Acute Cardiorenal Syndrome: Which Diagnostic Criterion to Use And What is its Importance for Prognosis?

Abstract

The absence of a consensus about the diagnostic criteria for acute cardiorenal syndrome (ACRS) affects its prognosis. This study aimed at assessing the diagnostic criteria for ACRS and their impact on prognosis. A systematic review was conducted using PRISMA methodology and PICO criteria in the MEDLINE, EMBASE and LILACS databases. The search included original publications, such as clinical trials, cohort studies, case-control studies, and meta-analyses, issued from January 1998 to June 2018. Neither literature nor heart failure guidelines provided a clear definition of the diagnostic criteria for ACRS. The serum creatinine increase by at least 0.3 mg/dL from baseline creatinine is the most used diagnostic criterion. However, the definition of baseline creatinine, as well as which serum creatinine should be used as reference for critical patients, is still controversial. This systematic review suggests that ACRS criteria should be revised to include the diagnosis of ACRS on hospital admission. Reference serum creatinine should reflect baseline renal function before the beginning of acute kidney injury.

Cardiorenal Syndrome; Renal Insufficiency; Creatinine; Prognosis; Heart Failure; Systematic Review

Resumo

A indefinição de critérios diagnósticos para síndrome cardiorrenal aguda (SCRA) impacta em diferentes resultados prognósticos. Objetivou-se avaliar os critérios diagnósticos da SCRA e o impacto no prognóstico. Procedeu-se à revisão sistemática utilizando-se a metodologia PRISMA e os critérios PICO nas bases MEDLINE, EMBASE e LILACS. A pesquisa incluiu artigos originais do tipo ensaio clínico, coorte, caso-controle e meta-análises publicados no período de janeiro de 1998 até junho de 2018. Não foi encontrada na literatura nem nas diretrizes de insuficiência cardíaca uma definição clara dos critérios diagnósticos da SCRA. O critério diagnóstico mais comumente utilizado é o aumento da creatinina sérica de pelo menos 0,3 mg/dl em relação à basal. Entretanto, existem controvérsias na definição de creatinina basal e de qual deveria ser a creatinina sérica de referência dos pacientes críticos. Esta revisão sistemática sugere que os critérios de SCRA devem ser revistos para que se inclua o diagnóstico de SCRA na admissão hospitalar. A creatinina sérica de referência deve refletir a função renal basal antes do início da injúria renal aguda.

Síndrome Cardiorrenal; Insuficiência Renal; Creatinina; Prognóstico; Insuficiência Cardíaca; Revisão Sistemática

Introduction

Heart failure (HF) is a clinical challenge and a growing epidemiological problem worldwide, with high morbidity and mortality.¹ In the ARIC study,² the case fatality rates within 30 days, 1 year and 5 years from hospitalization due to HF were 10.4%, 22.0% and 42.3%, respectively. The I Brazilian Registry of Heart Failure (BREATHE),³ an observational study with 1263 patients from different Brazilian regions, has shown in-hospital mortality of 12.6%.

Cardiorenal syndrome, defined as kidney injury caused by HF, was first described in 1951⁴ and categorized into five types in 2008 ( Table 1 ).⁵ Type 1 cardiorenal syndrome or acute cardiorenal syndrome (ACRS) is characterized by acute kidney injury (AKI) caused by decompensated HF (DHF). Some authors refer to ACRS as acute worsening of renal function in patients with HF, which is a frequent condition, present in 11% to 40% of hospitalizations due to DHF.⁶ , ⁷

Table 1
– Types of cardiorenal syndrome

Type	Name	Mechanism
1	Acute CRS	AKI induced by acute cardiac dysfunction
2	Chronic CRS	Progressive CKF secondary to chronic HF
3	Acute renocardiac syndrome	Acute HF precipitated by AKI
4	Chronic renocardiac syndrome	HF secondary to CKF
5	Secondary CRS	Myocardial and renal dysfunction due to systemic diseases

• CRS: cardiorenal syndrome; AKI: acute kidney injury; CKF: chronic kidney failure; HF: heart failure.
⁴⁰

Worsening of renal function is defined as an absolute increase in serum creatinine by 26.5 μmol/L, equivalent to 0.3 mg/dL, and/or a 25% increase in creatinine or a 20% decrease in glomerular filtration rate (GFR).⁸ The criterion of absolute 0.3-mg/dL increase in creatinine has been adopted by most authors as the cutoff point to define ACRS.

