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Diagnosis, evaluation, and management of acute kidney injury: a KDIGO summary (Part 1)

Open access
Kellum, John A, Lameire, Norbert, for the KDIGO AKI Guideline Work Group·2013·Critical Care
DOI 10.1186/cc11454PMC PMC4057151
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Abstract

Acute kidney injury (AKI) is a common and serious problem affecting millions and causing death and disability for many. In 2012, Kidney Disease: Improving Global Outcomes completed the first ever, international, multidisciplinary, clinical practice guideline for AKI. The guideline is based on evidence review and appraisal, and covers AKI definition, risk assessment, evaluation, prevention, and treatment. In this review we summarize key aspects of the guideline including definition and staging of AKI, as well as evaluation and nondialytic management. Contrast-induced AKI and management of renal replacement therapy will be addressed in a separate review. Treatment recommendations are based on systematic reviews of relevant trials. Appraisal of the quality of the evidence and the strength of recommendations followed the Grading of Recommendations Assessment, Development and Evaluation approach. Limitations of the evidence are discussed and a detailed rationale for each recommendation is provided.

AI snapshot

Written from the paper’s full text.

TL;DR

This KDIGO summary presents the 2012 international AKI guideline’s definition and staging, risk assessment, evaluation, and nondialytic management, based on 61 graded and 26 ungraded statements. It recommends staging by serum creatinine and urine output, risk stratification, isotonic crystalloids over colloids, and against diuretics, dopamine, fenoldopam, and natriuretic peptides for AKI prevention or treatment.

Key findings

  • AKI is defined as an increase in SCr by ≥0.3 mg/dl (≥26.5 μmol/l) within 48 hours, an increase in SCr to ≥1.5 times baseline within the prior 7 days, or urine volume <0.5 ml/kg/hour for 6 hours. Staging uses SCr and urine output, with stage 3 including SCr ≥3.0 times baseline, SCr ≥4.0 mg/dl (≥353.6 μmol/l), initiation of renal replacement therapy, or in patients <18 years a decrease in eGFR to <35 ml/minute per 1.73 m².
  • Increasing AKI severity is associated with higher mortality: in one large database, stage 1 AKI had an odds ratio of 2.2, stage 2 an odds ratio of 6.1, and stage 3 an odds ratio of 8.6 for hospital mortality. Hyperoncotic starch increased odds of AKI by 92% (OR = 1.92; 95% CI = 1.31 to 2.81; P = 0.0008), while hyperoncotic albumin decreased odds by 76%.
  • For prevention/treatment, the guideline recommends isotonic crystalloids rather than colloids as initial intravascular volume expansion (Grade 2B), vasopressors with fluids in vasomotor shock (Grade 1C), protocol-based hemodynamic/oxygenation management in high-risk perioperative or septic shock patients (Grade 2C), and insulin targeting plasma glucose 110 to 149 mg/dl (6.1 to 8.3 mmol/l) (Grade 2C). It recommends not using diuretics to prevent AKI (Grade 1B), not using low-dose dopamine (Grade 1A), and suggests not using fenoldopam (Grade 2C) or ANP (Grade 2C prevention, 2B treatment).
  • For nephrotoxins and surgical patients, the guideline suggests avoiding aminoglycosides unless no less nephrotoxic alternatives exist (Grade 2A), using lipid formulations of amphotericin B rather than conventional formulations (Grade 2A), and not selecting off-pump coronary artery bypass solely to reduce perioperative AKI or RRT need (Grade 2C). It recommends not using oral or intravenous N-acetylcysteine for prevention of postsurgical AKI (Grade 1A).

Methods

  • This is a summary of the first international, multidisciplinary KDIGO clinical practice guideline for AKI, covering definition/classification, prevention, pharmacologic treatment, and renal replacement therapy; domains A–D are presented here, while contrast-induced AKI and RRT are addressed in a separate review.
  • The Work Group included experts in nephrology, critical care medicine, internal medicine, pediatrics, cardiology, radiology, infectious diseases, and epidemiology, with an Evidence Review Team at Tufts Medical Center. They screened 18,385 citations and limited outcomes to development of AKI, need for or dependence on RRT, and all-cause mortality.
  • Evidence appraisal and recommendation grading followed the GRADE approach; strength was rated level 1 (strong) or level 2 (weak/discretionary), and evidence quality was graded A (high), B (moderate), C (low), or D (very low). The Work Group developed 61 graded recommendation statements and 26 ungraded statements.

