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    "textoCompleto" => "<span class="elsevierStyleSections"><span id="sec0005" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0065">Introduction</span><p id="par0005" class="elsevierStylePara elsevierViewall">Secondary amyloidosis &#40;AA&#41; is a serious complication associated with chronic inflammatory diseases&#44; highlighting among the most common&#58; rheumatoid arthritis &#40;RA&#41;&#44; familial Mediterranean fever and chronic infections&#46; It is characterized by the systemic deposit of fibrillar protein AA&#44; with special repercussions at the renal level&#46;<a class="elsevierStyleCrossRef" href="#bib0005"><span class="elsevierStyleSup">1</span></a> This protein derives from a plasmatic precursor produced by hepatocytes as an acute phase reactant against persistent inflammatory stimuli or tissue necrosis&#46;<a class="elsevierStyleCrossRef" href="#bib0010"><span class="elsevierStyleSup">2</span></a> Its hepatic synthesis is regulated by various proinflammatory cytokines such as TNF-&#945;&#44; IL-1 and IL-6&#44; the latter being related to the activity and severity of the disease&#46;<a class="elsevierStyleCrossRef" href="#bib0015"><span class="elsevierStyleSup">3</span></a></p><p id="par0010" class="elsevierStylePara elsevierViewall">The basis of treatment lies in suppressing inflammation&#44; thus inhibiting fibrillar protein synthesis&#46; In recent years&#44; the appearance of biological agents that specifically block cytokines has revolutionized the treatment of some chronic inflammatory diseases&#46; In this line&#44; the use of tocilizumab &#40;TCZ&#41; stands out&#44; a humanized antibody that blocks the IL-6 receptor&#44; widely used in RA and that could be particularly useful in AA amyloidosis&#46;</p><p id="par0015" class="elsevierStylePara elsevierViewall">Several case series have shown good efficacy for the treatment of this disease&#44; even allowing the regression of renal deposits already present&#46; Our objective is to analyze the efficacy and safety of TCZ in AA amyloidosis with renal involvement in our center&#46;</p></span><span id="sec0010" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0070">Material and method</span><span id="sec0015" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0075">Patient selection</span><p id="par0020" class="elsevierStylePara elsevierViewall">Retrospective monocentric study that included patients with a histological diagnosis of AA amyloidosis who received treatment with TCZ during the years 2018&#8211;2019&#46; Clinical and demographic variables were recorded&#44; including previous immunosuppressive treatment&#44; tolerance&#44; and adverse effects&#46; Clinical follow-up was carried out from the diagnosis of amyloidosis until the end of the study &#40;January 2020&#41;&#46;</p></span><span id="sec0020" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0080">Clinical evaluation</span><p id="par0025" class="elsevierStylePara elsevierViewall">We evaluated renal function using serum creatinine values &#8203;&#8203;&#40;mg&#47;dl&#41;&#44; glomerular filtration rate calculated by the CKD-EPI formula &#40;GFR&#59; ml&#47;min&#47;1&#46;73&#8239;m<span class="elsevierStyleSup">2</span>&#41; and protein&#47;creatinine ratio &#40;CPI&#59; mg&#47;g&#41; at the 3&#44; 6 and 12 months of follow-up&#46; We define renal response as a &#62;30&#37; reduction in proteinuria and&#47;or stabilization or improvement in glomerular filtration rate&#46; The activity of amyloidosis and its response to treatment have been evaluated by serum amyloid protein &#40;PSA&#59; mg&#47;l&#41; and C-reactive protein &#40;CRP&#59; mg&#47;l&#41;&#46; We consider an anti-inflammatory response to be a decrease &#62;50&#37; in SAA protein and&#47;or CRP levels&#46;</p></span></span><span id="sec0025" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0085">Results</span><span id="sec0030" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0090">Characteristics of the patients</span><p id="par0030" class="elsevierStylePara elsevierViewall">We identified 3 patients receiving treatment with TCZ after diagnosis of AA renal amyloidosis by renal biopsy&#46; The baseline clinical characteristics of the subjects are shown in <a class="elsevierStyleCrossRef" href="#tbl0005">Table 1</a>&#46; The 3 cases presented renal involvement at the diagnosis of amyloidosis&#44; with the renal function parameters being collected in <a class="elsevierStyleCrossRef" href="#tbl0010">Table 2</a>&#46; There have been no adverse events attributable to the use from TCZ&#46;</p><elsevierMultimedia ident="tbl0005"></elsevierMultimedia><elsevierMultimedia ident="tbl0010"></elsevierMultimedia></span><span id="sec0035" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0095">Case 1</span><p id="par0035" class="elsevierStylePara elsevierViewall">A 55-year-old man who presented with postcontrast acute kidney injury requiring hemodialysis &#40;HD&#41; in the context of massive pulmonary thromboembolism&#46; Corticosteroid boluses were administered without renal recovery&#44; so a renal biopsy was finally performed&#46; This biopsy showed glomeruli with minimal widening due to increased cellularity&#44; without identifying inflammatory infiltrate&#44; mesangial deposits or fibrinoid necrosis&#46; The tubules presented focal edema&#59; the interstitium&#44; discrete focal fibrosis with mild nonspecific inflammatory infiltrate&#46; A slight increase in the size of the vascular wall was observed at the expense of the deposit of eosinophilic material with birefringence&#44; compatible with amyloid&#46; The immunofluorescence study was negative&#46;</p><p id="par0040" class="elsevierStylePara elsevierViewall">His personal history included a smoking habit of 20 cigarettes a day and a combined emphysema&#47;pulmonary fibrosis syndrome&#44; diagnosed 2 months before the biopsy and considered an underlying cause of AA amyloidosis&#46;</p><p id="par0045" class="elsevierStylePara elsevierViewall">In this case&#44; the subcutaneous presentation of TCZ was chosen&#44; starting at a dose of 162&#8239;mg per week as described in the drug&#8217;s data sheet&#46; Proteinuria levels decreased by 44&#46;5&#37; at 12 months&#44; with a slight increase in GFR from 16 to 20&#8239;ml&#47;min&#59; at the inflammatory level&#44; a reduction in PSA and CRP was observed&#44; without evidence of systemic clinical manifestations at any time&#46; Given these results&#44; and until the writing of the article&#44; the same dose of TCZ was maintained &#40;11 months of treatment&#41;&#46;</p></span><span id="sec0040" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0100">Case 2</span><p id="par0050" class="elsevierStylePara elsevierViewall">A 74-year-old woman diagnosed with arterial hypertension treated with losartan and diabetes mellitus treated with linagliptin&#44; both of which were well controlled&#46; As background&#44; rheumatoid arthritis of 4 years&#8217; evolution stands out&#44; for which he had undergone treatment with etanercept and methotrexate with adequate symptomatic control&#46; The subsequent diagnosis of Binet stage A chronic lymphatic leukemia forced the suspension of etanercept&#44; maintaining methotrexate as monotherapy&#59; after this&#44; he presented several episodes of arthritis requiring corticotherapy&#46; Ten months after the diagnosis of leukemia&#44; given the progressive deterioration of renal function&#44; a renal biopsy was performed&#46; Histological findings showed a membranoproliferative pattern with increased mesangial substance in glomeruli&#44; images of basement membrane duplication and nodularity with a tendency to sclerosis&#46; There was tubular atrophy&#44; interstitial fibrosis &#40;35&#37;&#8211;45&#37;&#41;&#44; discrete nonspecific inflammatory infiltrate&#44; and intimal hyperplasia with arteriolohyalinosis and reduplication of elastic bands&#46; Amyloid material was identified in vessels and interstitium&#46; The immunofluorescence study showed C3<span class="elsevierStyleSup">&#43;&#43;</span> and IgM<span class="elsevierStyleSup">&#43;</span> deposits&#46;</p><p id="par0055" class="elsevierStylePara elsevierViewall">Being on HD&#44; intravenous TCZ was administered&#46; The dose&#44; adjusted for body weight &#40;8&#8239;mg&#47;kg&#47;every 4 weeks&#41;&#44; was maintained until renal transplantation &#40;9 months of treatment&#41;&#46; The patient remained on HD&#44; performing only urine sediments at 5 and 7 months &#40;proteins 200&#8239;mg&#47;dl&#41;&#46; Although treatment with TCZ did not achieve recovery of kidney function&#44; it allowed an adequate anti-inflammatory response with a reduction in PSA and CRP&#46; In addition&#44; during the follow-up period&#44; the patient did not present inflammatory data suggestive of activation of her rheumatological disease&#46;</p></span><span id="sec0045" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0105">Case 3</span><p id="par0060" class="elsevierStylePara elsevierViewall">A 75-year-old man with arterial hypertension treated with amlodipine and subclinical hypothyroidism&#46; He was diagnosed with AA amyloidosis after an episode of nephrotic syndrome&#44; with no underlying disease recorded&#46; Renal biopsy showed glomeruli with slight acellular mesangial enlargements at the expense of amorphous&#44; eosinophilic material with birefringence&#44; compatible with amyloid&#46; Isolated hyaline cylinders were found in tubular lumens&#46; In the interstitium and arterial walls&#44; there were interstitial acellular widenings by material similar to that previously described&#46;</p><p id="par0065" class="elsevierStylePara elsevierViewall">Treatment with TCZ was started subcutaneously at 162&#8239;mg&#47;week&#46; The GFR progressively improved