The North American ADHERE registry⁹ is an observational study with more than 100,000 patients hospitalized with DHF, 35% of whom had moderate to severe renal dysfunction.

Worsening of renal function occurs in 30% to 50% of patients with DHF, depending on the definition used, and is associated with longer length of hospital stay, as well as higher health care costs and mortality.¹⁰ - ¹⁴ However, the absence of a consensus definition of ACRS contributes to the lack of clarity in its diagnosis and treatment.¹⁵ The choice of reference serum creatinine to anchor the diagnostic criteria for ACRS is a challenge. Ideally, reference serum creatinine should reflect the baseline renal function before AKI begins. Most of the time, however, that information is not available, leading to the use of surrogate reference values, which can result in misclassification of ACRS regarding its diagnosis and severity.¹⁶

Methods

This review was conducted according to the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) methodology.¹⁷ Data search in the MEDLINE, EMBASE and LILACS databases included the full texts of original publications, such as clinical trials, cohort studies, case-control studies and meta-analyses, issued from January 1998 to June 2018, written in English, Spanish and Portuguese. The database search was conducted with the following descriptors: ( cardiorenal syndrome ) OR (worsening renal function) AND ( heart failure ) AND ( diagnosis ) AND ( prognosis ).

This study used the PICO (Population, Intervention, Control and Outcome) framework for literature search and reviewed the diagnostic criteria for ACRS and their prognostic implication for the outcomes ‘in-hospital mortality’, ‘mortality after hospital discharge’, and ‘length of hospital stay’. Case reports and experimental animal models were excluded.

Results

Regarding database search, 368 abstracts met the established criteria. Other 9 articles were retrieved in other sources, while 278 duplicate abstracts were removed. Of the 99 abstracts left, 61 were selected, 35 of which were excluded for not meeting the previously established criteria (PICO). The full text of the resulting 26 articles was then assessed regarding their scientific quality, and 4 articles were excluded for not meeting the criteria. The remaining 22 articles were analyzed in this study ( Figure 1 ).

Figure 1
– Flowchart of the studies assessed (PRISMA methodology¹⁷).

Temporal classification of acute cardiorenal syndrome

Studies with access to pre-admission serum creatinine have revealed AKI in one third of the patients presenting to the emergency department,¹⁸ while 50% of patients have been reported to develop AKI within the first 48 hours from admission. Tayaka et al.,¹⁹ in a study comparing renal function changes up to the fourth day of hospitalization with those from the fifth day onward, have reported higher mortality within 1 year from hospital discharge in patients with late renal injury. A post hoc analysis of the Pre-RELAX study has shown that the drop in systolic blood pressure in the first 48 hours of vasodilator therapy was an independent predictor of AKI up to the fifth day of hospitalization.²⁰ Those results suggest that therapy-related reduction in renal perfusion pressure is one of the major mechanisms leading to AKI in the first days of hospitalization.

Acute cardiorenal syndrome can be classified into intermittent or persistent. Intermittent ACRS occurs when serum creatinine levels vary during hospitalization with a reduction in its values up to discharge time. Persistent ACRS occurs when either creatinine elevation or GFR decrease persist up to discharge time.²¹ , ²²

Incidence of acute cardiorenal syndrome

Studies have shown a large variation in the incidence of ACRS, whose estimates range from 19% to 45%. That variation can be attributed to differences among the studies regarding 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 databases¹⁰ - 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) classification²⁹ 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/1.73m²in 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.³²Table 2 summarizes the different diagnostic criteria for AKI found in the literature.

Table 2
– RIFLE34, AKIN35, KDIGO36 and WRF11 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.
³²

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/1.73m². 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

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 classification²⁹ 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

Intermittent ACRS reflects a reversible reduction in GFR and seems less harmful than persistent ACRS. Paradoxically, in cases of ACRS on admission, the decrease in creatinine during hospitalization can be associated with adverse outcomes.²⁸ , ⁵³ , ⁶² Considering renal congestion as the major pathophysiological mechanism of ACRS, diuretics are expected to have a beneficial effect on prognosis. A post hoc analysis of the DOSE trial⁶³ has shown that renal function improvement when associated with inadequate decongestive strategies had a worse prognosis.

