Association of aspartate aminotransferase with mortality in hemodialysis patients

Nephrol Dial Transplant (2016) 31: 814–822 doi: 10.1093/ndt/gfv310 Advance Access publication 1 September 2015 Association of aspartate aminotransferase with mortality in hemodialysis patients Vanessa Ravel 1 , Elani Streja 1 , Miklos Z. Molnar 2 , Sepideh Rezakhani 1 , Melissa Soohoo 1 , Csaba P. Kovesdy 2,3 , Kamyar Kalantar-Zadeh 1,4 and Hamid Moradi 1,5 Division of Nephrology and Hypertension, Harold Simmons Center for Kidney Disease Research and Epidemiology, University of California Irvine Medical Center, Orange, CA, USA, 2 Division of Nephrology, University of Tennessee Health Science Center, Memphis, TN, USA, Nephrology Section, Memphis Veterans Affairs Medical Center, Memphis, TN, USA, 4 Department of Medicine, UC Irvine School of Medicine, Irvine, CA, USA and 5 Nephrology Section, Long Beach VA Healthcare System, Long Beach, CA, USA ORIGINAL ARTICLE Correspondence and offprint requests to: Kamyar Kalantar-Zadeh; E-mail: kkz@uci.edu A B S T R AC T INTRODUCTION Background. Liver disease is a common comorbid condition in maintenance hemodialysis (MHD) patients and may be asso- ciated with poor survival. The relationship between aspartate aminotransferase (AST) and survival has not yet been ad- dressed in these patients. We hypothesized that higher AST level is associated with higher death risk in MHD patients. Methods. A 5-year (January 2007–December 2011) cohort of 109 718 MHD patients was studied in the USA in dialysis clinics where AST was measured in at least 50% of all outpatients in the baseline calendar quarter. Survival models were adjusted for demographic variables, and available clinical and laboratory surrogates of malnutrition-inﬂammation complex, and cubic survival splines were plotted. Results. A linear association existed between baseline serum AST levels and mortality. Increasing AST of >20 IU/L was in- crementally and almost linearly associated with higher death risk at all levels of adjustment. In fully adjusted models, AST levels of ≥40 IU/L were associated with the highest risk of mor- tality (hazard ratio: 1.46, 95% CI: 1.38–1.54). Low AST levels ( 20 IU/L is incrementally as- sociated with higher mortality in MHD patients whereas AST in the 15–20 IU/L range is associated with the greatest survival. These ﬁndings suggest that the assessment of liver function and improving liver disease may confer survival beneﬁt to MHD patients. End-stage renal disease (ESRD) is frequently accompanied by major chronic diseases such as coronary heart disease (13–24%), chronic heart failure (5–20%), diabetes mellitus (12–28%), hypertension (34–50%) and stroke or transient is- chemic attack (6–13%) [1]. While not as common, chronic liver disease can coexist with ESRD and its presence may be as- sociated with poor clinical outcomes. Hepatitis C virus (HCV) infection, which itself can lead to chronic kidney disease [2], is the most common cause of liver damage in maintenance hemo- dialysis (MHD) patients [3–8]. Some of the most useful laboratory tests to screen for liver disease are serum aspartate aminotransferase (AST) and serum alanine transaminase (ALT). Many studies report that serum AST levels are low in patients undergoing dialysis. This is true even in HCV-positive patients, and some of these studies suggest lowering the upper limits of normal AST and ALT levels in this patient population [9–14]. Previous investiga- tions have identiﬁed vitamin B6 deﬁciency as a potential mech- anism responsible for hypoaminotransferasemia in dialysis patients given that vitamin B6 is required as a co-enzyme for aminotransferases to express their activity [15–21]. However, subsequent investigations noted that hemodilution may also be another mechanism underlying the lower aminotransferase level in dialysis patients [22, 23]. While some studies have reported a positive association be- tween elevated liver enzymes and increased risk of mortality in MHD patients, the relationship between AST and all-cause mortality in MHD patients has not been thoroughly examined. The present study was therefore designed to determine the re- lationship between serum AST level and all-cause mortality in ESRD patients maintained on hemodialysis. To this end, we Keywords: all-cause mortality, aspartate aminotransferase, end-stage renal disease, hemodialysis, liver enzymes © The Author 2015. Published by Oxford University Press on behalf of ERA-EDTA. All rights reserved.