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  <front>
    <journal-meta>
      <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-loc>S&#227;o Paulo, SP, Brazil</publisher-loc>
      </publisher>
    </journal-meta>
    <article-meta>
      <article-id pub-id-type="publisher-id" specific-use="scielo-v3">JxBJktmVt9ZrSwwChhT63Nj</article-id>
      <article-id pub-id-type="publisher-id" specific-use="scielo-v2">S0066-782X2013003100007</article-id>
      <article-id pub-id-type="publisher-id" specific-use="scielo-v1">S0066-782X(13)10100500007</article-id>
      <article-id pub-id-type="doi">10.5935/abc.20130191</article-id>
      <article-categories>
        <subj-group subj-group-type="heading">
          <subject>Artigos Originais</subject>
        </subj-group>
      </article-categories>
      <title-group>
        <article-title>Avalia&#231;&#227;o da sensibilidade e especificidade dos exames n&#227;o invasivos no diagn&#243;stico da estenose de art&#233;ria renal</article-title>
      </title-group>
      <contrib-group>
        <contrib contrib-type="author">
          <name>
            <surname>Borelli</surname>
            <given-names>Flavio Antonio de Oliveira</given-names>
          </name>
          <xref ref-type="aff" rid="aff01"/>
        </contrib>
        <contrib contrib-type="author">
          <name>
            <surname>Pinto</surname>
            <given-names>Ibraim M. F.</given-names>
          </name>
          <xref ref-type="aff" rid="aff01"/>
        </contrib>
        <contrib contrib-type="author">
          <name>
            <surname>Amodeo</surname>
            <given-names>Celso</given-names>
          </name>
          <xref ref-type="aff" rid="aff01"/>
        </contrib>
        <contrib contrib-type="author">
          <name>
            <surname>Smanio</surname>
            <given-names>Paola E. P.</given-names>
          </name>
          <xref ref-type="aff" rid="aff01"/>
        </contrib>
        <contrib contrib-type="author">
          <name>
            <surname>Kambara</surname>
            <given-names>Antonio M.</given-names>
          </name>
          <xref ref-type="aff" rid="aff01"/>
        </contrib>
        <contrib contrib-type="author">
          <name>
            <surname>Petisco</surname>
            <given-names>Ana Claudia G.</given-names>
          </name>
          <xref ref-type="aff" rid="aff01"/>
        </contrib>
        <contrib contrib-type="author">
          <name>
            <surname>Moreira</surname>
            <given-names>Samuel M.</given-names>
          </name>
          <xref ref-type="aff" rid="aff01"/>
        </contrib>
        <contrib contrib-type="author">
          <name>
            <surname>Paiva</surname>
            <given-names>Ricardo Calil</given-names>
          </name>
          <xref ref-type="aff" rid="aff01"/>
        </contrib>
        <contrib contrib-type="author">
          <name>
            <surname>Lopes</surname>
            <given-names>Hugo Belotti</given-names>
          </name>
          <xref ref-type="aff" rid="aff01"/>
        </contrib>
        <contrib contrib-type="author">
          <name>
            <surname>Sousa</surname>
            <given-names>Amanda G. M. R.</given-names>
          </name>
          <xref ref-type="aff" rid="aff01"/>
        </contrib>
      </contrib-group>
      <aff id="aff01">
        <addr-line>
          <named-content content-type="city">S&#227;o Paulo</named-content>
          <named-content content-type="state">S&#227;o Paulo</named-content>
        </addr-line>
        <institution content-type="orgname">Instituto Dante Pazzanese de Cardiologia</institution>
        <country country="BR">Brazil</country>
      </aff>
      <pub-date date-type="collection" publication-format="electronic">
        <month>11</month>
        <year>2013</year>
      </pub-date>
      <volume>101</volume>
      <issue>5</issue>
      <fpage>423</fpage>
      <lpage>433</lpage>
      <history>
        <date date-type="received">
          <day>08</day>
          <month>11</month>
          <year>2012</year>
        </date>
        <date date-type="accepted">
          <day>04</day>
          <month>03</month>
          <year>2013</year>
        </date>
        <date date-type="rev-recd">
          <day>30</day>
          <month>11</month>
          <year>2012</year>
        </date>
      </history>
      <permissions>
        <license license-type="open-access" xlink:href="http://creativecommons.org/licenses/by-nc/4.0/" xml:lang="en">
          <license-p>This work is licensed under a Creative Commons Attribution-NonCommercial 4.0 International License.</license-p>
        </license>
      </permissions>
      <abstract>
        <p>FUNDAMENTO: O envelhecimento e a aterosclerose est&#227;o relacionados &#224; hipertens&#227;o renovascular em indiv&#237;duos idosos. Independentemente das comorbidades, a estenose de art&#233;ria renal &#233;, por si s&#243;, importante causa de morbidade e mortalidade cardiovascular. OBJETIVO: Definir a sensibilidade, a especificidade, o valor preditivo positivo e o valor preditivo negativo dos exames n&#227;o invasivos utilizados no diagn&#243;stico de estenose da art&#233;ria renal. M&#201;TODOS: Um grupo de 61 pacientes recrutados permitiram a an&#225;lise de 122 art&#233;rias e a defini&#231;&#227;o de sensibilidade, especificidade e da contribui&#231;&#227;o relativa de cada exame realizado (Doppler, cintilografia e angiotomografia, comparados a arteriografia renal). RESULTADOS: A m&#233;dia das idades foi de 65,43 (desvio padr&#227;o: 8,7) anos. Das vari&#225;veis relacionadas &#224; popula&#231;&#227;o do estudo e comparadas &#224; arteriografia, duas estiveram correlacionadas &#224; estenose da art&#233;ria renal, &#224; disfun&#231;&#227;o renal e aos triglicer&#237;deos. A mediana do ritmo de filtra&#231;&#227;o glomerular foi de 52,8 mL/min/m&#178;. O Doppler identificou sensibilidade de 82,90%, especificidade de 70%, valor preditivo positivo de 85% e valor preditivo negativo de 66,70%. Para a tomografia, encontraram-se sensibilidade de 66,70%, especificidade de 80%, valor preditivo positivo de 87,50% e valor preditivo negativo de 55,20%. Esses achados permitiram identificar os exames que melhor detectavam a estenose. CONCLUS&#195;O: A tomografia e o Doppler mostraram qualidade e grande possibilidade no diagn&#243;stico de estenose da art&#233;ria renal, com vantagem para o segundo, pois n&#227;o h&#225; necessidade do uso de meio de contraste na avalia&#231;&#227;o de uma doen&#231;a que, frequentemente, ocorre em diab&#233;ticos e associa-se &#224; disfun&#231;&#227;o renal e &#224; disfun&#231;&#227;o ventricular esquerda grave.</p>
      </abstract>
      <kwd-group xml:lang="pt" kwd-group-type="author-generated">
        <kwd>Estenose da Art&#233;ria Renal</kwd>
        <kwd>Ecocardiografia Doppler</kwd>
        <kwd>Estenose da Art&#233;ria Renal</kwd>
        <kwd>Imagem por Resson&#226;ncia Magn&#233;tica</kwd>
        <kwd>Hipertens&#227;o Renovascular</kwd>
      </kwd-group>
      <pub-date publication-format="electronic" date-type="pub">
        <day>24</day>
        <month>09</month>
        <year>2013</year>
      </pub-date>
    </article-meta>
  </front>
  <body>
    <p>
      <bold>Avalia&#231;&#227;o da sensibilidade e especificidade dos exames n&#227;o invasivos no diagn&#243;stico da estenose de art&#233;ria renal</bold>
    </p>
    <p>
      <bold>Flavio Antonio de Oliveira Borelli; Ibraim M. F. Pinto; Celso Amodeo; Paola E. P. Smanio; Antonio M. Kambara; Ana Claudia G. Petisco; Samuel M. Moreira; Ricardo Calil Paiva; Hugo Belotti Lopes; Amanda G. M. R. Sousa</bold>
    </p>
    <p>Instituto Dante Pazzanese de Cardiologia, S&#227;o Paulo, SP - Brasil</p>
    <p>
      <xref ref-type="corresp" rid="enda">Correspond&#234;ncia</xref>
    </p>
    <p>
      <bold>RESUMO</bold>
    </p>
    <p><bold>FUNDAMENTO:</bold> O envelhecimento e a aterosclerose est&#227;o relacionados &#224; hipertens&#227;o renovascular em indiv&#237;duos idosos. Independentemente das comorbidades, a estenose de art&#233;ria renal &#233;, por si s&#243;, importante causa de morbidade e mortalidade cardiovascular. </p>
    <p><bold>OBJETIVO:</bold> Definir a sensibilidade, a especificidade, o valor preditivo positivo e o valor preditivo negativo dos exames n&#227;o invasivos utilizados no diagn&#243;stico de estenose da art&#233;ria renal. </p>
    <p><bold>M&#201;TODOS:</bold> Um grupo de 61 pacientes recrutados permitiram a an&#225;lise de 122 art&#233;rias e a defini&#231;&#227;o de sensibilidade, especificidade e da contribui&#231;&#227;o relativa de cada exame realizado (Doppler, cintilografia e angiotomografia, comparados a arteriografia renal). </p>
    <p><bold>RESULTADOS:</bold> A m&#233;dia das idades foi de 65,43 (desvio padr&#227;o: 8,7) anos. Das vari&#225;veis relacionadas &#224; popula&#231;&#227;o do estudo e comparadas &#224; arteriografia, duas estiveram correlacionadas &#224; estenose da art&#233;ria renal, &#224; disfun&#231;&#227;o renal e aos triglicer&#237;deos. A mediana do ritmo de filtra&#231;&#227;o glomerular foi de 52,8 mL/min/m<sup>2</sup>. O Doppler identificou sensibilidade de 82,90%, especificidade de 70%, valor preditivo positivo de 85% e valor preditivo negativo de 66,70%. Para a tomografia, encontraram-se sensibilidade de 66,70%, especificidade de 80%, valor preditivo positivo de 87,50% e valor preditivo negativo de 55,20%. Esses achados permitiram identificar os exames que melhor detectavam a estenose. </p>
    <p><bold>CONCLUS&#195;O:</bold> A tomografia e o Doppler mostraram qualidade e grande possibilidade no diagn&#243;stico de estenose da art&#233;ria renal, com vantagem para o segundo, pois n&#227;o h&#225; necessidade do uso de meio de contraste na avalia&#231;&#227;o de uma doen&#231;a que, frequentemente, ocorre em diab&#233;ticos e associa-se &#224; disfun&#231;&#227;o renal e &#224; disfun&#231;&#227;o ventricular esquerda grave. </p>
    <p><bold>Palavras-chave:</bold> Estenose da Art&#233;ria Renal / diagn&#243;stico; Ecocardiografia Doppler; Estenose da Art&#233;ria Renal / cintilografia; Imagem por Resson&#226;ncia Magn&#233;tica; Hipertens&#227;o Renovascular.</p>
    <p>
      <bold>Introdu&#231;&#227;o</bold>
    </p>
    <p>A Hipertens&#227;o Arterial (HA) &#233; problema de sa&#250;de p&#250;blica. Sua rela&#231;&#227;o com outras doen&#231;as, como Diabetes Melito (DM), Insufici&#234;ncia Card&#237;aca (IC), Doen&#231;a Renal Cr&#244;nica (DRC) e Doen&#231;a Arterial Obstrutiva Perif&#233;rica (DAOP), modifica a morbidade e a mortalidade cardiovasculares<sup>1-3</sup>. A crescente incid&#234;ncia de aterosclerose na popula&#231;&#227;o adulta, a presen&#231;a de obstru&#231;&#227;o arterial provocando redu&#231;&#227;o do fluxo sangu&#237;neo renal e a consequente hipertens&#227;o renovascular t&#234;m despertado grande interesse na realiza&#231;&#227;o de pesquisas nessa &#225;rea. A identifica&#231;&#227;o de uma rela&#231;&#227;o de causa entre as estenoses arteriais e a HA apresenta a vantagem adicional de que procedimentos de revasculariza&#231;&#227;o possam ser decisivos no controle da press&#227;o arterial.</p>
