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Published ahead of print on June 25, 2008
Clin J Am Soc Nephrol 3: 933-934, 2008
© 2008 American Society of Nephrology
doi: 10.2215/CJN.02340508
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Editorials

Setting the Agenda

Paul M. Palevsky

Renal Section, VA Pittsburgh Healthcare System and Professor of Medicine, Renal-Electrolyte Division, University of Pittsburgh School of Medicine Pittsburgh, Pennsylvania

Correspondence: Dr. Paul M. Palevsky, VA Pittsburgh Healthcare System, Room 7E123 (111F-U), University Drive, Pittsburgh, PA 15240. Phone: 412-688-6000, x815932; Fax: 412-688-6908; E-mail: palevsky{at}pitt.edu


   Introduction
Top
 Introduction
Disclosures
 References
 
In March, the U.S. Centers for Disease Control and Prevention published data on trends in hospitalizations for kidney disease from 1980 through 2005 (1). During this 25-year period, there was a greater than 20-fold increase in hospitalizations for acute kidney injury (AKI), from an age-adjusted rate of 18 per 100,000 population in 1980 to 365 per 100,000 population in 2005. During the same period, hospitalizations for chronic kidney disease increased less than two-fold, from 74 to 138 per 100,000 population. Although the majority of kidney disease research has focused on chronic and end-stage disease, these data highlight the pressing need to understand the causes for this explosive increase in acute kidney disease and improve clinical strategies for its prevention and treatment.

Understanding the epidemiology of AKI has been hampered by the multiplicity of definitions that have been used in clinical studies (2). The need for a consensus definition and classification system for AKI was recognized by the Acute Dialysis Quality Initiative, resulting in the development of the RIFLE (Risk, Injury, Failure, Loss of kidney function and End-stage disease) criteria in 2002 (3). These criteria were further refined by the Acute Kidney Injury Network (AKIN), a collaboration of nephrology and critical care societies from around the world, at its first meeting in September 2005 (4).

At its second meeting, in September 2006, the AKIN group shifted its focus from standardization of the definition and classification of acute kidney injury to formulation of a conceptual framework and prioritization of a clinical research agenda. In a series of articles published in the May issue (5–10) and an additional article by Himmelfarb et al. (11) in this issue of CJASN, the AKIN group details the processes and outcomes of this meeting.

In the conceptual framework (Figure 1), sequential stages of AKI (subclinical damage, decreased GFR, overt kidney failure) are placed in a spectrum spanning antecedent status (normal patients and patients with increased risk for acute kidney injury) to outcomes (nonfatal complications and death). Using this conceptual framework as a basis for deliberations, six workgroups were formed, charged with prioritizing clinical research questions regarding the epidemiology of AKI (9), evaluation and initial management of patients with AKI (11), and management of renal replacement therapy in patients with acute kidney injury (7,8). The research questions identified by the individual workgroups were then ranked by all participants in a modified Delphi process (10).


Figure 1
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  		Figure 1. The AKIN conceptual model of acute kidney injury.

 
Of 20 clinical research questions identified, the highest priority was assigned to issues of epidemiology (what is the incidence of acute kidney injury?), diagnosis (do other GFR markers predict clinical outcomes better than serum creatinine; are there biomarkers that predict severity and recovery of kidney injury?), management (when should renal replacement therapy be initiated; does timing affect outcome; what dose is required to maximize patient and renal survival?), and prognosis (does acute kidney injury lead to chronic kidney disease; does severity of acute kidney injury predict renal and nonrenal clinical outcomes?). The scope and fundamental nature of these questions clearly indicates how much we need to learn in order to improve the care of patients with this increasingly common form of kidney disease.

