LIVER TRANSPLANTATION 21:662–669, 2015
ORIGINAL ARTICLE
Macrophage Migration Inhibitory Factor as a Potential Predictor for Requirement of Renal Replacement Therapy After Orthotopic Liver Transplantation Joanna Stefaniak,1 Judith Schiefer,1 Edmund John Miller,2,3 Claus Georg Krenn,1 David Marek Baron,1 and Peter Faybik1 1 Department of Anesthesia, General Intensive Care, and Pain Management, Medical University of Vienna, Vienna, Austria; 2Feinstein Institute for Medical Research, North Shore Long Island Jewish Health System, Manhasset, NY; and 3Hofstra North Shore-LIJ School of Medicine, Hofstra University, Hempstead, NY
Acute kidney injury (AKI) after orthotopic liver transplantation (OLT) is associated with a poor clinical outcome. Because there is no specific treatment for postoperative AKI, early recognition and prevention are fundamental therapeutic approaches. Concentrations of the proinflammatory cytokine macrophage migration inhibitory factor (MIF) are elevated in patients with kidney disease. We hypothesized that plasma MIF concentrations would be greater in patients developing AKI after OLT compared with patients with normal kidney function. Twenty-eight patients undergoing OLT were included in the study. Kidney injury was classified according to AKI network criteria. Fifteen patients (54%) developed severe AKI after OLT, 11 (39%) requiring renal replacement therapy (RRT). On the first postoperative day, patients with severe AKI had greater plasma MIF concentrations (237 6 123 ng/mL) than patients without AKI (95 6 63 ng/mL; P < 0.001). The area under the receiver operating characteristic (ROC) curve for predicting severe AKI was 0.87 [95% confidence interval (CI), 0.69-0.97] for plasma MIF, 0.61 (95% CI, 0.40-0.79) for serum creatinine (sCr), and 0.90 (95% CI, 0.72-0.98) for delta serum creatinine (DsCr). Plasma MIF (P 5 0.02) and DsCr (P 5 0.01) yielded a better predictive value than sCr for the development of severe AKI. Furthermore, the area under the ROC curve to predict the requirement of RRT was 0.87 (95% CI, 0.68-0.96) for plasma MIF, 0.65 (95% CI, 0.44-0.82) for sCr, and 0.72 (95% CI, 0.52-0.88) for DsCr. Plasma MIF had a better predictive value than sCr for the requirement of RRT (P 5 0.02). In conclusion, postoperative plasma MIF concentrations were elevated in patients who developed severe AKI after OLT. Furthermore, plasma MIF concentrations showed a good prognostic value for identifying patients developing severe AKI or requiring postoperative RRT after OLT. Liver Transpl 21:662-669, C 2015 AASLD. 2015. V Received August 20, 2014; accepted February 8, 2015.
Abbreviations: DsCr, delta serum creatinine; AKI, acute kidney injury; AKIN, Acute Kidney Injury Network; ANOVA, analysis of variance; AUC, area under the curve; BMI, body mass index; CI, confidence interval; COPD, chronic obstructive pulmonary disease; eGFR, estimated glomerular filtration rate; ESLD, end-stage liver disease; IL, interleukin; IQR, interquartile range; IVC, inferior vena cava; MELD, Model for End-Stage Liver Disease; MIF, macrophage migration inhibitory factor; OLT, orthotopic liver transplantation; ROC, receiver operating characteristic; RRT, renal replacement therapy; sCr, serum creatinine; TP, time point. Potential conflict of interest: Nothing to report. Financial support for this work was provided by departmental funds. This work was registered at EudraCT (2014-002530-31). Address reprint requests to Joanna Stefaniak, M.D., Department of Anesthesia, General Intensive Care, and Pain Management, Medical University of Vienna, Waehringer Guertel 18-20, 1090 Vienna, Austria. Telephone: 43-1-40400-41500; FAX: 43-1-40400-40280; E-mail: joanna. [email protected] DOI 10.1002/lt.24103 View this article online at wileyonlinelibrary.com. LIVER TRANSPLANTATION.DOI 10.1002/lt. Published on behalf of the American Association for the Study of Liver Diseases
C 2015 American Association for the Study of Liver Diseases. V
LIVER TRANSPLANTATION, Vol. 21, No. 5, 2015
STEFANIAK ET AL. 663
TABLE 1. Classification of AKI Using the AKIN Criteria Stage 1 2 3†
sCr*
Urine Output*
Increase > 0.3 mg/dL or 1.5- to 2-fold from baseline Increase 2- to 3-fold from baseline Increase >3-fold from baseline