until reaching 39&#8239;ml&#47;min at 6 months&#44; so it was decided to reduce the dose of TCZ to 162&#8239;mg subcutaneously fortnightly&#46; Seven months later&#44; he presented a sudden drop in GFR in the context of nephrotic syndrome&#44; and a new dose increase to 162&#8239;mg&#47;week was agreed upon&#46; Until the writing of the article&#44; he maintained stable renal function parameters &#40;13 months of treatment&#41;&#46; At the inflammatory level&#44; a decrease in PSA and CRP values &#8203;&#8203;was observed&#44; although with a slight rebound in PSA&#44; coinciding with the aforementioned deterioration in renal function&#46; He has not presented systemic clinical manifestations prior to the start of treatment with TCZ or during follow-up&#46;</p></span></span><span id="sec0050" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0110">Discussion</span><p id="par0070" class="elsevierStylePara elsevierViewall">IL-6 is a proinflammatory cytokine with an important role in the regulation of immune activity&#44; participating in most inflammatory responses&#46;<a class="elsevierStyleCrossRef" href="#bib0025"><span class="elsevierStyleSup">5</span></a> One of the mechanisms through which this cytokine acts is the stimulation of hepatic synthesis of SAA protein&#59; hence&#44; it is considered a key element in the development of amyloidosis&#46;</p><p id="par0075" class="elsevierStylePara elsevierViewall">TCZ is a humanized antibody that blocks the IL-6 receptor&#44; thus inhibiting this mechanism of action&#46; It is considered an effective specific treatment in the treatment of chronic inflammatory diseases such as RA&#44; although few data have been published on its use in AA amyloidosis&#46;</p><p id="par0080" class="elsevierStylePara elsevierViewall">We report a series of 3 cases of patients with AA renal amyloidosis treated with TCZ&#46; In patients 1 and 3&#44; a slight increase in GFR was observed after the start of TCZ&#44; although they maintained proteinuria values &#8203;&#8203;similar to those detected prior to treatment&#46; Patient 2 did not show improvement in renal function parameters&#44; although she preserved residual diuresis until the time of transplantation and maintained adequate control of RA with the use of TCZ&#46;</p><p id="par0085" class="elsevierStylePara elsevierViewall">The renal biopsy of the latter patient showed other renal lesions in addition to the amyloid deposit&#44; such as a pattern of membranoproliferative damage&#44; a poor prognostic finding in histology&#46; This finding&#44; added to the degree of chronicity&#44; could justify the lack of improvement in GFR&#46; Probably&#44; earlier initiation of TCZ would have allowed better results at the renal level&#46;</p><p id="par0090" class="elsevierStylePara elsevierViewall">We have defined renal response as a &#62;30&#37; reduction in proteinuria and&#47;or stabilization or improvement in GFR&#46;<a class="elsevierStyleCrossRef" href="#bib0020"><span class="elsevierStyleSup">4</span></a> In our series&#44; the GFR remained stable in patients 1 and 3&#44; obtaining a renal response to the effects of proteinuria in the first&#46; However&#44; proteinuria in this patient was not too high at the start of treatment&#44; so the results could be limited&#46;</p><p id="par0095" class="elsevierStylePara elsevierViewall">The variability of the baseline characteristics of the patients&#44; in terms of inflammatory disease&#44; renal stage and histological data&#44; could influence the response to treatment with TCZ&#46; It would be interesting to carry out new studies that analyze the possible prognostic factors of renal evolution&#46;</p><p id="par0100" class="elsevierStylePara elsevierViewall">We define anti-inflammatory response as a &#62;50&#37; decrease in SAA protein and&#47;or CRP levels&#46; All patients experience a rapid decrease in acute phase reactants after the start of TCZ&#44; which would translate into a reduction in the inflammatory state of these subjects&#46; In this sense&#44; we could conclude that the anti-inflammatory response to TCZ treatment in AA amyloidosis is 100&#37; in our series&#46; Lane et al&#46; demonstrated that TCZ can be effective in reducing inflammation by reducing SAA protein levels in patients with chronic inflammatory diseases and amyloidosis&#46;<a class="elsevierStyleCrossRef" href="#bib0025"><span class="elsevierStyleSup">5</span></a> Uda and Saiki suggest that the use of this drug not only lowers CRP and SAA levels&#44; but also delays the start of HD in patients with amyloidosis and advanced chronic kidney disease&#46;<a class="elsevierStyleCrossRef" href="#bib0030"><span class="elsevierStyleSup">6</span></a></p><p id="par0105" class="elsevierStylePara elsevierViewall">Both the efficacy and safety of TCZ in patients with kidney disease have been reported in different publications&#44; including even HD patients&#46;<a class="elsevierStyleCrossRefs" href="#bib0035"><span class="elsevierStyleSup">7&#44;8</span></a> In the study by Mori et al&#46;<a class="elsevierStyleCrossRef" href="#bib0045"><span class="elsevierStyleSup">9</span></a> no differences were found in terms of safety in the group of patients with chronic kidney disease compared to those without this complication&#44; showing significant improvements in clinical activity indices in all groups&#46; In our series&#44; TCZ has been administered with good tolerance and no adverse effects have been recorded during follow-up&#46;</p><p id="par0110" class="elsevierStylePara elsevierViewall">Therefore&#44; the use of TCZ in patients with AA renal amyloidosis seems to be effective and safe&#44; even in situations of progressive kidney damage&#46; Its administration has been shown to be useful in stabilizing or improving GFR and reducing inflammatory markers&#44; so its indication seems reasonable in patients who do not respond to other treatments or even be considered as the first therapeutic option&#44; in the absence of randomized prospective studies&#46;</p><p id="par0115" class="elsevierStylePara elsevierViewall">Our study contains some limitations&#46; This is a monocentric review&#44; with a small number of subjects&#44; which makes it difficult to obtain significant results&#44; as well as their extrapolation to the population&#46; The retrospective nature of the study&#44; although practically unavoidable as it is a rare disease&#44; limits the proper recording of the initially proposed variables&#46; New&#44; prospective&#44; randomized studies with long-term clinical assessment would be necessary&#46;</p></span><span id="sec0055" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0115">Conclusions</span><p id="par0120" class="elsevierStylePara elsevierViewall">IL-6 plays an important role in the pathophysiology of AA amyloidosis&#44; so TCZ could represent a therapeutic option to consider in these patients&#46; Our results show its efficacy both at the renal level and in the control of the underlying disease&#44; especially in patients with a high inflammatory component in whom it starts early&#46; The absence of adverse effects associated with TCZ in our series&#44; as in previous studies&#44; supports the safety of this drug in patients with kidney disease&#46; TCZ should be considered within the therapeutic arsenal for the treatment of AA renal amyloidosis&#44; as it may improve the long-term prognosis of these patients&#46;</p></span><span id="sec0060" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0120">Financing</span><p id="par0125" class="elsevierStylePara elsevierViewall">This research has not received specific aid from public sector agencies&#44; the commercial sector or non-profit entities&#46;</p></span><span id="sec0065" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0125">Conflict of interests</span><p id="par0130" class="elsevierStylePara elsevierViewall">The authors declare that they have no conflict of interest&#46;</p></span></span>"
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              "titulo" => "Characteristics of the patients"
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              "titulo" => "Case 1"
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    "pdfFichero" => "main.pdf"
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    "fechaRecibido" => "2020-08-17"
    "fechaAceptado" => "2021-01-17"
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          "identificador" => "xpalclavsec1503239"
          "palabras" => array:3 [
            0 => "AA amyloidosis"
            1 => "Interleukin-6"
            2 => "Tocilizumab"
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          "clase" => "keyword"
          "titulo" => "Palabras clave"
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          "palabras" => array:3 [
            0 => "Amiloidosis AA"
            1 => "Interleucina 6"
            2 => "Tocilizumab"
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        "titulo" => "Abstract"