Other studies have shown that, with diuretic therapy and hemoconcentration, worsening renal function has a lower impact on prognosis than in patients with persistent congestion and no hemoconcentration.²⁸ , ⁶⁴ Those findings are partially due to confounding factors in serum creatinine assessment. In the context of measures of decongestion, the increase in serum creatinine can result from other mechanisms regardless of GFR reduction, such as hemoconcentration that reduces the distribution of creatinine. That renal change is harmless and transient, and named pseudo-AKI. The concept of pseudo-AKI can explain why biomarkers of tubular lesion were poor predictors of ACRS, considering that previous studies have made no distinction between AKI and pseudo-AKI.⁶² , ⁶⁵ During aggressive diuretic therapy, serum creatinine increased in 22% of the patients with DHF without increase in biomarkers, suggesting a potentially high proportion of pseudo-AKI.⁶⁵

It is not easy to determine whether the therapy is effective and pseudo-AKI can induce inadequate discontinuation of treatment. It is worth assessing the clinical parameters of perfusion, urine output, body weight loss and hemoconcentration. In addition, biomarkers seem to be good to guide therapy.⁶⁶ Measuring cardiac output and other hemodynamic parameters can help ensure an adequate and directed diuretic therapy,⁶⁷ in addition to enabling better understanding of ACRS.

Conclusions

The different references of baseline serum creatinine limit the capacity of accurate comparisons between studies and interfere with the estimates of ACRS diagnosis, overestimating or underestimating it.

This study suggests that the ACRS criteria should be revised to include the diagnosis of ACRS on hospital admission. Reference creatinine should reflect baseline renal function before AKI begins.

