ABC | Volume 115, Nº1, July 2020

Review Article Leite et al. Acute cardiorenal syndrome Arq Bras Cardiol. 2020; 115(1):127-133 their diagnostic criteria, their inclusion and exclusion criteria, their sample sizes, and the clinical findings of the populations studied. Most studies involve retrospective, secondary and/or post hoc analyses of large databases 10-12,23-25 or clinical trials of drug therapy. 26 Diagnostic criteria for acute cardiorenal syndrome The first study to assess the impact of worsening renal function on the elderly admitted with DHF, published in 2000, adopted the 0.3-mg/dL increase in creatinine as the criterion. 10 Another study has shown that 0.1-mg/dL increases in creatinine during hospitalization were associated with higher in-hospital mortality and longer length of hospital stay. In addition, that study reported that creatinine increase ≥0.3 mg/dL had higher sensitivity and specificity to predict both death (81% and 62%, respectively) and length of hospital stay longer than 10 days (64% and 65%, respectively). 11 Absolute creatinine increase by 0.3 mg/dL has been adopted by most authors as the criterion defining ACRS. 27 Some authors, however, disagree, because that criterion does not consider the previous degree of renal dysfunction, and they suggest using one of three different classifications to define AKI, 28 which, however, are not specific for DHF and have been developed to define and classify AKI in different clinical scenarios. The RIFLE (Risk, Injury, Failure, Loss and End-stage renal disease) classification 29 was proposed in 2004 to define and stratify the severity of AKI, which is determined by the most altered parameter (creatinine variation, GFR and urine output). The classification proposed by the Acute Kidney Injury Network (AKIN) 30 excludes the stages of ‘renal function loss’ and ‘end-stage renal disease’, as well as the ‘GFR-based criteria”. Staging should be performed after correcting the patient’s blood volume, excluding urinary tract obstruction, and considering the most altered criterion. In 2012, the Kidney Disease – Improving Global Outcomes (KDIGO) 31 group proposed a classification modifying the previous one by adding to its third stage GFR reduction to values below 35mL/min/1.73m 2 in patients under the age of 18 years and excluding the need for the minimum 0.5-mg/dL increase for patients with creatinine greater than 4 mg/dL. A cohort study assessing 637 hospitalizations due to DHF with 30-day and 1-year follow-up assessments has compared the diagnostic criterion of creatinine increase ≥0.3 mg/dL with those from KDIGO, RIFLE and AKIN regarding prediction of the following outcomes: ‘death’, ‘readmission due to HF’ or ‘initiation of dialysis’. Regarding the ability to determine adverse events, the four criteria performed similarly. The benefit of using the AKI classification systems (RIFLE, AKIN, KDIGO) is the possibility to identify patients with more severe AKI who will have adverse events in 30 days and 1 year. 32 Table 2 summarizes the different diagnostic criteria for AKI found in the literature. The most used diagnostic criterion is serum creatinine increase by at least 0.3 mg/dL or 25% in the first five days of hospitalization, which differs from the current KDIGO definition for AKI. 33 In addition, the definition of worsening renal function does not include AKI on admission, which is associated with mortality and cardiovascular events. 34 Common approaches to the ACRS diagnosis include the use of the following reference values of baseline creatinine, from which the creatinine increase defines ACRS: a) serum creatinine on admission; b) the lowest creatinine during hospitalization; c) serum creatinine levels of other hospitalizations; or d) outpatient measurements of serum creatinine. The original criteria of the RIFLE classification do not specify the reference creatinine but recommend its calculation from an estimated GFR of 75mL/min/1.73m 2 . Other approaches include the assessment of creatinine variation in the first 48 hours from admission, to reduce the need for the pre-hospital value (AKIN), and the lowest serum creatinine during hospitalization, when the outpatient measurement of serum creatinine is absent (KDIGO). 35 Table 2 – RIFLE 34 , AKIN 35 , KDIGO 36 and WRF 11 criteria for definition of AKI Criteria WRF RIFLE AKIN KDIGO Years 2002 2004 2007 2012 Classification sCr increase sCr increase GFR decrease sCr increase sCr increase Stage 1 / Risk ≥ 0.3 mg/dL ≥ 1.5x bCr ≥ 25% > 1.5-1.9x bCr or ≥ 0.3 mg/dL ≥ 1.5x bCr or ≥ 0.3 mg/dL Stage 2 / Injury - ≥ 2x bCr ≥ 50% > 2-2.9x bCr ≥ 2x bCr Stage 3 / Failure - ≥ 3x bCr ≥ 75% ≥ 3x bCr ≥ 3x bCr - Or sCr ≥ 4mg/dL and a 0.5-mg/dL increase Or sCr ≥ 4mg/dL and a 0.5-mg/dL increase or initiation of dialysis Or sCr ≥ 4mg/dL Minimum time for AKI to occur sCr can increase at any time during hospitalization sCr changes over 1-7 days for more than 24 h Acute sCr changes within a 48-h period during hospitalization SCr changes ≥ 1.5x bCr within 7 days, or 0.3-mg/ dL minimum increase in sCr within a 48-h period WRF, worsening renal function; AKI, acute kidney injury; sCr, serum creatinine; GFR, glomerular filtration rate; bCr, baseline creatinine. Source: Adapted from Roy et al. 32 129