        "resumen" => "<span id="abst0005" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0010">Introduction</span><p id="spar0035" class="elsevierStyleSimplePara elsevierViewall">AA &#40;secondary&#41; amyloidosis is a severe complication of chronic inflammatory disorders&#46; It is characterized by the systemic deposition of an abnormal protein called amyloid&#44; affecting mainly renal function&#46; IL-6 is a cytokine with a relevant role in this disease development&#46; Interleukin-receptor antagonists&#44; like Tocilizumab &#40;TCZ&#41;&#44; have become possible treatment choice for AA amyloidosis&#46; In published reports&#44; TCZ has shown good efficacy for AA amyloidosis&#44; being associated with regression of renal amyloid deposits&#46;</p></span> <span id="abst0010" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0015">Methods</span><p id="spar0040" class="elsevierStyleSimplePara elsevierViewall">Retrospective review that included patients with histological diagnosis of AA renal amyloidosis under treatment with TCZ during the years 2018&#8211;2019 in our center&#46; We have registered clinical and demographic variables&#46; Renal function was measured by means of CKD-EPI equation to estimate the glomerular filtration rate &#40;FG&#41; and protein&#47;creatinine ratio &#40;IPC&#41; at 3&#44; 6 and 12 months&#46; We define renal response as a decrease by at least 30&#37; of proteinuria and&#47;or stabilization or improvement of FG&#46; We consider that an anti-inflammatory response is a decrease of more than 50&#37; in serum amyloid protein &#40;PSA&#41; and&#47;or C-reactive protein &#40;CRP&#41;&#46;</p></span> <span id="abst0015" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0020">Results</span><p id="spar0045" class="elsevierStyleSimplePara elsevierViewall">We collected 3 cases of patients with histologically proven AA amyloidosis treated with TCZ &#40;2 men&#59; 1 woman&#59; aged 55&#44; 74 and 75 years&#41;&#46; The follow-up was 13&#44; 14 and 75 months&#46; FG was stabilized in two patients&#46; The third patient remained on hemodialysis during follow-up&#44; although with excellent control of her underlying inflammatory disease&#46; In all three cases&#44; reduced PSA and CRP were observed&#46; There have been no adverse events&#46;</p></span> <span id="abst0020" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0025">Conclusions</span><p id="spar0050" class="elsevierStyleSimplePara elsevierViewall">The TCZ may be an effective and safe option in treatment of AA amyloidosis with renal involvement&#46; Our results position it as an interesting therapeutic option to consider in these cases&#44; although prospective studies would be necessary to evaluate the global role of TCZ in AA amyloidosis&#46;</p></span>"
        "secciones" => array:4 [
          0 => array:2 [
            "identificador" => "abst0005"
            "titulo" => "Introduction"
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          1 => array:2 [
            "identificador" => "abst0010"
            "titulo" => "Methods"
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          2 => array:2 [
            "identificador" => "abst0015"
            "titulo" => "Results"
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            "titulo" => "Conclusions"
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        "titulo" => "Resumen"
        "resumen" => "<span id="abst0025" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0035">Introducci&#243;n</span><p id="spar0055" class="elsevierStyleSimplePara elsevierViewall">La amiloidosis secundaria &#40;AA&#41; es una complicaci&#243;n grave asociada a enfermedades inflamatorias&#46; Se caracteriza por el dep&#243;sito sist&#233;mico de prote&#237;na fibrilar AA&#44; con especial repercusi&#243;n renal&#46; La participaci&#243;n de la interleucina 6 en su mecanismo patog&#233;nico ha supuesto que tocilizumab &#40;TCZ&#41; sea considerado una opci&#243;n terap&#233;utica en estos pacientes&#46; Varias series publicadas muestran su eficacia en el tratamiento de la amiloidosis AA&#44; permitiendo incluso la regresi&#243;n de dep&#243;sitos renales ya presentes&#46;</p></span> <span id="abst0030" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0040">Material y m&#233;todo</span><p id="spar0060" class="elsevierStyleSimplePara elsevierViewall">Revisi&#243;n retrospectiva que incluy&#243; pacientes con diagn&#243;stico histol&#243;gico de amiloidosis renal AA en tratamiento con TCZ durante los a&#241;os 2018&#8211;2019 en nuestro centro&#46; Registramos variables cl&#237;nicas y demogr&#225;ficas&#59; evaluamos la funci&#243;n renal mediante filtrado glomerular &#40;FG&#41; calculado por CKD-EPI e &#237;ndice prote&#237;na&#47;creatinina a los 3&#44; 6 y 12 meses de seguimiento&#46; Definimos &#171;respuesta renal&#187; como la disminuci&#243;n&#8239;&#62;&#8239;30&#37; de la proteinuria y&#47;o estabilizaci&#243;n o mejor&#237;a del FG&#46; Consideramos &#171;respuesta antiinflamatoria&#187; la disminuci&#243;n&#8239;&#62;&#8239;50&#37; de las cifras de prote&#237;na s&#233;rica amiloide &#40;PSA&#41; y&#47;o prote&#237;na C reactiva &#40;PCR&#41;&#46;</p></span> <span id="abst0035" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0045">Resultados</span><p id="spar0065" class="elsevierStyleSimplePara elsevierViewall">Presentamos una serie de 3 pacientes &#40;2 varones y una mujer&#59; 55&#44; 74 y 75 a&#241;os&#44; respectivamente&#41;&#44; con un tiempo de seguimiento de 13&#44; 14 y 75 meses&#44; respectivamente&#46; Con la terapia con TCZ&#44; el FG se estabiliz&#243; en 2 pacientes&#59; el tercero permaneci&#243; en hemodi&#225;lisis durante el seguimiento&#44; aunque con excelente control de su enfermedad inflamatoria de base&#59; a los 12 meses recibi&#243; un trasplante renal&#46; En los 3 casos se objetiv&#243; reducci&#243;n de prote&#237;na PSA y PCR&#46; No se han producido eventos adversos&#46;</p></span> <span id="abst0040" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0050">Conclusiones</span><p id="spar0070" class="elsevierStyleSimplePara elsevierViewall">El TCZ es una opci&#243;n terap&#233;utica eficaz y segura para los pacientes con amiloidosis AA y afectaci&#243;n renal&#46; Nuestros resultados lo posicionan como una opci&#243;n terap&#233;utica a considerar en estos casos&#44; aunque ser&#237;a necesario la realizaci&#243;n de estudios prospectivos en los que se eval&#250;e el papel global de TCZ en la amiloidosis AA&#46;</p></span>"
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            "titulo" => "Resultados"
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        "etiqueta" => "&#9734;"
        "nota" => "<p class="elsevierStyleNotepara" id="npar0005">Please cite this article as&#58; Almenara-Tejederas M&#44; Alonso-Garc&#237;a F&#44; Aguillera-Morales WA&#44; de la Prada-&#193;lvares F&#44; Salgueira-Lazo M&#46; La inhibici&#243;n de la interleucina-6 como posible diana terap&#233;utica en la amiloidosis AA&#46; Nefrologia&#46; 2022&#59;42&#58;28&#8211;32&#46;</p>"
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          "leyenda" => "<p id="spar0010" class="elsevierStyleSimplePara elsevierViewall">AA duration&#58; time from diagnosis of amyloidosis to initiation of TCZ&#59; ETA&#58; etanercept&#59; HD&#58; hemodialysis&#59; IS&#58; immunosuppressive treatment&#59; M&#58; woman&#59; MTX&#58; methotrexate&#59; TCZ&#58; tocilizumab&#59; V&#58; male&#46;</p>"
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                  \t\t\t\t" scope="col" style="border-bottom: 2px solid black">&nbsp;\t\t\t\t\t\t\n
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                  \t\t\t\t" scope="col" style="border-bottom: 2px solid black">Patient 1&nbsp;\t\t\t\t\t\t\n
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                  \t\t\t\t  " align="center" valign="\n
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                  \t\t\t\t">Sex&nbsp;\t\t\t\t\t\t\n
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                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
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                  \t\t\t\t">V&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
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                  \t\t\t\t  " align="left" valign="\n
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                  \t\t\t\t">M&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">V&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">Age&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
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                  \t\t\t\t  " align="left" valign="\n
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                  \t\t\t\t">55&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
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                  \t\t\t\t">74&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">75&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">Underlying disease&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">Emphysema&#47;fibrosis&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">Rheumatoid arthritis&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">Unidentified&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">Charlson index&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">4&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">8&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">5&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">AA duration&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">2 months&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">4 months&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">62 months&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">Biopsy type&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">Renal&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">Renal&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">Renal&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">Initial GF&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">HD&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">HD&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">18&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">Previous SI&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">No&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">ETA&#44; MTX&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">No&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">Concomitant