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Preventing AKI with Urinary Biomarkers

After Surgery


Acute Kidney Injury (AKI) contributes to morbidity and mortality after cardiac surgery. Urinary bio-markers are able to identify patients at risk for AKI, allowing for the activation of protocols designed to reduce or prevent this complication.

ERAS Cardiac Society Recommendation

Early detection of kidney stress and interventions to avoid acute kidney injury are recommended following surgery.

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Even transient stage-1 (mild) AKI has a significant long-term impact on post cardiac surgery mortality. Urinary biomarkers, including tissue inhibitor of metalloproteinases-2 (TIMP-2) and insulin-like growth factor binding protein 7 (IGFBP7) have been shown to identify kidney's under stress (i.e. prior to injury), which are at risk for developing AKI. These markers are more sensitive then traditional measures of kidney function such as serum creatinine or urinary output.

(Data from: Linder A, Fjell C, Levin A, Walley KR, Russell JA, Boyd JH. Small acute increases in serum creatinine are associated with decreased long-term survival in the critically ill. American journal of respiratory and critical care medicine 2014;189:1075-81.)

Kidney Disease: Improving Global Outcomes (KDIGO) Guidelines

The KDIGO Guidelines is the primary international source guideline for classification, diagnosis, management, and prevention of AKI. Published in 2012, KDIGO offers graded AKI-risk interventions for kidneys under stress, prior to the occurrence of staged AKI.

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Elevated Serum Creatinine and Decreased Urine Output are Insufficient

Diagnosing renal dysfunction by elevated serum creatinine may be too late, as it may not increase until as much as 50% of the glomerular filtration rate is lost. Since several factors can influence the urine output, this parameter has a low specificity for renal injury.

Urinary biomarkers aim to identify patients at high-risk, prior to injury. This allows for the initiation of protocols, or AKI-prevention bundles, which generally include minimizing further nephro-toxic insults, use of additional monitoring, and optimizing hemodynamics and fluid management through goal-directed therapy.

Protocols to Prevent AKI Measuring Urinary Biomarkers

Previous studies have shown, in both non-cardiac and cardiac surgery, that implementing protocols based on urinary biomarkers can reduce the incidence of AKI.

Many protocols exist and, despite institutional variability, share several commonalities. These include:

1) Identifying patients at risk for AKI (which in the case of CV surgery may be ALL patients).

2) Measuring urinary biomarkers early in the patient's care, before major renal injury has occurred.

3) Having a multi-disciplinary, team-based approach to diagnosis, monitoring, assessment, and interventions for patients identified at-risk for AKI.

4) Making use of a formal AKI Prevention Bundle, which maximizes the use of algorithms and goal-directed interventions/decisions, to deliver consistent care.

Examples of AKI-Prevention Protocols Currently in Use

We have been provided with existing protocols from two institutions, which can be used as a guide for developing a local AKI-prevention strategy as part of an ERAS Cardiac Program. Both protocols can be downloaded in PDF format at the bottom of this page.

Protocol 1: Baystate Health, Daniel Engelman MD.

Protocol 2: AdventHealth Watermark, Louis Guzzi MD.

Key references

1. Cummings JJ, Shaw AD, Shi J, Lopez MG, O'Neal JB, Billings FT. Intraoperative prediction of cardiac surgery-associated acute kidney injury using urinary biomarkers of cell cycle arrest. The Journal of thoracic and cardiovascular surgery 2019;157:1545-53.e5.

2. Engelman DT, Crisafi C, Germain M, et al. Using urinary biomarkers to reduce acute kidney injury following cardiac surgery. J Thorac Cardiovasc Surg. 2019 [Epub ahead of print] doi: 10.1016/j.jtcvs.2019.10.034

3. Gocze I, Jauch D, Gotz M, et al. Biomarker-guided Intervention to Prevent Acute Kidney Injury After Major Surgery: The Prospective Randomized BigpAK Study. Annals of surgery 2018;267:1013-20.

4. Guzzi LM, Bergler T, Binnall B, et al. Clinical use of [TIMP-2]*[IGFBP7] biomarker testing to assess risk of acute kidney injury in critical care: guidance from an expert panel. Critical care (London, England) 2019;23:225.

5. Hobson C, Ozrazgat-Baslanti T, Kuxhausen A, et al. Cost and Mortality Associated With Postoperative Acute Kidney Injury. Annals of surgery 2015;261:1207-14.

6. Husain-Syed F, Ferrari F, Sharma A, et al. Persistent decrease of renal functional reserve in patients after cardiac surgery-associated acute kidney injury despite clinical recovery. Nephrology, dialysis, transplantation : official publication of the European Dialysis and Transplant Association - European Renal Association 2019;34:308-17.

7. Kashani K, Al-Khafaji A, Ardiles T, et al. Discovery and validation of cell cycle arrest biomarkers in human acute kidney injury. Critical care (London, England) 2013;17:R25.

8. Meersch M, Schmidt C, Hoffmeier A, et al. Prevention of cardiac surgery-associated AKI by implementing the KDIGO guidelines in high risk patients identified by biomarkers: the PrevAKI randomized controlled trial. Intensive care medicine 2017;43:1551-61.

9. Nadim MK, Forni LG, Bihorac A, et al. Cardiac and Vascular Surgery-Associated Acute Kidney Injury: The 20th International Consensus Conference of the ADQI (Acute Disease Quality Initiative) Group. Journal of the American Heart Association 2018;7.

10. Ostermann M, McCullough PA, Forni LG, et al. Kinetics of Urinary Cell Cycle Arrest Markers for Acute Kidney Injury Following Exposure to Potential Renal Insults. Critical care medicine 2018;46:375-83.

Additional Educational Links

1. Assessing & Preventing Acute Kidney Injury Through Kidney Stress Biomarker Series.

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2. General AKI and CRRT Online Learning Resource.

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3. Preventing AKI in Cardiac Surgery: KDIGO Controversies Conference on AKI, Rome, Italy, 2019

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Educational materials produced by the Society for Enhanced Recovery After Cardiac Surgery (ERAS® Cardiac) may be considered Open Access. Non-commercial use of ERAS® Cardiac educational materials, including images, audio, and video, in whole or in part, is permitted with the following conditions: 1) the content is not altered, 2) the listed authors of the content and ERAS® Cardiac are appropriately referenced, and 3) a URL address or hyperlink to the original material or the main web site [] is included in the reproduction.


Editors: Alexander Gregory MD, Alexander Zarbock MD, and Daniel Engelman MD

Original artwork created by Mark Cromwell.