title: Blood transfusions are associated with urinary biomarkers of kidney injury in cardiac surgery.
abstract: OBJECTIVE
  Cardiac surgery is a major cause of acute kidney injury. In this setting, receipt of blood transfusions seems to be associated with a higher risk of acute kidney injury, as measured using serum creatinine values. We examined this association further by using urinary biomarkers of kidney injury.
  
  
  METHODS
  A total of 1210 adults underwent cardiac surgery and were divided into 3 groups on the basis of the receipt of intraoperative packed red blood cell units: no blood (n = 894), 2 or less packed red blood cell units (n = 206), and more than 2 packed red blood cell units (n = 110). Acute kidney injury was defined as (1) doubling of serum creatinine from the preoperative value; (2) first postoperative urinary interleukin-18 in the fifth quintile; and (3) first postoperative urinary neutrophil gelatinase-associated lipocalin in the fifth quintile. We determined the relative risk for acute kidney injury outcome according to packed red blood cell units group after adjusting for 12 preoperative and surgical variables. By using the Sobel test for mediation analysis, we also evaluated the role of biomarkers in causing acute kidney injury through alternative pathways.
  
  
  RESULTS
  Acute kidney injury was more common in those who received more than 2 packed red blood cell units. In patients receiving more than 2 packed red blood cell units, the adjusted relative risks were 2.3 (95% confidence interval, 1.2-4.4, P .01), 1.36 (95% confidence interval, 1.0-1.9, P .05), and 1.34 (95% confidence interval, 1.0-1.8, P .06) for doubling of serum creatinine, urinary interleukin-18 in the fifth quintile (>60 pg/mL), and urinary neutrophil gelatinase-associated lipocalin in the fifth quintile (>102 ng/mL), respectively. Furthermore, the effect of packed red blood cell units transfusion on acute kidney injury was partially mediated by interleukin-18.
  
  
  CONCLUSIONS
  Receipt of 2 or more packed red blood cell units during cardiac surgery is associated with a greater risk of acute kidney injury defined by serum creatinine and kidney injury biomarkers.
authors.affiliation: Section of Nephrology, Yale University School of Medicine, Veterans Affairs Medical Center, and the Program of Applied Translational Research, New Haven, Conn.
authors.forename: Usman A
authors.initials: UA
authors.lastname: Khan
authors.affiliation: Section of Nephrology, Yale University School of Medicine, Veterans Affairs Medical Center, and the Program of Applied Translational Research, New Haven, Conn.
authors.forename: Steven G
authors.initials: SG
authors.lastname: Coca
authors.affiliation: Section of Nephrology, Yale University School of Medicine, Veterans Affairs Medical Center, and the Program of Applied Translational Research, New Haven, Conn.
authors.forename: Kwangik
authors.initials: K
authors.lastname: Hong
authors.affiliation: Section of Nephrology, Department of Medicine, University of Chicago, Chicago, Ill.
authors.forename: Jay L
authors.initials: JL
authors.lastname: Koyner
authors.affiliation: Division of Nephrology, Department of Medicine, Western University, London, Ontario, Canada.
authors.forename: Amit X
authors.initials: AX
authors.lastname: Garg
authors.affiliation: Department of Cardiothoracic Surgery, Danbury Hospital, Danbury, Conn; University of Vermont College of Medicine, Burlington, Vt.
authors.forename: Cary S
authors.initials: CS
authors.lastname: Passik
authors.affiliation: Division of Cardiothoracic Anesthesiology and Critical Care Medicine, Department of Anesthesiology, Duke University School of Medicine, Durham, NC.
authors.forename: Madhav
authors.initials: M
authors.lastname: Swaminathan
authors.affiliation: Department of Anesthesiology, Yale University School of Medicine, New Haven, Conn.
authors.forename: Susan
authors.initials: S
authors.lastname: Garwood
authors.affiliation: Division of Nephrology, Department of Medicine, Duke University School of Medicine, Durham, NC.
authors.forename: Uptal D
authors.initials: UD
authors.lastname: Patel
authors.affiliation: Department of Surgery, Yale University School of Medicine, New Haven, Conn.
authors.forename: Sabet
authors.initials: S
authors.lastname: Hashim
authors.affiliation: Division of Cardiac Surgery, London Health Sciences Centre, London, Ontario, Canada.
authors.forename: Mackenzie A
authors.initials: MA
authors.lastname: Quantz
authors.affiliation: Section of Nephrology, Yale University School of Medicine, Veterans Affairs Medical Center, and the Program of Applied Translational Research, New Haven, Conn. Electronic address: chirag.parikh@yale.edu.
authors.forename: Chirag R
authors.initials: CR
authors.lastname: Parikh
mesh_terms: D058186:Acute Kidney Injury / Q000097:blood / Q000175:diagnosis / Q000209:etiology* / Q000652:urine*; D000209:Acute-Phase Proteins / Q000652:urine*; D000368:Aged; D000369:Aged, 80 and over; D015415:Biomarkers / Q000097:blood / Q000652:urine; D006348:Cardiac Surgical Procedures / Q000009:adverse effects*; D003404:Creatinine / Q000097:blood; D017707:Erythrocyte Transfusion / Q000009:adverse effects*; D005260:Female; D006801:Humans; D020382:Interleukin-18 / Q000652:urine*; D000071068:Lipocalin-2; D054834:Lipocalins / Q000652:urine*; D008297:Male; D008875:Middle Aged; D011446:Prospective Studies; D011518:Proto-Oncogene Proteins / Q000652:urine*; D012307:Risk Factors; D015854:Up-Regulation
chemical_list: D000209:Acute-Phase Proteins; D015415:Biomarkers; D020382:Interleukin-18; C489506:LCN2 protein, human; D000071068:Lipocalin-2; D054834:Lipocalins; D011518:Proto-Oncogene Proteins; D003404:Creatinine