Referências

• ¹
  Rohde LEP, Montera, MW, Bocchi EA, Clausell NO, Albuquerque DC, Rassi S, Colafranceschi AS, et al. Diretriz Brasileira de Insuficiência Cardíaca Crônica e Aguda. Arq Bras Cardiol. 2018;111(3):436-539.
• ²
  Yancy CW, Jessup M, Bozkurt B, Butler J, Casey DE Jr, Drazner MH, et al. 2013 ACCF/AHA guideline for the management of heart failure: a report of the American College of Cardiology Foundation/American Heart Association Task Force on Practice Guidelines. J Am Coll Cardiol. 2013;62(16):e147-239.
• ³
  Albuquerque DC, Neto JDS, Bacal F, Rohde LEP, Bernardez-Pereira S, Berwanger O, et al. I Brazilian registry of heart failure - clinical aspects, care quality and hospitalization outcomes. Arq Bras Cardiol. 2015;104(6):433-42.
• ⁴
  Ledoux P. Cardiorenal syndrome. Avenir Med. 1951;48(8):149-53.
• ⁵
  Ronco C, McCullough P, Anker SD, Anand I, Aspromonte N, Bagshaw SM, et al. Cardio-renal Syndromes: report from the consensus conference of the Acute Dialysis Quality Initiative. Eur Heart J. 2010;31(6):703-11.
• ⁶
  Verdiani V, Lastrucci V, Nozzoli C. Worsening renal function in patients hospitalized with acute heart failure: risk factors and prognostic significances. Intern J Nephrol. 2010 Oct 11;2011:785974.
• ⁷
  Mullens, W, Abrahams Z, Skouri HN, Francis GS, Taylor DO, Starling RC, et al. Elevated intra-abdominal pressure in acute decompensated heart failure a potential contributor to worsening renal function? J Am Coll Cardiol. 2008;51(3):300-6.
• ⁸
  Ponikowski P, Voors AA, Anker SD, Bueno H, Cleland JG, Coats AJ, et al. 2016 ESC Guidelines for the diagnosis and treatment of acute and chronic heart failure: The Task Force for the diagnosis and treatment of acute and chronic heart failure of the European Society of Cardiology (ESC). Developed with the special contribution of the Heart Failure Association (HFA) of the ESC. Eur Heart J. 2016;37(27):2129-2200.
• ⁹
  Heywood JT, Fonarow GC, Costanzo MR, Mathur VS, Wigneswaran JR, Wynne J, et al. High prevalence of renal dysfunction and its impact on outcome in 118,465 patients hospitalized with acute decompensated heart failure: a report from the ADHERE database. J Card Fail. 2007;13(6):422-30.
• ¹⁰
  Krumholz HM, Chen YT, Vaccarino V, Wang Y, Radford MJ, Bradford WD, et al. Correlates and impact on outcomes of worsening renal function in patients > or =65 years of age with heart failure. Am J Cardiol. 2000;85(9):1110-3.
• ¹¹
  Gottlieb S, Abraham W, Butler J, Forman DE, Loh E, Massie BM, et al. The prognostic importance of different definitions of worsening renal failure in congestive heart failure. J Card Fail. 2002;8(3):136-41.
• ¹²
  Forman DE, Butler J, Wang Y, Abraham WT, O’ Connor CM, Gottlieb SS, et al. Incidence, predictors at admission, and impact of worsening renal function among patients hospitalized with heart failure. J Am Coll Cardiol. 2004;43(1):61-7.
• ¹³
  Damman K, Navis G, Voors AA, Asselbergs FW, Smilde TD, Cleland JG, et al. Worsening renal function and prognosis in heart failure: systematic review and meta-analysis. J Card Fail. 2007;13(8):599-608.
• ¹⁴
  Damman K, Valente MA, Voors AA, O’Connor CM, van Veldhuisen DJ, Hillege HL. Renal impairment, worsening renal function, and outcome in patients with heart failure: an updated meta-analysis. Eur Heart J. 2014;35(7):455-69.
• ¹⁵
  Patel J, Heywood JT. Management of the cardiorenal syndrome in heart failure. Curr Cardiol Rep. 2006;8(3):211-6.
• ¹⁶
  Siew ED, Matheny ME. Choice of reference serum creatinine in defining acute kidney injury. Nephron. 2015;131(2):107-12.
• ¹⁷
  Moher D, Liberati A, Tetzlaff J, Altman DG, PRISMA Group. Preferred reporting items for systematic reviews and meta-analyses: the PRISMA statement. Ann Intern Med. 2009;151(4):264-9.
• ¹⁸
  Uthoff H, Breidthardt T, Klima T, Aschwanden M, Arenja N, Socrates T, et al. Central venous pressure and impaired renal function in patients with acute heart failure. Eur J Heart Fail. 2011;13(4):432-9.