From the practical standpoint, a key question is how should these research priorities to be implemented? Although one of the AKIN goals is to develop and facilitate international and interdisciplinary research initiatives in the diagnosis, prevention, and treatment of AKI, clinical research is expensive. Well-designed and effectively implemented clinical studies will require substantial funding from governments, foundations, and industry. A review of clinical trial registries shows increasing numbers of AKI studies, but most are small, single-center trials that tend to have insufficient statistical power to inform clinical practice. Large, multicenter trials, such as the recently completed VA/NIH Acute Renal Failure Trial Network study (12), are expensive, often with budgets in excess of $10 million to $20 million. The National Institute of Diabetes and Digestive and Kidney Diseases has solicited proposals for participation in an Acute Kidney Injury Natural History Consortium in an attempt to leverage smaller short-term studies involving patients with AKI, such as biomarker validation and short-term intervention studies, to assess longer-term outcomes, including whether AKI predicts or accelerates the long-term development of chronic kidney disease. More such initiatives will be necessary to validate new biomarkers for early diagnosis and prognosis of AKI and for evaluation of interventions to prevent the development or decrease the morbidity and mortality of AKI. The Acute Kidney Injury Network has helped set the agenda; success will depend on its implementation.


   Disclosures
Top
 Introduction
 Disclosures
References
 
None.


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

See related article, "Evaluation and Initial Management of Acute Kidney Injury," on pages 962–967.


   References
Top
 Introduction
 Disclosures
 References
 

  1. Hospitalization discharge diagnoses for kidney disease–United States, 1980–2005. MMWR Morb Mortal Wkly Rep57 :309 –312,2008[Medline]
  2. Mehta RL, Chertow GM: Acute renal failure definitions and classification: time for change? J Am Soc Nephrol14 :2178 –2187,2003[Free Full Text]
  3. Bellomo R, Ronco C, Kellum JA, Mehta RL, Palevsky P: Acute renal failure-definition, outcome measures, animal models, fluid therapy and information technology needs: the Second International Consensus Conference of the Acute Dialysis Quality Initiative (ADQI) Group. Crit Care8 :R204 –R12,2004[CrossRef][Medline]
  4. 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]
  5. Levin A, Kellum JA, Mehta RL: Acute kidney injury: toward an integrated understanding through development of a research agenda. Clin J Am Soc Nephrol3 :862 –863,2008[Free Full Text]
  6. Murray PT, Devarajan P, Levey AS, Eckardt KU, Bonventre JV, Lombardi R, Herget-Rosenthal S, Levin A: A framework and key research questions in AKI diagnosis and staging in different environments. Clin J Am Soc Nephrol3 :864 –868,2008[Abstract/Free Full Text]
  7. Davenport A, Bouman C, Kirpalani A, Skippen P, Tolwani A, Mehta RL, Palevsky PM: Delivery of renal replacement therapy in acute kidney injury: what are the key issues? Clin J Am Soc Nephrol3 :869 –875,2008[Abstract/Free Full Text]
  8. Gibney N, Hoste E, Burdmann EA, Bunchman T, Kher V, Viswanathan R, Mehta RL, Ronco C: Timing of initiation and discontinuation of renal replacement therapy in AKI: unanswered key questions. Clin J Am Soc Nephrol3 :876 –880,2008[Abstract/Free Full Text]
  9. Cerda J, Lameire N, Eggers P, Pannu N, Uchino S, Wang H, Bagga A, Levin A: Epidemiology of acute kidney injury. Clin J Am Soc Nephrol3 :881 –886,2008[Abstract/Free Full Text]
  10. Kellum JA, Mehta RL, Levin A, Molitoris BA, Warnock DG, Shah SV, Joannidis M, Ronco C: 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]
  11. Himmelfarb J, Joannidis M, Molitoris B, Schietz M, Okusa MD, Warnock D, Laghi F, Goldstein SL, Prielipp R, Parikh CR, Pannu N, Lobo SM, Shah S, D'Intini V, Kellum JA: Evaluation and initial management of acute kidney injury. Clin J Am Soc Nephrol3 :962 –967,2008[Abstract/Free Full Text]
  12. Palevsky PM, Zhang JH, O'Connor TZ, Chertow GM, Crowley ST, Choudhury D, Finkel K, Kellum JA, Paganini E, Schein RMH, Smith MW, Swanson KM, Thompson BT, Vijayan A, Watnick S, Star RA, Peduzzi P: Intensity of renal support in critically ill patients with acute kidney injury. N Engl J Med2008 [Epub ahead of print]

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