Letter to the Editor
ANCA-negative idiopathic pulmonary fibrosis developed into ANCA-positive rapidly progressive glomerulonephritis after 12 years follow up
Fibrosis pulmonar idiopática ANCA negativa desarrollada en la glomerulonefritis de evolución rápida en ANCA positiva después de 12 años de seguimiento
a Division of Nephrology, Department of Internal Medicine, Tri-Service General Hospital, National Defense Medical Center, Taipei, Taiwan
b Department of Pathology, Tri-Service General Hospital, National Defense Medical Center, Taipei, Taiwan
c Department of Medicine, Providence St. Vincent Medical Center, Portland, OR, United States
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(A) Chest X ray – Interstitial reticular fibrotic infiltration with honey comb appearance over both lungs. (B) Non-contrast computed tomography of the chest shows pulmonary fibrosis with cystic change in bilateral lung fields, with lower lung zones predominance. Infiltrates and ground-glass opacity in bilateral peri-hilar regions were also noted. (C) Renal biopsy (400×) – Glomeruli showed mesoangiocapillary proliferation and segmental sclerosis. Fibro-cellular crescents are also seen.</p>" ] ] ] "textoCompleto" => "<span class="elsevierStyleSections"><p id="par0005" class="elsevierStylePara elsevierViewall">Idiopathic pulmonary fibrosis (IPF) is a chronic, progressive fibrotic disorder of the lung parenchyma. Rapidly progressive glomerulonephritis (RPGN) is a disease characterized by acute loss of renal function with glomerulonephritis, which is diagnosed by a pathologic pattern of crescent formation. A subgroup of RPGN is associated with anti-neutrophil cytoplasmic antibodies (ANCA). ANCA are abnormal auto-antibodies which are particularly related to small-vessel vasculitis in the kidneys. The perinuclear (p-ANCA) and cytoplasmic (c-ANCA) immunofluorescent patterns mainly correspond to antibodies directed against myeloperoxidase (MPO) and proteinase-3 (PR3), respectively. Herein, we report a case of a 37-year-old man with a history of ANCA (−) IPF who abruptly developed ANCA (+) RPGN with pulmonary renal syndrome after 12.5 years.</p><p id="par0010" class="elsevierStylePara elsevierViewall">A 37-year-old man had a history of ANCA (−) IPF and gouty arthritis under control with prednisolone 5<span class="elsevierStyleHsp" style=""></span>mg QOD and colchicines 0.5<span class="elsevierStyleHsp" style=""></span>mg QD for over 12.5 years. A month prior to presentation, he began to experience intermittent muscle aches, arthralgias over bilateral hands and foamy urine. He finally presented to the emergency department with complaints of progressive shortness of breath, hemoptysis, poor urine output, and bilateral lower leg edema for one week. The physical examination was notable for respiratory discomfort, bilateral rales and grade 1 pitting edema of bilateral lower limbs. No petechiae, ecchymosis or costovertebral angle tenderness were noted. Blood tests showed leukocytosis, azotemia (BUN: 159<span class="elsevierStyleHsp" style=""></span>mg/dL, creatinine: 21.1<span class="elsevierStyleHsp" style=""></span>mg/dL), hyperkalemia, and anion gap metabolic acidosis. Urinalysis revealed proteinuria and hematuria. Immunologic studies showed mildly decreased C3 (76.5<span class="elsevierStyleHsp" style=""></span>mg/dL, reference range: 90–180<span class="elsevierStyleHsp" style=""></span>mg/dL) and positive MPO-ANCA (28<span class="elsevierStyleHsp" style=""></span>IU/ml, reference range: negative <3.5, positive >5<span class="elsevierStyleHsp" style=""></span>IU/mL). Chest X-ray showed infiltrates in both lungs. Non-contrast computed tomography of the chest showed interstitial reticular fibrotic infiltration with honeycomb appearance of bilateral lungs and consolidation in the left lung zone. Renal ultrasonography demonstrated normal-sized kidneys with increased cortical echogenicity. Ultrasound-guided renal biopsy was performed and revealed a proliferative glomerulonephritis with sclerosis and crescentic formation (<a class="elsevierStyleCrossRef" href="#fig0005">Fig. 1</a>). Immunofluorescent microscopy of the glomeruli was negative for staining of IgA, IgG, IgM, C1 and C3. Based on the above-mentioned examination results and clinical manifestations, severe MPO-ANCA (+) RPGN with pulmonary-renal syndrome was diagnosed. During the initial admission, emergent hemodialysis and plasmapheresis (5 sessions) were performed. Immunosuppressant therapy including pulse steroids (methylprednisolone 500<span class="elsevierStyleHsp" style=""></span>mg daily for 6 days) followed by oral prednisolone (5<span class="elsevierStyleHsp" style=""></span>mg BID) and azathioprine (50<span class="elsevierStyleHsp" style=""></span>mg daily) and targeted therapy with rituximab (total 3<span class="elsevierStyleHsp" style=""></span>g over 3 divided fractions) were also added. Nonetheless, high ANCA titers and poor renal function persisted so immunosuppression therapy and hemodialysis were maintained. Unfortunately, the patient died 1.5 years later from septic shock due to community-acquired pneumonia.