    <p>N&#227;o h&#225;, em l&#237;ngua portuguesa, estudo que tenha avaliado, em uma mesma popula&#231;&#227;o, a sensibilidade, a especificidade e os valores preditivo positivo e negativo. Em levantamento realizado no endere&#231;o eletr&#244;nico <ext-link ext-link-type="uri" xlink:href="http://www.ncbi.nlm.nih.gov"><italic>www.ncbi.nlm.nih.gov</italic></ext-link>, foi encontrada a an&#225;lise comparativa entre os m&#233;todos diagn&#243;sticos para Estenose da Art&#233;ria Renal (EAR) em poucos estudos publicados recentemente<sup>4,5</sup>.</p>
    <p>O Doppler, a cintilografia renal e a tomografia computadorizada das art&#233;rias renais foram os exames realizados e comparados com o padr&#227;o de refer&#234;ncia, ou seja, a arteriografia digital das art&#233;rias renais. O teste da renina e a angiorresson&#226;ncia faziam parte do estudo, por&#233;m, pela baixa reprodutibilidade do primeiro em predizer a EAR e pelo fato de a angiorresson&#226;ncia apresentar resultados muito pr&#243;ximos dos resultados da tomografia, esses dois m&#233;todos diagn&#243;sticos foram exclu&#237;dos<sup>4-7</sup>.</p>
    <p>
      <bold>Objetivo</bold>
    </p>
    <p>Definir o n&#237;vel da sensibilidade, da especificidade, o valor preditivo positivo e o negativo de cada um dos exames n&#227;o invasivos.</p>
    <p>Avaliar se h&#225; rela&#231;&#227;o entre os fatores de risco para doen&#231;a ateroscler&#243;tica e a presen&#231;a de obstru&#231;&#245;es significativas identific&#225;veis &#224; angiografia invasiva das art&#233;rias renais.</p>
    <p>
      <bold>M&#233;todos</bold>
    </p>
    <p>Estudo prospectivo de coorte que envolveu 61 indiv&#237;duos recrutados entre janeiro de 2008 a agosto de 2011. Os participantes estavam devidamente matriculados e em acompanhamento em nossa institui&#231;&#227;o. O estudo foi aprovado pelo Comit&#234; de &#201;tica em Pesquisa da institui&#231;&#227;o, sob n&#250;mero 3592. </p>
    <p>Todos os candidatos foram orientados em rela&#231;&#227;o &#224; natureza do trabalho e convidados a assinar o Termo de Consentimento Livre e Esclarecido. A seguir, procedeu-se &#224; realiza&#231;&#227;o dos exames diagn&#243;sticos n&#227;o invasivos e invasivos, para definir a presen&#231;a ou a aus&#234;ncia de EAR.</p>
    <p>O fluxograma com a sequ&#234;ncia dos procedimentos realizados foi seguido igualmente para todos os envolvidos.</p>
    <p>A primeira etapa consistiu de anamnese, exame cl&#237;nico e medida da press&#227;o arterial, conforme padronizado nas VI Diretrizes Brasileiras de Hipertens&#227;o Arterial<sup>8</sup>. Em seguida, registrava-se a medica&#231;&#227;o em uso, e o paciente recebia orienta&#231;&#245;es adicionais em rela&#231;&#227;o ao correto emprego dos anti-hipertensivos. Aqueles em uso de f&#225;rmacos que pudessem interferir no eixo renina-angiotensina-aldosterona tiveram tais medica&#231;&#245;es substitu&#237;das por outra classe, sem preju&#237;zo ao controle da press&#227;o arterial, com o objetivo de mant&#234;-los com n&#237;veis iguais ou menores a 140 x 90 mmHg.</p>
    <p>Os pacientes diab&#233;ticos que usavam metformina tiveram a medica&#231;&#227;o suspensa pelo menos 48 horas antes de qualquer procedimento que utilizasse meio de contraste iodado. A medica&#231;&#227;o foi reintroduzida 72 horas ap&#243;s a utiliza&#231;&#227;o do contraste iodado, devido &#224; possibilidade de comprometimento da fun&#231;&#227;o renal<sup>9</sup>.</p>
    <p>Foram inclu&#237;dos apenas portadores de HA com suspeita cl&#237;nica de doen&#231;a renovascular, de etiologia ateroscler&#243;tica, que fizessem uso de medica&#231;&#227;o anti-hipertensiva no momento da sele&#231;&#227;o, independentemente da idade, g&#234;nero, ra&#231;a, religi&#227;o, condi&#231;&#227;o socioecon&#244;mica, doen&#231;as cardiovasculares ou outras comorbidades, desde que preenchessem os crit&#233;rios de inclus&#227;o e tamb&#233;m n&#227;o apresentassem nenhum dos crit&#233;rios de exclus&#227;o. Selecionamos apenas os casos que apresentassem pelo menos dois dos indicadores de m&#233;dia ou alta probabilidade propostos por Pickering<sup>10</sup> (<xref ref-type="table" rid="aop_5262tab01">Tabela 1</xref>). Posteriormente, todos os pacientes realizaram os exames selecionados para este estudo.</p>
    <p content-type="asset">
      <table-wrap id="aop_5262tab01">
        <graphic xlink:href="1678-4170-abc-101-05-0423-30191-gt01.jpg"/></table-wrap>
    </p>
    <p>
      <bold>Crit&#233;rios de inclus&#227;o</bold>
    </p>
    <p>Constituem os crit&#233;rios de inclus&#227;o: idade entre 18 e 80 anos; quadro cl&#237;nico compat&#237;vel com aterosclerose; portadores de HA (controlada ou n&#227;o); hipertens&#227;o est&#225;gios 2, 3 ou resistente; hipertens&#227;o de in&#237;cio anterior aos 30 anos ou posterior aos 50 anos de idade; presen&#231;a de sopros abdominais ou lombares; doen&#231;a ateromatosa evidente em art&#233;rias coron&#225;rias, car&#243;tidas ou vasos de extremidades; tabagistas; assimetria de pulsos; insufici&#234;ncia renal n&#227;o definida por outras causas; edema pulmonar agudo sem causa aparente; hipotens&#227;o arterial importante com uso de inibidores da enzima conversora da angiotensina; HA refrat&#225;ria ou maligna com insufici&#234;ncia renal progressiva; eleva&#231;&#227;o da creatinina s&#233;rica com o uso de inibidores da enzima conversora da angiotensina; assimetria de tamanho ou fun&#231;&#227;o renal; concord&#226;ncia em participar do estudo; ter assinado o termo de consentimento livre e esclarecido.</p>
    <p>
      <bold>Crit&#233;rios de exclus&#227;o</bold>
    </p>
    <p>S&#227;o os crit&#233;rios de exclus&#227;o: hist&#243;ria de rea&#231;&#227;o al&#233;rgica ao meio de contraste iodado; mulheres em idade gestacional sem prova negativa de gravidez; incapacidade ou recusa de entender o estudo e assinar o Termo de Consentimento Livre e Esclarecido; c&#225;lculo estimado da filtra&#231;&#227;o glomerular menor que 30 mL/min/m<sup>2</sup>; portadores de Insufici&#234;ncia Card&#237;aca Congestiva (ICC); portadores de di&#225;teses hemorr&#225;gicas; pacientes com disfun&#231;&#227;o ventricular esquerda (fra&#231;&#227;o de eje&#231;&#227;o &lt; 40%); infarto do mioc&#225;rdio recente (nos 6 meses que antecederam a realiza&#231;&#227;o deste estudo); s&#237;ndromes coron&#225;rias agudas, acidente vascular encef&#225;lico recente (nos 6 meses que antecederam a realiza&#231;&#227;o deste estudo).</p>
    <p>
      <bold>Exames diagn&#243;sticos</bold>
    </p>
    <p>
      <bold>An&#225;lises cl&#237;nicas</bold>
    </p>
    <p>Todos os pacientes realizaram as seguintes dosagens laboratoriais: glicemia de jejum, &#225;cido &#250;rico, s&#243;dio e pot&#225;ssio, ureia e creatinina, hemograma, Horm&#244;nio Estimulante da Tireoide (TSH), colesterol total e fra&#231;&#245;es e triglicer&#237;deos. A estimativa do <italic>clearance</italic> de creatinina, que era importante para avalia&#231;&#227;o do comprometimento da fun&#231;&#227;o renal e para decis&#245;es em outras etapas do estudo, foi realizada pela f&#243;rmula de Cockcroft Gault ajustada para a superf&#237;cie corp&#243;rea e corrigida para o g&#234;nero<sup>11</sup>. </p>
    <p>
      <bold>Exames de imagem n&#227;o invasivos</bold>
    </p>
    <p>
      <italic>Doppler de art&#233;rias renais </italic>
    </p>
    <p>O equipamento empregado era de alta resolu&#231;&#227;o, da marca Toshiba, com transdutor convexo, multifrequencial (3 a 5 MHZ). O armazenamento das imagens foi feito em VHS e incluiu medidas para detec&#231;&#227;o de estenose das art&#233;rias renais de forma direta e indireta. A origem de ambas as art&#233;rias renais foi avaliada a partir de corte transverso da aorta, ao modo B e com fluxo colorido, procurando-se visualizar a maior extens&#227;o poss&#237;vel do trajeto do vaso, a presen&#231;a de turbul&#234;ncia e anormalidades do fluxo, observando a rela&#231;&#227;o entre as curvas de velocidade sist&#243;lica e diast&#243;lica, e a realiza&#231;&#227;o do c&#225;lculo do &#205;ndice Renal-Aorta (IRA). A partir desse c&#225;lculo, tornou-se poss&#237;vel definir se as art&#233;rias eram livres de estenoses, verificar a presen&#231;a de casos com estenoses inferiores a 60% do di&#226;metro dos vasos e os portadores de obstru&#231;&#245;es de 60% ou mais da luz arterial, segundo os crit&#233;rios descritos na <xref ref-type="table" rid="tab02">Tabela 2</xref><sup>12</sup>. </p>
    <table-wrap id="tab02">
      <graphic xlink:href="1678-4170-abc-101-05-0423-30191-gt02.jpg"/></table-wrap>
    <p>O estudo das art&#233;rias renais foi complementado pela an&#225;lise indireta, feita com o paciente em dec&#250;bito lateral esquerdo e em dec&#250;bito lateral direito. A partir desses registros, realizou-se a compara&#231;&#227;o dos di&#226;metros longitudinais dos rins. Essas imagens tamb&#233;m permitiram melhor explora&#231;&#227;o do segmento distal das art&#233;rias renais e nelas se procedeu &#224; avalia&#231;&#227;o do fluxo intrarrenal ao Doppler, nas art&#233;rias segmentares ou interlobares, em tr&#234;s segmentos distintos (superior, m&#233;dio e inferior), e obten&#231;&#227;o das curvas de velocidade (sist&#243;lica e diast&#243;lica) com o objetivo de analisar o &#205;ndice de Resist&#234;ncia (IR), sabendo-se que o normal varia entre 0,56 a 0,7, e o Tempo de Acelera&#231;&#227;o do fluxo (TA) normal, quando menor que 70 ms.</p>
    <p>
      <italic>Cintilografia renal com DTPA-Tc-99m </italic>
    </p>
    <p>As avalia&#231;&#245;es cintilogr&#225;ficas foram conduzidas empregando gama-c&#226;mara do tipo Millennium VG (GE Medical Systems, Milwaukee, EUA).</p>
    <p>A utiliza&#231;&#227;o dos inibidores da angiotensina e/ou dos bloqueadores do receptor da angiotensina II foi suspensa nos 3 dias que antecediam a realiza&#231;&#227;o do exame.</p>
    <p>Para a aquisi&#231;&#227;o da fase basal do nefrograma radioisot&#243;pico, os pacientes foram posicionados em dec&#250;bito dorsal, de modo a situar a gama-c&#226;mara pr&#243;xima aos rins e em rela&#231;&#227;o direta com esses &#243;rg&#227;os. Obteve-se acesso venoso suficiente para que, em seu interior, pudesse avan&#231;ar uma agulha de calibre maior ou igual a 7 Gauge. Ap&#243;s a calibra&#231;&#227;o adequada da c&#226;mara, procedeu-se &#224; inje&#231;&#227;o em b&#243;lus do radiotra&#231;ador na dose de 150 uCi/kg, at&#233; atingir o volume m&#225;ximo de 1 mL e, a partir desse momento, iniciou-se o registro das imagens. </p>
    <p>Findada essa aquisi&#231;&#227;o inicial, passou-se &#224; obten&#231;&#227;o dos dados por meio do inibidor da enzima conversora da angiotensina II. Nessa fase, repetiu-se a administra&#231;&#227;o de 150 uCi/kg de &#193;cido Triamino Dietileno Pentac&#233;tico Marcado com Tecn&#233;cio-99 (DTPA-Tc-99m) at&#233; o volume m&#225;ximo de 1 mL e os pacientes, 60 minutos antes dessa etapa, receberam um comprimido de Captopril, na dose de 50 mg, permanecendo sob controle da press&#227;o arterial. A gama-c&#226;mara permaneceu na mesma posi&#231;&#227;o da etapa anterior, empregando-se o mesmo acesso venoso e a mesma t&#233;cnica de administra&#231;&#227;o do radiomarcador. </p>
    <p>Quando se considerava necess&#225;rio, o mapeamento era repetido ap&#243;s a inje&#231;&#227;o endovenosa de 40 mg de furosemida, 20 minutos ap&#243;s a inje&#231;&#227;o do de DTPA-Tc-99m.</p>