IS&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">No&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">No&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">No&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">Sclerosed glomeruli&#47;total&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">0&#47;24&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">2&#47;9&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">1&#47;12&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">Renal interstitium&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">Discrete focal fibrosis&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">Moderate fibrosis &#40;IFTA 45&#37;&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">No fibrosis&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">TCZ dosage&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">162&#8239;mg&#47;week&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">400&#8239;mg&#47;month&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">162&#8239;mg&#47;week&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">Duration TCZ&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">11 months&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">9 months&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">13 months&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">Follow-up time&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">13 months&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">14 months&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">75 months&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">Adverse effects&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">No&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">No&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">No&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr></tbody></table>
                  """
              ]
              "imagenFichero" => array:1 [
                0 => "xTab2885059.png"
              ]
            ]
          ]
        ]
        "descripcion" => array:1 [
          "en" => "<p id="spar0005" class="elsevierStyleSimplePara elsevierViewall">Clinical and demographic characteristics of the patients included in the study&#46;</p>"
        ]
      ]
      1 => array:8 [
        "identificador" => "tbl0010"
        "etiqueta" => "Table 2"
        "tipo" => "MULTIMEDIATABLA"
        "mostrarFloat" => true
        "mostrarDisplay" => false
        "detalles" => array:1 [
          0 => array:3 [
            "identificador" => "at0010"
            "detalle" => "Table "
            "rol" => "short"
          ]
        ]
        "tabla" => array:2 [
          "leyenda" => "<p id="spar0020" class="elsevierStyleSimplePara elsevierViewall">Alb&#47;C&#58; albumin&#47;creatinine ratio &#40;mg&#47;g&#41;&#59; GFR&#58; glomerular filtration rate &#40;CKD-EPI&#59; ml&#47;min&#41;&#59; HD&#58; hemodialysis&#59; Prot&#47;C&#58; protein&#47;creatinine ratio &#40;mg&#47;g&#41;&#59; Tx&#58; kidney transplant&#46;</p><p id="spar0025" class="elsevierStyleSimplePara elsevierViewall">Values&#58; 0&#58; prior to TCZ&#59; 3&#58; third month after TCZ&#59; 6&#58; sixth month after TCZ&#59; 12&#58; twelfth month after TCZ&#46;</p><p id="spar0030" class="elsevierStyleSimplePara elsevierViewall">AA&#58; secondary amyloidosis&#59; RA&#58; rheumatoid arthritis&#59; TCZ&#58; tocilizumab&#59; GFR&#58; glomerular filtration calculated by CKD-EPI&#59; CPI&#58; urine protein&#47;creatinine ratio&#59; IAC&#58; urine albumin&#47;creatinine ratio&#59; PSA&#58; amyloid serum protein&#59; CRP&#58; C-reactive protein&#59; HD&#58; hemodialysis&#46;</p>"
          "tablatextoimagen" => array:1 [
            0 => array:2 [
              "tabla" => array:1 [
                0 => """
                  <table border="0" frame="\n
                  \t\t\t\t\tvoid\n
                  \t\t\t\t" class=""><thead title="thead"><tr title="table-row"><th class="td" title="\n
                  \t\t\t\t\ttable-head\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t" scope="col" style="border-bottom: 2px solid black">&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t\t\t</th><th class="td" title="\n
                  \t\t\t\t\ttable-head\n
                  \t\t\t\t  " align="center" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t" scope="col" style="border-bottom: 2px solid black">GF<span class="elsevierStyleSup">0</span>&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t\t\t</th><th class="td" title="\n
                  \t\t\t\t\ttable-head\n
                  \t\t\t\t  " align="center" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t" scope="col" style="border-bottom: 2px solid black">Prot&#47;C<span class="elsevierStyleSup">0</span>&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t\t\t</th><th class="td" title="\n
                  \t\t\t\t\ttable-head\n
                  \t\t\t\t  " align="center" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t" scope="col" style="border-bottom: 2px solid black">Alb&#47;C<span class="elsevierStyleSup">0</span>&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t\t\t</th><th class="td" title="\n
                  \t\t\t\t\ttable-head\n
                  \t\t\t\t  " align="center" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t" scope="col" style="border-bottom: 2px solid black">GF<span class="elsevierStyleSup">3</span>&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t\t\t</th><th class="td" title="\n
                  \t\t\t\t\ttable-head\n
                  \t\t\t\t  " align="center" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t" scope="col" style="border-bottom: 2px solid black">Prot&#47;C<span class="elsevierStyleSup">3</span>&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t\t\t</th><th class="td" title="\n
                  \t\t\t\t\ttable-head\n
                  \t\t\t\t  " align="center" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t" scope="col" style="border-bottom: 2px solid black">Alb&#47;C<span class="elsevierStyleSup">3</span>&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t\t\t</th><th class="td" title="\n
                  \t\t\t\t\ttable-head\n
                  \t\t\t\t  " align="center" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t" scope="col" style="border-bottom: 2px solid black">GF<span class="elsevierStyleSup">6</span>&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t\t\t</th><th class="td" title="\n
                  \t\t\t\t\ttable-head\n
                  \t\t\t\t  " align="center" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t" scope="col" style="border-bottom: 2px solid black">Prot&#47;C<span class="elsevierStyleSup">6</span>&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t\t\t</th><th class="td" title="\n
                  \t\t\t\t\ttable-head\n
                  \t\t\t\t  " align="center" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t" scope="col" style="border-bottom: 2px solid black">Alb&#47;C<span class="elsevierStyleSup">6</span>&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t\t\t</th><th class="td" title="\n
                  \t\t\t\t\ttable-head\n
                  \t\t\t\t  " align="center" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t" scope="col" style="border-bottom: 2px solid black">GF<span class="elsevierStyleSup">12</span>&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t\t\t</th><th class="td" title="\n
                  \t\t\t\t\ttable-head\n
                  \t\t\t\t  " align="center" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t" scope="col" style="border-bottom: 2px solid black">Prot&#47;C<span class="elsevierStyleSup">12</span>&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t\t\t</th><th class="td" title="\n
                  \t\t\t\t\ttable-head\n
                  \t\t\t\t  " align="center" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t" scope="col" style="border-bottom: 2px solid black">Alb&#47;C<span class="elsevierStyleSup">12</span>&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t\t\t</th></tr></thead><tbody title="tbody"><tr title="table-row"><td class="td-with-role" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">One&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">16&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">184&#46;77&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">55&#46;30&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
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Short Original
Blockade of interleukin-6 as a possible therapeutic target for AA amyloidosis
La inhibición de la interleucina-6 como posible diana terapéutica en la amiloidosis AA
Marina Almenara-Tejederas
Corresponding author
, Fabiola Alonso-García, Wenceslao Adrián Aguillera-Morales, Francisco de la Prada-Álvares, Mercedes Salgueira-Lazo
Servicio de Nefrología, Hospital Universitario Virgen Macarena, Sevilla, Spain