Limitations

  • The paper states that existing AKI criteria remain limited: there is still inconsistency in application, a minority of studies include urine output criteria, many studies exclude patients whose initial SCr is already elevated, and many community-acquired cases may be missed by limiting analysis to documented SCr increases. It also notes that SCr and urine output have limitations for detecting AKI, and that biomarkers may identify additional or earlier patients in the future.
  • The paper states that evidence limitations affected recommendations: there have been no RCTs directly evaluating fluids versus placebo for AKI prevention except in contrast-induced AKI; the SAFE trial included very few patients receiving >5 l fluid resuscitation; a large HES trial was only scheduled; the most effective vasopressor is unknown; early goal-directed therapy risks/benefits are unclear; nutrition thresholds were never directly examined in RCTs; mannitol studies were often retrospective or underpowered; and no adequately powered multicenter trials with clinically significant endpoints support fenoldopam.
  • Evident from the text: this is a guideline summary rather than a primary study, many recommendations are weak (level 2) or ungraded, and the GRADE system is described as best suited to comparative effectiveness, with diagnosis and staging topics handled as ungraded consensus statements.

Model-written summary. Check it against the paper before relying on it.

Integrity signals

Registry

Crossref · 10.1186/cc11454

Cites

162 of 162 references verified0 citation errors · 0 not checkable

Statistics

Nothing to recompute.

Claims the paper makes

0 of 169 cited sources checked · 0 supported · 0 flagged

  • Findingcitation

    Our systematic review found no significant inconsistencies in the findings of two adequate-size/quality ANP treatment trials that combined included 720 subjects (351 treated with ANP).

    “Only two of the treatment studies included in Nigwekar and colleagues' analysis [84,85] were of adequate size and quality to meet the criteria for our systematic review, which found no significant inconsistencies in the findings of both trials that (combined) included 720 subjects (351 treated with ANP).”
    Quote in the paperSubstantial claim0 of 2 sources checked
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  • Findingown data

    Our analysis of existing data from suitable prophylactic studies of adequate size and study design that reported AKI incidence in patients randomized to fenoldopam versus placebo revealed a pooled relative risk (RR) of 0.96 (95% CI = 0.76 to 1.2; P = not significant).

    “Our analysis of existing data from suitable prophylactic studies of adequate size and study design that reported AKI incidence in patients randomized to fenoldopam versus placebo revealed a pooled relative risk (RR) of 0.96 (95% CI = 0.76 to 1.2; P = not significant).”
    Quote in the paperSubstantial claim
  • Premisecitation

    Increasing RIFLE stage leads to increased risk of death.

    “and that increasing RIFLE stage leads to increased risk of death [9-14].”
    Quote in the paperSubstantial claim0 of 6 sources checked
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    • cites [11]

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  • Interpretationreasoning

    The generalizability of results from one particular setting to the next is uncertain.

    “the generalizability of results from one particular setting to the next is uncertain.”
    Quote in the paperNot a substantial claim
  • Premisecitation

    Increased severity of AKI was associated with an increased risk of death independent of comorbidity.

    “Thakar and colleagues found that increased severity of AKI was associated with an increased risk of death independent of comorbidity [12].”
    Quote in the paperSubstantial claim0 of 1 sources checked
    • cites [12]

      Couldn’t be matched to a paper in Crossref, so it can’t be checked.

  • Classified as probably not a substantial claim. 13
  • May combine two claims. 17
  • The quote only partly states this claim. 1

  • Probably not a substantial claim: may not pass S3 (load-bearing).

    Premisecitation

    The KDIGO guideline is the first international, interdisciplinary clinical practice guideline on AKI.

    “KDIGO), a nonprofit foundation, has published the first international, interdisciplinary clinical practice guideline on AKI [1]”
    Quote in the paperNot a substantial claim0 of 1 sources checked
    • cites [1]

      Couldn’t be matched to a paper in Crossref, so it can’t be checked.

  • Probably not a substantial claim: may not pass S3 (load-bearing).

    Premisecitation

    An additional modification to the RIFLE criteria has been proposed for pediatric patients to better classify small children with acute-on-chronic disease.