    <p>A interpreta&#231;&#227;o do exame compreendeu a marca&#231;&#227;o do tempo de tr&#226;nsito do radiof&#225;rmaco, da aorta abdominal at&#233; os rins, cujo valor normal &#233; de at&#233; 6 segundos. Outro par&#226;metro aferido foi o tempo de ac&#250;mulo do indicador nos rins, que reflete a taxa de filtra&#231;&#227;o glomerular, cujo normal &#233;, habitualmente, entre 3 e 5 minutos, seguida da fase de excre&#231;&#227;o que, em geral, fica ao redor de 20 a 30 minutos. </p>
    <p>
      <italic>Angiotomografia dos rins e art&#233;rias renais</italic>
    </p>
    <p>O tom&#243;grafo de m&#250;ltiplos detectores empregado neste estudo foi o Aquilion<sup>&#174;</sup> 64 (Toshiba Medical Systems, Ottawara, Jap&#227;o).</p>
    <p>O processo de obten&#231;&#227;o de imagens das art&#233;rias iniciou-se com a pun&#231;&#227;o de uma veia perif&#233;rica suficientemente calibrosa para permitir a administra&#231;&#227;o de meio de contraste iodado, na velocidade de, pelo menos, 3,5 mL/s. Assim, a aquisi&#231;&#227;o dos dados tomogr&#225;ficos foi iniciada pelo registro de um simples localizador, para identificar o posicionamento do segmento a ser estudado, e, ap&#243;s a defini&#231;&#227;o da &#225;rea de interesse espec&#237;fica a ser documentada, foram obtidas imagens acompanhadas da inje&#231;&#227;o de 1,50 mL/kg de peso de meio de contraste, na velocidade de, pelo menos, 3,50 mL/s. A programa&#231;&#227;o incluiu o uso de colima&#231;&#227;o de 1 mm, com tempo de rota&#231;&#227;o do tubo de 500 ms e velocidade de deslocamento da mesa de 1,50 mm por rota&#231;&#227;o do tubo. Durante todo o registro de imagens, solicitou-se aos pacientes que mantivessem apneia, de modo a limitar a quantidade de artefatos decorrentes do movimento respirat&#243;rio. </p>
    <p>Para facultar a representa&#231;&#227;o volum&#233;trica da anatomia dos rins e das art&#233;rias renais, o incremento entre os cortes anat&#244;micos, isto &#233;, a dist&#226;ncia de uma imagem para a seguinte foi menor do que a espessura das sec&#231;&#245;es transversais obtidas. Ap&#243;s a aquisi&#231;&#227;o, os dados foram transferidos para uma esta&#231;&#227;o de trabalho (V&#237;trea, Vital Images, Calif&#243;rnia, EUA), na qual se realizou o p&#243;s-processamento, permitindo a reconstru&#231;&#227;o da anatomia do paciente em diferentes planos. Algoritmos de mensura&#231;&#227;o semiobjetiva procedia-se &#224;s medidas dos di&#226;metros de refer&#234;ncia e do di&#226;metro m&#237;nimo da luz que, por sua vez, facultavam o diagn&#243;stico da presen&#231;a de estenoses e, em caso positivo, da estimativa da gravidade destas. </p>
    <p>
      <bold>Exames invasivos</bold>
    </p>
    <p>O padr&#227;o-ouro escolhido nesta pesquisa foi a avalia&#231;&#227;o invasiva da anatomia das art&#233;rias renais, empregando-se, para tal fim, a angiografia das art&#233;rias renais. Uma vez que a avalia&#231;&#227;o dos vasos &#233; feita de modo mais efetivo com a contrasta&#231;&#227;o das art&#233;rias alvo, utilizou-se o meio de contraste iodado. Devido a tal procedimento, quando havia disfun&#231;&#227;o renal caracterizada por <italic>clearence</italic> de creatinina entre 90 mL/min/1,73m<sup>2</sup> e 30 mL/min/1,73m<sup>2</sup>, realizou-se hidrata&#231;&#227;o endovenosa, com administra&#231;&#227;o de solu&#231;&#227;o salina antes e depois da realiza&#231;&#227;o do exame. Administraram-se 10 mL/kg de peso de solu&#231;&#227;o salina antes da obten&#231;&#227;o das imagens e 10 mL/kg de peso ap&#243;s o exame, em velocidades de inje&#231;&#227;o, que variavam conforme o estado cl&#237;nico e a fun&#231;&#227;o ventricular dos pacientes.</p>
    <p>
      <italic>Angiografia digital de art&#233;rias renais </italic>
    </p>
    <p>A angiografia das art&#233;rias renais foi realizada pela Se&#231;&#227;o de Radiologia Intervencionista, empregando equipamento para angiografia digital, <italic>flat</italic> detector para cardiovascular modelo Axiom Artis, 2005 (Simens, Alemanha). O procedimento iniciou-se com o posicionamento do paciente em dec&#250;bito dorsal em sala de hemodin&#226;mica digital e pun&#231;&#227;o da art&#233;ria femoral ap&#243;s anestesia local com xiloca&#237;na a 2% sem vasoconstritor. Em seguida, avan&#231;ou-se com um introdutor 5F valvulado no interior da art&#233;ria femoral direita e, por seu interior, introduziu-se um fio-guia 0,35, sobre o qual progredia um cateter <italic>pigtail</italic> de alto fluxo, utilizado para opacifica&#231;&#227;o da aorta abdominal. Em seguida, procedeu-se &#224; cateteriza&#231;&#227;o seletiva das art&#233;rias renais, com observa&#231;&#227;o das fases arterial, parenquimatosa e venosa. O material de contraste utilizado foi o hidrossol&#250;vel, i&#244;nico, de baixa osmolaridade. As imagens foram adquiridas com filtro de subtra&#231;&#227;o digital e armazenadas em disco compacto para posterior an&#225;lise. </p>
    <p>Ap&#243;s aquisi&#231;&#227;o das imagens, procedeu-se &#224; retirada do introdutor e manteve-se a compress&#227;o local efetiva por um per&#237;odo m&#237;nimo necess&#225;rio.</p>
    <p>Baseados em estudos pr&#233;vios, adotou-se como valor lim&#237;trofe para caracterizar estenose significativa as que reduzissem a luz arterial em pelo menos 60%, uma vez que existem dados sugerindo que essas placas sejam as que promovam gradiente sist&#243;lico m&#233;dio superior a 20 mmHg, sendo capazes, assim, de levar &#224; isquemia tecidual renal<sup>13,14</sup>.</p>
    <p>
      <bold>An&#225;lise estat&#237;stica</bold>
    </p>
    <p>Os dados foram descritos por estat&#237;sticas de frequ&#234;ncias absoluta (n) e relativa (%), quando medida qualitativa, e por estat&#237;sticas sum&#225;rias de m&#233;dia, desvio padr&#227;o (DP), mediana e percentis 25 e 75 (Per 25 e Per 75), quando medida quantitativa. </p>
    <p>O efeito dos fatores de risco e dos demais testes diagn&#243;sticos no resultado do exame de refer&#234;ncia - a arteriografia - foi avaliado. Teste do qui-quadrado de Pearson ou exato de Fisher foi aplicado para avalia&#231;&#227;o da associa&#231;&#227;o entre medidas qualitativas e o exame de refer&#234;ncia. A compara&#231;&#227;o de medidas quantitativas entre as categorias de resposta da arteriografia foi feita por teste <italic>t </italic>de Student ou Mann-Whitney.</p>
    <p>Foram apresentadas informa&#231;&#245;es relacionadas aos valores de sensibilidade e especificidade, valores preditivo positivo e negativo. A intensidade da concord&#226;ncia entre dois m&#233;todos diagn&#243;sticos com a arteriografia digital foi avaliada pelo m&#233;todo Kappa. </p>
    <p>Valores positivos dos exames diagn&#243;sticos deveriam ocorrer quando o di&#226;metro de estenose era &gt; 60%.</p>
    <p>O n&#237;vel de signific&#226;ncia dos testes foi de 5%. </p>
    <p>As an&#225;lises foram obtidas com aux&#237;lio do software <italic>Statistical Package for the Social Science</italic> (SPSS) 19.0 (SPSS Inc., Chicago IL, 2004).</p>
    <p>
      <bold>Resultados</bold>
    </p>
    <p>Entre janeiro de 2008 e agosto de 2011, foram recrutados 63 indiv&#237;duos, dos quais 61 realizaram todos os exames, com exce&#231;&#227;o de um &#250;nico caso, o de um paciente que n&#227;o realizou o nefrograma radioisot&#243;pico com DTPA. Havia 33 do g&#234;nero feminino; a m&#233;dia das idades foi 65,43 (&#177; 8,7) anos, do peso foi de 71,45 (&#177; 11,83) kg e da estatura de 1,59 (&#177; 0,97) m. Cerca de metade da popula&#231;&#227;o estudada apresentou DM e houve manifesta&#231;&#227;o cl&#237;nica de aterosclerose em diversos pacientes, por&#233;m tabagismo e DAOP estiveram presentes em um n&#250;mero n&#227;o expressivo dos participantes. A <xref ref-type="table" rid="aop_5262tab03">Tabela 3</xref> mostra os dados demogr&#225;ficos e as caracter&#237;sticas cl&#237;nicas dos pacientes pesquisados neste trabalho.</p>
    <p content-type="asset">
      <table-wrap id="aop_5262tab03">
        <graphic xlink:href="1678-4170-abc-101-05-0423-30191-gt03.jpg"/></table-wrap>
    </p>
    <p>Em mais de um ter&#231;o dos casos, houve altera&#231;&#245;es do perfil lip&#237;dico quanto a triglic&#233;rides, colesterol total e fra&#231;&#245;es. A fun&#231;&#227;o renal, avaliada pela f&#243;rmula de Cockcroft Gault ajustada, revelou disfun&#231;&#227;o renal na maior parte dos casos. </p>
    <p>Os exames n&#227;o invasivos revelaram altera&#231;&#245;es sugestivas da presen&#231;a de estenoses significativas nas art&#233;rias renais em mais de dois ter&#231;os da popula&#231;&#227;o do estudo, e esses resultados foram semelhantes &#224;queles encontrados pela arteriografia invasiva. </p>
    <p>
      <bold>Sensibilidade, especificidade, valor preditivo dos exames n&#227;o invasivos</bold>
    </p>
    <p>A semelhan&#231;a dos resultados encontrados pelos exames incruentos e pelo estudo invasivo foi avaliada comparando-se os resultados individuais de cada um dos casos deste trabalho. A an&#225;lise inicial mostrou que havia correla&#231;&#227;o significativa entre os resultados do Doppler e da tomografia com a angiografia invasiva (<xref ref-type="table" rid="aop_5262tab04">Tabela 4</xref>). Os resultados da avalia&#231;&#227;o cintilogr&#225;fica n&#227;o mostraram associa&#231;&#227;o significativa com o padr&#227;o-ouro da atual investiga&#231;&#227;o.</p>
    <p content-type="asset">
      <table-wrap id="aop_5262tab04">
        <graphic xlink:href="1678-4170-abc-101-05-0423-30191-gt04.jpg"/></table-wrap>
    </p>
    <p>Definiram-se, tamb&#233;m, os valores de sensibilidade, especificidade, valor preditivo positivo e valor preditivo negativo dos testes n&#227;o invasivos, assim como o valor de Kappa, adotando-se uma vez mais a arteriografia como exame de refer&#234;ncia. Os resultados das an&#225;lises por paciente e por vaso encontram-se nas <xref ref-type="table" rid="aop_5262tab05">Tabelas 5</xref> e <xref ref-type="table" rid="aop_5262tab06">6</xref>.</p>
    <p content-type="asset">
      <table-wrap id="aop_5262tab05">
        <graphic xlink:href="1678-4170-abc-101-05-0423-30191-gt05.jpg"/></table-wrap>
    </p>
    <p content-type="asset">
      <table-wrap id="aop_5262tab06">
        <graphic xlink:href="1678-4170-abc-101-05-0423-30191-gt06.jpg"/></table-wrap>
    </p>
    <p>
      <bold>Associa&#231;&#227;o entre fatores de risco e resultados da arteriografia renal</bold>
    </p>
    <p>Conforme proposto, foi analisada a associa&#231;&#227;o entre a presen&#231;a de estenoses acima de 60% e os diferentes fatores de risco de toda a popula&#231;&#227;o. Os resultados encontram-se expostos na <xref ref-type="table" rid="aop_5262tab07">Tabela 7</xref>. Observa-se que a presen&#231;a de n&#237;veis de triglic&#233;rides, a exist&#234;ncia de disfun&#231;&#227;o renal, os n&#237;veis elevados de creatinina e a redu&#231;&#227;o da taxa de filtra&#231;&#227;o glomerular foram preditores da exist&#234;ncia de placas obstrutivas significativas em, pelo menos, uma das art&#233;rias renais. </p>
    <p content-type="asset">
      <table-wrap id="aop_5262tab07">
        <graphic xlink:href="1678-4170-abc-101-05-0423-30191-gt07.jpg"/></table-wrap>
    </p>
