Hsp72 Is a Novel Biomarker to Predict Acute Kidney Injury in Critically Ill Patients

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Abstract

Background and Objectives

Acute kidney injury (AKI) complicates the course of disease in critically ill patients. Efforts to change its clinical course have failed because of the fail in the early detection. This study was designed to assess whether heat shock protein (Hsp72) is an early and sensitive biomarker of acute kidney injury (AKI) compared with kidney injury molecule (Kim-1), neutrophil gelatinase-associated lipocalin (NGAL), and interleukin-18 (IL-18) biomarkers.

Methods

A total of 56 critically ill patients fulfilled the inclusion criteria. From these patients, 17 developed AKI and 20 were selected as controls. In AKI patients, Kim-1, IL-18, NGAL, and Hsp72 were measured from 3 days before and until 2 days after the AKI diagnosis and in no-AKI patients at 1, 5 and 10 days after admission. Biomarker sensitivity and specificity were determined. To validate the results obtained with ROC curves for Hsp72, a new set of critically ill patients was included, 10 with AKI and 12 with no-AKI patients.

Results

Urinary Hsp72 levels rose since 3 days before the AKI diagnosis in critically ill patients; this early increase was not seen with any other tested biomarkers. Kim-1, IL-18, NGAL, and Hsp72 significantly increased from 2 days before AKI and remained elevated during the AKI diagnosis. The best sensitivity/specificity was observed in Kim-1 and Hsp72: 83/95% and 100/90%, respectively, whereas 1 day before the AKI diagnosis, the values were 100/100% and 100/90%, respectively. The sensibility, specificity and accuracy in the validation test for Hsp72 were 100%, 83.3% and 90.9%, respectively.

Conclusions

The biomarker Hsp72 is enough sensitive and specific to predict AKI in critically ill patients up to 3 days before the diagnosis.

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Most cited references 26

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Acute kidney injury, mortality, length of stay, and costs in hospitalized patients.

Glenn Chertow, Elisabeth Burdick, Melissa M Honour … (2005)

The marginal effects of acute kidney injury on in-hospital mortality, length of stay (LOS), and costs have not been well described. A consecutive sample of 19,982 adults who were admitted to an urban academic medical center, including 9210 who had two or more serum creatinine (SCr) determinations, was evaluated. The presence and degree of acute kidney injury were assessed using absolute and relative increases from baseline to peak SCr concentration during hospitalization. Large increases in SCr concentration were relatively rare (e.g., >or=2.0 mg/dl in 105 [1%] patients), whereas more modest increases in SCr were common (e.g., >or=0.5 mg/dl in 1237 [13%] patients). Modest changes in SCr were significantly associated with mortality, LOS, and costs, even after adjustment for age, gender, admission International Classification of Diseases, Ninth Revision, Clinical Modification diagnosis, severity of illness (diagnosis-related group weight), and chronic kidney disease. For example, an increase in SCr >or=0.5 mg/dl was associated with a 6.5-fold (95% confidence interval 5.0 to 8.5) increase in the odds of death, a 3.5-d increase in LOS, and nearly 7500 dollars in excess hospital costs. Acute kidney injury is associated with significantly increased mortality, LOS, and costs across a broad spectrum of conditions. Moreover, outcomes are related directly to the severity of acute kidney injury, whether characterized by nominal or percentage changes in serum creatinine.

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Acute kidney injury associates with increased long-term mortality.

Jean-Philippe Lafrance, Donald Miller (2010)

Acute kidney injury (AKI) associates with higher in-hospital mortality, but whether it also associates with increased long-term mortality is unknown, particularly after accounting for residual kidney function after hospital discharge. We retrospectively analyzed data from US veteran patients who survived at least 90 d after discharge from a hospitalization. We identified AKI events not requiring dialysis from laboratory data and classified them according to the ratio of the highest creatinine during the hospitalization to the lowest creatinine measured between 90 d before hospitalization and the date of discharge. We estimated mortality risks using multivariable Cox regression models adjusting for demographics, comorbidities, medication use, primary diagnosis of admission, length of stay, mechanical ventilation, and postdischarge estimated GFR (residual kidney function). Among the 864,933 hospitalized patients in the study cohort, we identified 82,711 hospitalizations of patients with AKI. In the study population of patients who survived at least 90 d after discharge, 17.4% died during follow-up (AKI 29.8%, without AKI 16.1%). The adjusted mortality risk associated with AKI was 1.41 (95% confidence interval [CI] 1.39 to 1.43) and increased with increasing AKI stage: 1.36 (95% CI 1.34 to 1.38), 1.46 (95% CI 1.42 to 1.50), and 1.59 (95% CI 1.54 to 1.65; P < 0.001 for trend). In conclusion, AKI that does not require dialysis associates with increased long-term mortality risk, independent of residual kidney function, for patients who survive 90 d after discharge. Long-term mortality risk is highest among the most severe cases of AKI.

