Controversies in acute kidney injury: conclusions from a Kidney Disease: Improving Global Outcomes (KDIGO) Conference

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Abstract

In 2012, Kidney Disease: Improving Global Outcomes (KDIGO) published a guideline on the classification and management of acute kidney injury (AKI). The guideline was derived from evidence available through February 2011. Since then, new evidence has emerged that has important implications for clinical practice in diagnosing and managing AKI. In April of 2019, KDIGO held a controversies conference entitled Acute Kidney Injury with the following goals: determine best practices and areas of uncertainty in treating AKI; review key relevant literature published since the 2012 KDIGO AKI guideline; address ongoing controversial issues; identify new topics or issues to be revisited for the next iteration of the KDIGO AKI guideline; and outline research needed to improve AKI management. Here, we present the findings of this conference and describe key areas that future guidelines may address.

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Epidemiology of acute kidney injury in critically ill patients: the multinational AKI-EPI study.

Eric Hoste, Sean Bagshaw, Rinaldo Bellomo … (2015)

Current reports on acute kidney injury (AKI) in the intensive care unit (ICU) show wide variation in occurrence rate and are limited by study biases such as use of incomplete AKI definition, selected cohorts, or retrospective design. Our aim was to prospectively investigate the occurrence and outcomes of AKI in ICU patients.

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Discovery and validation of cell cycle arrest biomarkers in human acute kidney injury

Kianoush B Kashani, Ali Al-Khafaji, Thomas Ardiles … (2013)

Introduction Acute kidney injury (AKI) can evolve quickly and clinical measures of function often fail to detect AKI at a time when interventions are likely to provide benefit. Identifying early markers of kidney damage has been difficult due to the complex nature of human AKI, in which multiple etiologies exist. The objective of this study was to identify and validate novel biomarkers of AKI. Methods We performed two multicenter observational studies in critically ill patients at risk for AKI - discovery and validation. The top two markers from discovery were validated in a second study (Sapphire) and compared to a number of previously described biomarkers. In the discovery phase, we enrolled 522 adults in three distinct cohorts including patients with sepsis, shock, major surgery, and trauma and examined over 300 markers. In the Sapphire validation study, we enrolled 744 adult subjects with critical illness and without evidence of AKI at enrollment; the final analysis cohort was a heterogeneous sample of 728 critically ill patients. The primary endpoint was moderate to severe AKI (KDIGO stage 2 to 3) within 12 hours of sample collection. Results Moderate to severe AKI occurred in 14% of Sapphire subjects. The two top biomarkers from discovery were validated. Urine insulin-like growth factor-binding protein 7 (IGFBP7) and tissue inhibitor of metalloproteinases-2 (TIMP-2), both inducers of G1 cell cycle arrest, a key mechanism implicated in AKI, together demonstrated an AUC of 0.80 (0.76 and 0.79 alone). Urine [TIMP-2]·[IGFBP7] was significantly superior to all previously described markers of AKI (P 0.72. Furthermore, [TIMP-2]·[IGFBP7] significantly improved risk stratification when added to a nine-variable clinical model when analyzed using Cox proportional hazards model, generalized estimating equation, integrated discrimination improvement or net reclassification improvement. Finally, in sensitivity analyses [TIMP-2]·[IGFBP7] remained significant and superior to all other markers regardless of changes in reference creatinine method. Conclusions Two novel markers for AKI have been identified and validated in independent multicenter cohorts. Both markers are superior to existing markers, provide additional information over clinical variables and add mechanistic insight into AKI. Trial registration ClinicalTrials.gov number NCT01209169.

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Acute kidney disease and renal recovery: consensus report of the Acute Disease Quality Initiative (ADQI) 16 Workgroup

Lakhmir S Chawla, Rinaldo Bellomo, Azra Bihorac … (2017)

Acute kidney injury (AKI) and chronic kidney disease are increasingly recognized as interconnected entities and the term acute kidney disease (AKD) has been proposed to define ongoing pathophysiologic processes following an episode of AKI. In this Consensus statement, the Acute Disease Quality Initiative 16 Workgroup propose definitions and staging criteria for AKD, and strategies for the management of affected patients. They also make recommendations for areas of future research with the aims of improving understanding of the underlying processes and improving outcomes.