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    "textoCompleto" => "<span class="elsevierStyleSections"><span id="sec0005" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0065">Introduction</span><p id="par0005" class="elsevierStylePara elsevierViewall">Secondary amyloidosis &#40;AA&#41; is a serious complication associated with chronic inflammatory diseases&#44; highlighting among the most common&#58; rheumatoid arthritis &#40;RA&#41;&#44; familial Mediterranean fever and chronic infections&#46; It is characterized by the systemic deposit of fibrillar protein AA&#44; with special repercussions at the renal level&#46;<a class="elsevierStyleCrossRef" href="#bib0005"><span class="elsevierStyleSup">1</span></a> This protein derives from a plasmatic precursor produced by hepatocytes as an acute phase reactant against persistent inflammatory stimuli or tissue necrosis&#46;<a class="elsevierStyleCrossRef" href="#bib0010"><span class="elsevierStyleSup">2</span></a> Its hepatic synthesis is regulated by various proinflammatory cytokines such as TNF-&#945;&#44; IL-1 and IL-6&#44; the latter being related to the activity and severity of the disease&#46;<a class="elsevierStyleCrossRef" href="#bib0015"><span class="elsevierStyleSup">3</span></a></p><p id="par0010" class="elsevierStylePara elsevierViewall">The basis of treatment lies in suppressing inflammation&#44; thus inhibiting fibrillar protein synthesis&#46; In recent years&#44; the appearance of biological agents that specifically block cytokines has revolutionized the treatment of some chronic inflammatory diseases&#46; In this line&#44; the use of tocilizumab &#40;TCZ&#41; stands out&#44; a humanized antibody that blocks the IL-6 receptor&#44; widely used in RA and that could be particularly useful in AA amyloidosis&#46;</p><p id="par0015" class="elsevierStylePara elsevierViewall">Several case series have shown good efficacy for the treatment of this disease&#44; even allowing the regression of renal deposits already present&#46; Our objective is to analyze the efficacy and safety of TCZ in AA amyloidosis with renal involvement in our center&#46;</p></span><span id="sec0010" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0070">Material and method</span><span id="sec0015" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0075">Patient selection</span><p id="par0020" class="elsevierStylePara elsevierViewall">Retrospective monocentric study that included patients with a histological diagnosis of AA amyloidosis who received treatment with TCZ during the years 2018&#8211;2019&#46; Clinical and demographic variables were recorded&#44; including previous immunosuppressive treatment&#44; tolerance&#44; and adverse effects&#46; Clinical follow-up was carried out from the diagnosis of amyloidosis until the end of the study &#40;January 2020&#41;&#46;</p></span><span id="sec0020" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0080">Clinical evaluation</span><p id="par0025" class="elsevierStylePara elsevierViewall">We evaluated renal function using serum creatinine values &#8203;&#8203;&#40;mg&#47;dl&#41;&#44; glomerular filtration rate calculated by the CKD-EPI formula &#40;GFR&#59; ml&#47;min&#47;1&#46;73&#8239;m<span class="elsevierStyleSup">2</span>&#41; and protein&#47;creatinine ratio &#40;CPI&#59; mg&#47;g&#41; at the 3&#44; 6 and 12 months of follow-up&#46; We define renal response as a &#62;30&#37; reduction in proteinuria and&#47;or stabilization or improvement in glomerular filtration rate&#46; The activity of amyloidosis and its response to treatment have been evaluated by serum amyloid protein &#40;PSA&#59; mg&#47;l&#41; and C-reactive protein &#40;CRP&#59; mg&#47;l&#41;&#46; We consider an anti-inflammatory response to be a decrease &#62;50&#37; in SAA protein and&#47;or CRP levels&#46;</p></span></span><span id="sec0025" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0085">Results</span><span id="sec0030" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0090">Characteristics of the patients</span><p id="par0030" class="elsevierStylePara elsevierViewall">We identified 3 patients receiving treatment with TCZ after diagnosis of AA renal amyloidosis by renal biopsy&#46; The baseline clinical characteristics of the subjects are shown in <a class="elsevierStyleCrossRef" href="#tbl0005">Table 1</a>&#46; The 3 cases presented renal involvement at the diagnosis of amyloidosis&#44; with the renal function parameters being collected in <a class="elsevierStyleCrossRef" href="#tbl0010">Table 2</a>&#46; There have been no adverse events attributable to the use from TCZ&#46;</p><elsevierMultimedia ident="tbl0005"></elsevierMultimedia><elsevierMultimedia ident="tbl0010"></elsevierMultimedia></span><span id="sec0035" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0095">Case 1</span><p id="par0035" class="elsevierStylePara elsevierViewall">A 55-year-old man who presented with postcontrast acute kidney injury requiring hemodialysis &#40;HD&#41; in the context of massive pulmonary thromboembolism&#46; Corticosteroid boluses were administered without renal recovery&#44; so a renal biopsy was finally performed&#46; This biopsy showed glomeruli with minimal widening due to increased cellularity&#44; without identifying inflammatory infiltrate&#44; mesangial deposits or fibrinoid necrosis&#46; The tubules presented focal edema&#59; the interstitium&#44; discrete focal fibrosis with mild nonspecific inflammatory infiltrate&#46; A slight increase in the size of the vascular wall was observed at the expense of the deposit of eosinophilic material with birefringence&#44; compatible with amyloid&#46; The immunofluorescence study was negative&#46;</p><p id="par0040" class="elsevierStylePara elsevierViewall">His personal history included a smoking habit of 20 cigarettes a day and a combined emphysema&#47;pulmonary fibrosis syndrome&#44; diagnosed 2 months before the biopsy and considered an underlying cause of AA amyloidosis&#46;</p><p id="par0045" class="elsevierStylePara elsevierViewall">In this case&#44; the subcutaneous presentation of TCZ was chosen&#44; starting at a dose of 162&#8239;mg per week as described in the drug&#8217;s data sheet&#46; Proteinuria levels decreased by 44&#46;5&#37; at 12 months&#44; with a slight increase in GFR from 16 to 20&#8239;ml&#47;min&#59; at the inflammatory level&#44; a reduction in PSA and CRP was observed&#44; without evidence of systemic clinical manifestations at any time&#46; Given these results&#44; and until the writing of the article&#44; the same dose of TCZ was maintained &#40;11 months of treatment&#41;&#46;</p></span><span id="sec0040" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0100">Case 2</span><p id="par0050" class="elsevierStylePara elsevierViewall">A 74-year-old woman diagnosed with arterial hypertension treated with losartan and diabetes mellitus treated with linagliptin&#44; both of which were well controlled&#46; As background&#44; rheumatoid arthritis of 4 years&#8217; evolution stands out&#44; for which he had undergone treatment with etanercept and methotrexate with adequate symptomatic control&#46; The subsequent diagnosis of Binet stage A chronic lymphatic leukemia forced the suspension of etanercept&#44; maintaining methotrexate as monotherapy&#59; after this&#44; he presented several episodes of arthritis requiring corticotherapy&#46; Ten months after the diagnosis of leukemia&#44; given the progressive deterioration of renal function&#44; a renal biopsy was performed&#46; Histological findings showed a membranoproliferative pattern with increased mesangial substance in glomeruli&#44; images of basement membrane duplication and nodularity with a tendency to sclerosis&#46; There was tubular atrophy&#44; interstitial fibrosis &#40;35&#37;&#8211;45&#37;&#41;&#44; discrete nonspecific inflammatory infiltrate&#44; and intimal hyperplasia with arteriolohyalinosis and reduplication of elastic bands&#46; Amyloid material was identified in vessels and interstitium&#46; The immunofluorescence study showed C3<span class="elsevierStyleSup">&#43;&#43;</span> and IgM<span class="elsevierStyleSup">&#43;</span> deposits&#46;</p><p id="par0055" class="elsevierStylePara elsevierViewall">Being on HD&#44; intravenous TCZ was administered&#46; The dose&#44; adjusted for body weight &#40;8&#8239;mg&#47;kg&#47;every 4 weeks&#41;&#44; was maintained until renal transplantation &#40;9 months of treatment&#41;&#46; The patient remained on HD&#44; performing only urine sediments at 5 and 7 months &#40;proteins 200&#8239;mg&#47;dl&#41;&#46; Although treatment with TCZ did not achieve recovery of kidney function&#44; it allowed an adequate anti-inflammatory response with a reduction in PSA and CRP&#46; In addition&#44; during the follow-up period&#44; the patient did not present inflammatory data suggestive of activation of her rheumatological disease&#46;</p></span><span id="sec0045" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0105">Case 3</span><p id="par0060" class="elsevierStylePara elsevierViewall">A 75-year-old man with arterial hypertension treated with amlodipine and subclinical hypothyroidism&#46; He was diagnosed with AA amyloidosis after an episode of nephrotic syndrome&#44; with no underlying disease recorded&#46; Renal biopsy showed glomeruli with slight acellular mesangial enlargements at the expense of amorphous&#44; eosinophilic material with birefringence&#44; compatible with amyloid&#46; Isolated hyaline cylinders were found in tubular lumens&#46; In the interstitium and arterial walls&#44; there were interstitial acellular widenings by material similar to that previously described&#46;</p><p id="par0065" class="elsevierStylePara elsevierViewall">Treatment with TCZ was started subcutaneously at 162&#8239;mg&#47;week&#46; The GFR progressively improved until reaching 39&#8239;ml&#47;min at 6 months&#44; so it was decided to reduce the dose of TCZ to 162&#8239;mg subcutaneously fortnightly&#46; Seven months later&#44; he presented a sudden drop in GFR in the context of nephrotic syndrome&#44; and a new dose increase to 162&#8239;mg&#47;week was agreed upon&#46; Until the writing of the article&#44; he maintained stable renal function parameters &#40;13 months of treatment&#41;&#46; At the inflammatory level&#44; a decrease in PSA and CRP values &#8203;&#8203;was observed&#44; although with a slight rebound in PSA&#44; coinciding with the aforementioned deterioration in renal function&#46; He has not presented systemic clinical manifestations prior to the start of treatment with TCZ or during follow-up&#46;</p></span></span><span id="sec0050" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0110">Discussion</span><p id="par0070" class="elsevierStylePara