Editorial comment
Putting creatinine and hemoconcentration in their place as prognostic predictors in the conundrum of acute heart failure
Assentar a creatinina e a hemoconcentração no lugar correto enquanto preditores prognósticos na insuficiência cardíaca aguda
Pedro Marques da Silva
Núcleo de Investigação Arterial, Medicina 4, Hospital de Santa Marta, Centro Hospitalar de Lisboa Central, EPE, Lisboa, Portugal
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O impacto prognóstico da hemoconcentração em doentes admitidos com insuficiência cardíaca aguda" ] ] "contieneResumen" => array:2 [ "en" => true "pt" => true ] "contieneTextoCompleto" => array:1 [ "en" => true ] "contienePdf" => array:1 [ "en" => true ] "resumenGrafico" => array:2 [ "original" => 0 "multimedia" => array:7 [ "identificador" => "fig0015" "etiqueta" => "Figure 3" "tipo" => "MULTIMEDIAFIGURA" "mostrarFloat" => true "mostrarDisplay" => false "figura" => array:1 [ 0 => array:4 [ "imagen" => "gr3.jpeg" "Alto" => 1090 "Ancho" => 1534 "Tamanyo" => 105289 ] ] "descripcion" => array:1 [ "en" => "<p id="spar0060" class="elsevierStyleSimplePara elsevierViewall">Survival curves grouped by presence or absence of hemoconcentration according to the Kidney Disease Improving Global Outcomes criteria. Log rank p=0.004. HR 1.6; 95% CI 1.10-2.34; p=0.02. 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HC: hemoconcentration; WRF: worsening renal function.</p>" ] ] ] "autores" => array:1 [ 0 => array:2 [ "autoresLista" => "José Luís Martins, Luís Santos, Ana Faustino, Jesus Viana, José Santos" "autores" => array:5 [ 0 => array:2 [ "nombre" => "José Luís" "apellidos" => "Martins" ] 1 => array:2 [ "nombre" => "Luís" "apellidos" => "Santos" ] 2 => array:2 [ "nombre" => "Ana" "apellidos" => "Faustino" ] 3 => array:2 [ "nombre" => "Jesus" "apellidos" => "Viana" ] 4 => array:2 [ "nombre" => "José" "apellidos" => "Santos" ] ] ] ] ] "idiomaDefecto" => "en" "EPUB" => "https://multimedia.elsevier.es/PublicationsMultimediaV1/item/epub/S2174204918302447?idApp=UINPBA00004E" "url" => "/21742049/0000003700000007/v1_201807190435/S2174204918302447/v1_201807190435/en/main.assets" ] ] "en" => array:13 [ "idiomaDefecto" => true "cabecera" => "<span class="elsevierStyleTextfn">Editorial comment</span>" "titulo" => "Putting creatinine and hemoconcentration in their place as prognostic predictors in the conundrum of acute heart failure" "tieneTextoCompleto" => true "paginas" => array:1 [ 0 => array:2 [ "paginaInicial" => "603" "paginaFinal" => "605" ] ] "autores" => array:1 [ 0 => array:3 [ "autoresLista" => "Pedro Marques da Silva" "autores" => array:1 [ 0 => array:3 [ "nombre" => "Pedro Marques" "apellidos" => "da Silva" "email" => array:1 [ 0 => "pmarques.silva@sapo.pt" ] ] ] "afiliaciones" => array:1 [ 0 => array:2 [ "entidad" => "Núcleo de Investigação Arterial, Medicina 4, Hospital de Santa Marta, Centro Hospitalar de Lisboa Central, EPE, Lisboa, Portugal" "identificador" => "aff0005" ] ] ] ] "titulosAlternativos" => array:1 [ "pt" => array:1 [ "titulo" => "Assentar a creatinina e a hemoconcentração no lugar correto enquanto preditores prognósticos na insuficiência cardíaca aguda" ] ] "textoCompleto" => "<span class="elsevierStyleSections"><p id="par0005" class="elsevierStylePara elsevierViewall"><span class="elsevierStyleDisplayedQuote" id="dsq0005"><p id="spar0005" class="elsevierStyleSimplePara elsevierViewall">“Homage to thee, O my heart! Homage to you, O my kidneys!”</p><p id="spar0010" class="elsevierStyleSimplePara elsevierViewall">The Egyptian Book of the Dead<a class="elsevierStyleCrossRef" href="#fn0005"><span class="elsevierStyleSup">a</span></a></p></span></p><p id="par0010" class="elsevierStylePara elsevierViewall">Many centuries ago, traditional Chinese medicine – today, quite rightly, a subject of some controversy in the Portuguese medical community – described a disorder termed “heart and kidney failing to link,” suggesting a close connection between dysfunction of the kidneys and of the heart. These may have been the first references to what is now known as cardiorenal syndrome (CRS), a complex “disorder of the heart and the kidneys whereby acute or chronic dysfunction in one organ may induce acute or chronic dysfunction of the other”.