</p><elsevierMultimedia ident="fig0005"></elsevierMultimedia><p id="par0015" class="elsevierStylePara elsevierViewall">IPF may be an insidious lesion of vasculitis or a separate entity. It is now known that a subset of IPF patients are ANCA positive.<a class="elsevierStyleCrossRef" href="#bib0055"><span class="elsevierStyleSup">1</span></a> A recent study examined the differences between ANCA positive and ANCA negative IPF. The levels of serum creatinine and C-reactive protein in patients with positive ANCA are significantly higher than those with negative ANCA. The survival rate of patients with higher titers of ANCA was less than patients with lower levels, implying the concentration of ANCA not only reflects the degree of systemic inflammation, but also indicates a more unfavorable prognosis. Most ANCA (+) IPF is MPO-ANCA, which is related to the development of crescentic glomerulonephritis in animal models<a class="elsevierStyleCrossRef" href="#bib0085"><span class="elsevierStyleSup">7</span></a> and could develop into RPGN clinically. In our literature search, we found 10 patients with acute ANCA (+) RPGN in IPF patients, all of whom had MPO-ANCA<a class="elsevierStyleCrossRefs" href="#bib0060"><span class="elsevierStyleSup">2–4,8–10</span></a> (<a class="elsevierStyleCrossRef" href="#tbl0005">Table 1</a>). Seven out of the 10 reported cases were Asians; however, the initial symptoms, time duration between IPF diagnosis and onset of RPGN, serum levels of MPO-ANCA varied widely, indicating the clinical manifestations of such cases are highly unpredictable. Recent studies have revealed two major pathways to tissue damage from ANCA associated vasculitis: the neutrophil pathway and the T-cell pathway. In the neutrophil pathway, an infection leads to the priming of neutrophils with an increase of adhesion molecules and ANCA-binding antigens on their surface. The binding of ANCA on neutrophils activates the degranulation process and cause damage to the endothelial layer. Under the T-cell pathway, regulatory T cells take over the function of tertiary lymphoid organs and promote further immune response. These two mechanisms interact with each other and magnify the cascade of inflammation and consequently causing vasculitis.<a class="elsevierStyleCrossRef" href="#bib0075"><span class="elsevierStyleSup">5</span></a></p><elsevierMultimedia ident="tbl0005"></elsevierMultimedia><p id="par0020" class="elsevierStylePara elsevierViewall">To the best of our knowledge, the present case was the youngest and the longest interval between IPF and RPGN diagnoses in the reported literature. Despite ANCA-negativity at IPF diagnosis 12.5 years ago, he subsequently developed ANCA-positive RPGN; the trigger of this seroconversion is unknown. The long duration might have been affected by the patient's regular use of prednisolone and colchicine, as colchicine may down-regulate multiple inflammatory responses and slow down the cascade of vasculitis.<a class="elsevierStyleCrossRef" href="#bib0080"><span class="elsevierStyleSup">6</span></a> In conclusion, this case highlights the importance of regular monitoring levels of ANCA and alertness for renal involvement in patients with IPF.</p><span id="sec0005" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0005">Conflict of interests</span><p id="par0025" class="elsevierStylePara elsevierViewall">The authors declare that they have no conflict of interests.</p></span></span>" "textoCompletoSecciones" => array:1 [ "secciones" => array:2 [ 0 => array:2 [ "identificador" => "sec0005" "titulo" => "Conflict of interests" ] 1 => array:1 [ "titulo" => "References" ] ] ] "pdfFichero" => "main.pdf" "tienePdf" => true "multimedia" => array:2 [ 0 => array:7 [ "identificador" => "fig0005" "etiqueta" => "Fig. 1" "tipo" => "MULTIMEDIAFIGURA" "mostrarFloat" => true "mostrarDisplay" => false "figura" => array:1 [ 0 => array:4 [ "imagen" => "gr1.jpeg" "Alto" => 485 "Ancho" => 1861 "Tamanyo" => 212865 ] ] "descripcion" => array:1 [ "en" => "<p id="spar0005" class="elsevierStyleSimplePara elsevierViewall">Imaging studies of the lungs and microscopic slides of renal tissue. (A) Chest X ray – Interstitial reticular fibrotic infiltration with honey comb appearance over both lungs. (B) Non-contrast computed tomography of the chest shows pulmonary fibrosis with cystic change in bilateral lung fields, with lower lung zones predominance. Infiltrates and ground-glass opacity in bilateral peri-hilar regions were also noted. (C) Renal biopsy (400×) – Glomeruli showed mesoangiocapillary proliferation and segmental sclerosis. Fibro-cellular crescents are also seen.