    <p>A consist&#234;ncia dos resultados dos exames n&#227;o invasivos foi verificada por meio da an&#225;lise dos resultados da interpreta&#231;&#227;o interobservadores, ou seja, solicitou-se a outros examinadores experientes que graduassem o porcentual de estenose nas art&#233;rias renais entre 12 e 18 meses ap&#243;s a an&#225;lise inicial. Os resultados inclu&#237;dos na an&#225;lise, por sua vez, foram decididos por consenso entre os dois operadores, caso houvesse disc&#243;rdia nos achados.</p>
    <p>Os resultados que se encontram na <xref ref-type="table" rid="tab08">Tabela 8</xref> mostram elevado grau de concord&#226;ncia entre os exames, com exce&#231;&#227;o feita &#224; medicina nuclear, que mostrou resultados intermedi&#225;rios que, por outro lado, tamb&#233;m atingiram grau de signific&#226;ncia.</p>
    <table-wrap id="tab08">
      <graphic xlink:href="1678-4170-abc-101-05-0423-30191-gt08.jpg"/></table-wrap>
    <p>
      <bold>Discuss&#227;o</bold>
    </p>
    <p>A arteriografia permanece como exame de elei&#231;&#227;o para o diagn&#243;stico de estenoses nas art&#233;rias renais, mas ela ainda se acompanha da incid&#234;ncia de complica&#231;&#245;es, em especial nos casos de maior risco e com maior n&#250;mero de comorbidades<sup>15</sup>. </p>
    <p>Os resultados deste estudo demonstram que a associa&#231;&#227;o de exames n&#227;o invasivos pode fornecer dados importantes a respeito da presen&#231;a de estenose significativa das art&#233;rias renais. Altera&#231;&#245;es vistas no Doppler e na tomografia frequentemente se acompanham de redu&#231;&#245;es significativas da luz arterial; contudo, algumas particularidades deste estudo merecem considera&#231;&#227;o especial. </p>
    <p>A popula&#231;&#227;o inclu&#237;da neste trabalho reproduziu muitos dos aspectos ligados &#224; presen&#231;a de placa de ateroma obstrutiva nas art&#233;rias renais descritos na literatura.</p>
    <p>Habitualmente, idade acima de 60 anos e etnia branca, caracter&#237;sticas dos pacientes deste trabalho, s&#227;o os maiores preditores para doen&#231;a ateroscler&#243;tica<sup>16</sup>.</p>
    <p>Um dos fatores de risco frequentemente associados &#224; doen&#231;a renovascular de etiologia ateroscler&#243;tica &#233; o tabagismo, principalmente quando a DAOP est&#225; presente. Este estudo mostrou uma realidade diferente daquela vista na literatura, porque havia propor&#231;&#227;o n&#227;o relevante de fumantes ou de portadores de DAOP, respectivamente 13,1% e 21,3%.</p>
    <p>Em se tratando de uma popula&#231;&#227;o de alto risco cardiovascular, esperava-se maior expressividade de doen&#231;a arterial coronariana e doen&#231;a carot&#237;dea, pois, mesmo utilizando os mais diferentes m&#233;todos para identific&#225;-las, a representatividade delas foi muito baixa: 39,3% e 26,2%, respectivamente. </p>
    <p>O fato dos pacientes terem sido recrutados no Instituto Dante Pazzanese de Cardiologia, onde existem campanhas antitabaco, uso frequente de antilip&#234;micos e orienta&#231;&#245;es diet&#233;ticas adequadas, pode ter sido a raz&#227;o da menor incid&#234;ncia dessas vari&#225;veis. </p>
    <p>Uma meta-an&#225;lise, voltada &#224; preval&#234;ncia de doen&#231;a renovascular em v&#225;rios grupos de risco, encontrou DM em 20% de sua popula&#231;&#227;o<sup>17</sup>. Os dados do presente estudo apresentaram preval&#234;ncia 2,5 vezes maior (50,8%). </p>
    <p>Embora, a hiperlipemia esteja frequentemente identificada nas popula&#231;&#245;es portadoras de doen&#231;a ateroscler&#243;tica, at&#233; o momento nenhum estudo confirmou ser essa associa&#231;&#227;o preditora de EAR<sup>18</sup>. Neste estudo, n&#237;veis elevados de colesterol total e da fra&#231;&#227;o LDL do colesterol n&#227;o foram identificados e estiveram representados por n&#237;veis absolutamente compat&#237;veis com a normalidade. Esse padr&#227;o lip&#237;dico pode permitir um melhor horizonte cl&#237;nico nessa popula&#231;&#227;o, mesmo se considerado o fato de que 78,7% dos participantes apresentaram n&#237;veis de HDL-colesterol menor que o m&#237;nimo necess&#225;rio para o g&#234;nero. Acompanhando esses achados, o perfil dos triglicer&#237;deos na popula&#231;&#227;o estudada tamb&#233;m revelou valores abaixo daqueles considerados aterog&#234;nicos. Isso tamb&#233;m pode ser explicado pelo fato de todos os pacientes estarem sob um r&#237;gido controle dos n&#237;veis plasm&#225;ticos de l&#237;pides<sup>19</sup>.</p>
    <p>
      <bold>Diagn&#243;stico da EAR e os testes diagn&#243;sticos</bold>
    </p>
    <p>O Doppler, a angiotomografia e a resson&#226;ncia magn&#233;tica t&#234;m conquistado extraordin&#225;ria aceita&#231;&#227;o como exames para o diagn&#243;stico de doen&#231;as da aorta tor&#225;cica, abdominal e tamb&#233;m para os vasos infrainguinais. Por&#233;m, este &#233; um fato que n&#227;o se repete quando se estudam as art&#233;rias renais por meio de t&#233;cnicas n&#227;o invasivas.</p>
    <p>Na an&#225;lise da associa&#231;&#227;o entre os exames incruentos e a arteriografia digital, percebe-se uma n&#237;tida correla&#231;&#227;o entre o Doppler e a angiotomografia com a arteriografia digital, na an&#225;lise por paciente e por vasos, todas alcan&#231;ando um valor de p <underline>&lt;</underline> 0,05. Isso n&#227;o foi observado para a cintilografia.</p>
    <p>
      <bold>Avalia&#231;&#227;o da sensibilidade, da especificidade, do valor preditivo positivo e do valor preditivo negativo dos testes diagn&#243;sticos n&#227;o invasivos</bold>
    </p>
    <p>Foi comparado o papel de cada m&#233;todo de imagem em indiv&#237;duos suspeitos, propondo-se, ent&#227;o, a melhorar a sele&#231;&#227;o desta popula&#231;&#227;o e a identificar os exames que melhor orientassem o diagn&#243;stico.</p>
    <p>
      <bold>Doppler</bold>
    </p>
    <p>As medidas apresentadas para a avalia&#231;&#227;o da sensibilidade e da especificidade do Doppler de art&#233;rias renais na prov&#225;vel EAR evidenciou, respectivamente, 82,90% e 70%, n&#250;meros representados por um valor preditivo positivo de 85% e negativo de 66,70%. A medida Kappa de 0,523 revelou moderado n&#237;vel de concord&#226;ncia com o padr&#227;o de refer&#234;ncia, caracterizada por p &lt; 0,001. </p>
    <p>Essas medidas permitem fazer do Doppler uma op&#231;&#227;o diagn&#243;stica interessante na investiga&#231;&#227;o da doen&#231;a renovascular ateroscler&#243;tica, pois o teste foi capaz de identificar a estenose na popula&#231;&#227;o portadora de EAR, exclu&#237;-la entre os n&#227;o portadores e identific&#225;-la entre os que possuem teste positivo. Isso com razo&#225;vel seguran&#231;a e valores do atual estudo que reproduzem os apresentados na literatura.</p>
    <p>Conclui-se, ent&#227;o, que a sensibilidade, a especificidade e os valores preditivo positivo e negativo permitem fazer desse exame, importante ferramenta diagn&#243;stica na investiga&#231;&#227;o da doen&#231;a renovascular ateroscler&#243;tica, mesmo havendo in&#250;meras limita&#231;&#245;es descritas na literatura sobre a aplicabilidade do m&#233;todo<sup>20,21</sup>. </p>
    <p>
      <bold>Cintilografia renal</bold>
    </p>
    <p>Com valores baixos de sensibilidade e valor preditivo positivo (12,50% e 45,50%, respectivamente), e com uma razo&#225;vel especificidade, mas com valor preditivo negativo baixo (70% e 28,60%, respectivamente), a medicina nuclear n&#227;o mostrou, nesta popula&#231;&#227;o, o mesmo desempenho do Doppler, conclus&#227;o traduzida pelo encontro de valor de Kappa de (-) 0,128. Valores menores do que zero identificam total discord&#226;ncia entre os achados, medicina nuclear e arteriografia digital renal. </p>
    <p>Considere-se tamb&#233;m que valores de baixa expressividade tamb&#233;m est&#227;o presentes nas demais an&#225;lises realizadas, tanto para os pacientes quanto para as art&#233;rias. </p>
    <p>Esse m&#233;todo diagn&#243;stico est&#225; sustentado em curvas de chegada, ac&#250;mulo e excre&#231;&#227;o de um radiof&#225;rmaco, dependendo, assim, diretamente do grau de integridade da estrutura renal para identificar a estenose de um vaso. Portanto, estes resultados n&#227;o permitem que se considere a cintilografia das art&#233;rias renais como um exame indicado para o diagn&#243;stico de EAR em pacientes com d&#233;ficit da fun&#231;&#227;o renal. Ent&#227;o, &#233; poss&#237;vel definir que o uso da cintilografia, em popula&#231;&#245;es com disfun&#231;&#227;o renal, n&#227;o &#233; recomendado. </p>
    <p>Angiotomografia</p>
    <p>Com resultados superiores, mas muito pr&#243;ximos daqueles apresentados para o Doppler, a angiotomografia mostrou ser um exame de grande utilidade na identifica&#231;&#227;o do portador de EAR. Os valores discriminados para a sensibilidade, especificidade, preditivo positivo e negativo (respectivamente: 68,30%, 80%, 87,50% e 55,20%) identificaram este exame incruento, ferramenta diagn&#243;stica de grande utilidade. Valores da medida Kappa com moderada concord&#226;ncia (0,433) e um n&#237;vel de signific&#226;ncia de p &lt; 0,001 confirmam essa afirma&#231;&#227;o.</p>
    <p>Numerosos estudos utilizaram esse m&#233;todo diagn&#243;stico na investiga&#231;&#227;o da EAR<sup>22,23</sup>.</p>
    <p>Para a angiotomografia, as limita&#231;&#245;es ao uso do meio de contraste podem ser limita&#231;&#245;es importantes. Nas popula&#231;&#245;es mais jovens, a exposi&#231;&#227;o &#224; radia&#231;&#227;o deve ser considerada. </p>
    <p>
      <bold>An&#225;lise da associa&#231;&#227;o entre os fatores de risco e a arteriografia renal</bold>
    </p>
    <p>A an&#225;lise da rela&#231;&#227;o entre les&#245;es consideradas maiores que 60% de redu&#231;&#227;o da luz do vaso, quantificadas pela an&#225;lise visual do angiograma, foi realizada para identificar a presen&#231;a de associa&#231;&#227;o entre os fatores de risco e a arteriografia digital.</p>
    <p>Esta an&#225;lise permitiu identificar duas vari&#225;veis, a disfun&#231;&#227;o renal e o n&#237;vel de triglicer&#237;deos plasm&#225;ticos, entre os fatores de risco alocados neste estudo como capazes de associar uma rela&#231;&#227;o causal entre a placa obstrutiva na art&#233;ria renal e os fatores de risco j&#225; enunciados. </p>
    <p>Mesmo apresentando possibilidade de ser representada por qualquer uma das vari&#225;veis que identificam disfun&#231;&#227;o renal, foi o <italic>clearance</italic> de creatinina ajustado para a superf&#237;cie corp&#243;rea e corrigido para o g&#234;nero a vari&#225;vel escolhida para demonstrar a rela&#231;&#227;o existente entre a fun&#231;&#227;o renal e a presen&#231;a de estenose, pois h&#225; importante correla&#231;&#227;o entre seus valores e a morte por doen&#231;a cardiovascular. Assim, identificar a estenose de art&#233;ria renal &#233; condi&#231;&#227;o importante para minimizar a evolu&#231;&#227;o da pr&#243;pria doen&#231;a cardiovascular. </p>
    <p>Os achados deste estudo identificaram, entre os participantes, uma mediana de 52,8 (41,1; 74,4) mL/min/m<sup>2</sup>. Esses valores correspondem a n&#237;veis de filtra&#231;&#227;o glomerular compat&#237;veis com disfun&#231;&#227;o renal est&#225;gio 3, correspondendo, exatamente, aos indiv&#237;duos com maior predisposi&#231;&#227;o a eventos cardiovasculares<sup>24</sup>. </p>
    <p>Nessa popula&#231;&#227;o, 85,2% dos indiv&#237;duos participantes eram portadores de disfun&#231;&#227;o renal. Na avalia&#231;&#227;o estat&#237;stica das medidas quantificadas, esse fator de risco foi preditor da presen&#231;a de estenose &gt; 60%, em pelo menos uma das art&#233;rias renais, com p <underline>&lt;</underline> 0,002. </p>
