甲氨喋呤肾损害

MTX+米非司酮保守治疗异位妊娠致严重毒性反应病例分析,内蒙古医科大学附属医院肾内科 赵春梅,一、 保守治疗异位妊娠在临床广泛使用,我院近年异位妊娠基本情况终止异位妊娠方式本例患者的一些特点我院MTX致毒副作用病例,我院近年异位妊娠基本情况,异位妊娠住院患者平均年龄,异位妊娠住院患者平均住院时间,异位妊娠住院患者各时段总花费,异位妊娠住院患者各时段平均花费,2 终止异位妊娠方式,异位妊娠住院患者接受药物终止妊娠治疗比例,MTX+米非司酮保守治疗异位妊娠致严重毒性反应病例分析,3 本例患者的一些特点,1. 36岁，停经51天，既往有过敏性鼻炎史及家族史，有左氧氟沙星过敏史，无慢性肾脏病史2. 使用MTX80mg+米非司酮50mg bid*3 后逐渐出现口腔、鼻黏膜、消化道黏膜损害、皮肤关节损害、血液系统损害、心血管系统损害、急性肾损伤。,患者治疗期间HCG变化情况,在病程中血细胞计数变化较大,患者治疗期间血细胞变化情况,本例患者出现急性肾损伤的病因及相应对策,患者治疗期间肾功能变化情况,我院MTX致不良反应统计,AKI的定义和 诊断标准AKI的发病情况MTX肾损伤机理MTX致AKI虽不多见，但对预后影响很大如何处理MTX所致AKI,二 、MTX相关急性肾损伤的防治,A-AKI（acquired acute kidney injury，A-AKI）：起病前血清肌酐水平正常，随着疾病进展和各种医疗干预（如手术、造影检查、药物治疗等）导致肾功能迅速减退，符合AKI诊断标准。,AKI 在社区人群中发生率较低，住院患者中发生率高达13%18%，其中大部分患者都由非肾脏科医师诊治。2009年英国患者预后与死亡全国调查报道：死于AKI的患者仅50%接受恰当治疗。NICE（英国国家卫生与临床优化研究）指南主要针对非肾科医生，强调早期发现，风险评估，预防，早诊早治的重要性。,AKI诊断标准,MTX肾损伤机理：MTX直接损害肾小管,Assessment of the Role of Renal Organic Anion Transporters inrug-Induced Nephrotoxicity Yohannes Hagos Toxins 2010, 2, 2055-2082,PASX400,PASX1000,MTX致AKI虽不多见，但对预后影响很大,Resumption of High-dose Methotrexate after Acute Kidney Injury and Glucarpidase Use in Pediatric Oncology Patients Cancer. 2012 September 1; 118(17): 43214330,High Incidence of Methotrexate Associated Renal Toxicity inPatients with Lymphoma: A Retrospective Analysis.Jori May Leuk Lymphoma. 2014 July 16,MTX剂量越大，AKI发生率越高，MTX清除越困难,Creatinine clearance rate and serum creatinine concentration are related todelayed methotrexate elimination in children with lymphoblastic malignanciesJ. MAO, Neoplasma 61, 1, 2014,如何处理MTX所致AKI: 1 亚叶酸解毒,Acute Renal Failure Post High Dose Methotrexate Infusion Successfully Managed with High Dose Folinic Acid and High Flux Dialysis. SK Ramamoorthy Indian J Hematol Blood Transfus (Apr-June 2013) 29(2):9092.,2 羧肽酶解毒,High-dose methotrexate-induced nephrotoxicity in patients with osteosarcoma See comment in PubMed Commons belowCancer. 2004 May 15;100(10):2222-32,3 血液净化,High-dose methotrexate-induced nephrotoxicity in patients with osteosarcoma See comment in PubMed Commons belowCancer. 2004 May 15;100(10):2222-32,HA330-,HA330,HA280,HA230,HA130,各种血液净化滤器,其他治疗,More than 90% of MTX is cleared by the kidneys. MTX is poorly soluble at acidic pH, and its metabolites, 7-OHMTX and DAMPA, are six- to ten-fold less soluble than MTX, respectively. An increase in the urine pH from 6.0 to 7.0 results in greater solubility of MTX and its metabolites, a finding that underlies the recommendation of intravenous hydration (2.53.5 l of fluid perm2 per 24 h, beginning 12 h before MTX infusion and continuing for 2448 h) and urine alkalinization 4050 mEq sodium bicarbonate per liter of infused fluid) prior to, during, and after the administration of HDMTX.Shorter