素；采集晨尿样本以测量钙、磷和白蛋白与肌酐比值。在类固醇治疗期间的第4、7和30天重复相同的实验室检查。
在类固醇给药期间，血浆SIRT-1显著升高。血浆硬化素无显著变化。在整个研究过程中，SIRT-1水平变化与硬化素之间存在显著的线性负相关。在多元回归模型中，类固醇治疗引起的血浆硬化素变化解释了血浆SIRT-1相应变化的最大部分方差。
大剂量糖皮质激素治疗期间血浆SIRT-1升高与血浆硬化素变化呈负相关，这可能表明SIRT-1对类固醇治疗对骨骼的负面影响具有保护作用。