elsevierViewall">IL-6 is a proinflammatory cytokine with an important role in the regulation of immune activity&#44; participating in most inflammatory responses&#46;<a class="elsevierStyleCrossRef" href="#bib0025"><span class="elsevierStyleSup">5</span></a> One of the mechanisms through which this cytokine acts is the stimulation of hepatic synthesis of SAA protein&#59; hence&#44; it is considered a key element in the development of amyloidosis&#46;</p><p id="par0075" class="elsevierStylePara elsevierViewall">TCZ is a humanized antibody that blocks the IL-6 receptor&#44; thus inhibiting this mechanism of action&#46; It is considered an effective specific treatment in the treatment of chronic inflammatory diseases such as RA&#44; although few data have been published on its use in AA amyloidosis&#46;</p><p id="par0080" class="elsevierStylePara elsevierViewall">We report a series of 3 cases of patients with AA renal amyloidosis treated with TCZ&#46; In patients 1 and 3&#44; a slight increase in GFR was observed after the start of TCZ&#44; although they maintained proteinuria values &#8203;&#8203;similar to those detected prior to treatment&#46; Patient 2 did not show improvement in renal function parameters&#44; although she preserved residual diuresis until the time of transplantation and maintained adequate control of RA with the use of TCZ&#46;</p><p id="par0085" class="elsevierStylePara elsevierViewall">The renal biopsy of the latter patient showed other renal lesions in addition to the amyloid deposit&#44; such as a pattern of membranoproliferative damage&#44; a poor prognostic finding in histology&#46; This finding&#44; added to the degree of chronicity&#44; could justify the lack of improvement in GFR&#46; Probably&#44; earlier initiation of TCZ would have allowed better results at the renal level&#46;</p><p id="par0090" class="elsevierStylePara elsevierViewall">We have defined renal response as a &#62;30&#37; reduction in proteinuria and&#47;or stabilization or improvement in GFR&#46;<a class="elsevierStyleCrossRef" href="#bib0020"><span class="elsevierStyleSup">4</span></a> In our series&#44; the GFR remained stable in patients 1 and 3&#44; obtaining a renal response to the effects of proteinuria in the first&#46; However&#44; proteinuria in this patient was not too high at the start of treatment&#44; so the results could be limited&#46;</p><p id="par0095" class="elsevierStylePara elsevierViewall">The variability of the baseline characteristics of the patients&#44; in terms of inflammatory disease&#44; renal stage and histological data&#44; could influence the response to treatment with TCZ&#46; It would be interesting to carry out new studies that analyze the possible prognostic factors of renal evolution&#46;</p><p id="par0100" class="elsevierStylePara elsevierViewall">We define anti-inflammatory response as a &#62;50&#37; decrease in SAA protein and&#47;or CRP levels&#46; All patients experience a rapid decrease in acute phase reactants after the start of TCZ&#44; which would translate into a reduction in the inflammatory state of these subjects&#46; In this sense&#44; we could conclude that the anti-inflammatory response to TCZ treatment in AA amyloidosis is 100&#37; in our series&#46; Lane et al&#46; demonstrated that TCZ can be effective in reducing inflammation by reducing SAA protein levels in patients with chronic inflammatory diseases and amyloidosis&#46;<a class="elsevierStyleCrossRef" href="#bib0025"><span class="elsevierStyleSup">5</span></a> Uda and Saiki suggest that the use of this drug not only lowers CRP and SAA levels&#44; but also delays the start of HD in patients with amyloidosis and advanced chronic kidney disease&#46;<a class="elsevierStyleCrossRef" href="#bib0030"><span class="elsevierStyleSup">6</span></a></p><p id="par0105" class="elsevierStylePara elsevierViewall">Both the efficacy and safety of TCZ in patients with kidney disease have been reported in different publications&#44; including even HD patients&#46;<a class="elsevierStyleCrossRefs" href="#bib0035"><span class="elsevierStyleSup">7&#44;8</span></a> In the study by Mori et al&#46;<a class="elsevierStyleCrossRef" href="#bib0045"><span class="elsevierStyleSup">9</span></a> no differences were found in terms of safety in the group of patients with chronic kidney disease compared to those without this complication&#44; showing significant improvements in clinical activity indices in all groups&#46; In our series&#44; TCZ has been administered with good tolerance and no adverse effects have been recorded during follow-up&#46;</p><p id="par0110" class="elsevierStylePara elsevierViewall">Therefore&#44; the use of TCZ in patients with AA renal amyloidosis seems to be effective and safe&#44; even in situations of progressive kidney damage&#46; Its administration has been shown to be useful in stabilizing or improving GFR and reducing inflammatory markers&#44; so its indication seems reasonable in patients who do not respond to other treatments or even be considered as the first therapeutic option&#44; in the absence of randomized prospective studies&#46;</p><p id="par0115" class="elsevierStylePara elsevierViewall">Our study contains some limitations&#46; This is a monocentric review&#44; with a small number of subjects&#44; which makes it difficult to obtain significant results&#44; as well as their extrapolation to the population&#46; The retrospective nature of the study&#44; although practically unavoidable as it is a rare disease&#44; limits the proper recording of the initially proposed variables&#46; New&#44; prospective&#44; randomized studies with long-term clinical assessment would be necessary&#46;</p></span><span id="sec0055" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0115">Conclusions</span><p id="par0120" class="elsevierStylePara elsevierViewall">IL-6 plays an important role in the pathophysiology of AA amyloidosis&#44; so TCZ could represent a therapeutic option to consider in these patients&#46; Our results show its efficacy both at the renal level and in the control of the underlying disease&#44; especially in patients with a high inflammatory component in whom it starts early&#46; The absence of adverse effects associated with TCZ in our series&#44; as in previous studies&#44; supports the safety of this drug in patients with kidney disease&#46; TCZ should be considered within the therapeutic arsenal for the treatment of AA renal amyloidosis&#44; as it may improve the long-term prognosis of these patients&#46;</p></span><span id="sec0060" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0120">Financing</span><p id="par0125" class="elsevierStylePara elsevierViewall">This research has not received specific aid from public sector agencies&#44; the commercial sector or non-profit entities&#46;</p></span><span id="sec0065" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0125">Conflict of interests</span><p id="par0130" class="elsevierStylePara elsevierViewall">The authors declare that they have no conflict of interest&#46;</p></span></span>"
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          "titulo" => "Resumen"
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              "titulo" => "Introducci&#243;n"
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              "titulo" => "Patient selection"
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              "titulo" => "Clinical evaluation"
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          "titulo" => "Results"
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            0 => array:2 [
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              "titulo" => "Characteristics of the patients"
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              "titulo" => "Case 1"
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              "titulo" => "Case 2"
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    "pdfFichero" => "main.pdf"
    "tienePdf" => true
    "fechaRecibido" => "2020-08-17"
    "fechaAceptado" => "2021-01-17"
    "PalabrasClave" => array:2 [
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          "clase" => "keyword"
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          "identificador" => "xpalclavsec1503239"
          "palabras" => array:3 [
            0 => "AA amyloidosis"
            1 => "Interleukin-6"
            2 => "Tocilizumab"
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        0 => array:4 [
          "clase" => "keyword"
          "titulo" => "Palabras clave"
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          "palabras" => array:3 [
            0 => "Amiloidosis AA"
            1 => "Interleucina 6"
            2 => "Tocilizumab"
          ]
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    "resumen" => array:2 [
      "en" => array:3 [
        "titulo" => "Abstract"