• ¹⁹
  Takaya Y, Yoshihara F, Yokoyama H, Kanzaki H, Kitakaze M, Goto Y, et al. Impact of onset time of acute kidney injury on outcomes in patients with acute decompensated heart failure. Heart Vessels. 2016;31(1):60-5.
• ²⁰
  Voors AA, Davison BA, Felker GM, Ponikowski P, Unemori E, Cotter G, et al. Early drop in systolic blood pressure and worsening renal function in acute heart failure: renal results of Pre-RELAX-AHF. Eur J Heart Fail 2011;13(9):961-7.
• ²¹
  Spineti PPM, Salles EF, Ferreira PDFM, Perruso LI, Maia PD, Xavier SS, et al. Acute cardiorenal syndrome in decompensated heart failure: impact on outcomes after hospital discharge in Brazil. Global Heart. 2016;11:e143. [Cited in 2019 May 12] Available from:. https://esc365.escardio.org/Congress/HEART-FAILURE-2016/Poster-Session-2-Co-morbidities/134726-acute-cardiorenal-syndrome-in-decompensated-heart-failure-impact-on-outcomes-after-hospital-discharge-in-brazil)
  » https://esc365.escardio.org/Congress/HEART-FAILURE-2016/Poster-Session-2-Co-morbidities/134726-acute-cardiorenal-syndrome-in-decompensated-heart-failure-impact-on-outcomes-after-hospital-discharge-in-brazil
• ²²
  Spineti PPM. Síndrome cardiorrenal aguda na Insuficiência cardíaca descompensada: impacto nos desfechos após a alta hospitalar [Tese]. Rio de Janeiro: Universidade Federal do Rio de Janeiro; 2015.
• ²³
  Goldberg A, Hammerman H, Petcherski S, Zdorovyak A, Yalonetsky S, Kapeliovich M, et al. Inhospital and 1-year mortality of patients who develop worsening renal function following acute ST-elevation myocardial infarction. Am Heart J. 2005;150(2):330-7.
• ²⁴
  Newsome BB, Warnock DG, McClellan WM, Herzog CA, Kiefe CI, Eggers PW, Allison JJ. Long-term risk of mortality and end-stage renal disease among the elderly after small increases in serum creatinine level during hospitalization for acute myocardial infarction. Arch Intern Med. 2008;168(6):609-16.
• ²⁵
  Parikh CR, Coca SG, Wang Y, Masoudi FA, Krumholz HM. Long-term prognosis of acute kidney injury after acute myocardial infarction. Arch Intern Med. 2008;168(9):987-95.
• ²⁶
  Nohria A, Hasselblad V, Stebbins A, Pauly DF, Fonarow GC, Shah M, et al. Cardiorenal interactions: insights from the ESCAPE trial. J Am Coll Cardiol. 2008;51(13):1268-74.
• ²⁷
  Smith GL, Vaccarino V, Kosiborod M, Lichtman JH, Cheng S, Watnick SG, et al. Worsening renal function: what is a clinically meaningful change in creatinine during hospitalization with heart failure? J Card Fail. 2003;9(1):13-25.
• ²⁸
  Testani JM, McCauley BD, Kimmel SE, Shannon RP. Characteristics of patients with improvement or worsening in renal function during treatment of acute decompensated heart failure. Am J Cardiol. 2010;106(12):1763-9.
• ²⁹
  Bellomo R, Ronco C, Kellum JA, Mehta RL, Palevsky P; Acute Dialysis Quality Initiative Workgroup. Acute renal failure – definition, outcome measures, animal models, fluid therapy and information technology needs: the Second International Consensus Conference Of The Acute Dialysis Quality Initiative (ADQI) Group. Crit Care. 2004;8(4):R204-12.
• ³⁰
  Mehta RL, Kellum JA, Shah SV, Molitoris BA, Ronco C, Warnock DG, et al. Acute Kidney Injury Network: report of an initiative to improve outcomes in acute kidney injury. Crit Care. 2007;11(2):R31.
• ³¹
  Kellun JA, Lameire N, Aspelin P, Barsoum RS, Burdamnn EA, Goldstein SL, et al. Kidney Disease: Improving Global Outcomes (KDIGO) Acute Kidney Injury Work Group KDIGO clinical practice guideline for acute kidney injury. Kidney Int Suppl. 2012;2(1):1-138.
• ³²
  Roy AK, Mc Gorrian C, Treacy C, Kavanaugh E, Brennan A, Mahon NG, et al. A comparison of traditional and novel definitions (RIFLE, AKIN, and KDIGO) of acute kidney injury for the prediction of outcomes in acute decompensated heart failure. Cardiorenal Med. 2013;3(1):26-37.
