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.

Different Effects of Empagliflozin on Markers of Mineral-Bone Metabolism in Diabetic and Non-Diabetic Patients with Stage 3 Chronic Kidney Disease.

Background and objectives: Treatment with sodium-glucose co-transporter 2 (SGLT2) inhibitors decrease tubular reabsorption of phosphate, which may explain the reduction of bone mineral density and an excess of bone fractures observed in some studies with this class of drugs. Since an increased risk of bone fractures may also be a result of diabetes itself, our study aimed to compare the effect of empagliflozin on the markers of mineral-bone metabolism between diabetic (DKD) and non-diabetic (ND-CKD) patients with stage 3 chronic kidney disease (CKD). Materials and Methods: Forty-two patients with stage 3 CKD and A2 albuminuria, including 18 with DKD and 24 ND-CKD, were investigated. All subjects received 10 mg empagliflozin for 7 days. Serum calcium, phosphate, parathormone (PTH), calcitriol, bone alkaline phosphatase (BAP), FGF-23 and urine calcium, phosphate, albumin and the renal tubular maximum reabsorption rate of phosphate to the glomerular filtration rate (TmP-GFR) were measured before and after empagliflozin administration. Differences in biomarkers response to empagliflozin between DKD and ND-CKD were the main measures of outcome. Results: There was a significant increase of PTH, FGF-23 and phosphate in DKD but not in ND-CKD whereas BAP and TmP/GFR did not change in either group. The reduction of albuminuria was only significant in ND-CKD. Conclusions: The effect of SGLT2 inhibitor on serum mineral and bone markers and on albuminuria in patients with CKD may be differently modified by the presence of diabetes mellitus.

Two Faces of Vitamin C in Hemodialysis Patients: Relation to Oxidative Stress and Inflammation.

Hemodialysis (HD) is the most common method of renal replacement therapy. Besides toxins, it eliminates nutrients from the circulation, such as ascorbic acid (AA). HD-patients present AA deficiency more often than representatives of the general population, also due to dietary restrictions. This condition aggravates oxidative stress and inflammation related to uremia and extracorporeal circulation and increases cardiovascular risk followed by mortality. Supplementation of AA seems to be a promising approach in the treatment of hemodialysis patients. Many successful interventions restored plasma AA concentration in HD patients by enteral or intravenous supplementation, concomitantly inhibiting oxidative stress and inflammation. A significant number of studies reported opposite, serious pro-oxidant effects of AA. In this narrative review, we present studies, commenting on their limitations; on AA plasma or serum concentration and the influence of its supplementation on protein and lipid peroxidation, DNA damage, reactive oxygen species generation, paraoxonase activity, advanced glycation endproducts, and C-reactive protein (CRP) concentration. Moreover, in terms of safety, the possible development of oxalosis in HD patients regarding the intravenous or enteral route of AA administration is discussed. Unequivocal clinical results of recent studies on hemodialysis patients are displayed.