U1027 INSERM Pharmacoepidemiology Unit, Department of Clinical Pharmacology Centre Régional Midi-Pyrénées de PharmacoVigilance, de Pharmacoépidémiologie et d'Informations sur les Médicaments, Toulouse University Hospital, University of Toulouse, Toulouse, France.
Pharmacoepidemiol Drug Saf. 2012 Mar;21(3):314-9. doi: 10.1002/pds.2253. Epub 2011 Sep 28.
Risk factors for intravenous immunoglobulin-induced renal failure (IVIg-RF) were suspected from case series studies. This study was aimed at quantifying the risk of IVIg-RF associated with exposure to drugs that modify intrarenal hemodynamics.
We conducted a case-control study in the French Pharmacovigilance Database (FPVD). Adult IVIg-RF cases registered in the FPVD from 1996 to 2009 were reviewed. Controls were patients included in the FPVD for another IVIg adverse effect. Controls were matched for sucrose content of the preparation, year of adverse event and age. The predictors of IVIg-RF were exposure to angiotensin-converting enzyme inhibitors (ACE-I), angiotensin receptor antagonists (ARA), diuretics, age, gender and weight, IVIg delivered dose and infusion duration, chronic kidney disease, hypertension and diabetes mellitus. Acute IVIg-RF was defined as a calculated creatinine clearance less than 60 mL/min and, in the event of chronic kidney disease, (i) a more than 50% increase of serum creatinine, (ii) an indication of oligo-anuria or (iii) a requirement for dialysis.
We selected 71 cases and 71 controls. Forty-nine percent of the cases required transient hemodialysis. In the final multivariate model, exposure to ACE-I and/or ARA was the sole independent predictor associated with IVIg-RF (OR = 7.9, 95%CI = 1.3-49.2). There was an interaction between 'diabetes mellitus' (OR = 7.7, 95%CI = 2.3-25.5) and 'chronic kidney disease' (OR = 13.0, 95%CI = 3.1-54.7), both being strong risk factors in univariate models (p < 0.001). Chronic hypertension was a risk factor for hemodialysis.
Temporary interruption of ACE-I and ARA may be considered at the time of IVIg infusion.
静脉注射免疫球蛋白（IVIg）导致肾功能衰竭（IVIg-RF）的风险因素曾在病例系列研究中被怀疑。本研究旨在定量评估与改变肾内血液动力学的药物暴露相关的 IVIg-RF 风险。
我们在法国药物警戒数据库（FPVD）中进行了一项病例对照研究。对 1996 年至 2009 年期间在 FPVD 中登记的成人 IVIg-RF 病例进行了回顾。对照组为因其他 IVIg 不良反应而纳入 FPVD 的患者。对照组与制剂中的蔗糖含量、不良事件发生年份和年龄相匹配。IVIg-RF 的预测因素包括血管紧张素转换酶抑制剂（ACE-I）、血管紧张素受体拮抗剂（ARA）、利尿剂、年龄、性别和体重、IVIg 给予剂量和输注时间、慢性肾脏病、高血压和糖尿病。急性 IVIg-RF 定义为计算的肌酐清除率小于 60ml/min，在慢性肾脏病的情况下，（i）血清肌酐升高超过 50%，（ii）少尿或（iii）需要透析的指示。
我们选择了 71 例病例和 71 例对照。49%的病例需要短暂的血液透析。在最终的多变量模型中，ACE-I 和/或 ARA 的暴露是与 IVIg-RF 唯一相关的独立预测因素（OR=7.9，95%CI=1.3-49.2）。“糖尿病”（OR=7.7，95%CI=2.3-25.5）和“慢性肾脏病”（OR=13.0，95%CI=3.1-54.7）之间存在交互作用，这两个因素在单变量模型中都是很强的风险因素（p<0.001）。慢性高血压是血液透析的一个危险因素。
在 IVIg 输注时，可能需要暂时中断 ACE-I 和 ARA。
