Serum Gamma-Glutamyltransferase Levels Predict Clinical Outcomes in Hemodialysis Patients

PLOS ONE, Dec 2019

Background Gamma-glutamyltransferase (GGT) is a biomarker of liver injury. GGT has also been reported to be a marker of oxidative stress and a predictor of mortality in the general population. Hemodialysis (HD) patients suffer from oxidative stress. The aim of our study was to investigate the relationship between serum GGT levels and clinical outcomes in HD patients. Methods A total of 1,634 HD patients were enrolled from the Clinical Research Center registry for end-stage renal disease, a prospective cohort in Korea. Patients were categorized into three groups by tertiles of serum GGT levels. The primary outcome was all-cause, cardiovascular, or infection-related mortality and hospitalization. Results During the median follow-up period of 30 months, the highest tertile of serum GGT levels had a significantly higher risk for all-cause mortality (hazard ratio (HR) 2.39, 95% confidence interval (CI), 1.55–3.69, P<0.001), cardiovascular mortality (HR 2.14, 95% CI, 1.07–4.26, P = 0.031) and infection-related mortality (HR 3.07, 95% CI, 1.30–7.25, P = 0.011) using tertile 1 as the reference group after adjusting for clinical variables including liver diseases. The highest tertile also had a significantly higher risk for first hospitalization (HR 1.22, 95% CI, 1.00–1.48, P = 0.048) and cardiovascular hospitalization (HR 1.42, 95% CI, 1.06–1.92, P = 0.028). Conclusions Our data demonstrate that high serum GGT levels were an independent risk factor for all-cause, cardiovascular, and infection-related mortality, as well as cardiovascular hospitalization in HD patients. These findings suggest that serum GGT levels might be a useful biomarker to predict clinical outcomes in HD patients.

A PDF file should load here. If you do not see its contents the file may be temporarily unavailable at the journal website or you do not have a PDF plug-in installed and enabled in your browser.

Alternatively, you can download the file locally and open with any standalone PDF reader:

https://journals.plos.org/plosone/article/file?id=10.1371/journal.pone.0138159&type=printable

Serum Gamma-Glutamyltransferase Levels Predict Clinical Outcomes in Hemodialysis Patients

