Kidney Damage Biomarkers: Novel Tools for the Diagnostic Assessment of Acute Kidney Injury in Cirrhosis See Article on Page 622
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enal dysfunction is a common complication of liver cirrhosis, occurring in approximately 20% of all patients with cirrhosis admitted into hospital.1 The majority of these cases are acute episodes of renal dysfunction, more commonly known as acute kidney injury (AKI). Two thirds of these AKI episodes are functional in nature, related to hemodynamic changes in cirrhosis, consisting of splanchnic and systemic arterial vasodilatation with resultant reduction in effective arterial blood volume,2 whereas the remainder of AKI episodes are related to renal structural damage, more commonly tubular than glomerular.1 The most severe form of AKI is type 1 hepatorenal syndrome (HRS-1),3 which, if left untreated, has a median survival of 7-10 days.4 Pharmacotherapy using vasoconstrictors for HRS-1 has led to improvement in renal function in approximately one third of patients.5,6 The reasons for this low response rate to vasoconstrictor therapy are unclear. Many clinicians believe that vasoconstrictor therapy for HRS-1 may be started too late in the course of the natural history of renal dysfunction, and therefore many patients may have crossed the threshold of “no return.” This may be related to the fact that serum creatinine, the commonly used index of renal function, tends to overestimate the glomerular fil-
Abbreviations: AKI, acute kidney injury; AKIN, Acute Kidney Injury Network; ATN, acute tubular necrosis; HRS-1, type 1 hepatorenal syndrome; IL18, interleukin-18; KIM-1, kidney injury molecule 1; L-FABP, liver type fatty acid binding protein; NGAL, neutrophil gelatinase-associated lipocalin. Received January 23, 2014; accepted February 6, 2014. Address reprint requests to: Florence Wong, M.D., FRACP, FRCPC, Department of Medicine, Toronto General Hospital, 9th Floor, North Wing, Room 983, 200 Elizabeth Street, University of Toronto, Toronto, Ontario M5G 2C4, Canada. E-mail: [email protected]; fax: 416-340-5019. Dr. Murray’s AKI biomarker research was supported by the Health Research Board (Ireland; grant HRA_POR 2011 128). C 2014 by the American Association for the Study of Liver Diseases. Copyright V View this article online at wileyonlinelibrary.com. DOI 10.1002/hep.27063 Potential conflict of interest: Dr. Murray consults for and is on the speakers’ bureau for Abbott. He consults for Astellas and AM Pharma. He advises EKF Diagnostics and FAST Diagnostics.
tration rate in decompensated cirrhosis,7 and this may contribute to a delay in initiating treatment for HRS-1. Prolonged renal ischemia in late-presenting HRS-1 can also lead to structural damage, such as acute tubular necrosis (ATN), as recent data have suggested,8,9 thus blurring the line between structural and functional causes of AKI in cirrhosis. In addition, ATN can present with the same features as HRS-1,10 thus making the differentiation of the different types of AKI and decisions on treatment plans difficult. To overcome some of these issues, the International Ascites Club and the Acute Dialysis Quality Initiative recently modified the AKI diagnostic criteria of the Acute Kidney Injury Network (AKIN) for the population with cirrhosis11 as an acute rise in serum creatinine by 26.4 lmol/L (0.3 mg/dL) in
R
enal dysfunction is a common complication of liver cirrhosis, occurring in approximately 20% of all patients with cirrhosis admitted into hospital.1 The majority of these cases are acute episodes of renal dysfunction, more commonly known as acute kidney injury (AKI). Two thirds of these AKI episodes are functional in nature, related to hemodynamic changes in cirrhosis, consisting of splanchnic and systemic arterial vasodilatation with resultant reduction in effective arterial blood volume,2 whereas the remainder of AKI episodes are related to renal structural damage, more commonly tubular than glomerular.1 The most severe form of AKI is type 1 hepatorenal syndrome (HRS-1),3 which, if left untreated, has a median survival of 7-10 days.4 Pharmacotherapy using vasoconstrictors for HRS-1 has led to improvement in renal function in approximately one third of patients.5,6 The reasons for this low response rate to vasoconstrictor therapy are unclear. Many clinicians believe that vasoconstrictor therapy for HRS-1 may be started too late in the course of the natural history of renal dysfunction, and therefore many patients may have crossed the threshold of “no return.” This may be related to the fact that serum creatinine, the commonly used index of renal function, tends to overestimate the glomerular fil-
Abbreviations: AKI, acute kidney injury; AKIN, Acute Kidney Injury Network; ATN, acute tubular necrosis; HRS-1, type 1 hepatorenal syndrome; IL18, interleukin-18; KIM-1, kidney injury molecule 1; L-FABP, liver type fatty acid binding protein; NGAL, neutrophil gelatinase-associated lipocalin. Received January 23, 2014; accepted February 6, 2014. Address reprint requests to: Florence Wong, M.D., FRACP, FRCPC, Department of Medicine, Toronto General Hospital, 9th Floor, North Wing, Room 983, 200 Elizabeth Street, University of Toronto, Toronto, Ontario M5G 2C4, Canada. E-mail: [email protected]; fax: 416-340-5019. Dr. Murray’s AKI biomarker research was supported by the Health Research Board (Ireland; grant HRA_POR 2011 128). C 2014 by the American Association for the Study of Liver Diseases. Copyright V View this article online at wileyonlinelibrary.com. DOI 10.1002/hep.27063 Potential conflict of interest: Dr. Murray consults for and is on the speakers’ bureau for Abbott. He consults for Astellas and AM Pharma. He advises EKF Diagnostics and FAST Diagnostics.
tration rate in decompensated cirrhosis,7 and this may contribute to a delay in initiating treatment for HRS-1. Prolonged renal ischemia in late-presenting HRS-1 can also lead to structural damage, such as acute tubular necrosis (ATN), as recent data have suggested,8,9 thus blurring the line between structural and functional causes of AKI in cirrhosis. In addition, ATN can present with the same features as HRS-1,10 thus making the differentiation of the different types of AKI and decisions on treatment plans difficult. To overcome some of these issues, the International Ascites Club and the Acute Dialysis Quality Initiative recently modified the AKI diagnostic criteria of the Acute Kidney Injury Network (AKIN) for the population with cirrhosis11 as an acute rise in serum creatinine by 26.4 lmol/L (0.3 mg/dL) in
