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  <front>
    <journal-meta>
      <journal-id journal-id-type="nlm-ta">Arq Bras Cardiol</journal-id>
      <journal-id journal-id-type="publisher-id">abc</journal-id>
      <journal-title-group>
        <journal-title>Arquivos Brasileiros de Cardiologia</journal-title>
        <abbrev-journal-title abbrev-type="publisher">Arq. Bras. Cardiol.</abbrev-journal-title>
      </journal-title-group>
      <issn pub-type="ppub">0066-782X</issn>
      <issn pub-type="epub">1678-4170</issn>
      <publisher>
        <publisher-name>Sociedade Brasileira de Cardiologia - SBC</publisher-name>
      </publisher>
    </journal-meta>
    <article-meta>
      <article-id specific-use="scielo-v3" pub-id-type="publisher-id">NXVPS4VfkpmzZQj85WNpvmn</article-id>
      <article-id specific-use="scielo-v2" pub-id-type="publisher-id">S0066-782X2021000701057</article-id>
      <article-id pub-id-type="publisher-id">abc.20210433</article-id>
      <article-id pub-id-type="doi">10.36660/abc.20210433</article-id>
      <article-categories>
        <subj-group subj-group-type="heading">
          <subject>Minieditorial</subject>
        </subj-group>
      </article-categories>
      <title-group>
        <article-title>Qual o Papel dos Biomarcadores de Les&#227;o Renal na Nefropatia Induzida por Contraste?</article-title>
      </title-group>
      <contrib-group>
        <contrib contrib-type="author">
          <contrib-id contrib-id-type="orcid">0000-0001-9891-676X</contrib-id>
          <name>
            <surname>Spineti</surname>
            <given-names>Pedro Pimenta de Mello</given-names>
          </name>
          <xref ref-type="aff" rid="aff1">
            <sup>1</sup>
          </xref>
          <xref ref-type="aff" rid="aff2">
            <sup>2</sup>
          </xref>
        </contrib>
      </contrib-group>
      <aff id="aff1">
        <label> 1 </label>
        <institution content-type="orgname">Hospital Universit&#225;rio Pedro Ernesto</institution>
        <addr-line>
          <named-content content-type="city">Rio de Janeiro</named-content>
          <named-content content-type="state">RJ</named-content>
        </addr-line>
        <country country="BR">Brasil</country>
        <institution content-type="original"> Hospital Universit&#225;rio Pedro Ernesto , Rio de Janeiro , RJ - Brasil </institution>
      </aff>
      <aff id="aff2">
        <label> 2 </label>
        <institution content-type="orgname">Hospital Unimed-Rio</institution>
        <addr-line>
          <named-content content-type="city">Rio de Janeiro</named-content>
          <named-content content-type="state">RJ</named-content>
        </addr-line>
        <country country="BR">Brasil</country>
        <institution content-type="original"> Hospital Unimed-Rio , Rio de Janeiro , RJ &#8211; Brasil </institution>
      </aff>
      <author-notes>
        <corresp id="c01">Correspond&#234;ncia: Pedro Pimenta de Mello Spineti &#8226; Hospital Universit&#225;rio Pedro Ernesto - Boulevard 28 de setembro, 77. CEP 20551-030, Vila Isabel, RJ &#8211; Brasil E-mail: <email>pedrospineti@yahoo.com.br</email> </corresp>
      </author-notes>
      <pub-date date-type="pub" publication-format="electronic">
        <day>14</day>
        <month>06</month>
        <year>2021</year>
      </pub-date>
      <pub-date date-type="collection" publication-format="electronic">
        <month>06</month>
        <year>2021</year>
      </pub-date>
      <volume>116</volume>
      <issue>6</issue>
      <fpage>1057</fpage>
      <lpage>1058</lpage>
      <permissions>
        <license license-type="open-access" xlink:href="https://creativecommons.org/licenses/by/4.0/" xml:lang="en">
