KDOQI Commentary
KDOQI US Commentary on the 2012 KDIGO Clinical Practice Guideline for Acute Kidney Injury

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In response to the recently released 2012 KDIGO (Kidney Disease: Improving Global Outcomes) clinical practice guideline for acute kidney injury (AKI), the National Kidney Foundation organized a group of US experts in adult and pediatric AKI and critical care nephrology to review the recommendations and comment on their relevancy in the context of current US clinical practice and concerns. The first portion of the KDIGO guideline attempts to harmonize earlier consensus definitions and staging criteria for AKI. While the expert panel thought that the KDIGO definition and staging criteria are appropriate for defining the epidemiology of AKI and in the design of clinical trials, the panel concluded that there is insufficient evidence to support their widespread application to clinical care in the United States. The panel generally concurred with the remainder of the KDIGO guidelines that are focused on the prevention and pharmacologic and dialytic management of AKI, although noting the dearth of clinical trial evidence to provide strong evidence-based recommendations and the continued absence of effective therapies beyond hemodynamic optimization and avoidance of nephrotoxins for the prevention and treatment of AKI.

Introduction

KDIGO (Kidney Disease: Improving Global Outcomes) is an international initiative to develop and implement clinical practice guidelines for patients with kidney disease. In March 2012, KDIGO published its guideline for the evaluation and management of acute kidney injury (AKI).1 This guideline covers numerous topics, including the definition and classification of AKI, the prevention and treatment of AKI in general with specific recommendations for the prevention of contrast-induced AKI, and the management of renal replacement therapy (RRT) in patients with AKI. Because international guidelines need to be adapted for the United States, the National Kidney Foundation–Kidney Disease Outcomes Quality Initiative (NKF-KDOQI) convened a multidisciplinary work group with expertise in adult and pediatric nephrology and critical care medicine to comment on the applicability and implementation of the KDIGO AKI guideline in the United States. This commentary provides a summary of the KDIGO recommendation statements along with the supporting rationales and comments on their applicability to clinical practice in the United States. The KDOQI Work Group congratulates KDIGO, the members of the AKI Guideline Work Group, and the evidence review team for producing such a comprehensive document and believes that this guideline will be of great value to health professionals and will advance both current clinical care of patients with AKI and future clinical research.

AKI represents the sudden loss of kidney function, generally occurring over the course of hours to days and resulting in the retention of metabolic waste products and dysregulation of fluid, electrolyte, and acid-base homeostasis. During the past decade, this acute loss of kidney function, previously referred to as acute renal failure, has been the subject of significant re-examination, with increased recognition of the importance of relatively small changes in kidney function on both short- and longer term clinical outcomes.2, 3, 4, 5, 6 This has resulted in the change in terminology from acute renal failure, for which the focus generally was limited to the most severe episodes with complete or near-complete loss of kidney function, to the current terminology of AKI, with increased focus on smaller decrements in kidney function.7, 8, 9

AKI may develop in a wide variety of settings, including in ambulatory outpatients, hospitalized patients, and, in particular, critically ill patients, for whom AKI represents a common complication of both underlying disease and treatment. AKI is associated with substantial morbidity and mortality. For example, severe AKI occurs in >5% of critically ill patients and is associated with mortality rates of 40%-70%.10, 11, 12 Although recovery of kidney function occurs in the majority of patients surviving an episode of AKI, many patients remain dialysis dependent or are left with severe renal impairment. More recently, it has been recognized that even patients who have complete or near-complete recovery of kidney function are at increased risk of progressive chronic kidney disease (CKD) and that superimposition of AKI on CKD is associated with acceleration in the rate of progression to end-stage disease.13, 14, 15, 16, 17