    <p>Triglicer&#237;deos plasm&#225;ticos foram outro fator de risco que mostrou associa&#231;&#227;o com estenose de art&#233;ria renal. Aqui, por&#233;m, o que se observou foi uma rela&#231;&#227;o inversa &#224; que habitualmente se encontra. Nesta popula&#231;&#227;o, identificava-se menor chance de EAR naqueles pacientes com n&#237;veis de triglicer&#237;deos plasm&#225;ticos &gt; 150 mg/dL. Outra forma de interpretar os dados seria imaginar que n&#237;veis maiores de triglicer&#237;deos trariam algum efeito protetor no desenvolvimento de placa obstrutiva renal. Tais achados alcan&#231;aram, nesta popula&#231;&#227;o estudada, n&#237;vel de signific&#226;ncia cl&#237;nica com valor de p &lt; 0,037 e, assim, devem ser interpretados. </p>
    <p>&#201; fato, por&#233;m, que a literatura n&#227;o identifica, em popula&#231;&#245;es como esta, a possibilidade do desenvolvimento, por si, de doen&#231;a ateroscler&#243;tica. Na presen&#231;a de n&#237;veis menores de triglicer&#237;deos, outras comorbidades poderiam estar presentes com a finalidade de se justificar o aparecimento de doen&#231;a ateroscler&#243;tica. </p>
    <p>Geralmente, encontram-se concentra&#231;&#245;es plasm&#225;ticas elevadas de triglicer&#237;deos associadas &#224; presen&#231;a de fatores de risco, como obesidade, s&#237;ndrome metab&#243;lica, estados pr&#243;-tromb&#243;ticos, pr&#243;-inflamat&#243;rios e DM tipo 2, todos contribuindo para um risco de doen&#231;a cardiovascular aumentado. O NCEP ATPIII<sup>25</sup> identifica em n&#237;veis &lt; 150 mg/dL e entre esse valor e 200 mg/dL menor participa&#231;&#227;o na avalia&#231;&#227;o do risco cardiovascular isoladamente. No entanto, valores &gt; 200 mg/dL (hipertrigliceridemia) j&#225; s&#227;o vistos como um fator de risco independente para a doen&#231;a cardiovascular. </p>
    <p>Devemos lembrar que esta popula&#231;&#227;o foi formada por indiv&#237;duos sabedores de sua condi&#231;&#227;o m&#243;rbida e que j&#225; usavam f&#225;rmacos que objetivavam n&#227;o apenas o controle da press&#227;o arterial, mas tamb&#233;m de todos os fatores de risco envolvidos na presen&#231;a da doen&#231;a ateroscler&#243;tica. </p>
    <p>A partir destes achados, &#233; poss&#237;vel afirmar que a presen&#231;a da doen&#231;a ateroscler&#243;tica em outros s&#237;tios, os componentes da s&#237;ndrome metab&#243;lica e outros fatores de risco presentes na popula&#231;&#227;o, que n&#227;o a disfun&#231;&#227;o renal e os triglicer&#237;deos, n&#227;o identificaram EAR. </p>
    <p>
      <bold>Conclus&#245;es</bold>
    </p>
    <p>Os resultados deste estudo demonstraram que &#233; poss&#237;vel identificar, na maior parte das vezes, a presen&#231;a de doen&#231;a renovascular a partir da associa&#231;&#227;o de exames n&#227;o invasivos. </p>
    <p>A sensibilidade, a especificidade e o valor preditivo positivo e negativo do Doppler e da tomografia s&#227;o satisfat&#243;rios, ao contr&#225;rio do que ocorre com a cintilografia renal. A presen&#231;a de disfun&#231;&#227;o renal e os n&#237;veis reduzidos de triglic&#233;rides foram os &#250;nicos fatores de risco associados &#224; presen&#231;a de estenose, por meio da an&#225;lise visual da arteriografia.</p>
    <p>Considerando, enfim, o processo de investiga&#231;&#227;o e toda a metodologia e as an&#225;lises realizadas, o Doppler e a angiotomografia apresentam correla&#231;&#227;o satisfat&#243;ria com a an&#225;lise da luz da art&#233;ria renal vista pelo angiograma. Ao contr&#225;rio do que ocorre com a medicina nuclear. Deve-se ter em mente, por&#233;m, que estes resultados se aplicam &#224; pacientes com caracter&#237;sticas semelhantes &#224;s da popula&#231;&#227;o deste trabalho e que a Doppler ultassonografia &#233; operador dependente. A tomografia, embora sofra menos a influ&#234;ncia do m&#233;dico que conduz o exame, &#233; menos dispon&#237;vel em territ&#243;rio nacional. </p>
    <p>
      <bold>Contribui&#231;&#227;o dos autores</bold>
    </p>
    <p>Concep&#231;&#227;o e desenho da pesquisa, An&#225;lise e interpreta&#231;&#227;o dos dados e Reda&#231;&#227;o do manuscrito: Borelli FAO, Pinto IMF, Amodeo C; Obten&#231;&#227;o de dados: Borelli FAO, Paiva RC, Lopes HB; An&#225;lise estat&#237;stica e Revis&#227;o cr&#237;tica do manuscrito quanto ao conte&#250;do intelectual: Borelli FAO, Pinto IMF; Realiza&#231;&#227;o de exames de medicina nuclear: Smanio PEP; Realiza&#231;&#227;o dos Doppler de art&#233;rias renais: Petisco ACG; Realiza&#231;&#227;o de todas as arteriografias renais: Kambara AM, Moreira SM; Infraestrutura hospitalar e ambulatorial: Sousa AGMR.</p>
    <p>
      <bold>Potencial Conflito de Interesses</bold>
    </p>
    <p>Declaro n&#227;o haver conflito de interesses pertinentes.</p>
    <p>
      <bold>Fontes de Financiamento</bold>
    </p>
    <p>O presente estudo n&#227;o teve fontes de financiamento externas.</p>
    <p>
      <bold>Vincula&#231;&#227;o Acad&#234;mica</bold>
    </p>
    <p>Este artigo &#233; parte de tese de Doutorado de Flavio Antonio de Oliveira Borelli pelo Instituto Dante Pazzanese de Cardiologia.</p>
    <p>
      <fn id="enda" fn-type="corresp">
        <label>
          <bold>Correspond&#234;ncia:</bold>
        </label>
        <p> Flavio Antonio de Oliveira Borelli </p>
        <p> Alameda dos Jurupis, 410, apto. 111 </p>
        <p> Indian&#243;polis. CEP 04088-001, S&#227;o Paulo, SP - Brasil </p>
        <p> E-mail: </p>
        <p><email xlink:href="fborelli@cardiol.br">fborelli@cardiol.br</email>, </p>
        <p>
          <email xlink:href="fborelli@uol.com.br">fborelli@uol.com.br</email>
        </p>
      </fn>
    </p>
    <p>Artigo recebido em 8/11/12; revisado em 30/11/12; aceito em 14/3/13.</p>
  </body>
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  <sub-article article-type="translation" id="TRen" xml:lang="en">
    <front-stub>
      <article-categories>
        <subj-group subj-group-type="heading">
          <subject>Original Articles</subject>
        </subj-group>
      </article-categories>
      <title-group>
        <article-title xml:lang="en">Analysis of the sensitivity and specificity of noninvasive imaging tests for the diagnosis of renal artery stenosis</article-title>
      </title-group>
      <abstract xml:lang="en">
        <p>BACKGROUND: Aging and atherosclerosis are related to renovascular hypertension in elderly individuals. Regardless of comorbidities, renal artery stenosis is itself an important cause of cardiovascular morbidity and mortality. OBJECTIVE: To define the sensitivity, specificity, positive predictive value, and negative predictive value of noninvasive imaging tests used in the diagnosis of renal artery stenosis. METHODS: In a group of 61 patients recruited, 122 arteries were analized, thus permitting the definition of sensitivity, specificity, and the relative contribution of each imaging study performed (Doppler, scintigraphy and computed tomographic angiography in comparison to renal arteriography). RESULTS: The mean age was 65.43 years (standard deviation: 8.7). Of the variables related to the study population that were compared to arteriography, two correlated with renal artery stenosis, renal dysfunction and triglycerides. The median glomerular filtration rate was 52.8 mL/min/m&#178;. Doppler showed sensitivity of 82.90%, specificity of 70%, a positive predictive value of 85% and negative predictive value of 66.70%. For tomography, sensitivity was 66.70%, specificity 80%, positive predictive value 87.50% and negative predictive value 55.20%. With these findings, we could identify the imaging tests that best detected stenosis. CONCLUSION: Tomography and Doppler showed good quality and efficacy in the diagnosis of renal artery stenosis, with Doppler having the advantage of not requiring the use of contrast medium for the assessment of a disease that is common in diabetics and is associated with renal dysfunction and severe left ventricular dysfunction.</p>
      </abstract>
      <kwd-group xml:lang="en">
        <kwd>Renal Artery Obstruction</kwd>
        <kwd>Doppler, Echocardiography</kwd>
        <kwd>Renal Artery Obstruction</kwd>
        <kwd>Magnetic Resonance Imaging</kwd>
        <kwd>Hypertension, Renovascular</kwd>
      </kwd-group>
    </front-stub>
    <body>
      <p>
        <fn id="end-body2">
          <label>
            <bold>Analysis of the sensitivity and specificity of noninvasive imaging tests for the diagnosis of renal artery stenosis</bold>
          </label>
          <p>
            <bold>Flavio Antonio de Oliveira Borelli; Ibraim M. F. Pinto; Celso Amodeo; Paola E. P. Smanio; Antonio M. Kambara; Ana Claudia G. Petisco; Samuel M. Moreira; Ricardo Calil Paiva; Hugo Belotti Lopes; Amanda G. M. R. Sousa</bold>
          </p>
        </fn>
      </p>
      <p>Instituto Dante Pazzanese de Cardiologia, S&#227;o Paulo, SP - Brazil</p>
      <p>Mailing Address</p>
      <p>
        <bold>ABSTRACT</bold>
      </p>
      <p><bold>BACKGROUND:</bold> Aging and atherosclerosis are related to renovascular hypertension in elderly individuals. Regardless of comorbidities, renal artery stenosis is itself an important cause of cardiovascular morbidity and mortality.</p>
      <p><bold>OBJECTIVE:</bold> To define the sensitivity, specificity, positive predictive value, and negative predictive value of noninvasive imaging tests used in the diagnosis of renal artery stenosis.</p>
      <p><bold>METHODS:</bold> In a group of 61 patients recruited, 122 arteries were analized, thus permitting the definition of sensitivity, specificity, and the relative contribution of each imaging study performed (Doppler, scintigraphy and computed tomographic angiography in comparison to renal arteriography).</p>
      <p><bold>RESULTS:</bold> The mean age was 65.43 years (standard deviation: 8.7). Of the variables related to the study population that were compared to arteriography, two correlated with renal artery stenosis, renal dysfunction and triglycerides. The median glomerular filtration rate was 52.8 mL/min/m<sup>2</sup>. Doppler showed sensitivity of 82.90%, specificity of 70%, a positive predictive value of 85% and negative predictive value of 66.70%. For tomography, sensitivity was 66.70%, specificity 80%, positive predictive value 87.50% and negative predictive value 55.20%. With these findings, we could identify the imaging tests that best detected stenosis.</p>
      <p><bold>CONCLUSION:</bold> Tomography and Doppler showed good quality and efficacy in the diagnosis of renal artery stenosis, with Doppler having the advantage of not requiring the use of contrast medium for the assessment of a disease that is common in diabetics and is associated with renal dysfunction and severe left ventricular dysfunction. (Arq Bras Cardiol. 2013; [online].ahead print, PP.0-0)</p>
      <p><bold>Keywords:</bold> Renal Artery Obstruction / diagnosis; Doppler, Echocardiography; Renal Artery Obstruction / radionuclide imaging; Magnetic Resonance Imaging; Hypertension, Renovascular.</p>
      <p>
        <bold>Introduction</bold>
      </p>
