ABC | Volume 115, Nº1, July 2020

Review Article Leite et al. Acute cardiorenal syndrome Arq Bras Cardiol. 2020; 115(1):127-133 Siew et al., 36 studying 4,863 in-hospital patients, have assessed three reference values of baseline creatinine: MDRD ( Modification of Diet in Renal Disease ), serum creatinine on admission, and the lowest creatinine during hospitalization. The use of MDRD and nadir creatinine inflated the incidence of AKI by about 50%; in contrast, the use of the admission value underestimated it by 46%. The use of the admission creatinine value as reference has the lowest sensitivity for the diagnosis of AKI acquired at the hospital and does not include the diagnosis of pre-admission AKI. Some authors consider as reference the pre-admission creatinine (outpatient measurement) when available, but only some of them have defined the time of maximum validity of the outpatient measurement up to admission. However, the outpatient value of creatinine is rarely available. The RIFLE classification 29 does not define specifically reference baseline creatinine. The most recent AKI criterion, KDIGO, recommends the lowest serum creatinine during hospitalization to be used as reference. 35 Few studies have considered baseline renal function correlated with increasing creatinine during the AKI episode. The use of biomarkers to characterize acute cardiorenal syndrome Although creatinine is the pillar of the diagnosis of ACRS, it has limitations as a marker of renal function, mainly in critical patients. Its serum level is influenced by factors, such as sex, age, body weight, and muscle mass. In addition, creatinine increases only 24 hours after kidney injury and its concentration does not increase significantly until half of renal function is impaired. Thus, creatinine is considered a slow marker of AKI. 37 The definition of baseline creatinine in critical patients is controversial because those patients have nutritional alterations, muscle mass loss and fluid overload. Useful biomarkers are those with clinical applicability and a recognized role in the pathophysiology of ACRS. The search for more reliable biomarkers for the early diagnosis of ACRS is encouraged, and kidney injury molecule-1 (KIM-1), neutrophil gelatinase-associated lipocalin (NGAL), interleukin 18 (IL-18), and cystatin C (Cys-C) are some of the new markers of kidney injury targeted in studies. However, none of the three renal tubular markers cited could predict accurately worsening renal function in patients with DHF. 38 Microalbuminuria is estimated to be present in 20% to 30% of patients with HF. Two studies have shown association with mortality in patients with micro- or macroalbuminuria as compared to those with normal albumin excretion. 39 The clinical condition of patients with ACRS deteriorates and they develop oliguria, despite the high levels of natriuretic peptides, which are known to have a diuretic effect. It is worth noting that NT-proBNP levels are reduced in patients undergoing hemodialysis with high-flux membrane. 40 The suppression of tumorigenicity-2 (ST2), a biomarker of congestion less influenced by renal function than NT-ProBNP, might be helpful for diagnostic and prognostic information. 41 Imaging methods for the diagnosis of acute cardiorenal syndrome Renal imaging with assessment of the waves of venous and arterial renal flows can signal worsening renal function before serum creatinine levels increase, providing a feasible and non- invasive assessment of renal hemodynamics. 42,43 Prognostic implications of acute cardiorenal syndrome Acute cardiorenal syndrome is associated with the following: higher all-cause and cardiovascular mortality in the short and long run; prolonged length of hospital stay; 10,11,44-46 re‑admissions; 27,47 progression to chronic kidney disease; 48 and higher health care costs. 10 Acute cardiorenal syndrome is apparently more severe in patients with reduced left ventricular ejection fraction (LVEF) as compared to those with preserved LVEF, reaching the incidence of 70% in patients with cardiogenic shock. 49 In addition, renal function impairment is an independent risk factor for 1-year mortality in patients with acute HF, including those with ST-elevation myocardial infarction. 23 Moreover, an acute decline in renal function not only acts as a marker of disease severity, but also speeds cardiovascular alterations up by activating inflammatory pathways. 48 Two studies have shown that the risk of poor prognosis remains independently of the ACRS type (intermittent or persistent) 45,47 and that even mild renal function changes can alter the risk of death. 49 Some studies have shown that persistent ACRS, as compared to intermittent ACRS, has worse prognosis after hospital discharge and that transient creatinine elevations did not relate to worse prognosis. 50-52 In the ADHERE study, 9 59% of the men and 68% of the women had moderate to severe renal dysfunction on admission, and those with worsening renal function during hospitalization had higher in-hospital mortality. Patients whose hospitalization is precipitated by ACRS have higher in-hospital mortality, longer length of hospital stay, more re-admissions and higher mortality rates after discharge as compared to patients with other precipitating factors. 53-55 Persistent ACRS within 1 year from hospital discharge was a strong predictor of cardiovascular and all-cause mortality. 56 At least one fourth of the patients hospitalized with DHF can develop ACRS, depending on the diagnostic criterion used. Among patients hospitalized with HF, serum creatinine increase is one of the major predictors of survival, 10,57 and mortality increases progressively as serum creatinine increases. 11,27,58,59 Not all changes in renal function have the same prognostic relevance. Serum creatinine elevation concomitantly with symptom improvement and body weight loss is not associated with an unfavorable outcome. 60 The presence of AKI indicates that a reversible or irreversible kidney lesion has occurred, while worsening renal function markers can represent a functional decline in GFR not directly related to an adverse outcome. 61 130