ORIGINAL ARTICLE
Macrophage Migration Inhibitory Factor as a Potential Predictor for Requirement of Renal Replacement Therapy After Orthotopic Liver Transplantation Joanna Stefaniak,1 Judith Schiefer,1 Edmund John Miller,2,3 Claus Georg Krenn,1 David Marek Baron,1 and Peter Faybik1 1 Department of Anesthesia, General Intensive Care, and Pain Management, Medical University of Vienna, Vienna, Austria; 2Feinstein Institute for Medical Research, North Shore Long Island Jewish Health System, Manhasset, NY; and 3Hofstra North Shore-LIJ School of Medicine, Hofstra University, Hempstead, NY
Acute kidney injury (AKI) after orthotopic liver transplantation (OLT) is associated with a poor clinical outcome. Because there is no specific treatment for postoperative AKI, early recognition and prevention are fundamental therapeutic approaches. Concentrations of the proinflammatory cytokine macrophage migration inhibitory factor (MIF) are elevated in patients with kidney disease. We hypothesized that plasma MIF concentrations would be greater in patients developing AKI after OLT compared with patients with normal kidney function. Twenty-eight patients undergoing OLT were included in the study. Kidney injury was classified according to AKI network criteria. Fifteen patients (54%) developed severe AKI after OLT, 11 (39%) requiring renal replacement therapy (RRT). On the first postoperative day, patients with severe AKI had greater plasma MIF concentrations (237 6 123 ng/mL) than patients without AKI (95 6 63 ng/mL; P < 0.001). The area under the receiver operating characteristic (ROC) curve for predicting severe AKI was 0.87 [95% confidence interval (CI), 0.69-0.97] for plasma MIF, 0.61 (95% CI, 0.40-0.79) for serum creatinine (sCr), and 0.90 (95% CI, 0.72-0.98) for delta serum creatinine (DsCr). Plasma MIF (P 5 0.02) and DsCr (P 5 0.01) yielded a better predictive value than sCr for the development of severe AKI. Furthermore, the area under the ROC curve to predict the requirement of RRT was 0.87 (95% CI, 0.68-0.96) for plasma MIF, 0.65 (95% CI, 0.44-0.82) for sCr, and 0.72 (95% CI, 0.52-0.88) for DsCr. Plasma MIF had a better predictive value than sCr for the requirement of RRT (P 5 0.02). In conclusion, postoperative plasma MIF concentrations were elevated in patients who developed severe AKI after OLT. Furthermore, plasma MIF concentrations showed a good prognostic value for identifying patients developing severe AKI or requiring postoperative RRT after OLT. Liver Transpl 21:662-669, C 2015 AASLD. 2015. V Received August 20, 2014; accepted February 8, 2015.
Abbreviations: DsCr, delta serum creatinine; AKI, acute kidney injury; AKIN, Acute Kidney Injury Network; ANOVA, analysis of variance; AUC, area under the curve; BMI, body mass index; CI, confidence interval; COPD, chronic obstructive pulmonary disease; eGFR, estimated glomerular filtration rate; ESLD, end-stage liver disease; IL, interleukin; IQR, interquartile range; IVC, inferior vena cava; MELD, Model for End-Stage Liver Disease; MIF, macrophage migration inhibitory factor; OLT, orthotopic liver transplantation; ROC, receiver operating characteristic; RRT, renal replacement therapy; sCr, serum creatinine; TP, time point. Potential conflict of interest: Nothing to report. Financial support for this work was provided by departmental funds. This work was registered at EudraCT (2014-002530-31). Address reprint requests to Joanna Stefaniak, M.D., Department of Anesthesia, General Intensive Care, and Pain Management, Medical University of Vienna, Waehringer Guertel 18-20, 1090 Vienna, Austria. Telephone: 43-1-40400-41500; FAX: 43-1-40400-40280; E-mail: joanna. [email protected] DOI 10.1002/lt.24103 View this article online at wileyonlinelibrary.com. LIVER TRANSPLANTATION.DOI 10.1002/lt. Published on behalf of the American Association for the Study of Liver Diseases
C 2015 American Association for the Study of Liver Diseases. V
LIVER TRANSPLANTATION, Vol. 21, No. 5, 2015
STEFANIAK ET AL. 663
TABLE 1. Classification of AKI Using the AKIN Criteria Stage 1 2 3†
sCr*
Urine Output*
Increase > 0.3 mg/dL or 1.5- to 2-fold from baseline Increase 2- to 3-fold from baseline Increase >3-fold from baseline