</p>" ] ] 1 => array:8 [ "identificador" => "tbl0005" "etiqueta" => "Table 1" "tipo" => "MULTIMEDIATABLA" "mostrarFloat" => true "mostrarDisplay" => false "detalles" => array:1 [ 0 => array:3 [ "identificador" => "at1" "detalle" => "Table " "rol" => "short" ] ] "tabla" => array:3 [ "leyenda" => "<p id="spar0015" class="elsevierStyleSimplePara elsevierViewall">ref.: reference, y: year, M: male, F: female, N/A: not applicable.</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="table-head " align="left" valign="top" scope="col" style="border-bottom: 2px solid black">Case<span class="elsevierStyleSup">(ref.)</span> \t\t\t\t\t\t\n \t\t\t\t</th><th class="td" title="table-head " align="center" valign="top" scope="col" style="border-bottom: 2px solid black">Age (y)/Sex \t\t\t\t\t\t\n \t\t\t\t</th><th class="td" title="table-head " align="center" valign="top" scope="col" style="border-bottom: 2px solid black">Duration<a class="elsevierStyleCrossRef" href="#tblfn0005"><span class="elsevierStyleSup">a</span></a> (y) \t\t\t\t\t\t\n \t\t\t\t</th><th class="td" title="table-head " align="center" valign="top" scope="col" style="border-bottom: 2px solid black">Initial symptoms \t\t\t\t\t\t\n \t\t\t\t</th><th class="td" title="table-head " align="center" valign="top" scope="col" style="border-bottom: 2px solid black">SCr<a class="elsevierStyleCrossRef" href="#tblfn0010"><span class="elsevierStyleSup">b</span></a> (mg/dL) \t\t\t\t\t\t\n \t\t\t\t</th><th class="td" title="table-head " align="center" valign="top" scope="col" style="border-bottom: 2px solid black">MPO-ANCA levels<br>(pre/post treatment)<a class="elsevierStyleCrossRef" href="#tblfn0015"><span class="elsevierStyleSup">c</span></a> \t\t\t\t\t\t\n \t\t\t\t</th><th class="td" title="table-head " align="center" valign="top" scope="col" style="border-bottom: 2px solid black">Seroconversion of ANCA \t\t\t\t\t\t\n \t\t\t\t</th><th class="td" title="table-head " align="center" valign="top" scope="col" style="border-bottom: 2px solid black">Renal histology \t\t\t\t\t\t\n \t\t\t\t</th><th class="td" title="table-head " align="left" valign="top" scope="col" style="border-bottom: 2px solid black">Treatment<a class="elsevierStyleCrossRef" href="#tblfn0020"><span class="elsevierStyleSup">d</span></a> \t\t\t\t\t\t\n \t\t\t\t</th><th class="td" title="table-head " align="left" valign="top" scope="col" style="border-bottom: 2px solid black">Renal outcome \t\t\t\t\t\t\n \t\t\t\t</th></tr></thead><tbody title="tbody"><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top">Hiromura et al.<a class="elsevierStyleCrossRef" href="#bib0060"><span class="elsevierStyleSup">2</span></a> \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">48/F \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">1 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">Dyspnea, cough, fever \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">2.5 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">225, 15 (EU/ml) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">N/A \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">Yes \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">S, C \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">Recovery \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top">Hiromura et al.<a class="elsevierStyleCrossRef" href="#bib0060"><span class="elsevierStyleSup">2</span></a> \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">77/M \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">5 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">Shortness of breath \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">4.4 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">998,109 (EU/ml) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">N/A \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">– \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">S, C \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">Recovery \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top">Hiromura et al.<a class="elsevierStyleCrossRef" href="#bib0060"><span class="elsevierStyleSup">2</span></a> \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">72/F \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">6 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">Fatigue, appetite loss \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">3.4 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">1379, decreased (EU/ml) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">N/A \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">Yes \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">S, C \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">Improved<a class="elsevierStyleCrossRef" href="#tblfn0025"><span class="elsevierStyleSup">e</span></a> \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top">Hiromura et al.