          <license-p>This is an Open Access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.</license-p>
        </license>
      </permissions>
      <kwd-group xml:lang="pt">
        <kwd>Les&#227;o Renal Aguda</kwd>
        <kwd>Nefropatias</kwd>
        <kwd>Meios de Contraste</kwd>
        <kwd>Biomarcadores</kwd>
        <kwd>Cateterismo Card&#237;aco</kwd>
        <kwd>Creatinina</kwd>
        <kwd>Lipocalina 2</kwd>
      </kwd-group>
      <counts>
        <fig-count count="0"/>
        <table-count count="0"/>
        <equation-count count="0"/>
        <ref-count count="7"/>
        <page-count count="2"/>
      </counts>
    </article-meta>
  </front>
  <body>
    <p>A les&#227;o renal aguda induzida por contraste (LRA-IC) &#233; uma complica&#231;&#227;o potencial e importante na utiliza&#231;&#227;o de meios de contraste radiol&#243;gicos iodados estando associada com maiores taxas de morbimortalidade e aumento no tempo de hospitaliza&#231;&#227;o em pacientes submetidos a cateterismo card&#237;aco. <sup><xref ref-type="bibr" rid="B1">1</xref></sup> Sua incid&#234;ncia &#233; vari&#225;vel na literatura de acordo com o crit&#233;rio utilizado para o seu diagn&#243;stico. A defini&#231;&#227;o LRA-IC mais frequentemente utilizada em ensaios cl&#237;nicos &#233; uma eleva&#231;&#227;o nos n&#237;veis de creatinina s&#233;rica (Cr) de 0,5 mg/dl ou de 25% em rela&#231;&#227;o ao valor basal, em at&#233; 72 h ap&#243;s a exposi&#231;&#227;o ao meio de contraste. <sup><xref ref-type="bibr" rid="B1">1</xref></sup></p>
    <p>No entanto, a Cr apresenta uma s&#233;rie de limita&#231;&#245;es como marcador da fun&#231;&#227;o renal. Seu n&#237;vel s&#233;rico &#233; influenciado por fatores externos como sexo, idade, cor da pele, peso e massa muscular. Ela subestima a fun&#231;&#227;o renal em mulheres, pessoas idosas ou com baixo peso. Sua varia&#231;&#227;o superestima o dano renal em indiv&#237;duos com disfun&#231;&#227;o renal pr&#233;via. Outra importante limita&#231;&#227;o deve-se ao fato de a Cr elevar-se somente ap&#243;s 24 h de uma les&#227;o renal aguda, sendo considerada um &#8220;marcador lento&#8221; de inj&#250;ria renal aguda. <sup><xref ref-type="bibr" rid="B1">1</xref> , <xref ref-type="bibr" rid="B2">2</xref></sup></p>
    <p>Novos biomarcadores t&#234;m sido avaliados no aux&#237;lio ao diagn&#243;stico da LRA-IC. Entre estes, destacam-se a cistatina C (Cis-C), a lipocalina associada &#224; gelatinase de neutr&#243;filos (NGAL) e a mol&#233;cula de inj&#250;ria renal 1 (KIM-1).</p>
    <p>A Cis-C &#233; um pept&#237;deo de 122 amino&#225;cidos com baixo peso molecular (13,36 Kda), da fam&#237;lia dos inibidores de protease da ciste&#237;na. Ela &#233; produzida de forma constante pela maioria das c&#233;lulas nucleadas e sua s&#237;ntese n&#227;o &#233; influenciada por processos inflamat&#243;rios, pela massa muscular ou pelo sexo do indiv&#237;duo. Devido ao seu baixo peso molecular e &#224; carga positiva, ela &#233; livremente filtrada pelo glom&#233;rulo renal e, ent&#227;o, reabsorvida e metabolizada no t&#250;bulo renal proximal, n&#227;o ocorrendo secre&#231;&#227;o renal ou extra-renal. Logo, sua determina&#231;&#227;o s&#233;rica reflete, exclusivamente, a filtra&#231;&#227;o glomerular e seu aumento no soro significa uma redu&#231;&#227;o dessa taxa. <sup><xref ref-type="bibr" rid="B2">2</xref></sup> A Cis-C atinge seu pico 24 h ap&#243;s a exposi&#231;&#227;o ao contraste em pacientes com LRA-IC e permanece elevada at&#233; 48 hs. <sup><xref ref-type="bibr" rid="B3">3</xref></sup></p>