<a class="elsevierStyleCrossRefs" href="#bib0085"><span class="elsevierStyleSup">1–3</span></a></p><p id="par0015" class="elsevierStylePara elsevierViewall">Five subtypes of CRS are now recognized, but in all of them, both organs (heart and kidneys) show or develop structural and/or functional alterations.<a class="elsevierStyleCrossRefs" href="#bib0100"><span class="elsevierStyleSup">4,5</span></a> Type 1 (acute CRS) – the subject of this editorial – refers to acute worsening of heart function leading to acute kidney injury (AKI) and/or dysfunction,<a class="elsevierStyleCrossRefs" href="#bib0085"><span class="elsevierStyleSup">1–3</span></a> and can be found in 19-45% of patients with acute decompensated heart failure (ADHF) presenting with AKI.<a class="elsevierStyleCrossRef" href="#bib0100"><span class="elsevierStyleSup">4</span></a> AKI mostly occurs early, within 3-5 days of hospitalization, and appears to be a predictor of even worse prognosis, associated with higher short- and long-term all-cause and cardiovascular mortality and prolonged hospitalization. The well-documented risk factors for AKI in the context of AHF are a history of diabetes, severity of cardiac dysfunction on admission, use of high-dose diuretics (particularly loop diuretics, but also thiazides), vasodilator therapy, and use of larger radiocontrast volumes.<a class="elsevierStyleCrossRef" href="#bib0100"><span class="elsevierStyleSup">4</span></a></p><p id="par0020" class="elsevierStylePara elsevierViewall">The clinical presentation of type 1 CRS usually includes rapid worsening renal function (WRF) (suggestive of altered renal perfusion, unless proven otherwise), resulting in volume overload with signs and symptoms of fluid retention, pulmonary rales and systemic congestion, less frequently in low cardiac output with peripheral hypoperfusion, and in poor response to diuretics.<a class="elsevierStyleCrossRefs" href="#bib0090"><span class="elsevierStyleSup">2,4,5</span></a> It should be borne in mind that in the context of AHF diuretic resistance is multifactorial and includes, in varying degrees, impaired renal blood flow, altered drug reabsorption, reduced glomerular filtration, low albumin concentrations, and increased levels of urea nitrogen and other organic acids competitively impeding diuretic availability at the site of action.<a class="elsevierStyleCrossRefs" href="#bib0110"><span class="elsevierStyleSup">6,7</span></a> Ideally, in order to recognize renal dysfunction and to stratify the severity of AKI, the risk, injury, failure, loss of kidney function, and end-stage kidney disease (RIFLE) and Acute Kidney Injury Network (AKIN) classifications should be applied. The former is based on changes in serum creatinine (SCr) or glomerular filtration rate (GFR) and/or urine output, and is a good predictor of AKI severity and outcome. The AKIN classification is a modified adaptation of RIFLE, and can increase the sensitivity and specificity of AKI diagnosis. Although clinically available biomarkers are sometimes inadequate for a diagnosis of CRS and detection of AKI in ADHF, in clinical practice the suspicion of type 1 CRS derives from an increase in SCr and blood urea nitrogen (BUN).</p><p id="par0025" class="elsevierStylePara elsevierViewall">BUN is a serum by-product of protein metabolism and is probably one of the oldest short- as well as long-term prognostic markers in patients with heart failure. In the Acute Decompensated Heart Failure National Registry (ADHERE) database, BUN ≥43 mg/dl was the single best predictor, followed by systolic blood pressure <115 mmHg on admission and SCr ≥2.75 mg/dl (243.1 μmol/l), of in-hospital mortality among 65<span class="elsevierStyleHsp" style=""></span>275 AHF admissions. These findings have been replicated in other studies and BUN levels should be measured in routine prognostic assessment of ADHF.