      <p>Arterial Hypertension (AH) is a public health problem. Its relation to other diseases such as diabetes mellitus (DM), heart failure (HF), chronic kidney disease (CKD), and peripheral obstructive arterial disease (POAD) modifies the cardiovascular morbidity and mortality<sup>1-3</sup>. The growing incidence of atherosclerosis in the adult population, the presence of arterial obstruction leading to reduced renal blood flow and subsequent renovascular hypertension have aroused great interest for studies to be conducted in this field. The identification of a causal relation between arterial stenoses and AH has the additional advantage that revascularization procedures may be decisive for blood pressure control.</p>
      <p>No study on the assessment of the sensitivity, specificity, and positive and negative predictive values of imaging tests for the diagnosis of renal artery stenosis in the same population is available in the Portuguese language. In a search conducted at the electronic address <ext-link ext-link-type="uri" xlink:href="http://www.ncbi.nlm.nih.gov">www.ncbi.nlm.nih.gov</ext-link>, the comparative analysis between diagnostic methods for renal artery stenosis (RAS) was found in few studies published recently<sup>4,5</sup>.</p>
      <p>Doppler, renal scintigraphy and computed tomography of the renal arteries were the imaging tests performed and compared with the reference standard, i.e, digital renal arteriography. The renin test and magnetic resonance angiography were also part of the study. However, due to the poor reproducibility of the renin test to predict RAS and because magnetic resonance angiography results were very similar to those of tomography, these two diagnostic methods were excluded<sup>4-7</sup>.</p>
      <p>
        <bold>Objective</bold>
      </p>
      <p>To define the sensitivity, specificity, positive and negative predictive values of each of the noninvasive imaging tests.</p>
      <p>To evaluate if there is a relation between risk factors for atherosclerotic disease and the presence of significant obstructions detected on invasive angiography of the renal arteries.</p>
      <p>
        <bold>Methods</bold>
      </p>
      <p>Prospective cohort study including 61 patients recruited between January 2008 and August 2011. Participants were duly registered and being followed up in our institution. The study was approved by the Institutional Research Ethics Committee, under number 3592.</p>
      <p>All volunteers were informed about the nature of the study and gave written informed consent. Then, invasive and noninvasive diagnostic tests were performed to determine the presence or absence or RAS.</p>
      <p>The flowchart containing the sequence of procedures performed was equally followed for all participants.</p>
      <p>The first stage encompassed history taking, clinical examination and blood pressure measurement, according to the standardization of the VI Brazilian Guidelines on Arterial Hypertension<sup>8</sup>. Then, the medication used was recorded, and the patient received additional advice on how to correctly use the antihypertensive drugs. Patients using drugs that could interfere with the renin-angiotensin-aldosterone axis had these medications replaced by another class, without affecting blood pressure control, with the objective of maintaining their blood pressure levels equal to or lower than 140 x 90 mmHg.</p>
      <p>Diabetic patients on metformin had the medication discontinued for at least 48 hours prior to any procedure using iodinated contrast medium. The medication was resumed 72 hours after the use of the iodinated contrast medium, due to the possibility of renal function impairment<sup>9</sup>.</p>
      <p>Only patients with AH and clinically suspected renovascular disease of atherosclerotic etiology who used antihypertensive medication at the moment of patient selection were included, regardless of age, gender, race, religion, socioeconomic condition, cardiovascular diseases or other comorbidities, provided that they met the inclusion criteria but not the exclusion criteria. We selected only cases presenting with at least two indicators of a medium or high probability as proposed by Pickering<sup>10</sup> (<xref ref-type="table" rid="en_aop5262tab01-body2">Table 1</xref>). Later, all patients underwent the tests selected for the present study.</p>
      <p content-type="asset">
        <table-wrap id="en_aop5262tab01-body2">
          <graphic xlink:href="1678-4170-abc-101-05-0423-30191-gt01-en.jpg"/></table-wrap>
      </p>
      <p>
        <bold>Inclusion criteria</bold>
      </p>
      <p>The inclusion criteria were: age between 18 and 80 years; clinical picture consistent with atherosclerosis; patients with AH (whether controlled or not); stages 2, 3 or resistant hypertension; onset of hypertension before 30 years of age or after 50 years of age; presence of abdominal or lumbar murmurs; evident atheromatous disease in coronary arteries, carotid arteries or peripheral vessels; smokers; pulse asymmetry; renal failure not related to other causes; acute pulmonary edema with no apparent cause; significant arterial hypotension during treatment with angiotensin converting enzyme inhibitors; refractory or malignant AH with progressive renal failure; elevation of serum creatinine with the use of angiotensin enzyme inhibitors; asymmetry of renal size or function; agreement to participate in the study; giving written informed consent.</p>
      <p>
        <bold>Exclusion criteria</bold>
      </p>
      <p>The exclusion criteria were: history of allergic reaction to iodinated contrast medium; women of childbearing age without a negative pregnancy test; inability or refusal to understand the study and give written informed consent; estimated calculation of glomerular filtration lower than 30 mL/min/m<sup>2</sup>; patients with congestive heart failure (CHF); patients with coagulation disorders; patients with left ventricular dysfunction (ejection fraction &lt; 40%); recent myocardial infarction (within the 6 months prior to the beginning of the study); acute coronary syndromes, recent stroke (within the 6 months prior to the beginning of the study).</p>
      <p>
        <bold>Diagnostic tests</bold>
      </p>
      <p>
        <bold>Laboratory tests</bold>
      </p>
      <p>All patients were tested for the following laboratory tests: fasting blood glucose, uric acid, sodium and potassium, BUN and creatinine, complete blood count, thyroid stimulating hormone (TSH), and lipid profile. Creatinine clearance, which was important for the assessment of renal function impairment and for decision making in other stages of the study, was estimated using the Cockcroft Gault formula adjusted for body surface and corrected for gender<sup>11</sup>.</p>
      <p>
        <bold>Noninvasive imaging tests</bold>
      </p>
      <p>
        <italic>Renal artery Doppler</italic>
      </p>
      <p>A Toshiba high-resolution device with a convex multi-frequency transducer (3 to 5 MHZ) was used. Images were stored in VHS and included measurements for the detection of renal artery stenosis both direct and indirectly. The origin of both renal arteries was assessed from a cross-sectional view of the aorta, in B mode and with color flow, seeking to visualize the longest possible extent of the vessel, the presence of turbulence and flow abnormalities, observing the relationship between the systolic and diastolic velocity curves, and the calculation of the renal-aortic ratio (RAR). From this calculation, we were able to define whether the arteries were free from stenosis, and to verify the presence of cases with stenoses affecting more or less than 60% of the vessel diameter, according to criteria described in <xref ref-type="table" rid="tab2-body2">Table 2</xref><sup>12</sup>.</p>
      <table-wrap id="tab2-body2">
        <graphic xlink:href="1678-4170-abc-101-05-0423-30191-gt02-en.jpg"/></table-wrap>
      <p>The imaging study of the renal arteries was complemented by the indirect analysis carried out with the patient in the left lateral position and right lateral position. From these recordings, the longitudinal diameter of the kidneys was compared. These images also permitted a better exploration of the distal portion of the renal arteries in which the intrarenal blood flow was evaluated using Doppler in the segmental or interlobar arteries, in three different segments (upper, mid- and lower); and the acquisition of velocity curves (systolic and diastolic) with the objective of analyzing the resistance index (RI), considering that normal values range from 0.56 and 0.7, and normal values for the flow acceleration time (AT) when shorter than 70 ms.</p>
      <p>
        <italic>Tc-99m DTPA renal scintigraphy </italic>
      </p>
      <p>Scintigraphic assessments were made using a Millennium VG gamma camera (GE Medical Systems, Milwaukee, USA).</p>
      <p>Angiotensin inhibitors and/or angiotensin II-receptor blockers were discontinued for three days prior to the test.</p>
      <p>For the baseline acquisition of the radioisotope renogram, the patients were placed in the supine position, so as to place the gamma-camera next to the kidneys and in direct relation to these organs. An intravenous access large enough to support a 7-Gauge or larger needle was established. After proper camera calibration, the radiotracer at a dose of 150 uCi/kg was injected in bolus until a maximum volume of 1 mL was reached. From this moment on, image recording was started.</p>
      <p>After this initial acquisition, data started to be obtained using an angiotensin II converting enzyme inhibitor. In this phase, the administration of technetium-99-labeled diethylenetriaminepentaacetic acid 150 uCi/kg was repeated up to the maximum volume of 1 mL. Sixty minutes prior to this phase, the patients received a Captopril pill at a dose of 50 mg and had their blood pressure monitored. The gamma-camera remained in the same position as in the previous phase, and the same intravenous access and technique for radiotracer administration were used.</p>
      <p>When necessary, mapping was repeated after intravenous injection of furosemide 40 mg, 20 minutes after the Tc-99m DTPA injection.</p>
      <p>Interpretation of the imaging test included the recording of the radiotracer transit time from the abdominal aorta to the kidneys, considering a normal value of up to 6 seconds. Another parameter analyzed was the tracer accumulation time in the kidneys, which reflects the glomerular filtration rate, whose normal value is usually between 3 and 5 minutes, followed by the excretion phase which in general lasts 20 to 30 minutes.</p>
      <p>
        <italic>Computed tomographic angiography of the kidneys and renal arteries</italic>
      </p>
      <p>The Aquilion<sup>&#174;</sup> 64 multiple-detector tomographer (Toshiba Medical Systems, Ottawara, Japan) was used in this study.</p>
      <p>Image acquisition of the arteries started by puncture of a peripheral vein large enough to permit the administration of the iodinated contrast medium at a rate of at least 3 mL/s. Thus, the acquisition of tomographic data was started by the record of a single localizer to identify the positioning of the segment to be studied. After the specific area of interest to be documented was defined, images were obtained using the injection of the contrast medium at a dose of 1.50 mL/kg of body weight at a rate of at least 3.50 mL/s. The programming included the use of 1-mm collimation, with a tube rotation time of 500 ms and table speed of 1.50 mm per tube rotation. During image recording, the patients were asked to perform a breath-hold, so as to limit the amount of artifacts resulting from the respiratory movements.</p>