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Increased risk of death and de novo chronic kidney disease following reversible acute kidney injury.

Ion Bucaloiu, H Kirchner, Evan R Norfolk … (2012)

Acute kidney injury increases mortality risk among those with established chronic kidney disease. In this study we used a propensity score-matched cohort method to retrospectively evaluate the risks of death and de novo chronic kidney disease after reversible, hospital-associated acute kidney injury among patients with normal pre-hospitalization kidney function. Of 30,207 discharged patients alive at 90 days, 1610 with reversible acute kidney injury that resolved within the 90 days were successfully matched across multiple parameters with 3652 control patients who had not experienced acute kidney injury. Median follow-up was 3.3 and 3.4 years (injured and control groups, respectively). In Cox proportional hazard models, the risk of death associated with reversible acute kidney injury was significant (hazard ratio 1.50); however, adjustment for the development of chronic kidney injury during follow-up attenuated this risk (hazard ratio 1.18). Reversible acute kidney injury was associated with a significant risk of de novo chronic kidney disease (hazard ratio 1.91). Thus, a resolved episode of hospital-associated acute kidney injury has important implications for the longitudinal surveillance of patients without preexisting, clinically evident kidney disease.

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Author and article information

Contributors

Antonio C. Seguro: Role: Editor

Journal

Journal ID (nlm-ta): PLoS One

Journal ID (iso-abbrev): PLoS ONE

Journal ID (publisher-id): plos

Journal ID (pmc): plosone

Title: PLoS ONE

Publisher: Public Library of Science (San Francisco, USA )

ISSN (Electronic): 1932-6203

Publication date Collection: 2014

Publication date (Electronic): 14 October 2014

Volume: 9

Issue: 10

Electronic Location Identifier: e109407

Affiliations

[1 ]Department of Nephrology Nefrología y Metabolismo Mineral, Instituto Nacional de Ciencias Médicas y Nutrición Salvador Zubirán, México City, México

[2 ]Unidad de Fisiología Molecular, Instituto de Investigaciones Biomédicas, Universidad Nacional Autónoma de México, México City, México

University of São Paulo School of Medicine, Brazil

Author notes

* E-mail: luis_buenrostro@ 123456yahoo.com (LEMB); nab@ 123456biomedicas.unam.mx (NAB)

Competing Interests: Dr. Luis E. Morales Buenrostro is an speaker of Novartis, Roche, and Sanofi México. He also has participated in advisory boards of Boehringer Ingelheim México, Eli Lilly Mexico, Astra Zeneca México and Bristol-Myers Squibb, Mexico. Dr. Norma A. Bobadilla and Dr. Jonatan Barrera have presented patent applications in México Canada, China, Europe, and US (Diagnostic method for detecting acute kidney injury using Hsp72 as a sensitive biomarker, US 2013/0065239 A1). The rest of the authors declare that there are no financial competing interests. This does not alter the authors' adherence to PLOS ONE policies on sharing data and materials.

Conceived and designed the experiments: LEMB NAB. Performed the experiments: JBCH RPV OISN GCA SIS. Analyzed the data: LEMB JBCH OISN NAB. Contributed reagents/materials/analysis tools: JBCH RPV NAB. Contributed to the writing of the manuscript: LEMB NAB.

Article

Publisher ID: PONE-D-14-36329

DOI: 10.1371/journal.pone.0109407

PMC ID: 4196900

PubMed ID: 25313566

SO-VID: 64992354-e242-4127-9137-bd13d2da53db

License:

This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.

History

Date received : 13 August 2014

Date accepted : 3 September 2014

Page count

Pages: 7

Funding

This project was supported by grants from the Mexican Council of Science and Technology (CONACyT) (181267 to NAB), http://www.conacyt.mx/ And from the National University of Mexico (IN203412-3 to NAB), http://dgapa.unam.mx/html/papiit/papit.html. The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.

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Data Availability The authors confirm that all data underlying the findings are fully available without restriction. All relevant data are within the paper and its Supporting Information files.

Hsp72 Is a Novel Biomarker to Predict Acute Kidney Injury in Critically Ill Patients

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Abstract

Background and Objectives

Methods

Results

Conclusions

Related collections

PLOS Climate

Most cited references 26

Acute kidney injury, mortality, length of stay, and costs in hospitalized patients.

Acute kidney injury associates with increased long-term mortality.

Increased risk of death and de novo chronic kidney disease following reversible acute kidney injury.

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