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World J Nephrol. Jul 6, 2017; 6(4): 176-187
Published online Jul 6, 2017. doi: 10.5527/wjn.v6.i4.176
Causal relationship between hypoalbuminemia and acute kidney injury
Christian J Wiedermann, Wolfgang Wiedermann, Michael Joannidis
Christian J Wiedermann, Department of Research, College of Health Professions Claudiana, 39100 Bolzano, Italy
Wolfgang Wiedermann, Department of Educational, School and Counseling Psychology, University of Missouri College of Education, Columbia, MO 65211, United States
Michael Joannidis, Department of Internal Medicine, Division of Emergency and Intensive Care Medicine, Medical University of Innsbruck, 6020 Innsbruck, Austria
Author contributions: Wiedermann CJ and Joannidis M equally contributed to this paper with regard to conception, design and literature review; Wiedermann W and Joannidis M assessed data extraction and analysis performed by Wiedermann CJ who also drafted the manuscript; all authors are responsible for critical revision and editing, and approved the final version.
Conflict-of-interest statement: Christian J Wiedermann has received travel cost reimbursements from CSL Behring. Wolfgang Wiedermann has no conflict of interest to report. Michael Joannidis has received speaker’s honoraria from Astute Medical, Fresenius and Ortho Clinical Diagnostics.
Open-Access: This article is an open-access article which was selected by an in-house editor and fully peer-reviewed by external reviewers. It is distributed in accordance with the Creative Commons Attribution Non Commercial (CC BY-NC 4.0) license, which permits others to distribute, remix, adapt, build upon this work non-commercially, and license their derivative works on different terms, provided the original work is properly cited and the use is non-commercial. See: http://creativecommons.org/licenses/by-nc/4.0/
Correspondence to: Christian J Wiedermann, MD, Department of Research, College of Health Professions Claudiana, Lorenz-Böhler-Street 13, 39100 Bolzano, Italy. christian.wiedermann@claudiana.bz.it
Telephone: +39-04-71067300 Fax: +39-04-71067310
Received: February 14, 2017
Peer-review started: February 14, 2017
First decision: April 14, 2017
Revised: April 21, 2017
Accepted: May 3, 2017
Article in press: May 6, 2017
Published online: July 6, 2017
Processing time: 136 Days and 4 Hours
Abstract

Our meta-analysis published in 2010 provided evidence that low levels of serum albumin (hypoalbuminemia) are a significant independent predictor of acute kidney injury (AKI) and death following AKI. Since then, a large volume of additional data from observational clinical studies has been published further evaluating the relationship between serum albumin and AKI occurrence. This is an updated review of the literature to re-evaluate the hypothesis that hypoalbuminemia is independently associated with increased AKI risk. Eligible studies published from September 2009 to December 2016 were sought in PubMed (MEDLINE) and forty-three were retained, the great majority being retrospective observational cohort studies. These included a total of about 68000 subjects across a diverse range of settings, predominantly cardiac surgery and acute coronary interventions, infectious diseases, transplant surgery, and cancer. Appraisal of this latest data set served to conclusively corroborate and confirm our earlier hypothesis that lower serum albumin is an independent predictor both of AKI and death after AKI, across a range of clinical scenarios. The body of evidence indicates that hypoalbuminemia may causally contribute to development of AKI. Furthermore, administration of human albumin solution has the potential to prevent AKI; a randomized, controlled study provides evidence that correcting hypoalbuminemia may be renal-protective. Therefore, measurement of serum albumin to diagnose hypoalbuminemia may help identify high-risk patients who may benefit from treatment with exogenous human albumin. Multi-center, prospective, randomized, interventional studies are warranted, along with basic research to define the mechanisms through which albumin affords nephroprotection.

Keywords: Acute kidney injury; Acute renal failure; Hypoalbuminemia; Mortality; Prevention

Core tip: The relationship between hypoalbuminemia and acute kidney injury (AKI)-related morbidity/mortality is now confirmed. This association is consistently evident in a wealth of observational studies conducted across a wide range of clinical settings, and suggests a causal link. Prospective studies adequately powered to assess severe AKI, mortality and causality are needed, as is evaluation of the trigger and appropriate target serum levels and albumin dose necessary to confer renal protection. Basic research is also warranted to define the mechanisms through which albumin affords nephroprotection. Serum albumin should be measured to identify patients with increased AKI risk who may benefit from treatment correcting underlying hypoalbuminemia.