<a class="elsevierStyleCrossRef" href="#bib0120"><span class="elsevierStyleSup">8</span></a> Creatinine is a breakdown product of creatine phosphate in muscle tissue, and increases in the blood when GFR decreases, an indication of renal dysfunction. Increases in SCr elevations are also associated with worse outcomes in heart failure patients, and are a strong independent predictor of both one- and five-year mortality.<a class="elsevierStyleCrossRef" href="#bib0120"><span class="elsevierStyleSup">8</span></a></p><p id="par0030" class="elsevierStylePara elsevierViewall">However, as Martins et al.<a class="elsevierStyleCrossRef" href="#bib0125"><span class="elsevierStyleSup">9</span></a> note in this issue of the <span class="elsevierStyleItalic">Journal</span>, an increase of SCr in AHF patients does not always imply renal dysfunction or worse prognosis. As the authors point out, AHF patients with mild creatinine elevation but without established renal failure have a better prognosis, since these changes are due to hemoconcentration (HC) rather than to true WRF. It should be noted that in this case, HC arises from an absolute or relative loss of water from blood plasma (deshydremia). In Martins et al.’s paper, HC was defined as an increase in hemoglobin during hospital stay, estimated by subtracting hemoglobin at discharge from hemoglobin at admission; a similar definition has been used by other investigators.<a class="elsevierStyleCrossRefs" href="#bib0130"><span class="elsevierStyleSup">10–14</span></a> In their study, as in others, HC was associated with a better prognosis in patients with or without WRF, acting as a surrogate for anticongestive therapy, and had prognostic value in AHF patients without CKD but with elevated SCr. It would therefore be a mistake to argue that a simple increase in SCr indicates AKI, and in fact when associated with HC<a class="elsevierStyleCrossRef" href="#bib0095"><span class="elsevierStyleSup">3</span></a> – with no renal failure or chronic kidney disease – it is associated with better prognosis and survival. Such cases should be reclassified as ‘pseudo-WRF’.</p><p id="par0035" class="elsevierStylePara elsevierViewall">On the whole, the article by Martins et al. is clear, credible and well researched, with an accurate and judicious description of its limitations: its single-center and retrospective nature, the importance of missing data such as SCr and left ventricular ejection fraction, and the fact that pharmacological therapy at discharge was not recorded (with possible effects on prognosis).</p><p id="par0040" class="elsevierStylePara elsevierViewall">Diuretics (mainly, but not only, loop diuretics) are the cornerstone of ADHF and CRS treatment. They relieve renal venous congestion and fluid overload and improve patients’ symptoms and comfort, and their early use in severe ADHF can reduce mortality.<a class="elsevierStyleCrossRefs" href="#bib0105"><span class="elsevierStyleSup">5,6</span></a> However, they are a double-edged sword: they may worsen kidney function and trigger even more neurohormonal systems. The use and effects of diuretic therapy must therefore be carefully monitored.<a class="elsevierStyleCrossRefs" href="#bib0105"><span class="elsevierStyleSup">5,6</span></a> HC may be linked with increased risk of WRF during hospitalization, increased diuretic doses, and greater weight loss.<a class="elsevierStyleCrossRef" href="#bib0155"><span class="elsevierStyleSup">15</span></a> However, in multivariate analysis, HC is not linked with mortality, and an early increase (in the first week) in hemoglobin is independently associated with a favorable outcome, despite a slight worsening of renal function.