    “An additional modification to the RIFLE criteria has been proposed for pediatric patients in order to better classify small children with acute-on-chronic disease [16].”
    Quote in the paperNot a substantial claim0 of 1 sources checked
    • cites [16]

      Couldn’t be matched to a paper in Crossref, so it can’t be checked.

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    Study design and conductnone given

    Work Group members reviewed all retrieved relevant articles, data extraction forms, summary tables, and evidence profiles for accuracy and completeness.

    “Work Group members reviewed all retrieved relevant articles, data extraction forms, summary tables, and evidence profiles for accuracy and completeness.”
    Quote in the paperNot a substantial claim

  • Classified as probably not a substantial claim.

    Study design and conductnone given

    The KDIGO AKI guideline is based on evidence review and appraisal.

    “The guideline is based on evidence review and appraisal”
    Quote in the paperSubstantial claim

  • Probably not a substantial claim: may not pass S3 (load-bearing).

    Study design and conductcitation

    The evidence selection, appraisal, and presentation followed methodology previously described in KDIGO clinical practice guidelines.

    “The evidence selection, appraisal, and presentation have followed methodology previously described in KDIGO clinical practice guidelines [4].”
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    • cites [4]

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    Study design and conductcitation

    Appraisal of the quality of evidence and strength of recommendations followed the GRADE approach.

    “The grading approach followed in this guideline and the wording of each recommendation are adopted from the Grading of Recommendations Assessment, Development and Evaluation system [4,5].”
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    Study design and conductown data

    Overall, 18,385 citations were screened.

    “Overall, we screened 18,385 citations.”
    Quote in the paperNot a substantial claim

  • Classified as probably not a substantial claim.

    Study design and conductnone given

    Treatment recommendations in the guideline are based on systematic reviews of relevant trials.

    “Treatment recommendations are based on systematic reviews of relevant trials.”
    Quote in the paperSubstantial claim

  • May combine two claims.

    Interpretationcitation

    The use of isotonic saline as the standard of care for intravascular volume expansion to prevent or treat AKI is based upon the lack of clear evidence that colloids are superior and some evidence that specific colloids may cause AKI.

    “The use of isotonic saline as the standard of care for intravascular volume expansion to prevent or treat AKI is thus based upon the lack of clear evidence that colloids are superior for this purpose, along with some evidence that specific colloids may cause AKI, in addition to their higher costs.”
    Quote in the paperSubstantial claim

  • May combine two claims.

    Premisecitation

    The NICE-SUGAR study found a 90-day mortality of 27.5% in the intensive insulin therapy group and 24.9% in the conventional glucose control group (OR for intensive control = 1.14; 95% CI = 1.02 to 1.28; P = 0.02).

    “The international Normoglycemia in Intensive Care Evaluation and Survival Using Glucose Algorithm Regulation study found a 90-day mortality of 27.5% in the intensive insulin therapy group (target blood glucose range 81 to 108 mg/dl (4.5 to 6.0 mmol/l)) and a 90-day mortality of 24.9% in the conventional glucose control (target ≤180 mg/dl (≤10.0 mmol/l)) (OR for intensive control = 1.14; 95% CI = 1”
    Quote in the paperSubstantial claim0 of 1 sources checked
    • cites [37]

      Couldn’t be matched to a paper in Crossref, so it can’t be checked.

  • May combine two claims.

    Premisecitation

    There is no difference in need for and duration of renal replacement therapy between albumin and isotonic saline.

    “The study demonstrated no difference in need for and duration of RRT [25].”
    Quote in the paperSubstantial claim0 of 1 sources checked
    • cites [25]

      Couldn’t be matched to a paper in Crossref, so it can’t be checked.

  • May combine two claims.

    Premisecitation

    Compared with norepinephrine, vasopressin increases blood pressure and enhances diuresis.

    “Compared with norepinephrine, vasopressin increases blood pressure and enhances diuresis, but has not been proven to enhance survival or to reduce the need for RRT [32].”
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    • cites [32]

      Couldn’t be matched to a paper in Crossref, so it can’t be checked.

  • May combine two claims.

    Premisecitation

    Furosemide therapy was ineffective and possibly harmful when used to treat AKI.

