A European Renal Best Practice (ERBP) position statement on the Kidney Disease Improving Global Outcomes (KDIGO) Clinical Practice Guidelines on Acute Kidney Injury: Part 1: definitions, conservative management and contrast-induced nephropathy
The broad clinical syndrome of acute kidney injury (AKI) encompasses various aetiologies, including specific kidney diseases (e.g. acute interstitial nephritis), non-specific conditions (e.g. renal ischaemia) as well as extrarenal pathology (e.g. post-renal obstruction). AKI is a serious condition that affects kidney structure and function acutely, but also in the long term. Recent epidemiological evidence supports the notion that even mild, reversible AKI conveys the risk of persistent tissue damage, and severe AKI can be accompanied by an irreversible decline of kidney function and progression to end-stage kidney failure [1–3]. The Kidney Disease Improving Global Outcomes (KDIGO) Clinical Practice Guidelines for AKI [4] were designed to systematically compile information on this topic by experts in the field. These guidelines are based on the systematic review of relevant trials published before February 2011. Nevertheless, for many sections of the guidelines, appropriate supporting evidence is lacking in the literature. As a consequence, variations in practice will inevitably occur when clinicians take into account the needs of individual patients, available resources and limitations unique to a region, an institution or type of practice. Therefore, in line with its philosophy [5], the European Renal Best Practice (ERBP) wanted to issue a position statement on these guidelines. A working group was established to produce guidance from the European nephrology perspective, based on the compiled evidence as presented, with an update of the literature up to March 2012, following the methodology as explained in the ERBP instructions to authors [6]. The present document will deal with the diagnosis and prevention of AKI, and contrast-induced nephropathy (CIN) (Sections 1–4 of the KDIGO document), and other chapters will be discussed in a separate position statement. As a general rule, we will only mention those guideline statements of the KDIGO document that we have amended, even when the change is small. If a KDIGO recommendation is not repeated, it can be considered as endorsed by ERBP as is, unless specifically stated otherwise. 1.1.1 We recommend using a uniform definition of AKI, based on urinary output and on changes in serum creatinine (SCr) level. It is important that both criteria are taken into account. (1C) 1.1.2 We recommend diagnosing and indicating the severity of AKI according to the criteria in the table below: (ungraded statement) Serum creatinine increased 1.5–1.9 times baseline Serum creatinine increase >0.3mg/dl (26.5 µmol/l) Urinary ouotput < 0.5ml/kg/h during a 6 hour block Serum creatinine increase 2.0–2.9 times baseline Urinary output <0.5ml/kg/h during two 6 hour blocks Serum creatinine increase >3 times baseline Serum creatinine increases to >4.0mg/dl (353 µmol/l) Initiation of renal replacement therapy Urinary output <0.3ml/kg/h during more than 24 hours Anuria for more than 12 hours The ERBP workgroup stresses that this classification should be considered as a severity scoring rather than a nosological definition 1.1.2a We recommend using the first documented serum creatinine value of the episode as ‘baseline’, rather than historical creatinines or a calculated value based on a presumed glomerular filtration rate (GFR) of 75 mL/min. (1C) 1.1.2b We suggest using ‘shift-based’ calculation of the urinary output criteria, especially in patients without a bladder catheter (1C). We recommend to use the ideal weight rather than the true weight in calculating the diuresis in mL/min/kg. (Ungraded statement) 1.1.3 The cause of AKI should be determined whenever possible. As a minimal work-up, the presence of hypovolaemia, post-renal causes, low cardiac output, use of nephrotoxic agents, acute glomerulonephritis and renal micro-angiopathy as underlying contributors to AKI should be evaluated. (Ungraded statement) In the past, a myriad of definitions for acute renal failure and AKI existed in parallel, making comparison of results difficult. In the KDIGO Clinical Practice Guidelines for AKI, definition and staging of AKI is based on a combination of the Risk, Injury, Failure; Loss, End-Stage Renal Disease (RIFLE) [7] and Acute Kidney Injury Network (AKIN) criteria [8]. Both criteria rely on GFR, and its proxy serum creatinine, and urinary output as the most useful overall indices of acute changes of kidney function. Changes in serum creatinine concentration and/or urine output are used as surrogates for acute changes in kidney function. The recommended diagnostic criteria establish a solid ground for standardized AKI assessment and classification in everyday clinical practice as well as in research conditions [9, 10]. As such, ERBP considers them as a good starting point towards a more standardized approach to AKI definition and particularly for the assessment of the predictive power of AKI with respect to overall and renal outcome (staging of severity) [11]. However, ERBP wants to update and fine-tune the classification by specifically underscoring and more extensively clarifying (i) the need to use the first available (admission) serum creatinine in that episode as baseline creatinine; and (ii) draw attention to the fact that urinary volume should be expressed using ideal body weight rather than real body weight when calculating the urinary output in mL/min/kg. ERBP also felt that it was necessary to explicitly state that both criteria should be applied to classify patients. Indeed, after publication of the RIFLE criteria, it became rapidly apparent that different interpretations were still given to ‘baseline creatinine’, and that the urinary output criterion was either omitted, or calculated on 24-h urine output [12, 13]. For baseline creatinine, some authors suggested using an estimation of serum creatinine, by backward calculation from a presumed ‘standard GFR’ of 75 mL/min/1.73 m²; others suggested using the last