        "resumen" => "<span id="abst0005" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0010">Introduction</span><p id="spar0035" class="elsevierStyleSimplePara elsevierViewall">AA &#40;secondary&#41; amyloidosis is a severe complication of chronic inflammatory disorders&#46; It is characterized by the systemic deposition of an abnormal protein called amyloid&#44; affecting mainly renal function&#46; IL-6 is a cytokine with a relevant role in this disease development&#46; Interleukin-receptor antagonists&#44; like Tocilizumab &#40;TCZ&#41;&#44; have become possible treatment choice for AA amyloidosis&#46; In published reports&#44; TCZ has shown good efficacy for AA amyloidosis&#44; being associated with regression of renal amyloid deposits&#46;</p></span> <span id="abst0010" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0015">Methods</span><p id="spar0040" class="elsevierStyleSimplePara elsevierViewall">Retrospective review that included patients with histological diagnosis of AA renal amyloidosis under treatment with TCZ during the years 2018&#8211;2019 in our center&#46; We have registered clinical and demographic variables&#46; Renal function was measured by means of CKD-EPI equation to estimate the glomerular filtration rate &#40;FG&#41; and protein&#47;creatinine ratio &#40;IPC&#41; at 3&#44; 6 and 12 months&#46; We define renal response as a decrease by at least 30&#37; of proteinuria and&#47;or stabilization or improvement of FG&#46; We consider that an anti-inflammatory response is a decrease of more than 50&#37; in serum amyloid protein &#40;PSA&#41; and&#47;or C-reactive protein &#40;CRP&#41;&#46;</p></span> <span id="abst0015" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0020">Results</span><p id="spar0045" class="elsevierStyleSimplePara elsevierViewall">We collected 3 cases of patients with histologically proven AA amyloidosis treated with TCZ &#40;2 men&#59; 1 woman&#59; aged 55&#44; 74 and 75 years&#41;&#46; The follow-up was 13&#44; 14 and 75 months&#46; FG was stabilized in two patients&#46; The third patient remained on hemodialysis during follow-up&#44; although with excellent control of her underlying inflammatory disease&#46; In all three cases&#44; reduced PSA and CRP were observed&#46; There have been no adverse events&#46;</p></span> <span id="abst0020" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0025">Conclusions</span><p id="spar0050" class="elsevierStyleSimplePara elsevierViewall">The TCZ may be an effective and safe option in treatment of AA amyloidosis with renal involvement&#46; Our results position it as an interesting therapeutic option to consider in these cases&#44; although prospective studies would be necessary to evaluate the global role of TCZ in AA amyloidosis&#46;</p></span>"
        "secciones" => array:4 [
          0 => array:2 [
            "identificador" => "abst0005"
            "titulo" => "Introduction"
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          1 => array:2 [
            "identificador" => "abst0010"
            "titulo" => "Methods"
          ]
          2 => array:2 [
            "identificador" => "abst0015"
            "titulo" => "Results"
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            "identificador" => "abst0020"
            "titulo" => "Conclusions"
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        "titulo" => "Resumen"
        "resumen" => "<span id="abst0025" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0035">Introducci&#243;n</span><p id="spar0055" class="elsevierStyleSimplePara elsevierViewall">La amiloidosis secundaria &#40;AA&#41; es una complicaci&#243;n grave asociada a enfermedades inflamatorias&#46; Se caracteriza por el dep&#243;sito sist&#233;mico de prote&#237;na fibrilar AA&#44; con especial repercusi&#243;n renal&#46; La participaci&#243;n de la interleucina 6 en su mecanismo patog&#233;nico ha supuesto que tocilizumab &#40;TCZ&#41; sea considerado una opci&#243;n terap&#233;utica en estos pacientes&#46; Varias series publicadas muestran su eficacia en el tratamiento de la amiloidosis AA&#44; permitiendo incluso la regresi&#243;n de dep&#243;sitos renales ya presentes&#46;</p></span> <span id="abst0030" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0040">Material y m&#233;todo</span><p id="spar0060" class="elsevierStyleSimplePara elsevierViewall">Revisi&#243;n retrospectiva que incluy&#243; pacientes con diagn&#243;stico histol&#243;gico de amiloidosis renal AA en tratamiento con TCZ durante los a&#241;os 2018&#8211;2019 en nuestro centro&#46; Registramos variables cl&#237;nicas y demogr&#225;ficas&#59; evaluamos la funci&#243;n renal mediante filtrado glomerular &#40;FG&#41; calculado por CKD-EPI e &#237;ndice prote&#237;na&#47;creatinina a los 3&#44; 6 y 12 meses de seguimiento&#46; Definimos &#171;respuesta renal&#187; como la disminuci&#243;n&#8239;&#62;&#8239;30&#37; de la proteinuria y&#47;o estabilizaci&#243;n o mejor&#237;a del FG&#46; Consideramos &#171;respuesta antiinflamatoria&#187; la disminuci&#243;n&#8239;&#62;&#8239;50&#37; de las cifras de prote&#237;na s&#233;rica amiloide &#40;PSA&#41; y&#47;o prote&#237;na C reactiva &#40;PCR&#41;&#46;</p></span> <span id="abst0035" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0045">Resultados</span><p id="spar0065" class="elsevierStyleSimplePara elsevierViewall">Presentamos una serie de 3 pacientes &#40;2 varones y una mujer&#59; 55&#44; 74 y 75 a&#241;os&#44; respectivamente&#41;&#44; con un tiempo de seguimiento de 13&#44; 14 y 75 meses&#44; respectivamente&#46; Con la terapia con TCZ&#44; el FG se estabiliz&#243; en 2 pacientes&#59; el tercero permaneci&#243; en hemodi&#225;lisis durante el seguimiento&#44; aunque con excelente control de su enfermedad inflamatoria de base&#59; a los 12 meses recibi&#243; un trasplante renal&#46; En los 3 casos se objetiv&#243; reducci&#243;n de prote&#237;na PSA y PCR&#46; No se han producido eventos adversos&#46;</p></span> <span id="abst0040" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0050">Conclusiones</span><p id="spar0070" class="elsevierStyleSimplePara elsevierViewall">El TCZ es una opci&#243;n terap&#233;utica eficaz y segura para los pacientes con amiloidosis AA y afectaci&#243;n renal&#46; Nuestros resultados lo posicionan como una opci&#243;n terap&#233;utica a considerar en estos casos&#44; aunque ser&#237;a necesario la realizaci&#243;n de estudios prospectivos en los que se eval&#250;e el papel global de TCZ en la amiloidosis AA&#46;</p></span>"
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            "titulo" => "Material y m&#233;todo"
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            "titulo" => "Resultados"
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            "titulo" => "Conclusiones"
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        "etiqueta" => "&#9734;"
        "nota" => "<p class="elsevierStyleNotepara" id="npar0005">Please cite this article as&#58; Almenara-Tejederas M&#44; Alonso-Garc&#237;a F&#44; Aguillera-Morales WA&#44; de la Prada-&#193;lvares F&#44; Salgueira-Lazo M&#46; La inhibici&#243;n de la interleucina-6 como posible diana terap&#233;utica en la amiloidosis AA&#46; Nefrologia&#46; 2022&#59;42&#58;28&#8211;32&#46;</p>"
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          "leyenda" => "<p id="spar0010" class="elsevierStyleSimplePara elsevierViewall">AA duration&#58; time from diagnosis of amyloidosis to initiation of TCZ&#59; ETA&#58; etanercept&#59; HD&#58; hemodialysis&#59; IS&#58; immunosuppressive treatment&#59; M&#58; woman&#59; MTX&#58; methotrexate&#59; TCZ&#58; tocilizumab&#59; V&#58; male&#46;</p>"
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                  <table border="0" frame="\n
                  \t\t\t\t\tvoid\n
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                  \t\t\t\t\ttable-head\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t" scope="col" style="border-bottom: 2px solid black">&nbsp;\t\t\t\t\t\t\n
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                  \t\t\t\t\ttable-head\n
                  \t\t\t\t  " align="center" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t" scope="col" style="border-bottom: 2px solid black">Patient 1&nbsp;\t\t\t\t\t\t\n
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                  \t\t\t\t\ttable-head\n
                  \t\t\t\t  " align="center" valign="\n
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                  \t\t\t\t" scope="col" style="border-bottom: 2px solid black">Patient 2&nbsp;\t\t\t\t\t\t\n
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                  \t\t\t\t\ttable-head\n
                  \t\t\t\t  " align="center" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t" scope="col" style="border-bottom: 2px solid black">Patient 3&nbsp;\t\t\t\t\t\t\n
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                  \t\t\t\t\ttable-entry\n
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                  \t\t\t\t">Sex&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">V&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">M&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">V&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">Age&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">55&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">74&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">75&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">Underlying disease&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">Emphysema&#47;fibrosis&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">Rheumatoid arthritis&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">Unidentified&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">Charlson index&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">4&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">8&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">5&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">AA duration&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">2 months&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">4 months&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">62 months&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">Biopsy type&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">Renal&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">Renal&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">Renal&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">Initial GF&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">HD&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">HD&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">18&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">Previous