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Author and article information

Journal

Journal ID (nlm-journal-id): 0323470

Journal ID (pubmed-jr-id): 5428

Journal ID (nlm-ta): Kidney Int

Journal ID (iso-abbrev): Kidney Int

Title: Kidney international

ISSN (Print): 0085-2538

ISSN (Electronic): 1523-1755

Publication date Nihms-submitted: 24 September 2021

Publication date (Electronic): 26 April 2020

Publication date (Print): August 2020

Publication date PMC-release: 29 September 2021

Volume: 98

Issue: 2

Pages: 294-309

Affiliations

[1 ]Department of Critical Care, King’s College London, Guy’s & St. Thomas’ Hospital, King’s College London, London, UK

[2 ]Centre for Integrated Critical Care, The University of Melbourne, Melbourne, Victoria, Australia

[3 ]Laboratório de Investigação Médica 12, Division of Nephrology, University of Sao Paulo Medical School, Sao Paulo, Sao Paulo, Brazil

[4 ]Department of Emergency and Critical Care Medicine, The University of Tokyo, Tokyo, Japan

[5 ]Prince of Wales Hospital and Clinical School, University of New South Wales, Randwick, NSW, Australia

[6 ]Department of Pediatrics, University of Cincinnati College of Medicine, Cincinnati, Ohio, USA

[7 ]Department of Pediatrics, Cincinnati Children’s Hospital, Cincinnati, Ohio, USA

[8 ]Department of Pharmacy and Therapeutics, University of Pittsburgh School of Pharmacy, Pittsburgh, Pennsylvania, USA

[9 ]Department of Medicine, Division of Nephrology, University of California, San Francisco, San Francisco, California, USA

[10 ]Department of Anesthesia, Division of Critical Care Medicine, University of California, San Francisco, San Francisco, California, USA

[11 ]William Harvey Research Institute, Barts and The London School of Medicine & Dentistry, Queen Mary University of London, London, UK

[12 ]Department of Anesthesiology and Pain Medicine, University of Alberta, Edmonton, Alberta, Canada

[13 ]Division of Nephrology, Department of Medicine, Faculty of Medicine, Chulalongkorn University, Bangkok, Thailand

[14 ]Critical Care Nephrology Research Unit, Faculty of Medicine, Chulalongkorn University, Bangkok, Thailand

[15 ]Tropical Medicine Cluster, Chulalongkorn University, Bangkok, Thailand

[16 ]Excellence Center for Critical Care Nephrology, King Chulalongkorn Memorial Hospital, Bangkok, Thailand

[17 ]Academy of Science, Royal Society of Thailand, Bangkok, Thailand

[18 ]Kidney Disease: Improving Global Outcomes (KDIGO), Brussels, Belgium

[19 ]Cliniques Universitaires Saint Luc, Université Catholique de Louvain, Brussels, Belgium

[20 ]Selzman Institute for Kidney Health, Section of Nephrology, Department of Medicine, Baylor College of Medicine, Houston, Texas, USA

[21 ]Department of Critical Care Medicine, University of Pittsburgh School of Medicine, Pittsburgh, Pennsylvania, USA

Author notes

[22]

See Appendix for list of Conference Participants.

Correspondence: Marlies Ostermann, Department of Critical Care, King’s College London, Guy’s and St Thomas’ NHS Foundation Trust, London SE1 7EH, UK. Marlies.Ostermann@ 123456gstt.nhs.uk ; or John A. Kellum, Department of Critical Care Medicine, Center for Critical Care Nephrology, The CRISMA Center, University of Pittsburgh School of Medicine, 3347 Forbes Avenue, Suite 220, Pittsburgh, Pennsylvania 15213, USA. kellum@ 123456pitt.edu

Article

Manuscript ID: NIHMS1741702

DOI: 10.1016/j.kint.2020.04.020

PMC ID: 8481001

PubMed ID: 32709292

SO-VID: b942b284-7db8-4494-808c-7f1cf1f47571

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This is an open access article under the CC BY-NC-ND license ( http://creativecommons.org/licenses/by-nc-nd/4.0/).

Controversies in acute kidney injury: conclusions from a Kidney Disease: Improving Global Outcomes (KDIGO) Conference

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Karger: Nephrology

Most cited references 151

Epidemiology of acute kidney injury in critically ill patients: the multinational AKI-EPI study.

Discovery and validation of cell cycle arrest biomarkers in human acute kidney injury

Acute kidney disease and renal recovery: consensus report of the Acute Disease Quality Initiative (ADQI) 16 Workgroup

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