September Serum Gamma-Glutamyltransferase Levels Predict Clinical Outcomes in Hemodialysis Patients Woo Yeong Park 0 1 2 3 Eun Sil Koh 0 1 2 3 Su-Hyun Kim 0 1 2 3 Young Ok Kim 0 1 2 3 Dong Chan Jin 0 1 2 3 Ho Chul Song 0 1 2 3 Euy Jin Choi 0 1 2 3 Yong-Lim Kim 0 1 2 3 Yon-Su Kim 0 1 2 3 Shin-Wook Kang 0 1 2 3 Nam- Ho Kim 0 1 2 3 Chul Woo Yang 0 1 2 3 Yong Kyun Kim 0 1 2 3 0 Competing Interests: The authors have declared that no competing interests exist 1 Funding: This work was supported by a grant of the Korea Healthcare Technology R&D Project, Ministry of Health and Welfare, Republic of Korea , HI10C2020 2 Editor: Ming-Lung Yu, Kaohsiung Medical University Hospital, Kaohsiung Medical University , TAIWAN 3 1 Department of Internal Medicine, College of Medicine, The Catholic University of Korea , Seoul , Korea , 2 Department of Internal Medicine, College of Medicine, Chung-Ang University , Seoul , Korea , 3 Department of Internal Medicine, Kyungpook National University School of Medicine , Daegu , Korea , 4 Department of Internal Medicine, College of Medicine, Seoul National University , Seoul , Korea , 5 Department of Internal Medicine, College of Medicine, Yonsei University , Seoul , Korea , 6 Department of Internal Medicine, Chonnam National University Medical School , Gwangju , Korea , 7 Cell Death Disease Research Center, The Catholic University of Korea , Seoul , Korea Gamma-glutamyltransferase (GGT) is a biomarker of liver injury. GGT has also been reported to be a marker of oxidative stress and a predictor of mortality in the general population. Hemodialysis (HD) patients suffer from oxidative stress. The aim of our study was to investigate the relationship between serum GGT levels and clinical outcomes in HD A total of 1,634 HD patients were enrolled from the Clinical Research Center registry for end-stage renal disease, a prospective cohort in Korea. Patients were categorized into three groups by tertiles of serum GGT levels. The primary outcome was all-cause, cardiovascular, or infection-related mortality and hospitalization. During the median follow-up period of 30 months, the highest tertile of serum GGT levels had a significantly higher risk for all-cause mortality (hazard ratio (HR) 2.39, 95% confidence interval (CI), 1.55-3.69, P<0.001), cardiovascular mortality (HR 2.14, 95% CI, 1.074.26, P = 0.031) and infection-related mortality (HR 3.07, 95% CI, 1.30-7.25, P = 0.011) using tertile 1 as the reference group after adjusting for clinical variables including liver diseases. The highest tertile also had a significantly higher risk for first hospitalization (HR 1.22, 95% CI, 1.00-1.48, P = 0.048) and cardiovascular hospitalization (HR 1.42, 95% CI, 1.06-1.92, P = 0.028). - ☯ These authors contributed equally to this work. * Our data demonstrate that high serum GGT levels were an independent risk factor for allcause, cardiovascular, and infection-related mortality, as well as cardiovascular hospitalization in HD patients. These findings suggest that serum GGT levels might be a useful biomarker to predict clinical outcomes in HD patients. End-stage renal disease (ESRD) patients undergoing hemodialysis (HD) therapy have higher mortality and morbidity compared with the general population [1]. Common causes of mortality in HD patients are cardiovascular and infection-related diseases [2]. Many studies have evaluated biomarkers for predicting clinical outcomes in HD patients. Oxidative stress is one of the useful targets for biomarker because oxidative stress is increased in HD patients and increased oxidative stress is associated with mortality [3]. Gamma-glutamyltransferase (GGT) is a widely used biomarker for liver diseases. In addition, GGT has been known as one of the markers of oxidative stress because it is an enzyme playing an important role in the extracellular catabolism of glutathione (GSH), the representative intracellular antioxidant [4–6]. Oxidative stress mediated by GGT can influence coronary atherosclerotic plaques and endothelial dysfunction [6–8]. Serum GGT levels have been reported to be associated with all-cause mortality and cardiovascular and/or cancer mortality in the general population and in patients with coronary artery disease and type 2 diabetes mellitus [9,10]. In HD patients, there are only few studies on the association between serum GGT levels and clinical outcomes. A previous study reported that high serum GGT levels are associated with all-cause and cardiovascular mortality in HD patients [11]. However, whether GGT is associated with cause-specific mortality and hospitalization remains unclear. In this study, we investigated the association between serum GGT levels and all-cause, cardiovascular and infection-related mortality in addition to hospitalization from the Clinical Research Center (CRC) registry for ESRD cohort in Korea. Patients and Methods Study population This study is a prospective observational cohort study in the CRC registry for ESRD coll (...truncated)


This is a preview of a remote PDF: https://journals.plos.org/plosone/article/file?id=10.1371/journal.pone.0138159&type=printable

Woo Yeong Park, Eun Sil Koh, Su-Hyun Kim, Young Ok Kim, Dong Chan Jin, Ho Chul Song, Euy Jin Choi, Yong-Lim Kim, Yon-Su Kim, Shin-Wook Kang, Nam-Ho Kim, Chul Woo Yang, Yong Kyun Kim. Serum Gamma-Glutamyltransferase Levels Predict Clinical Outcomes in Hemodialysis Patients, PLOS ONE, 2015, Volume 10, Issue 9, DOI: 10.1371/journal.pone.0138159