      <p>In order to obtain the volumetric representation of the morphology of the kidneys and renal arteries, the increment between anatomical sections, i.e. , the distance from one image to the next was shorter than the thickness of the cross-sectional views obtained. After acquisition, data were transferred to a work station (Vitrea, Vital Images, California, USA), in which the post-processing was carried out, thus permitting the reconstruction of the patient's anatomy in different planes. Semi-objective measurement algorithms were used to measure the reference diameters and minimum lumen diameter which, in turn, could allow the diagnosis of the presence of stenoses and, in positive cases, the estimate of their severity.</p>
      <p>
        <bold>Invasive imaging tests</bold>
      </p>
      <p>The gold-standard chosen in this study was the invasive assessment of the anatomy of the renal arteries using angiography. Since the vessels are more effectively assessed by contrasting the target arteries, an iodinated contrast medium was used. Because of this procedure, saline solution was administered before and after the test when renal dysfunction, as characterized by a creatinine clearance between 90 mL/min/1.73m<sup>2</sup> and 30 mL/min/1.73m<sup>2</sup>, was present. Saline solution was administered at a dose of 10 mL/kg of body weight before and after image acquisition, at a rate that varied according to the patients' clinical status and ventricular function.</p>
      <p>
        <italic>Digital renal arteriography </italic>
      </p>
      <p>Renal arteriography was performed by the Section of Interventionist Radiology, using an Axiom Artis 2005 digital angiography equipment (Siemens, Germany), with flat detector for cardiovascular diagnosis. The procedure started by positioning the patient in the supine position in the digital hemodynamic laboratory; puncture of the femoral artery after local anesthesia with 2% lidocaine without vasoconstrictor was then performed. Next, a 5F valved introducer was advanced inside the right femoral artery; within which a 0.35 guide wire was introduced; a high-flow pigtail catheter was then advanced over the guide wire. It was used to opacify the abdominal aorta. Then, the renal arteries were selectively catheterized and the arterial, parenchymatous and venous phases were observed. The contrast material used was a water-soluble, ionic, low-osmolarity medium. Images were acquired using a digital subtraction filter and stored in a compact disc for further analysis.</p>
      <p>After image acquisition, the introducer was removed and effective local compression was kept for a minimum period required.</p>
      <p>Based on previous studies, the criterion used for the definition of a significant stenosis was an arterial lumen reduction by at least 60%, since there are data suggesting that these plaques are those which promote an average systolic gradient higher than 20 mmHg, thus being able to lead to renal tissue ischemia<sup>13,14</sup>.</p>
      <p>
        <bold>Statistical analysis</bold>
      </p>
      <p>Data were described as absolute (n) and relative (%) frequencies for qualitative measures. Mean summary statistics, standard deviation (SD), median and 25th and 75th percentiles (Per 25 and Per 75) were used for quantitative measures.</p>
      <p>The effect of the risk factors and other diagnostic tests on the results of the reference test (arteriography) was analyzed. The Pearson chi square test or Fisher's exact test was used to analyze the association between qualitative measures and the reference test. Comparison of quantitative measures between the response categories of arteriography was made using the Student's or Mann-Whitney t test.</p>
      <p>Information regarding sensitivity and specificity, positive and negative predictive values are presented.</p>
      <p>The agreement level between two diagnostic methods and digital arteriography was analyzed using the Kappa method.</p>
      <p>Positive values of the diagnostic tests should occur when the stenosis diameter was &gt; 60%.</p>
      <p>The significance level of the tests was set at 5%.</p>
      <p>The analyses were carried out using the Statistical Package for the Social Sciences (SPSS) 19.0 (SPSS Inc. , Chicago IL, 2004) software program.</p>
      <p>
        <bold>Results</bold>
      </p>
      <p>Between January 2008 and August 2011, 63 individuals were recruited. Of these, 61 underwent all tests, except for one patient who did not undergo DTPA radioisotope renogram. Thirty three patients were women; the mean age was 65.43 (&#177; 8.7) years, the mean weight was 71.45 (&#177; 11.83) kg and the mean height was 1.59 (&#177; 0.97) m. Approximately half of the study population had DM and several patients had clinical manifestations of atherosclerosis; however, the number of participants with smoking habit and POAD was not significant. Patient demographics and their clinical characteristics are shown in <xref ref-type="table" rid="en_aop5262tab03-body2">Table 3</xref>.</p>
      <p content-type="asset">
        <table-wrap id="en_aop5262tab03-body2">
          <graphic xlink:href="1678-4170-abc-101-05-0423-30191-gt03-en.jpg"/></table-wrap>
      </p>
      <p>Lipid profile abnormalities were found in more than one third of cases. Renal function, as assessed using the adjusted Cockcroft Gault formula, showed renal dysfunction in most of the cases.</p>
      <p>The noninvasive imaging tests revealed abnormalities suggestive of the presence of significant stenoses in renal arteries in more than two thirds of the study population. These results were similar to those found in invasive arteriography.</p>
      <p>
        <bold>Sensitivity, specificity, and predictive value of the noninvasive imaging tests</bold>
      </p>
      <p>The relation between the results obtained with invasive and noninvasive imaging tests was analyzed by comparing the individual results of each study patient. The initial analysis showed a significant correlation of the results of Doppler and tomography with invasive angiography (<xref ref-type="table" rid="en_aop5262tab04-body2">Table 4</xref>). The results of the scintigraphic study were not significantly associated with those of angiography.</p>
      <p content-type="asset">
        <table-wrap id="en_aop5262tab04-body2">
          <graphic xlink:href="1678-4170-abc-101-05-0423-30191-gt04-en.jpg"/></table-wrap>
      </p>
      <p>Sensitivity, specificity, positive and negative predictive values of the noninvasive imaging tests, as well as the Kappa value were also defined. Again, arteriography was used as the reference test. Results of the analyses per patient and per vessel are shown in <xref ref-type="table" rid="en_aop5262tab05-body2">Tables 5</xref> and <xref ref-type="table" rid="en_aop5262tab06-body2">6</xref>.</p>
      <p content-type="asset">
        <table-wrap id="en_aop5262tab05-body2">
          <graphic xlink:href="1678-4170-abc-101-05-0423-30191-gt05-en.jpg"/></table-wrap>
      </p>
      <p content-type="asset">
        <table-wrap id="en_aop5262tab06-body2">
          <graphic xlink:href="1678-4170-abc-101-05-0423-30191-gt06-en.jpg"/></table-wrap>
      </p>
      <p>
        <bold>Association between risk factors and renal arteriography findings</bold>
      </p>
      <p>As proposed, the association between the presence of stenoses above 60% and the different risk factors of the whole population was analyzed. Results are shown in <xref ref-type="table" rid="en_aop5262tab07-body2">Table 7</xref>. The presence of abnormal triglyceride levels, renal dysfunction, high creatinine levels, and decreased glomerular filtration rate were predictive of the existence of significant obstructive plaques in at least one of the renal arteries.</p>
      <p content-type="asset">
        <table-wrap id="en_aop5262tab07-body2">
          <graphic xlink:href="1678-4170-abc-101-05-0423-30191-gt07-en.jpg"/></table-wrap>
      </p>
      <p>Consistency of noninvasive imaging test results was verified by analyzing the results of the interobserver interpretation, i.e. , other experienced examiners were asked to quantify the percentage of stenosis in the renal arteries 12 to 18 months after the initial analysis. The results included in the analysis, in turn, were decided by consensus between the two operators, in case of disagreement regarding the findings.</p>
      <p>The results presented in <xref ref-type="table" rid="tab8-body2">Table 8</xref> show a high level of agreement between tests, except for scintigraphy, which showed intermediate results, albeit significant.</p>
      <table-wrap id="tab8-body2">
        <graphic xlink:href="1678-4170-abc-101-05-0423-30191-gt08-en.jpg"/></table-wrap>
      <p>
        <bold>Discussion</bold>
      </p>
      <p>Arteriography remains as the gold-standard test for the diagnosis of renal artery stenoses; however, it is still related to the occurrence of complications, especially in cases of higher risk and greater number of comorbidities<sup>15</sup>.</p>
      <p>The findings of this study demonstrate that the association of noninvasive imaging tests may provide important information on the presence of significant renal artery stenosis. Abnormalities found in Doppler and tomography are frequently accompanied by significant reductions in the arterial lumen; however, some peculiarities of this study deserve special consideration.</p>
      <p>The study population reproduced many of the aspects associated with the presence of obstructive atheromatous plaques in the renal arteries described in the literature.</p>
      <p>Age above 60 years and white ethnicity - characteristics found in our study patients, are usually the major predictors of atherosclerotic disease<sup>16</sup>.</p>
      <p>One of the risk factors commonly associated with renovascular disease of atherosclerotic origin is cigarette smoking, especially in the presence of POAD. The present study showed a situation different from that seen in the literature, because the proportion of smokers or patients with POAD was not significant, of 13.1% and 21.3%, respectively.</p>
      <p>Given that this is a population at a high cardiovascular risk, a higher incidence of coronary artery disease and carotid artery disease was expected. However, even with the use of different methods to identify these diseases, the incidence found was low, of 39.3% and 26.2%, respectively.</p>
      <p>Patients were recruited from the Dante Pazzanese Institute of Cardiology, where anti-tobacco campaigns, frequent use of lipid-lowering drugs and proper dietary guidance are in place, and this may have been the reason for the lower incidence found for those diseases.</p>
      <p>A meta-analysis on the prevalence of renovascular disease in several risk groups found DM in 20% of their study population<sup>17</sup>. The prevalence found in our study is 2.5 times higher (50.8%).</p>