    “Finally, furosemide therapy was also ineffective and possibly harmful when used to treat AKI [51,60].”
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    Interpretationcitation

    These figures provide an orientation for the macronutrient supply typically achieved in and tolerated by children with AKI receiving CRRT.

    “Although not validated by outcome studies, these figures provide an orientation for the macronutrient supply typically achieved in and tolerated by children with AKI receiving CRRT.”
    Quote in the paperNot a substantial claim

  • May combine two claims.

    Premisereasoning

    It is not known which vasopressor agent is most effective for management of shock in general, or for the kidney specifically.

    “Once the intravascular volume has been optimized, it is not known which vasopressor agent is most effective for management of shock in general, or for the kidney specifically.”
    Quote in the paperSubstantial claim

  • May combine two claims.

    Premisecitation

    Vasopressin has not been proven to enhance survival or to reduce the need for renal replacement therapy.

    “Compared with norepinephrine, vasopressin increases blood pressure and enhances diuresis, but has not been proven to enhance survival or to reduce the need for RRT [32].”
    Quote in the paperSubstantial claim0 of 1 sources checked
    • cites [32]

      Couldn’t be matched to a paper in Crossref, so it can’t be checked.

  • May combine two claims.

    Interpretationreasoning

    The renal effects of hyperoncotic colloid solutions appeared to be colloid specific, with albumin displaying renoprotection and hyperoncotic starch showing nephrotoxicity.

    “The renal effects of hyperoncotic colloid solutions appeared to be colloid specific, with albumin displaying renoprotection and hyperoncotic starch showing nephrotoxicity.”
    Quote in the paperSubstantial claim

  • May combine two claims.

    Premisecitation

    About 0.2 g amino acids are lost per liter of filtrate, amounting to a total daily loss of 10 to 15 g amino acids.

    “about 0.2 g amino acids are lost per liter of filtrate, amounting to a total daily loss of 10 to 15 g amino acids.”
    Quote in the paperSubstantial claim0 of 1 sources checked
    • cites [43]

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  • May combine two claims.

    Premisecitation

    Fenoldopam mesylate is a pure dopamine type-1 receptor agonist that has similar hemodynamic renal effects as low-dose dopamine, without systemic α-adrenergic or β-adrenergic stimulation.

    “Fenoldopam mesylate is a pure dopamine type-1 receptor agonist that has similar hemodynamic renal effects as low-dose dopamine, without systemic α-adrenergic or β-adrenergic stimulation [78].”
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  • Probably not a substantial claim: may not pass S3 (load-bearing).

    Premisecitation

    AKI occurs in 60% of neonates suffering from perinatal asphyxia.

    “AKI occurs in 60% of neonates suffering from perinatal asphyxia [92]”
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    • cites [92]

      Couldn’t be matched to a paper in Crossref, so it can’t be checked.

  • Probably not a substantial claim: may not pass S3 (load-bearing).

    Premisecitation

    Low-dose ANP preparations were associated with significant reduction in RRT requirement (OR = 0.34; 95% CI = 0.12 to 0.96; P = 0.04).

    “However, low-dose ANP preparations were associated with significant reduction in RRT requirement (OR = 0.34; 95% CI = 0.12 to 0.96; P = 0.04).”
    Quote in the paperNot a substantial claim0 of 1 sources checked
    • cites [83]

      Couldn’t be matched to a paper in Crossref, so it can’t be checked.

  • May combine two claims.

    Premisecitation

    In three randomized placebo-controlled trials including 171 term neonates, theophylline was associated with significantly higher GFR, higher urine output with more negative fluid balance, and lower urinary β2-microglobulin excretion compared with placebo during the first 3 to 5 days of life.

    “All three studies observed significantly higher glomerular filtration rate, higher urine output with more negative fluid balance, and lower urinary β2- microglobulin excretion with theophylline as compared with placebo during the first 3 to 5 days of life.”
    Quote in the paperSubstantial claim0 of 3 sources checked
    • cites [94]

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    • cites [96]

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  • May combine two claims.

    Premisecitation

    Dopamine can trigger tachyarrhythmias and myocardial ischemia, decrease intestinal blood flow, cause hypopituitarism, and suppress T-cell function.