    <p>A NGAL &#233; uma glicoprote&#237;na de 178 amino&#225;cidos que pertence &#224; superfam&#237;lia das lipocalinas. Ela &#233; expressada pelos neutr&#243;filos e por certos epit&#233;lios, como os t&#250;bulos renais. Ela &#233; filtrada livremente pelo glom&#233;rulo e posteriormente reabsorvida pelas c&#233;lulas do t&#250;bulo proximal. Seus n&#237;veis s&#233;ricos e urin&#225;rios basais s&#227;o muito baixos, elevando-se em diversos cen&#225;rios cl&#237;nicos como, inflama&#231;&#227;o sist&#234;mica, c&#226;ncer e aterosclerose. <sup><xref ref-type="bibr" rid="B2">2</xref></sup> Seus n&#237;veis elevam-se agudamente 4 h ap&#243;s exposi&#231;&#227;o ao contraste em casos de LRA-IC e retornam aos n&#237;veis basais em 48. <sup><xref ref-type="bibr" rid="B3">3</xref></sup></p>
    <p>Revis&#227;o sistem&#225;tica recente sobre o papel da NGAL e da Cis-C analisou 37 estudos e concluiu que ambas podem servir como indicadores diagn&#243;sticos precoces de LRA-IC, e que a cistatina C pode ter um desempenho melhor do que a NGAL. N&#227;o houve diferen&#231;a no desempenho da NGAL s&#233;rica, comparada &#224; urin&#225;ria. <sup><xref ref-type="bibr" rid="B4">4</xref></sup></p>
    <p>A KIM-1 humana &#233; uma glicoprote&#237;na transmembrana do tipo um, com um dom&#237;nio de imunoglobulina e mucina que n&#227;o &#233; detect&#225;vel em tecido renal normal ou na urina, mas &#233; expresso em n&#237;veis muito elevados em c&#233;lulas desdiferenciadas do epit&#233;lio tubular proximal renal ap&#243;s les&#227;o isqu&#234;mica ou t&#243;xica. H&#225; in&#250;meras caracter&#237;sticas que poderiam torn&#225;-la um atraente biomarcador de les&#227;o renal, tais como: aus&#234;ncia em rim normal, aumento da sua express&#227;o ap&#243;s um insulto isqu&#234;mico agudo e sua persist&#234;ncia nas c&#233;lulas do epit&#233;lio tubular at&#233; sua recupera&#231;&#227;o completa. <sup><xref ref-type="bibr" rid="B2">2</xref></sup></p>
    <p>Nesta edi&#231;&#227;o dos Arquivos Brasileiros de Cardiologia, o Dr. Huyut <sup><xref ref-type="bibr" rid="B5">5</xref></sup> avaliou a associa&#231;&#227;o entre os n&#237;veis s&#233;ricos de KIM-1 e LRA-IC em pacientes idosos com infarto do mioc&#225;rdio sem supradesnivelamento do segmento ST. Apesar do pequeno tamanho da popula&#231;&#227;o estudada, ele pode demonstrar que esta mol&#233;cula esteve associada de forma independente &#224; LRA-IC com uma boa &#225;rea sob a curva-ROC. A LRA-IC, como esperado, esteve associada a maior morbimortalidade.</p>
    <p>Embora o achado seja interessante, dois estudos recentes comparando NGAL e KIM-1 demonstraram que esta parece ter uma performance pior na predi&#231;&#227;o de LRA-IC. <sup><xref ref-type="bibr" rid="B6">6</xref> , <xref ref-type="bibr" rid="B7">7</xref></sup> Estas diverg&#234;ncias de resultados podem ser atribu&#237;das &#224; diferentes defini&#231;&#245;es de LRA-IC utilizadas pelos estudos, assim como pontos de corte distintos para os biomarcadores.</p>
    <p>Em conclus&#227;o, os novos biomarcadores apresentam vantagens em rela&#231;&#227;o &#224; creatinina para avalia&#231;&#227;o de LRA-IC, por&#233;m ainda h&#225; incerteza quanto ao melhor deles para esta indica&#231;&#227;o. S&#227;o necess&#225;rios novos estudos que avaliem n&#227;o s&#243; a associa&#231;&#227;o entre biomarcadores de LRA-IC, mas tamb&#233;m a custo-efetividade da incorpora&#231;&#227;o &#224; pr&#225;tica cl&#237;nica di&#225;ria.</p>
  </body>
  <back>
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    <fn-group>
      <fn fn-type="other">
        <p>Minieditorial referente ao artigo: A Mol&#233;cula de Les&#227;o Renal-1 est&#225; Associada &#224; Nefropatia Induzida por Contraste em Pacientes Idosos com IAMSSST</p>
      </fn>
    </fn-group>
  </back>
  <sub-article article-type="translation" id="TRen" xml:lang="en">