<a class="elsevierStyleCrossRef" href="#bib0160"><span class="elsevierStyleSup">16</span></a></p><p id="par0045" class="elsevierStylePara elsevierViewall">Future research needs to focus on the differences between and determinants of late and early HC in AHF and to determine the cutoffs between them – because, apparently, only late HC is associated with improved survival<a class="elsevierStyleCrossRef" href="#bib0130"><span class="elsevierStyleSup">10</span></a> – and, bearing in mind that HC can be a surrogate for successful decongestion in AHF, to clarify why in some patients there is a conflict between HC and clinical assessment of venous congestion, with persistent congestion at discharge linked with increased mortality that is not HC-dependent. Finally, as Martins et al. suggest, HC is associated with better outcomes but cannot replace clinical assessment in the initial diagnosis of AHF and a proper diagnostic workup that includes specific biomarkers, as well as BUN, SCr, hemoglobin and hematocrit. In the meantime, all patients with AHF should promptly start pharmacological and non-pharmacological treatment in parallel, as recommended in the most recent guidelines.<a class="elsevierStyleCrossRefs" href="#bib0105"><span class="elsevierStyleSup">5,6</span></a></p><span id="sec0005" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0005">Conflicts of interest</span><p id="par0050" class="elsevierStylePara elsevierViewall">The author has no conflicts of interest to declare.</p></span></span>" "textoCompletoSecciones" => array:1 [ "secciones" => array:2 [ 0 => array:2 [ "identificador" => "sec0005" "titulo" => "Conflicts of interest" ] 1 => array:1 [ "titulo" => "References" ] ] ] "pdfFichero" => "main.pdf" "tienePdf" => true "NotaPie" => array:1 [ 0 => array:3 [ "etiqueta" => "a" "nota" => "<p class="elsevierStyleNotepara" id="npar0005">Eknoyan G. The kidneys in the Bible: what happened? 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| Year/Month | Html | Total | |
|---|---|---|---|
| 2024 October | 43 | 37 | 80 |
| 2024 September | 63 | 34 | 97 |
| 2024 August | 57 | 21 | 78 |
| 2024 July | 47 | 30 | 77 |
| 2024 June | 37 | 23 | 60 |
| 2024 May | 51 | 25 | 76 |
| 2024 April | 38 | 21 | 59 |
| 2024 March | 29 | 14 | 43 |
| 2024 February | 31 | 24 | 55 |
| 2024 January | 43 | 20 | 63 |
| 2023 December | 43 | 26 | 69 |
| 2023 November | 54 | 26 | 80 |
| 2023 October | 62 | 18 | 80 |
| 2023 September | 42 | 19 | 61 |
| 2023 August | 41 | 12 | 53 |
| 2023 July | 51 | 16 | 67 |
| 2023 June | 55 | 45 | 100 |
| 2023 May | 76 | 30 | 106 |
| 2023 April | 69 | 9 | 78 |
| 2023 March | 56 | 23 | 79 |
| 2023 February | 43 | 14 | 57 |
| 2023 January | 43 | 20 | 63 |
| 2022 December | 41 | 21 | 62 |
| 2022 November | 57 | 30 | 87 |
| 2022 October | 49 | 19 | 68 |
| 2022 September | 44 | 43 | 87 |
| 2022 August | 47 | 25 | 72 |
| 2022 July | 36 | 44 | 80 |
| 2022 June | 34 | 25 | 59 |
| 2022 May | 34 | 26 | 60 |
| 2022 April | 46 | 39 | 85 |
| 2022 March | 56 | 56 | 112 |
| 2022 February | 35 | 31 | 66 |
| 2022 January | 39 | 28 | 67 |
| 2021 December | 39 | 40 | 79 |
| 2021 November | 42 | 31 | 73 |
| 2021 October | 60 | 55 | 115 |
| 2021 September | 50 | 32 | 82 |
| 2021 August | 41 | 37 | 78 |
| 2021 July | 54 | 28 | 82 |
| 2021 June | 46 | 21 | 67 |
| 2021 May | 47 | 46 | 93 |
| 2021 April | 181 | 25 | 206 |
| 2021 March | 122 | 19 | 141 |
| 2021 February | 91 | 14 | 105 |
| 2021 January | 66 | 19 | 85 |
| 2020 December | 64 | 12 | 76 |
| 2020 November | 40 | 17 | 57 |
| 2020 October | 33 | 16 | 49 |
| 2020 September | 57 | 13 | 70 |
| 2020 August | 48 | 8 | 56 |
| 2020 July | 57 | 16 | 73 |
| 2020 June | 49 | 10 | 59 |
| 2020 May | 41 | 6 | 47 |
| 2020 April | 42 | 21 | 63 |
| 2020 March | 44 | 8 | 52 |
| 2020 February | 113 | 19 | 132 |
| 2020 January | 42 | 8 | 50 |
| 2019 December | 52 | 11 | 63 |
| 2019 November | 35 | 12 | 47 |
| 2019 October | 89 | 13 | 102 |
| 2019 September | 78 | 13 | 91 |
| 2019 August | 36 | 10 | 46 |
| 2019 July | 59 | 8 | 67 |
| 2019 June | 52 | 10 | 62 |
| 2019 May | 78 | 21 | 99 |
| 2019 April | 35 | 18 | 53 |
| 2019 March | 79 | 13 | 92 |
| 2019 February | 70 | 13 | 83 |
| 2019 January | 24 | 6 | 30 |
| 2018 December | 17 | 9 | 26 |
| 2018 November | 44 | 15 | 59 |
| 2018 October | 81 | 10 | 91 |
| 2018 September | 23 | 18 | 41 |
| 2018 August | 29 | 17 | 46 |
| 2018 July | 19 | 11 | 30 |
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