    “Dopamine can trigger tachyarrhythmias and myocardial ischemia, decrease intestinal blood flow, cause hypopituitarism, and suppress T-cell function [77].”
    Quote in the paperSubstantial claim0 of 1 sources checked
    • cites [77]

      Couldn’t be matched to a paper in Crossref, so it can’t be checked.

  • May combine two claims.

    Premisecitation

    Once-daily dosing strategies for aminoglycosides generally result in less AKI compared with multiple-dose dosing strategies, although the benefit is modest and inconsistent across studies.

    “The cumulative results of this evidence-based review and numerous meta-analyses indicate that once-daily dosing strategies generally result in less AKI when compared with multiple-dose dosing strategies, although the benefit accrued by the single-daily dose strategy is modest and inconsistent across a number of these studies.”
    Quote in the paperSubstantial claim0 of 10 sources checked
    • cites [110]

      Couldn’t be matched to a paper in Crossref, so it can’t be checked.

    • cites [111]

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    • cites [112]

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    • cites [113]

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    • cites [114]

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    • cites [115]

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    • cites [117]

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    • cites [118]

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    • cites [119]

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  • May combine two claims.

    Interpretationreasoning

    While theophylline clearly improves renal function in the first week of life in postasphyctic neonates, the overall benefit from this intervention in neonatal intensive care is less evident in view of complete long-term recovery of renal function in placebo-treated controls and absence of effect on patient survival.

    “Hence, while theophylline clearly improves renal function in the first week of life in postasphyctic neonates, the overall benefit from this intervention in neonatal intensive care is less evident in view of the complete long-term recovery of renal function in the placebo-treated controls and the absence of an effect on patient survival.”
    Quote in the paperSubstantial claim

  • May combine two claims.

    Premisecitation

    The beneficial effect of theophylline was selective for kidney function, whereas the incidence of extra-renal complications was unaltered.

    “The beneficial effect was selective for kidney function, whereas the incidence of extra-renal complications was unaltered.”
    Quote in the paperSubstantial claim0 of 3 sources checked
    • cites [94]

      Couldn’t be matched to a paper in Crossref, so it can’t be checked.

    • cites [95]

      Couldn’t be matched to a paper in Crossref, so it can’t be checked.

    • cites [96]

      Couldn’t be matched to a paper in Crossref, so it can’t be checked.

  • May combine two claims.

    Premisecitation

    The trials in the off-pump meta-analysis were clinically heterogeneous, particularly regarding definitions of kidney outcomes, and mostly of poor to fair quality based on Jadad score.

    “It is apparent from this meta-analysis that the trials were clinically heterogeneous, particularly with regard to their definitions of kidney outcomes, and mostly were of poor to fair quality (based on the Jadad score).”
    Quote in the paperSubstantial claim0 of 1 sources checked
    • cites [148]

      Couldn’t be matched to a paper in Crossref, so it can’t be checked.

  • Classified as probably not a substantial claim.

    Interpretationreasoning

    The Work Group concluded that there was not enough evidence at present to recommend off-pump coronary artery bypass for reducing AKI or the need for RRT.

    “The Work Group concluded that there was not enough evidence at present to recommend off-pump coronary artery bypass for reducing AKI or the need for RRT.”
    Quote in the paperSubstantial claim

  • May combine two claims.

    Premisecitation

    Only a single study has compared N-acetylcysteine with placebo in critically ill patients with hypotension and was also negative.

    “Only a single study has compared N-acetylcysteine with placebo in critically ill patients with hypotension and was also negative [150].”
    Quote in the paperSubstantial claim0 of 1 sources checked
    • cites [150]

      Couldn’t be matched to a paper in Crossref, so it can’t be checked.

  • Probably not a substantial claim: may not pass S3 (load-bearing). The quote only partly states this claim.

    Interpretationnone given

    There is a question of publication bias in the off-pump meta-analysis.

    “There is also a question of publication bias.”
    Quote in the paperNot a substantial claim
30 of 30

  • The paper relies on this without support.

    AKI is common and imposes a heavy burden of illness (morbidity and mortality).

    “Acute kidney injury (AKI) is common and imposes a heavy burden of illness (morbidity and mortality).”

  • The paper relies on this without support.

    AKI is amenable to prevention, early detection and treatment.

    “AKI is amenable to prevention, early detection and treatment.”

  • The paper relies on this without support.

    The costs of care for patients with AKI are high and there is considerable variability in practice.