      <p>Although hyperlipidemia is frequently identified in populations with atherosclerotic disease, to date no study has confirmed that this association is predictive of RAS<sup>18</sup>. In this study, high total cholesterol and LDL-cholesterol levels were not found; the levels verified were strictly within normal limits. This lipid profile may provide this population with a better clinical perspective, even considering the fact that 78.7% of participants showed HDL-cholesterol levels lower than the minimum gender-required levels. Also, the triglyceride profile in the study population also showed values lower than those considered atherogenic. This may also be explained by the fact that all patients' plasma lipid levels were under strict control<sup>19</sup>.</p>
      <p>
        <bold>Diagnosis of RAS and the diagnostic tests</bold>
      </p>
      <p>Doppler, CT angiography and magnetic resonance imaging have been exceptionally accepted as tests for the diagnosis of diseases of the thoracic and abdominal aorta, as well as for those of the infrainguinal vessels. However, this is not valid for the study of the renal arteries.</p>
      <p>The analysis of the association between noninvasive tests and digital arteriography shows a clear correlation of Doppler and CT angiography with digital arteriography, both in the analysis per patient and per vessels, all with p values <underline>&lt;</underline> 0.05. This was not observed for scintigraphy.</p>
      <p>
        <bold>Analysis of sensitivity, specificity, positive and negative predictive values of the noninvasive diagnostic tests</bold>
      </p>
      <p>The role of each imaging method used in individuals with suspected renal artery stenosis was compared. We then proposed a better population selection and the identification of the best tests to guide the diagnosis.</p>
      <p>
        <bold>Doppler</bold>
      </p>
      <p>Measurements found for the assessment of sensitivity and specificity of Doppler of the renal arteries in probable RAS showed values of 82.90% and 70%, respectively, which correspond to a positive predictive value of 85% and a negative predictive value of 66.70%. The Kappa value of 0.523 showed a moderate level of agreement with the reference standard, with p &lt; 0.001.</p>
      <p>These values make Doppler an interesting diagnostic option for the investigation of atherosclerotic renovascular disease, because the test was able to identify stenosis in a population with RAS, to rule out the disease in patients not having it, and to identify it among those with a positive test. This was achieved with reasonable safety, and the values found in the present study corroborate those reported in the literature.</p>
      <p>We may conclude that sensitivity, specificity and the positive and negative predictive values make this test an important diagnostic tool for the investigation of atherosclerotic renovascular disease, despite the many limitations regarding the applicability of the method described in the literature<sup>20,21</sup>.</p>
      <p>
        <bold>Renal scintigraphy</bold>
      </p>
      <p>With low sensitivity and positive predictive values (12.50% and 45.50%, respectively), and reasonable specificity, but a low negative predictive value (70% and 28.60%, respectively), the performance of scintigraphy in this population was not as good as that of Doppler, and this was reflected in the finding of a Kappa value of (-) 0.128. Values lower than zero identify total disagreement between the findings from scintigraphy and digital renal arteriography</p>
      <p>We should also point out that low significance values were found for the other analyses carried out, both for patients and for arteries.</p>
      <p>This diagnostic method is based on the radiotracer arrival, accumulation and clearance curves, thus directly depending on the degree of the renal structure integrity to identify stenosis of a vessel. Therefore, these results do not allow us to consider scintigraphy of the renal arteries as a test indicated for the diagnosis of RAS in patients with impaired renal function. Thus, we can conclude that scintigraphy is not recommended in populations with renal dysfunction.</p>
      <p>
        <bold> CT angiography</bold>
      </p>
      <p>With superior results, although very close to those found using Doppler, CT angiography proved to be a very useful test for the identification of individuals with RAS. The sensitivity, specificity, positive and negative predictive values found (68.30%, 80.00%, 87.50% and 55.20%, respectively) showed that this noninvasive imaging test is a very useful diagnostic tool. Kappa values showing moderate agreement (0.433) and a significance level of p &lt; 0.001 confirm this statement.</p>
      <p>Several studies have used this diagnostic method to investigate RAS<sup>22,23</sup>.</p>
      <p>For CT angiography, limitations regarding the use of a contrast medium may be important. In younger populations, radiation exposure should be considered.</p>
      <p>
        <bold>Analysis of the association between risk factors and renal arteriography</bold>
      </p>
      <p>The relationship between lesions considered greater than a 60% reduction in vessel lumen, as quantified by visual analysis of the angiogram, was analyzed in order to identify the presence of an association between risk factors and digital arteriography.</p>
      <p>This analysis permitted the identification of two variables - renal dysfunction and plasma triglyceride levels, among the risk factors allocated in this study, as being able to establish a causal relationship between an obstructive plaque in the renal artery and the risk factors previously mentioned.</p>
      <p>Even with the possibility of being represented by any of the variables that identify renal dysfunction, the body surface-adjusted creatinine clearance corrected by gender was the variable chosen to demonstrate the relationship between renal dysfunction and the presence of stenosis, because there is an important correlation between its values and cardiovascular disease mortality. Thus, identifying renal artery stenosis is an important condition to minimize the progression of the cardiovascular disease itself.</p>
      <p>
        <bold>Conclusions</bold>
      </p>
      <p>The findings of the present study identified a median creatinine clearance of 52.8 (41.1; 74.4) mL/min/m<sup>2</sup>. These values correspond to glomerular filtration rates consistent with stage-3 renal dysfunction, which precisely characterize individuals at a higher risk for cardiovascular events<sup>24</sup>.</p>
      <p>In this study, 85.2% of the participants had renal dysfunction. In the statistical analysis of the quantified measures, this risk factor was predictive of the presence of stenosis &gt; 60% in at least one of the renal arteries, with p <underline>&lt;</underline> 0.002.</p>
      <p>Plasma triglyceride levels were another risk factor that showed an association with renal artery stenosis. However, we observed an inverse relation to the one usually found. In this population, we found a lower chance of RAS in patients with plasma triglyceride levels &gt; 150 mg/dL. Another form of interpreting the results would be to imagine that higher triglyceride levels could bring some protective effective in the development of the obstructive renal plaque. In our study population, these findings reached a clinical significance level, with p &lt; 0.037, and should thus be interpreted.</p>
      <p>However, it is a fact that the literature does not identify the possibility of the development of atherosclerotic disease per se in populations like this. In the presence of lower triglyceride levels, other comorbidities could be present to justify the development of atherosclerotic disease.</p>
      <p>Increased plasma triglyceride levels are usually associated with the presence of risk factors such as obesity, metabolic syndrome, pro-thrombotic states, pro-inflammatory states and type-2 DM, all contributing for an increased risk of cardiovascular diseases. The NCEP ATPIII<sup>25</sup> identified that levels &lt; 150 mg/dL and between this value and 200 mg/dL had a smaller participation in the assessment of the cardiovascular risk alone. However, values &gt; 200 mg/dL (hypertriglyceridemia) are already considered as an independent risk factor for cardiovascular diseases.</p>
      <p>We should remember that this population comprised individuals aware of their morbid condition and who were already taking medications that aimed not only to control their blood pressure, but also all the risk factors involved in atherosclerotic diseases.</p>
      <p>From these findings, we can state that the presence of atherosclerotic disease in other sites, the metabolic syndrome components, and other risk factors that are present in the population, other than renal dysfunction and triglyceride levels, did not identify RAS.</p>
      <p>The findings of the present study demonstrated that it is possible to identify the presence of renovascular disease using an association of noninvasive imaging tests in most of the cases.</p>
      <p>Sensitivity, specificity, and the positive and negative predictive values of Doppler and tomography are satisfactory, unlike what was observed with renal scintigraphy. Renal dysfunction and low triglyceride levels were the only risk factors associated with the presence of stenosis, as detected by the visual analysis of arteriography.</p>
      <p>Finally, considering the investigation process and all the methodology and analyses carried out, Doppler and CT angiography showed a satisfactory correlation with the analysis of the renal artery lumen as seen in the angiogram, unlike in scintigraphy. However, we should bear in mind that these results apply to patients with characteristics similar to those of this study population, and that Doppler ultrasonography is operator-dependent. Although tomography is under less influence of the physician who conducts the test, it is less frequently available in Brazil.</p>
      <p>
        <bold>Author contributions</bold>
      </p>
      <p>Conception and design of the research, Analysis and interpretation of the data and Writing of the manuscript: Borelli FAO, Pinto IMF, Amodeo C; Acquisition of data: Borelli FAO, Paiva RC, Lopes HB; Statistical analysis and Critical revision of the manuscript for intellectual content: Borelli FAO, Pinto IMF; Examinations of nuclear medicine: Smanio PEP; Realization of Doppler renal arteries: Petisco ACG; Performance of all renal arteriography: Kambara AM, Moreira SM; Infrastructure inpatient and outpatient: Sousa AGMR.</p>
      <p>
        <bold>Potential Conflict of Interest</bold>
      </p>
      <p>No potential conflict of interest relevant to this article was reported.</p>
      <p>
        <bold>Sources of Funding</bold>
      </p>
      <p>There were no external funding sources for this study.</p>
      <p>
        <bold>Study Association</bold>
      </p>
      <p>This article is part of the thesis of doctoral submitted by Flavio Antonio de Oliveira Borelli, from Instituto Dante Pazzanese de Cardiologia.</p>
      <p>
        <bold>References</bold>
      </p>
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  </sub-article>
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