• ³³
  Schefold JC, Filippatos G, Hasenfuss G, Anker SD, von Haehling S. Heart failure and kidney dysfunction: epidemiology, mechanisms and management. Nat Rev Nephrol. 2016;12(10):610-23.
• ³⁴
  Shirakabe A, Hata N, Kobayashi N, Okazaki H, Matsushita M, Shibata Y, et al. Worsening renal function definition is insufficient for evaluating acute renal failure in acute heart failure. ESC Heart Fail. 2018;5(3):322-31.
• ³⁵
  Kellum JA, Lameire N; KDIGO AKI Guideline Work Group. Diagnosis, evaluation, and management of acute kidney injury: a KDIGO summary (Part 1). Crit Care. 2013;17(1):204.
• ³⁶
  Siew ED, Matheny ME, Ikizler TA, Lewis JB, Miller RA, Waitman LR, et al. Commonly used surrogates for baseline renal function affect the classification and prognosis of acute kidney injury. Kidney Int. 2010;77(6):536-42.
• ³⁷
  Núñez J, Miñana G, Santas E, Bertomeu-González V. Cardiorenal syndrome in acute heart failure: revisiting paradigms. Rev Esp Cardiol. 2015;68(5):426-35.
• ³⁸
  Legrand M, De Berardinis B, Gaggin HK, Magrini L, Belcher A, Zancla B, et al. Evidence of uncoupling between renal dysfunction and injury in cardiorenal syndrome: insights from the BIONICS study. PLoS One. 2014;9(11):e112313.
• ³⁹
  Masson S, Latini R, Milani V, Moretti L, Rossi MG, Carbonieri E, et al. Prevalence and prognostic value of elevated urinary albumin excretion in patients with chronic heart failure: data from the GISSI-Heart Failure trial. Circ Heart Fail. 2010;3(1):65-72.
• ⁴⁰
  Di Lullo L, Bellasi A, Russo D, Cozzolino M, Ronco C. Cardiorenal acute kidney injury: epidemiology, presentation, causes, pathophysiology and treatment. Int J Cardiol. 2017 Jan 15;227:143-50.
• ⁴¹
  van Vark LC, Lesman-Leegte I, Baart SJ, Postmus D, Pinto YM, Orsel JG, et al. Prognostic value of serial ST2 measurements in patients with acute heart failure. J Am Coll Cardiol. 2017;70(19):2378-88.
• ⁴²
  Grande D, Gioia Ml, Terlizzese P, Iacovello M. Heart failure and kidney disease. Adv Exp Med Biol. 2018;1067:219-38.
• ⁴³
  Grande D, Terlizzese P, Iacoviello M. Role of imaging in the evaluation of renal dysfunction in heart failure patients. World J Nephrol. 2017;6(3):123-31.
• ⁴⁴
  Cowie MR, Komajda M, Murray-Thomas T, Underwood J, Ticho B, POSH Investigators. Prevalence and impact of worsening renal function in patients hospitalized with decompensated heart failure: results of the prospective outcomes study in heart failure (POSH). Eur Heart J. 2006;27(10):1216-22.
• ⁴⁵
  Logeart D, Tabet JY, Hittinger L, Thabut G, Jourdain P, Maison P, et al. Transient worsening of renal function during hospitalization for acute heart failure alters outcome. Int J Cardiol. 2008;127(2):228-32.
• ⁴⁶
  Metra M, Nodari S, Parrinello G, Bordonali T, Bugatti S, Danesi R, et al. Worsening renal function in patients hospitalized for acute heart failure: clinical implications and prognostic significance. Eur J Heart Fail. 2008;10(2):188-95.
• ⁴⁷
  Latchamsetty R, Fang J, Kline-Rogers E, Mukherjee D, Otten RF, LaBounty TM, et al. Prognostic value of transient and sustained increase in in-hospital creatinine on outcomes of patients admitted with acute coronary syndrome. Am J Cardiol. 2007;99(7):939-42.
• ⁴⁸
  Ronco C, Haapio M, House A, Anavekar N, Bellomo R. Cardiorenal syndrome. J Am Coll Cardiol. 2008;52(19):1527-39.
• ⁴⁹
  Jose P, Skali H, Anavekar N, Tomson C, Krumholz HM, Rouleau JL, et al. Increase in creatinine and cardiovascular risk in patients with systolic dysfunction after myocardial infarction. J Am Soc Nephrol 2006;17(10):2886-91.
• ⁵⁰
  Lanfear DE, Peterson EL, Campbell J, Phatak H, Wu D, Wells K, et al. Relation of worsened renal function during hospitalization for heart failure to long-term outcomes and rehospitalization. Am J Cardiol. 2011;107(1):74-8.
• ⁵¹