    <front-stub>
      <article-categories>
        <subj-group subj-group-type="heading">
          <subject>Short Editorial</subject>
        </subj-group>
      </article-categories>
      <title-group>
        <article-title>What Is the Role of Kidney Injury Biomarkers in Contrast-Induced Nephropaty?</article-title>
      </title-group>
      <contrib-group>
        <contrib contrib-type="author">
          <contrib-id contrib-id-type="orcid">0000-0001-9891-676X</contrib-id>
          <name>
            <surname>Spineti</surname>
            <given-names>Pedro Pimenta de Mello</given-names>
          </name>
          <xref ref-type="aff" rid="aff1001">
            <sup>1</sup>
          </xref>
          <xref ref-type="aff" rid="aff2001">
            <sup>2</sup>
          </xref>
        </contrib>
      </contrib-group>
      <aff id="aff1001">
        <label>1</label>
        <country country="BR">Brazil</country>
        <institution content-type="original">Hospital Universit&#225;rio Pedro Ernesto, Rio de Janeiro, RJ - Brazil</institution>
      </aff>
      <aff id="aff2001">
        <label>2</label>
        <country country="BR">Brazil</country>
        <institution content-type="original">Hospital Unimed-Rio, Rio de Janeiro, RJ - Brazil</institution>
      </aff>
      <author-notes>
        <corresp id="c01001">Mailing Address: Pedro Pimenta de Mello Spineti &#8226; Hospital Universit&#225;rio Pedro Ernesto - Boulevard 28 de setembro, 77. Postal Code 20551-030, Vila Isabel, RJ &#8211; Brazil E-mail: pedrospineti@yahoo.com.br</corresp>
      </author-notes>
      <kwd-group xml:lang="en">
        <kwd>Acute Kidney Injury</kwd>
        <kwd>Kidney Diseases</kwd>
        <kwd>Contrast Media</kwd>
        <kwd>Biomarkers</kwd>
        <kwd>Cardiac Catheterization</kwd>
        <kwd>Creatinine</kwd>
        <kwd>Lipocalin 2</kwd>
      </kwd-group>
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      <p>Contrast-induced acute kidney injury (CI-AKI) is a potential severe complication in the use of iodinated radiological contrast media and is associated with higher rates of morbidity and mortality and increased length of hospital stay in patients undergoing cardiac catheterization.<sup><xref ref-type="bibr" rid="B1">1</xref></sup> Its incidence is variable in the literature according to the criteria used for its diagnosis. The CI-AKI definition most often used in clinical trials is an increase in serum creatinine (Cr) levels of 0.5 mg/dl or 25% over baseline within 72 h after exposure to contrast medium.<sup><xref ref-type="bibr" rid="B1">1</xref></sup></p>
      <p>However, Cr has a number of limitations as a marker of renal function. Its serum level is influenced by external factors such as sex, age, skin color, weight and muscle mass. It underestimates renal function in women, in the elderly or in underweight individuals. Its variation overestimates renal damage in individuals with previous kidney failure. Another important limitation is the fact that Cr rises only after 24 h of an acute kidney injury, being considered a &#8220;slow marker&#8221; of acute kidney injury.<sup><xref ref-type="bibr" rid="B1">1</xref> , <xref ref-type="bibr" rid="B2">2</xref></sup></p>
      <p>New biomarkers have been evaluated to help diagnose CI-AKI. These include cystatin C (CysC), the lipocalin associated with neutrophil gelatinase (NGAL) and kidney injury molecule 1 (KIM-1).</p>