Our understanding of the epidemiology of AKI and interpretation of results across clinical trials has been hindered by the prior absence of a broadly accepted clinical definition, with more than 30 operational definitions of AKI used in published studies.18 During the past decade, there has been a considerable effort to forge a consensus definition. The first attempt at developing a consensus definition, known as the RIFLE criteria, was developed by the Acute Dialysis Quality Initiative (ADQI) in 2002 (Table 1).19 This definition considered 3 strata of severity (risk, injury, and failure) based on the magnitude of increase in serum creatinine level and/or the duration of oliguria, as well as 2 outcome stages (loss of kidney function and end-stage kidney disease). The risk, injury, and failure categories were constructed to provide gradations in severity of kidney dysfunction, with greater sensitivity associated with risk and greater specificity with failure. The RIFLE criteria subsequently were modified by the AKI Network (AKIN) by the addition of an absolute increase in serum creatinine level >0.3 mg/dL to the definition of AKI, a shortening of the time for the increase in serum creatinine level from 7 days to no more than 48 hours, and elimination of the 2 outcome criteria (Table 1).7, 8 A modification of the RIFLE criteria for use in pediatric patients (pRIFLE) has also been developed (Table 2).20 Validation studies using these definitions have demonstrated increased mortality risk associated with progressively more severe stages of AKI. The KDIGO AKI guideline builds upon these earlier efforts in defining AKI, with a full section of the guideline devoted to the definition of AKI.

The development of successful therapeutic strategies for the prevention and treatment of most forms of AKI has been disappointing. Although numerous agents have shown promise in experimental models, none has demonstrated utility in clinical care. A particular area of focus has been in the prevention of contrast-induced AKI. This common cause of AKI has been the focus of multiple preventative interventions because individuals at high risk of contrast-induced AKI can be readily identified and the timing of exposure can be predetermined, allowing an opportunity for intervention. In the absence of effective pharmacologic therapy, the management of established AKI is predominantly supportive care, with the use of RRT in severe AKI. There has been tremendous advancement in the technology and modalities available for providing RRT; however, the optimal approach to management of RRT in this setting remains controversial. The KDIGO AKI guideline provides specific recommendations, based on the current literature, for best practices in the prevention and management of AKI. In this KDOQI commentary, we have attempted to place this international guideline in the context of care practices in the United States. However, our commentary should be viewed in conjunction with the full KDIGO document when making clinical decisions.

Section snippets

Review and Approval Process for This Commentary

This commentary was developed by a Work Group convened by the NKF-KDOQI, beginning with selecting Co-Chairs by the KDOQI steering committee and individual members selected based on their clinical expertise and interest in the guideline process. Teleconferences took place during 2011 and 2012 to determine the specific areas for focus for this commentary. Individual sections focusing on each of the topical areas of the KDIGO AKI guideline were drafted by groups of coauthors based on detailed

Assessment of Guideline Quality

The KDIGO AKI guideline contains 87 individual recommendations, of which 26 (30%) are ungraded, 39 (45%) are level 2 recommendations, and only 22 (25%) are level 1 recommendations, reflecting the relative paucity of high-level data guiding the management of AKI (Fig 1). In addition, many of the level 1 recommendations advise against the use of specific agents or therapeutic interventions.

All members of the Work Group completed the AGREE (Appraisal of Guideline for Research and Evaluation) II

Commentary

Overview. The first group of recommendation statements in the KDIGO AKI Guideline addresses the definition of AKI (Box 1). Of these 13 recommendation statements, 12 are not graded. The KDIGO Work Group began by defining AKI by harmonizing the prior RIFLE and AKIN criteria.7, 19 In the RIFLE criteria (Table 1), AKI was defined based on a ≥50% increase in serum creatinine level occurring over 1-7 days or the presence of oliguria for more than 6 hours. The AKIN criteria added an absolute increase

Research

Throughout the guideline, the KDIGO Work Group makes multiple recommendations of areas that require further research. Our KDOQI Work Group concurs with the critical importance for further research in these areas. In particular, we note that the majority of the KDIGO recommendation statements are based on relatively low levels of evidence. Research in these areas is needed to develop the evidence upon which future practice guidelines can be based.

Conclusion

The KDIGO Clinical Practice Guideline for AKI represents a landmark effort in improving the care of patients with AKI. The guideline is broad in scope, spanning the spectrum from definition and staging through prevention and nondialytic management and the management of short-term RRT. While our KDOQI Work Group concurred with many of the KDIGO recommendations, we had reservations regarding several aspects of the guideline. Our Work Group recognizes the need for a consensus definition of AKI and

Acknowledgements

Guideline recommendations included in this article originally were published in Kidney International Supplements and were reproduced with permission from KDIGO.

We thank Drs Jeffrey Berns, Michael Choi, Holly Kramer, Michael Rocco, and Joseph Vassalotti for careful review of this manuscript; and Kerry Willis and Emily Howell from the National Kidney Foundation for their help in coordinating the work of the group and preparing the manuscript.

Financial Disclosure: Dr Chawla has consulted for

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    Originally published online March 18, 2013

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