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      Liver Transplant Patients with High Levels of Preoperative Serum Ammonia Are at Increased Risk for Postoperative Acute Kidney Injury: A Retrospective Study

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          Abstract

          Acute kidney injury (AKI) is one of the most frequent postoperative complications after liver transplantation (LT). Increased serum ammonia levels due to the liver disease itself may affect postoperative renal function. This study aimed to compare the incidence of postoperative AKI according to preoperative serum ammonia levels in patients after LT. Medical records from 436 patients who underwent LT from January 2010 to February 2020 in a single university hospital were retrospectively reviewed. The patients were then categorized according to changes in plasma creatinine concentrations within 48 h of LT using the Acute Kidney Injury Network criteria. A preoperative serum ammonia level above 45 mg/dL was associated with postoperative AKI ( p < 0.0001). Even in patients with a normal preoperative creatinine level, when the ammonia level was greater than 45 μg/dL, the incidence of postoperative AKI was significantly higher ( p < 0.0001); the AKI stage was also higher in this group than in the group with preoperative ammonia levels less than or equal to 45 μg/dL ( p < 0.0001). Based on the results of our research, an elevation in preoperative serum ammonia levels above 45 μg/dL is related to postoperative AKI after LT.

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          Pathophysiology of acute kidney injury.

          Acute kidney injury (AKI) is the leading cause of nephrology consultation and is associated with high mortality rates. The primary causes of AKI include ischemia, hypoxia, or nephrotoxicity. An underlying feature is a rapid decline in glomerular filtration rate (GFR) usually associated with decreases in renal blood flow. Inflammation represents an important additional component of AKI leading to the extension phase of injury, which may be associated with insensitivity to vasodilator therapy. It is suggested that targeting the extension phase represents an area potential of treatment with the greatest possible impact. The underlying basis of renal injury appears to be impaired energetics of the highly metabolically active nephron segments (i.e., proximal tubules and thick ascending limb) in the renal outer medulla, which can trigger conversion from transient hypoxia to intrinsic renal failure. Injury to kidney cells can be lethal or sublethal. Sublethal injury represents an important component in AKI, as it may profoundly influence GFR and renal blood flow. The nature of the recovery response is mediated by the degree to which sublethal cells can restore normal function and promote regeneration. The successful recovery from AKI depends on the degree to which these repair processes ensue and these may be compromised in elderly or chronic kidney disease (CKD) patients. Recent data suggest that AKI represents a potential link to CKD in surviving patients. Finally, earlier diagnosis of AKI represents an important area in treating patients with AKI that has spawned increased awareness of the potential that biomarkers of AKI may play in the future. © 2012 American Physiological Society. Compr Physiol 2:1303-1353, 2012.
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            Urea and Ammonia Metabolism and the Control of Renal Nitrogen Excretion.

            Renal nitrogen metabolism primarily involves urea and ammonia metabolism, and is essential to normal health. Urea is the largest circulating pool of nitrogen, excluding nitrogen in circulating proteins, and its production changes in parallel to the degradation of dietary and endogenous proteins. In addition to serving as a way to excrete nitrogen, urea transport, mediated through specific urea transport proteins, mediates a central role in the urine concentrating mechanism. Renal ammonia excretion, although often considered only in the context of acid-base homeostasis, accounts for approximately 10% of total renal nitrogen excretion under basal conditions, but can increase substantially in a variety of clinical conditions. Because renal ammonia metabolism requires intrarenal ammoniagenesis from glutamine, changes in factors regulating renal ammonia metabolism can have important effects on glutamine in addition to nitrogen balance. This review covers aspects of protein metabolism and the control of the two major molecules involved in renal nitrogen excretion: urea and ammonia. Both urea and ammonia transport can be altered by glucocorticoids and hypokalemia, two conditions that also affect protein metabolism. Clinical conditions associated with altered urine concentrating ability or water homeostasis can result in changes in urea excretion and urea transporters. Clinical conditions associated with altered ammonia excretion can have important effects on nitrogen balance.
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              Acute kidney injury following liver transplantation: definition and outcome.

              The incidence of acute kidney injury (AKI) has been reported to vary between 17% and 95% post-orthotopic liver transplantation. This variability may be related to the absence of a uniform definition of AKI in this setting. The purpose of this study was to identify the degree of AKI that is associated with long-term adverse outcome. Furthermore, to determine the best definition (for use in future studies) of AKI not requiring dialysis in post-liver transplant patients, we retrospectively reviewed the effect of 3 definitions of AKI post-orthotopic liver transplantation on renal and patient outcome between 1997 and 2005. We compared patients with AKI to a control group without AKI by each definition. AKI was defined in 3 groups as an acute rise in serum creatinine, from the pretransplant baseline, of >0.5 mg/dL, >1.0 mg/dL, or >50% above baseline to a value above 2 mg/dL. In all groups, the glomerular filtration rate was significantly lower at both 1 and 2 years post-transplant. Patient survival was worse in all groups. Graft survival was worse in all groups. The incidence of AKI was highest in the group with a rise in creatinine of >0.5 mg/dL (78%) and lowest in patients with a rise in creatinine of >50% above 2.0 mg/dL (14%). Even mild AKI, defined as a rise in serum creatinine of >0.5 mg/dL, was associated with reduced patient and graft survival. However, in comparison with the other definitions, the definition of AKI with the greatest impact on patient's outcome post-liver transplant was a rise in serum creatinine of >50% above baseline to >2 mg/dL.
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                Author and article information

                Journal
                J Clin Med
                J Clin Med
                jcm
                Journal of Clinical Medicine
                MDPI
                2077-0383
                28 May 2020
                June 2020
                : 9
                : 6
                : 1629
                Affiliations
                [1 ]Department of Anaesthesiology and Pain Medicine, Ansan Hospital, Korea University, College of Medicine, Ansan 15355, Korea; yslee4719@ 123456gmail.com (Y.S.L.); pbskumc57@ 123456gmail.com (B.S.P.)
                [2 ]Department of Pediatrics, Korea University Hospital, Ansan 15355, Korea; czrabbit@ 123456korea.ac.kr
                [3 ]Department of Biostatistics, Clinical Trial Center, Biomedical Research Institute, Pusan National University Hospital, Pusan 49241, Korea; statsjm@ 123456pnuh.co.kr
                [4 ]Department of Anesthesiology and Pain Medicine, Daedong Hospital, Busan 47737, Korea; monojp@ 123456naver.com
                [5 ]Department of Anaesthesia and Pain Medicine, Pusan National University Yangsan Hospital, Yangsan 50612, Korea; johnri@ 123456naver.com
                [6 ]Division of Hepato-Biliary-Pancreatic Surgery and Transplantation, Department of Surgery, Pusan National University Yangsan Hospital, Pusan National University School of Medicine, Yangsan 50612, Korea; ryujhhim@ 123456hanmail.net
                Author notes
                [* ]Correspondence: yoonji07@ 123456gmail.com ; Tel.: +82-10-7900-7825
                Author information
                https://orcid.org/0000-0003-3031-357X
                https://orcid.org/0000-0002-4642-3717
                Article
                jcm-09-01629
                10.3390/jcm9061629
                7356740
                32481585
                3ae3f10f-de71-4b0b-bd2e-1f05c964f61e
                © 2020 by the authors.

                Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license ( http://creativecommons.org/licenses/by/4.0/).

                History
                : 17 April 2020
                : 18 May 2020
                Categories
                Article

                acute kidney injury,ammonia,complication,liver transplantation

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