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Published ahead of print on March 5, 2008
Clin J Am Soc Nephrol 3: 862-863, 2008
© 2008 American Society of Nephrology
doi: 10.2215/CJN.04841107
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Moving Points in Nephrology

Acute Kidney Injury: Toward an Integrated Understanding through Development of a Research Agenda

Adeera Levin*, John A. Kellum{dagger}, Ravindra L. Mehta{ddagger}; for the Acute Kidney Injury Network (AKIN)

* Division of Nephrology, University of British Columbia, Vancouver, British Columbia, Canada; {dagger} Department of Critical Care, University of Pittsburgh, Pittsburgh, Pennsylvania; and {ddagger} Division of Nephrology, University of California at San Diego, San Diego, California

Correspondence: Dr. Adeera Levin, Division of Nephrology UBC, St. Pauls Hospital, Providence Wing, Room 6010A, 1160 Burrard Street, Vancouver BC, V6Z1Y8, Canada. Phone: 604-682-2344, ext. 62232; Fax: 604-806-8120; E-mail: alevin{at}providencehealth.bc.ca


   Introduction
Top
 Introduction
Disclosures
 References
 
Acute kidney injury (AKI) is widely recognized as an important predictor of morbidity and mortality and as an antecedent to chronic kidney disease (1). In the past 5 yr, there has been increasing interest in understanding this entity, at the both basic science and clinical levels. Recent advances in methodology have led to the description of both serum and urine biomarkers and the imaging of events occurring at the cellular level (2–5). Advances in understanding of and technology associated with dialysis in acute care settings have also contributed to the increasing recognition and treatment of AKI in these settings and the development of research studies to define its appropriate use (6–9).

The purpose of this collection of articles is to describe the development of a research agenda, using a modified Delphi approach, that is based on a conceptual framework and a refined definition of AKI. Although each article is written in a different format, the key messages are similar: There is a limited evidence base about most aspects of AKI, and there is a need, through a concerted effort of clinicians and researchers, to address questions that will have an impact on patient outcomes. We acknowledge that AKI is a term that actually encompasses multiple etiologies. For the purposes of defining a research agenda, it is clear that an overarching term is preferred: Specific etiologies can then be more clearly investigated or evaluated within the contextual framework described here.

In this edition of CJASN, the first series describe the conceptual model of AKI and how it can be used to answer specific questions, as well as remaining questions regarding the epidemiology of AKI. In particular, we stress the need for better understanding and definitions that are applicable in a multitude of situations. The next article defines the evaluation and early management of AKI, with a major emphasis on the need to distinguish between volume-responsive and volume-unresponsive AKI in a systematic way. The last two articles describe the issues related to renal replacement therapy, particularly indications for and choices of therapy, and again describe key questions related to timing of therapy, defining optimal and minimal dosages of therapy. All of the articles use the definition of AKI recently published (1).

The importance of a conceptual model in which to study AKI cannot be overstated. Building on previous work in chronic kidney disease and using the expertise of basic and clinical science, a conceptual model of AKI was developed and refined, initially within one workgroup and subsequently with input from the entire 43 participants at the Vancouver AKIN meeting (September 2007). Briefly, the key aspects of the model include the description of a trajectory of disease from normal populations to at-risk populations to those with early reversible and late nonreversible disease, the ability to define a clear research agenda (both clinical and basic) at every stage of the model, and the concordance with existing accepted models of chronic kidney disease. The second article describes this model in detail.

This series of articles serves to focus the community on the importance of AKI as an entity, describe the myriad of possibilities in terms of research and clinical practice opportunities, and describe the current state of knowledge. Through ongoing clinical and research initiatives and leveraging the newly established Acute Kidney Injury Network, we hope to gain an understanding of how best to prevent and treat AKI so that ultimately we are able to improve patient outcomes.

The Vancouver conference and the articles in this CJASN selection build on the first AKIN conference held in Amsterdam in 2005 (1). The specific method used is described in the article by Kellum et al. (11) in this series and thus is not repeated in each article.


   Disclosures
Top
 Introduction
 Disclosures
References
 
None.


   Footnotes
 
Published online ahead of print. Publication date available at www.cjasn.org.


   References
Top
 Introduction
 Disclosures
 References
 

  1. Mehta RL, Kellum JA, Shah SV, Molitoris BA, Ronco C, Warnock DG, Levin A, Acute Kidney Injury Network: Report of an initiative to improve outcomes in acute kidney injury. Crit Care11 :R31 ,2007[CrossRef][Medline]
  2. Murray PT, Le Gall JR, Dos Reis Miranda D, Pinsky MR, Tetta C: Physiologic endpoints (efficacy) for acute renal failure studies. Curr Opin Crit Care8 :519 –525,2002[CrossRef][Medline]
  3. Han WK, Bailly V, Abichandani R, Thadani R, Bonventre JV: Kidney injury molecule-1 (KIM-1): A novel biomarker for human renal proximal tubule injury. Kidney Int62 :237 –244,2002[CrossRef][Medline]
  4. Mishra J, Dent C, Tarabishi R, Mitsnefes MM, Ma Q, Kelly C, Ruff SM, Zahedia K, Shao M, Bean J, Mori K, Barasch J, Devarajan P: Neutrophil gelatinase-associated lipocalin (NGAL) as a biomarker for acute renal injury after cardiac surgery. Lancet365 :1231 –1238,2005[CrossRef][Medline]
  5. Parikh CR, Abraham E, Ancukiewicz M, Edelstein CL: Urine IL-18 is an early diagnostic marker for acute kidney injury and predicts mortality in the intensive care unit. J Am Soc Nephrol16 :3046 –3052,2005[Abstract/Free Full Text]
  6. Uchino S, Kellum JA, Bellomo R, Doig GS, Morimatsu H, Morgera S, Schetz M, Tan I, Bouman C, Macedo E, Gibney N, Tolwani A, Ronco C, Beginning and Ending Supportive Therapy for the Kidney (BEST Kidney) Investigators: Acute renal failure in critically ill patients: A multinational, multicenter study. JAMA294 :813 –818,2005[Abstract/Free Full Text]
  7. Ricci Z, Ronco C, D'Amico G, De Felice R, Rossi S, Bolgan I, Bonello M, Zamperetti N, Petras D, Salvatori G, Dan M, Piccinni P: Practice patterns in the management of acute renal failure in the critically ill patient: An international survey. Nephrol Dial Transplant21 :690 –696,2006[Abstract/Free Full Text]
  8. Mehta RL: Indications for dialysis in the ICU: Renal replacement vs. renal support. Blood Purif19 :227 –232,2001[CrossRef][Medline]
  9. Liu KD, Himmelfarb J, Paganini E, Ikizler TA, Soroko SH, Mehta RL, Chertow GM: Timing of initiation of dialysis in critically ill patients with acute kidney injury. Clin J Am Soc Nephrol1 :915 –919,2006[Abstract/Free Full Text]
  10. Kellum JA: The Acute Dialysis Quality Initiative: Methodology. Adv Ren Replace Ther9 :245 –247,2002[CrossRef][Medline]
  11. Kellum JA, Mehta RL, Levin A, Molitoris BA, Warnock DG, Shah SV, Joannidis M, Ronco C, for the Acute Kidney Injury Network (AKIN): Development of a clinical research agenda for acute kidney injury using an international, interdisciplinary, three-step modified Delphi process. Clin J Am Soc Nephrol3 :887 –894,2008[Abstract/Free Full Text]



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Setting the Agenda
Clin. J. Am. Soc. Nephrol., July 1, 2008; 3(4): 933 - 934.
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