SI&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">No&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">ETA&#44; MTX&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">No&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">Concomitant IS&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">No&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">No&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">No&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">Sclerosed glomeruli&#47;total&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">0&#47;24&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">2&#47;9&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">1&#47;12&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">Renal interstitium&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">Discrete focal fibrosis&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">Moderate fibrosis &#40;IFTA 45&#37;&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">No fibrosis&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">TCZ dosage&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">162&#8239;mg&#47;week&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">400&#8239;mg&#47;month&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">162&#8239;mg&#47;week&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">Duration TCZ&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">11 months&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">9 months&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">13 months&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">Follow-up time&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">13 months&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">14 months&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">75 months&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">Adverse effects&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">No&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">No&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">No&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr></tbody></table>
                  """
              ]
              "imagenFichero" => array:1 [
                0 => "xTab2885059.png"
              ]
            ]
          ]
        ]
        "descripcion" => array:1 [
          "en" => "<p id="spar0005" class="elsevierStyleSimplePara elsevierViewall">Clinical and demographic characteristics of the patients included in the study&#46;</p>"
        ]
      ]
      1 => array:8 [
        "identificador" => "tbl0010"
        "etiqueta" => "Table 2"
        "tipo" => "MULTIMEDIATABLA"
        "mostrarFloat" => true
        "mostrarDisplay" => false
        "detalles" => array:1 [
          0 => array:3 [
            "identificador" => "at0010"
            "detalle" => "Table "
            "rol" => "short"
          ]
        ]
        "tabla" => array:2 [
          "leyenda" => "<p id="spar0020" class="elsevierStyleSimplePara elsevierViewall">Alb&#47;C&#58; albumin&#47;creatinine ratio &#40;mg&#47;g&#41;&#59; GFR&#58; glomerular filtration rate &#40;CKD-EPI&#59; ml&#47;min&#41;&#59; HD&#58; hemodialysis&#59; Prot&#47;C&#58; protein&#47;creatinine ratio &#40;mg&#47;g&#41;&#59; Tx&#58; kidney transplant&#46;</p><p id="spar0025" class="elsevierStyleSimplePara elsevierViewall">Values&#58; 0&#58; prior to TCZ&#59; 3&#58; third month after TCZ&#59; 6&#58; sixth month after TCZ&#59; 12&#58; twelfth month after TCZ&#46;</p><p id="spar0030" class="elsevierStyleSimplePara elsevierViewall">AA&#58; secondary amyloidosis&#59; RA&#58; rheumatoid arthritis&#59; TCZ&#58; tocilizumab&#59; GFR&#58; glomerular filtration calculated by CKD-EPI&#59; CPI&#58; urine protein&#47;creatinine ratio&#59; IAC&#58; urine albumin&#47;creatinine ratio&#59; PSA&#58; amyloid serum protein&#59; CRP&#58; C-reactive protein&#59; HD&#58; hemodialysis&#46;</p>"
          "tablatextoimagen" => array:1 [
            0 => array:2 [
              "tabla" => array:1 [
                0 => """
                  <table border="0" frame="\n
                  \t\t\t\t\tvoid\n
                  \t\t\t\t" class=""><thead title="thead"><tr title="table-row"><th class="td" title="\n
                  \t\t\t\t\ttable-head\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t" scope="col" style="border-bottom: 2px solid black">&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t\t\t</th><th class="td" title="\n
                  \t\t\t\t\ttable-head\n
                  \t\t\t\t  " align="center" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t" scope="col" style="border-bottom: 2px solid black">GF<span class="elsevierStyleSup">0</span>&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t\t\t</th><th class="td" title="\n
                  \t\t\t\t\ttable-head\n
                  \t\t\t\t  " align="center" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t" scope="col" style="border-bottom: 2px solid black">Prot&#47;C<span class="elsevierStyleSup">0</span>&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t\t\t</th><th class="td" title="\n
                  \t\t\t\t\ttable-head\n
                  \t\t\t\t  " align="center" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t" scope="col" style="border-bottom: 2px solid black">Alb&#47;C<span class="elsevierStyleSup">0</span>&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t\t\t</th><th class="td" title="\n
                  \t\t\t\t\ttable-head\n
                  \t\t\t\t  " align="center" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t" scope="col" style="border-bottom: 2px solid black">GF<span class="elsevierStyleSup">3</span>&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t\t\t</th><th class="td" title="\n
                  \t\t\t\t\ttable-head\n
                  \t\t\t\t  " align="center" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t" scope="col" style="border-bottom: 2px solid black">Prot&#47;C<span class="elsevierStyleSup">3</span>&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t\t\t</th><th class="td" title="\n
                  \t\t\t\t\ttable-head\n
                  \t\t\t\t  " align="center" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t" scope="col" style="border-bottom: 2px solid black">Alb&#47;C<span class="elsevierStyleSup">3</span>&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t\t\t</th><th class="td" title="\n
                  \t\t\t\t\ttable-head\n
                  \t\t\t\t  " align="center" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t" scope="col" style="border-bottom: 2px solid black">GF<span class="elsevierStyleSup">6</span>&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t\t\t</th><th class="td" title="\n
                  \t\t\t\t\ttable-head\n
                  \t\t\t\t  " align="center" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t" scope="col" style="border-bottom: 2px solid black">Prot&#47;C<span class="elsevierStyleSup">6</span>&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t\t\t</th><th class="td" title="\n
                  \t\t\t\t\ttable-head\n
                  \t\t\t\t  " align="center" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t" scope="col" style="border-bottom: 2px solid black">Alb&#47;C<span class="elsevierStyleSup">6</span>&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t\t\t</th><th class="td" title="\n
                  \t\t\t\t\ttable-head\n
                  \t\t\t\t  " align="center" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t" scope="col" style="border-bottom: 2px solid black">GF<span class="elsevierStyleSup">12</span>&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t\t\t</th><th class="td" title="\n
                  \t\t\t\t\ttable-head\n
                  \t\t\t\t  " align="center" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t" scope="col" style="border-bottom: 2px solid black">Prot&#47;C<span class="elsevierStyleSup">12</span>&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t\t\t</th><th class="td" title="\n
                  \t\t\t\t\ttable-head\n
                  \t\t\t\t  " align="center" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t" scope="col" style="border-bottom: 2px solid black">Alb&#47;C<span class="elsevierStyleSup">12</span>&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t\t\t</th></tr></thead><tbody title="tbody"><tr title="table-row"><td class="td-with-role" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">One&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">16&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">184&#46;77&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">55&#46;30&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">17&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">205&#46;04&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">52&#46;60&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">19&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">90&#46;24&nbsp;\t\t\t\t\t\t\n
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                  \t\t\t\t  " align="left" valign="\n
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                  \t\t\t\t">Twenty&nbsp;\t\t\t\t\t\t\n
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                  \t\t\t\t">25&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
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                  \t\t\t\t">39&nbsp;\t\t\t\t\t\t\n
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                  \t\t\t\t">2782&#46;00&nbsp;\t\t\t\t\t\t\n
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ISSN: 20132514
Original language: English
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Idiomas
Nefrología (English Edition)