<a class="elsevierStyleCrossRef" href="#bib0060"><span class="elsevierStyleSup">2</span></a> \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">70/M \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">4 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">Fatigue, fever \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">11.1 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">581, decreased (EU/ml) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">N/A \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">– \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">S, C \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">Hemodialysis \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top">Chikaraishi et al.<a class="elsevierStyleCrossRef" href="#bib0065"><span class="elsevierStyleSup">3</span></a> \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">52/M \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">9 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">Claudication, paresthesia, hematuria \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">0.7 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">80, 33 (EU/ml) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">Yes \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">Yes \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">S, C \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">Recovery \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top">Matsuyama et al.<a class="elsevierStyleCrossRef" href="#bib0070"><span class="elsevierStyleSup">4</span></a> \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">72/M \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">10 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">Fatigue, abdominal pain, fever \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">1.3 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">869, N/A (EU/ml) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">N/A \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">Yes \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">S \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">Recovery \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top">Eschun et al.<a class="elsevierStyleCrossRef" href="#bib0075"><span class="elsevierStyleSup">5</span></a> \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">67/F \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">4 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">Shortness of breath \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">2.2 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">High titer, N/A \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">N/A \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">Yes \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">S, C \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">Recovery \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top">Amir et al.<a class="elsevierStyleCrossRef" href="#bib0080"><span class="elsevierStyleSup">6</span></a> \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">69/F \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">0.8 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">Dyspnea \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">7.1 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">403, N/A (U/L) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">Yes \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">Yes \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">S, C, P \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">Recovery \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top">Pineton et al.<a class="elsevierStyleCrossRef" href="#bib0070"><span class="elsevierStyleSup">4</span></a> \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">71/F \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">3 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">Dyspnea \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">6.1 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">High titer, undetectable \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">Yes \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">Yes \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">S, C, P, R \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">Recovery \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top">Presented case \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">37/M \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">12.5 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">Shortness of breath, edema \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">21.1 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">28, 29 (IU/ml) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">Yes \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">Yes \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">S, A, P, R \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">Hemodialysis \t\t\t\t\t\t\n \t\t\t\t</td></tr></tbody></table> """ ] "imagenFichero" => array:1 [ 0 => "xTab1375926.png" ] ] ] "notaPie" => array:5 [ 0 => array:3 [ "identificador" => "tblfn0005" "etiqueta" => "a" "nota" => "<p class="elsevierStyleNotepara" id="npar0005">Duration between the onset of IPF and RPGN.