      <p>CysC is a peptide of 122 amino acids with low molecular weight (13.36 Kda), from the family of cysteine protease inhibitors. It is produced steadily by most nucleated cells and its synthesis is not influenced by inflammatory processes, muscle mass or sex of the individual. Due to its low molecular weight and positive charge, it is freely filtered by the renal glomerulus and then reabsorbed and metabolized in the proximal renal tubule, with no renal or extra-renal secretion. Therefore, its serum determination reflects exclusively glomerular filtration and its increase in serum means a reduction in this rate.<sup><xref ref-type="bibr" rid="B2">2</xref></sup> CysC reaches its peak 24 h after exposure to contrast in patients with CI-AKI and remains high for up to 48 h.<sup><xref ref-type="bibr" rid="B3">3</xref></sup></p>
      <p>NGAL is a 178 amino acid glycoprotein that belongs to the superfamily of lipocalins. It is expressed by neutrophils and certain epithelia, such as renal tubules. It is freely filtered by the glomerulus and later reabsorbed by the cells of the proximal tubule. Its basal serum and urinary levels are very low, rising in different clinical settings such as systemic inflammation, cancer and atherosclerosis.<sup><xref ref-type="bibr" rid="B2">2</xref></sup> Its levels rise sharply 4 h after exposure to contrast in cases of CI-AKI and return to baseline levels in 48h.<sup><xref ref-type="bibr" rid="B3">3</xref></sup></p>
      <p>A recent systematic review of the role of NGAL and CysC analyzed 37 studies and concluded that both can serve as early diagnostic indicators of CI-AKI, and that cystatin C may perform better than NGAL. There was no difference in the performance of serum NGAL compared to urine NGAL.<sup><xref ref-type="bibr" rid="B4">4</xref></sup></p>
      <p>Human KIM-1 is a type one transmembrane glycoprotein, with an immunoglobulin and mucin domain that is not detectable in normal renal tissue or in the urine, but it is expressed at very high levels in dedifferentiated cells of the renal proximal tubular epithelium after ischemic or toxic injury. There are numerous characteristics that could make it an attractive biomarker of kidney injury, such as: absence in normal kidney, increased expression after an acute ischemic insult and its persistence in the tubular epithelium cells until its complete recovery.<sup><xref ref-type="bibr" rid="B2">2</xref></sup></p>
      <p>In this edition of Arquivos Brasileiros de Cardiologia, Dr. Huyut<sup><xref ref-type="bibr" rid="B5">5</xref></sup> evaluated the association between serum levels of KIM-1 and CI-AKI in elderly patients with ST-segment elevation myocardial infarction. Despite the small size of the study population, he shows that this molecule was independently associated with CI-AKI with a good area under the ROC curve. CI-AKI, as expected, has been associated with increased morbidity and mortality.</p>
      <p>Although this is an interesting finding, two recent studies comparing NGAL and KIM-1 demonstrated that it appears to have a worse performance in predicting CI-AKI.<sup><xref ref-type="bibr" rid="B6">6</xref> , <xref ref-type="bibr" rid="B7">7</xref></sup> These inconsistent results can be attributed to the different definitions of CI-AKI used by the studies, as well as different cutoff points for the biomarkers.</p>
      <p>In conclusion, the new biomarkers have advantages on creatinine for the evaluation of CI-AKI, but there is still uncertainty about the best of them for this indication. Further studies are needed to assess not only the association between CI-AKI biomarkers, but also the cost-effectiveness of incorporating them into daily clinical practice.</p>
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          <p>Short Editorial related to the article: Kidney Injury Molecule-1 Is Associated with Contrast-Induced Nephropathy in Elderly Patients with Non-STEMI</p>
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