known value. This concept of a ‘universal baseline’ clashes with the current epidemiology of AKI, where an important subpopulation do not start from ‘normal renal function’, but do already have underlying CKD [14]. Siew et al. [15] demonstrated that the use of the value at admission in the episode under consideration was best associated with risk. Also in the AKIN criteria, the intention is to use the evolution of serum creatinine relative to the first observed value in that episode [8]. It was demonstrated that using admission creatinine rather than estimated creatinine from a presumed GFR of 75 mL/min improved the prediction of need for renal replacement therapy and mortality [16], and decreased misclassification [17, 18]. ERBP wants to stress that the use of estimated GFR (eGFR), using whatever formula, is obsolete in patients with AKI, as all these formulae presume that kidney function is stable, and markers of GFR are in steady state, which is of course contradictory with the fact that patients have AKI. Although diuresis is mentioned in both RIFLE and AKIN, little attention was initially given to it, and many studies on the accuracy of RIFLE did not take into account diuresis. Recent studies point out that diuresis might be a more sensitive marker of AKI than serum creatinine [19]. More importantly, Macedo et al. [20] demonstrated that the evaluation of diuresis in 6-h blocks is as accurate as hourly observation. This addresses the argument that diuresis is difficult to measure outside the intensive care unit (ICU): It should be possible, even in general wards, to organize monitoring of diuresis in 6- to 8-h intervals, even in patients without a bladder catheter. In view of the perils and co-morbidities associated with bladder catheterization, ERBP recommends to use 6- to 8-h observation blocks of urinary output, in patients with spontaneous miction, rather than performing a bladder catheterization just for the sake of hourly urinary output measurements. ERBP recommends that local nephrologists develop and implement strategies to monitor urinary output in hospitalized patients outside the ICU, but are at risk for AKI. Of note, up to 50% of patients with AKI developed this condition at the general ward, not in an ICU [14]. The use of a weight-adjusted urinary volume as the threshold makes some sense, but can lead to overdiagnosis (false-positive diagnosis) of AKI in obese patients or underdiagnosis (false negatives) in cachectic patients. Therefore, ERBP suggests that ‘ideal’ body weight is considered in these conditions. ‘Ideal’ should be interpreted as the age, length and gender normalized weight, so, e.g. without oedema. It should also be stressed that urinary output criteria should be evaluated in patients not receiving diuretics. The additional clinical benefit for differential diagnosis of AKI of newer markers of kidney function (e.g. cystatin C) or kidney injury parameters (e.g. neutrophil gelatinase-associated lipocalin) [21] has so far not been proved and is a matter of debate [22]. ERBP at this stage does not recommend their use for diagnostic purposes in clinical conditions. As hypovolaemia, post-renal causes and nephrotoxic drugs can result in reversible causes and can be readily diagnosed, these should be excluded as soon as possible. Although their prevalence as a cause of AKI is only limited, a minimal work-up for the presence of underlying rapidly progressive forms of glomerular disease should also be performed, especially in the absence of other potential explanations. 1.2.1 We recommend that patients be stratified for risk of AKI according to their susceptibilities, especially pre-existing proteinuria and CKD, and exposures to nephrotoxic medication or interventions. (1C) 1.2.2 We recommend monitoring patients at increased risk for AKI with measurements of serum creatinine and urine output to detect AKI at an early stage. (Ungraded statement). Frequency and duration of monitoring should be planned based on patient risk and clinical course. (Ungraded statement). 1.2.3 We recommend developing and implementing pathways of care at the broader hospital level, in close collaboration with the other individual specialities, to achieve the above-mentioned targets. (Ungraded statement). Risk for AKI is increased by exposure to factors that cause AKI (e.g. nephrotoxic medication) or the presence of factors that increase susceptibility to AKI [e.g. dehydration, co-morbidities, and also pre-existing proteinuria and chronic kidney disease (CKD)] [23, 24]. The interaction between susceptibility and the type and extent of exposure to insults determines the risk of AKI occurrence. Particularly in the hospital setting, the patient's susceptibility should be assessed on a regular basis and some factors modified or even avoided (e.g. of nephrotoxic ERBP wants to point out that in patients on but with it can be of to this after with a risk of of renal as of renal function is an important risk in this patient group As prevention is still the best of AKI, and as many of AKI do not occur in patients in the ICU or on the nephrology ward, but in general wards, ERBP stresses the of developing and implementing pathways of care to detect and monitor patients at risk of AKI outside nephrology and These pathways should be developed in collaboration with the different specialities, to the specific needs and patient patients are only after been to a risk still should be assessed in to those are more to develop AKI, as well as those will monitoring and general in to patients after AKI to the of the of CKD or of pre-existing (1C) in published epidemiological studies that in a of patients the acute clinical CKD or [1–3]. of patients should even the condition of AKI, and should monitoring for Although the after which an assessment should occur is a matter of clinical we that in kidney function should be not than after hospital should be according to appropriate guidelines CKD is In the absence of we recommend using rather than or as for of volume in patients at risk for AKI. We recommend the use of to in patients with or at risk AKI. 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