</p>" ] 1 => array:3 [ "identificador" => "tblfn0010" "etiqueta" => "b" "nota" => "<p class="elsevierStyleNotepara" id="npar0010">Serum creatinine level at RPGN diagnosed.</p>" ] 2 => array:3 [ "identificador" => "tblfn0015" "etiqueta" => "c" "nota" => "<p class="elsevierStyleNotepara" id="npar0015">MPO-ANCA levels before and after treatment during admission.</p>" ] 3 => array:3 [ "identificador" => "tblfn0020" "etiqueta" => "d" "nota" => "<p class="elsevierStyleNotepara" id="npar0020">S: steroids, C: cyclophosphamide, A: azathioprine, P: plasmapheresis, R: rituximab.</p>" ] 4 => array:3 [ "identificador" => "tblfn0025" "etiqueta" => "e" "nota" => "<p class="elsevierStyleNotepara" id="npar0025">The patient died during the treatment course due to respiratory failure.</p>" ] ] ] "descripcion" => array:1 [ "en" => "<p id="spar0010" class="elsevierStyleSimplePara elsevierViewall">Clinical characteristics of patients with idiopathic pulmonary fibrosis who developed into rapidly progressive glomerulonephritis.</p>" ] ] ] "bibliografia" => array:2 [ "titulo" => "References" "seccion" => array:1 [ 0 => array:2 [ "identificador" => "bibs0005" "bibliografiaReferencia" => array:10 [ 0 => array:3 [ "identificador" => "bib0055" "etiqueta" => "1" "referencia" => array:1 [ 0 => array:2 [ "contribucion" => array:1 [ 0 => array:2 [ "titulo" => "A comparison of the clinical features of ANCA-positive and ANCA-negative idiopathic pulmonary fibrosis patients" "autores" => array:1 [ 0 => array:2 [ "etal" => false "autores" => array:5 [ 0 => "T. 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| Year/Month | Html | Total | |
|---|---|---|---|
| 2024 November | 4 | 6 | 10 |
| 2024 October | 48 | 55 | 103 |
| 2024 September | 79 | 43 | 122 |
| 2024 August | 85 | 74 | 159 |
| 2024 July | 63 | 28 | 91 |
| 2024 June | 69 | 31 | 100 |
| 2024 May | 75 | 36 | 111 |
| 2024 April | 72 | 31 | 103 |
| 2024 March | 63 | 23 | 86 |
| 2024 February | 54 | 37 | 91 |
| 2024 January | 49 | 26 | 75 |
| 2023 December | 65 | 35 | 100 |
| 2023 November | 92 | 40 | 132 |
| 2023 October | 107 | 27 | 134 |
| 2023 September | 78 | 26 | 104 |
| 2023 August | 71 | 26 | 97 |
| 2023 July | 55 | 23 | 78 |
| 2023 June | 70 | 24 | 94 |
| 2023 May | 70 | 31 | 101 |
| 2023 April | 47 | 19 | 66 |
| 2023 March | 89 | 17 | 106 |
| 2023 February | 62 | 20 | 82 |
| 2023 January | 58 | 32 | 90 |
| 2022 December | 82 | 34 | 116 |
| 2022 November | 64 | 32 | 96 |
| 2022 October | 84 | 48 | 132 |
| 2022 September | 66 | 31 | 97 |
| 2022 August | 78 | 50 | 128 |
| 2022 July | 61 | 38 | 99 |
| 2022 June | 54 | 36 | 90 |
| 2022 May | 83 | 30 | 113 |
| 2022 April | 81 | 47 | 128 |
| 2022 March | 63 | 49 | 112 |
| 2022 February | 63 | 42 | 105 |
| 2022 January | 49 | 29 | 78 |
| 2021 December | 62 | 45 | 107 |
| 2021 November | 76 | 39 | 115 |
| 2021 October | 109 | 44 | 153 |
| 2021 September | 83 | 34 | 117 |
| 2021 August | 65 | 41 | 106 |
| 2021 July | 67 | 36 | 103 |
| 2021 June | 81 | 39 | 120 |
| 2021 May | 59 | 37 | 96 |
| 2021 April | 112 | 62 | 174 |
| 2021 March | 85 | 34 | 119 |
| 2021 February | 83 | 35 | 118 |
| 2021 January | 51 | 23 | 74 |
| 2020 December | 50 | 13 | 63 |
| 2020 November | 44 | 20 | 64 |
| 2020 October | 35 | 17 | 52 |
| 2020 September | 25 | 13 | 38 |
| 2020 August | 51 | 15 | 66 |
| 2020 July | 48 | 11 | 59 |
| 2020 June | 42 | 17 | 59 |
| 2020 May | 57 | 12 | 69 |
| 2020 April | 50 | 20 | 70 |
| 2020 March | 47 | 13 | 60 |
| 2020 February | 68 | 23 | 91 |
| 2020 January | 82 | 22 | 104 |
| 2019 December | 69 | 27 | 96 |
| 2019 November | 60 | 21 | 81 |
| 2019 October | 43 | 11 | 54 |
| 2019 September | 67 | 20 | 87 |
| 2019 August | 46 | 15 | 61 |
| 2019 July | 56 | 26 | 82 |
| 2019 June | 66 | 18 | 84 |
| 2019 May | 83 | 21 | 104 |
| 2019 April | 109 | 30 | 139 |
| 2019 March | 87 | 28 | 115 |
| 2019 February | 42 | 22 | 64 |
| 2019 January | 50 | 22 | 72 |
| 2018 December | 198 | 35 | 233 |
| 2018 November | 336 | 20 | 356 |
| 2018 October | 262 | 20 | 282 |
| 2018 September | 119 | 22 | 141 |
| 2018 August | 79 | 16 | 95 |
| 2018 July | 102 | 20 | 122 |
| 2018 June | 95 | 21 | 116 |
| 2018 May | 140 | 16 | 156 |
| 2018 April | 169 | 7 | 176 |
| 2018 March | 114 | 9 | 123 |
| 2018 February | 134 | 10 | 144 |
| 2018 January | 103 | 7 | 110 |
| 2017 December | 126 | 6 | 132 |
| 2017 November | 88 | 15 | 103 |
| 2017 October | 44 | 4 | 48 |
| 2017 September | 52 | 7 | 59 |
| 2017 August | 41 | 8 | 49 |
| 2017 July | 52 | 7 | 59 |
| 2017 June | 54 | 7 | 61 |
| 2017 May | 46 | 10 | 56 |
| 2017 April | 43 | 7 | 50 |
| 2017 March | 13 | 4 | 17 |
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