  Krishnamoorthy A, Greiner MA, Sharma PP, DeVore AD, Johnson KW, Fonarow GC, et al. Transient and persistent worsening renal function during hospitalization for acute heart failure. Am Heart J. 2014;168(6):891-900.
• ⁵²
  Aronson D, Burger AJ. The relationship between transient and persistent worsening renal function and mortality in patients with acute decompensated heart failure. J Card Fail. 2010;16(7):541-7.
• ⁵³
  Fonarow GC, Abraham WT, Albert NM, Stough WG, Gheorghiade M, Greenberg BH, et al. Factors identified as precipitating hospital admissions for heart failure and clinical outcomes: findings from OPTIMIZE-HF. Arch Intern Med. 2008;168(8):847-54.
• ⁵⁴
  Maeder MT, Rickli H, Pfisterer ME, Muzzarelli S, Ammann P, Fehr T, et al. Incidence, clinical predictors, and prognostic impact of worsening renal function in elderly patients with chronic heart failure on intensive medical therapy. Am Heart J. 2012;163(3):407-14.
• ⁵⁵
  Abo-Salem E, Sherif K, Dunlap S, Prabhakar S. Potential aetiologies and prognostic implications of worsening renal function in acute decompensated heart failure. Acta Cardiol. 2014;69(6):657-63.
• ⁵⁶
  Ueda T, Kawakami R, Sugawara Y, Okada S, Nishida T, Onoue K, et al. Worsening of renal function during 1 year after hospital discharge is a strong and independent predictor of all-cause mortality in acute decompensated heart failure. J Am Heart Assoc. 2014;3(6):e001174.
• ⁵⁷
  Villacorta H, Saenz-Tello BF, Santos EB, Steffen R, Wiefels C, Lima LC, et al. Renal dysfunction and anemia in patients with heart failure with reduced versus normal ejection fraction. Arq Bras Cardiol. 2010;94(3):378-84.
• ⁵⁸
  Damman K, Tang WH, Testani JM, McMurray JJ. Terminology and definition of changes renal function in heart failure. Eur Heart J. 2014;35(48):3413-6.
• ⁵⁹
  Damman K, Valente MAE, van Veldhuisen DJ, Cleland JGF, O’Connor CM, Metra M, et al. Plasma neutrophil gelatinase-associated lipocalin and predicting clinically relevant worsening renal function in acute heart failure. Int J Mol Sci. 2017;18(7):pii:E1470.
• ⁶⁰
  Jentzer JC, Chawla LS A Clinical approach to the acute cardiorenal syndrome. Crit Care Clin. 2015;31(4):685-703.
• ⁶¹
  Metra M, Davison B, Bettari L, Sun H, Edwards C, Lazzarini V, et al. Is worsening renal function an ominous prognostic sign in patients with acute heart failure? The role of congestion and its interaction with renal function. Circ Heart Fail. 2012;5(1):54-62.
• ⁶²
  Legrand M, Mebazaa A, Ronco C, Januzzi JL Jr. When cardiac failure, kidney dysfunction, and kidney injury intersect in acute conditions: the case of cardiorenal syndrome. Crit Care Med. 2014;42(9):2109-17.
• ⁶³
  Brisco MA, Zile MR, Hanberg JS, Wilson FP, Parikh CR, Coca SG, et al. Relevance of changes in serum creatinine during a heart failure trial of decongestive strategies: insights from the DOSE trial. J Card Fail. 2016;22(10):753-60.
• ⁶⁴
  Vaduganathan M, Greene SJ, Fonarow GC, Voors AA, Butler J, Gheordhiade M. Hemoconcentration-guided diuresis in heart failure. Am J Med. 2014;127(12):1154-9.
• ⁶⁵
  Ahmad T, Jackson K, Rao VS, Tang WHW, Brisco-Bacik MA, Chen GG, et al. Worsening renal function in acute heart failure patients undergoing aggressive diuresis is not associated with tubular injury. Circulation. 2018;137(19):2016-28.
• ⁶⁶
  Darmon M, Schetz M. What’s new in cardiorenal syndrome? Intensive Care Med. 2018;44(6):908-10.
• ⁶⁷
  Opdam HI, Wan L, Bellomo R. A pilot assessment of the FloTrac cardiac output monitoring system. Intensive Care Med. 2007;33(2):344-9.

• Study Association
  This article is part of the thesis of master submitted by Andréa de Melo Leite, from Universidade Federal Fluminense.

• Sources of Funding
  There were no external funding sources for this study.

Publication Dates

• Publication in this collection
  07 Aug 2020
• Date of issue
  July 2020

History

• Received
  05 Apr 2019
• Reviewed
  04 Aug 2019
• Accepted
  18 Aug 2019