title: Exposure to inhibitors of the renin-angiotensin system is a major independent risk factor for acute renal failure induced by sucrose-containing intravenous immunoglobulins: a case-control study.
abstract: OBJECTIVE
  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.
  
  
  METHODS
  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.
  
  
  RESULTS
  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.
  
  
  CONCLUSIONS
  Temporary interruption of ACE-I and ARA may be considered at the time of IVIg infusion.
authors.affiliation: 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. gmoulis@hotmail.com
authors.forename: Guillaume
authors.initials: G
authors.lastname: Moulis
authors.forename: Laurent
authors.initials: L
authors.lastname: Sailler
authors.forename: Agnès
authors.initials: A
authors.lastname: Sommet
authors.forename: Maryse
authors.initials: M
authors.lastname: Lapeyre-Mestre
authors.forename: Jean-Louis
authors.initials: JL
authors.lastname: Montastruc
mesh_terms: D058186:Acute Kidney Injury / Q000139:chemically induced*; D000368:Aged; D057911:Angiotensin Receptor Antagonists / Q000008:administration & dosage / Q000009:adverse effects*; D000806:Angiotensin-Converting Enzyme Inhibitors / Q000008:administration & dosage / Q000009:adverse effects*; D016022:Case-Control Studies; D003404:Creatinine / Q000097:blood; D004305:Dose-Response Relationship, Drug; D004347:Drug Interactions; D005260:Female; D006801:Humans; D016756:Immunoglobulins, Intravenous / Q000008:administration & dosage / Q000009:adverse effects* / Q000737:chemistry; D007262:Infusions, Intravenous; D007677:Kidney Function Tests; D008297:Male; D012084:Renin-Angiotensin System / Q000187:drug effects*; D012307:Risk Factors; D013395:Sucrose / Q000032:analysis*; D013997:Time Factors
chemical_list: D057911:Angiotensin Receptor Antagonists; D000806:Angiotensin-Converting Enzyme Inhibitors; D016756:Immunoglobulins, Intravenous; D013395:Sucrose; D003404:Creatinine