    “Furthermore, the costs of care for patients with AKI are high and there is considerable variability in practice.”

  • The paper relies on this without support.

    The majority of cases of AKI in the developing world are likely to be community acquired.

    “Indeed, the majority of cases of AKI in the developing world are likely to be community acquired.”

  • The paper relies on this without support.

    Many studies have excluded patients whose initial serum creatinine is already elevated.

    “many studies have excluded patients whose initial SCr is already elevated.”

  • The paper relies on this without support.

    In patients with AKI receiving continuous renal replacement therapy, 5 to 10 g protein are lost per day, depending on the type of therapy and dialyzer membrane.

    “In addition, 5 to 10 g protein are lost per day, depending on the type of therapy and dialyzer membrane.”

  • The paper relies on this without support.

    Treatments of AKI are dependent to a large degree on the underlying etiology.

    “Since treatments of AKI are dependent to a large degree on the underlying etiology”

  • The paper relies on this without support.

    There are few specific tests to establish the etiology of AKI.

    “There are few specific tests to establish the etiology of AKI.”

  • The paper relies on this without support.

    Response to therapy is an important part of the diagnostic approach to AKI.

    “response to therapy is an important part of the diagnostic approach.”

  • The authors state this as an assumption.

    Azole antifungal agents and/or echinocandins have equal therapeutic efficacy to conventional amphotericin B in the treatment of systemic mycoses or parasitic infections.

    “In the treatment of systemic mycoses or parasitic infections, we recommend using azoleantifungal agents and/or the echinocandins rather than conventional amphotericin B, if equal therapeutic efficacy can be assumed (Grade 1A)”

  • The paper relies on this without support.

    Furosemide may be useful in achieving fluid balance to facilitate mechanical ventilation according to the lung-protective ventilation strategy in hemodynamically stable patients with acute lung injury.

    “Furosemide may be useful in achieving fluid balance to facilitate mechanical ventilation according to the lung-protective ventilation strategy in hemodynamically stable patients with acute lung injury.”
11 of 11

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Authors
Kellum, J. A., Lameire, N., & for the KDIGO AKI Guideline Work Group
Affiliations
  • University of Pittsburgh (US)
  • Ghent University Hospital (BE)
Corresponding author
Kellum, John A
ORCID
Kellum, John A
Venue
Critical Care
Publisher
Springer Science and Business Media LLC
Published
2013
Volume
17
Issue
1
Pages
204
ISSN
1364-8535 (ISSN-L)
DOI
10.1186/cc11454
PMC
PMC4057151
OpenAlex
W2003500862
Semantic Scholar
17681190c1a33b9cdd1268857213d12f76ba98a7
Cited by
2,827
References
162
Citations by year
2026: 289 · 2025: 306 · 2024: 352 · 2023: 321 · 2022: 298 · 2021: 306 · 2020: 260 · 2019: 184 · 2018: 142 · 2017: 108 · 2016: 100 · 2015: 75 · 2014: 58 · 2013: 17
FWCI
55.19
Type
journal article
Language
en
Open access
Locations
  • Critical Care (publishedVersion)
  • PubMed (publishedVersion)
  • D-Scholarship@Pitt (University of Pittsburgh) (acceptedVersion)
  • Lirias (KU Leuven) (submittedVersion, other-oa)
  • PubMed Central (submittedVersion)
  • Ghent University Academic Bibliography (Ghent University) (submittedVersion, other-oa)
Topics
  • Health Sciences › Medicine › Nephrology › Acute Kidney Injury Research
  • Health Sciences › Medicine › Nephrology › Chronic Kidney Disease and Diabetes
  • Health Sciences › Medicine › Radiology, Nuclear Medicine and Imaging › Nephrotoxicity and Medicinal Plants
Keywords
acute kidney injury, KDIGO guidelines, AKI definitions, AKI staging, risk assessment, prevention, renal replacement therapy, treatment guidelines, quality of evidence
MeSH terms
Blood Glucose, Creatine, Decision Support Techniques, Diuretics, Fluid Therapy, Humans, Vasoconstrictor Agents, Vasodilator Agents, Practice Guidelines as Topic, Nutritional Support, Risk Assessment, Coronary Artery Bypass, Off-Pump, Acute Kidney Injury

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