Prytuła Agnieszka, Walle Johan Vande, Van Vlierberghe Hans, Kaufman Jean-Marc, Fiers Tom, Dehoorne Jo, Raes Ann
Pediatric Nephrology and Rheumatology Department, Ghent University Hospital, De Pintelaan 185, 9000, Ghent, Belgium.
Department of Gastroenterology and Hepatology, Ghent University Hospital, Ghent, Belgium.
Endocrine. 2016 Apr;52(1):93-102. doi: 10.1007/s12020-015-0757-9. Epub 2015 Oct 3.
The aim of the study was to identify factors associated with 1,25(OH)2D3 concentrations in liver transplant recipients with emphasis on the renal function and catabolism. We also tested the hypothesis that tacrolimus increases 1,25(OH)2D3 concentrations. Serum 25(OH)D3, 1,25(OH)2D3, and 24,25(OH)2D3 were measured in 41 patients before, at 2 weeks and 3 months after transplantation. Dose-adjusted tacrolimus concentration was used as a surrogate marker of CYP3A4 activity. Factors associated with 1,25(OH)2D3 were identified using multivariate linear regression analysis. The median 1,25(OH)2D3 levels remained stable: 55 versus 46 pg/ml (P = 0.36) despite an increase in 25(OH)D3 from 18 ng/ml at baseline to 26 ng/ml (P = 0.03), serum albumin (34 to 41 g/l, P = 0.02), and comparable eGFR at baseline and month 3 (94 and 92 ml/min, respectively, P = 0.15). At 3 months 19 % of patients had 1,25(OH)2D3 < 25 pg/ml. Low eGFR and a low dose-adjusted tacrolimus concentration were both independently associated with 1,25(OH)2D3 at 3 months. Liver transplant recipients with impaired renal function or a low dose-adjusted tacrolimus concentration suggesting a high CYP3A4 are at risk of low 1,25(OH)2D3 concentrations. The use of tacrolimus does not lead to an increase in 1,25(OH)2D3 concentrations in a clinical setting.
本研究的目的是确定肝移植受者中与1,25(OH)₂D₃浓度相关的因素，重点关注肾功能和分解代谢。我们还检验了他克莫司会增加1,25(OH)₂D₃浓度这一假设。在41例患者移植前、移植后2周和3个月时检测血清25(OH)D₃、1,25(OH)₂D₃和24,25(OH)₂D₂。将剂量调整后的他克莫司浓度用作CYP3A4活性的替代标志物。使用多元线性回归分析确定与1,25(OH)₂D₃相关的因素。尽管25(OH)D₃从基线时的18 ng/ml增至26 ng/ml（P = 0.03）、血清白蛋白从34 g/l增至41 g/l（P = 0.02），且基线和第3个月时的估算肾小球滤过率（eGFR）相当（分别为94和92 ml/min，P = 0.15），但1,25(OH)₂D₃的中位数水平保持稳定：分别为55和46 pg/ml（P = 0.36）。在3个月时，19%的患者1,25(OH)₂D₃< 25 pg/ml。低eGFR和低剂量调整后的他克莫司浓度均与3个月时的1,25(OH)₂D₃独立相关。肾功能受损或剂量调整后的他克莫司浓度低提示CYP3A4高的肝移植受者有1,25(OH)₂D₃浓度低的风险。在临床环境中，使用他克莫司不会导致1,25(OH)₂D₃浓度升高。
