C1q Nephropathy and Malignancy
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Severe glomerulosclerosis and tubular lesion" ] ] ] "autores" => array:1 [ 0 => array:2 [ "autoresLista" => "Carlos Mañero-Rodríguez, Antonio Navas-Parejo Casado, Mercedes Gómez, Raimundo García-del Moral, Antonio Osuna, Sebastián Cerezo-Morales" "autores" => array:6 [ 0 => array:2 [ "nombre" => "Carlos" "apellidos" => "Mañero-Rodríguez" ] 1 => array:2 [ "nombre" => "Antonio" "apellidos" => "Navas-Parejo Casado" ] 2 => array:2 [ "nombre" => "Mercedes" "apellidos" => "Gómez" ] 3 => array:2 [ "nombre" => "Raimundo" "apellidos" => "García-del Moral" ] 4 => array:2 [ "nombre" => "Antonio" "apellidos" => "Osuna" ] 5 => array:2 [ "nombre" => "Sebastián" "apellidos" => "Cerezo-Morales" ] ] ] ] ] "idiomaDefecto" => "en" "Traduccion" => array:1 [ "es" => array:9 [ "pii" => "X021169951200068X" "doi" => "10.3265/Nefrologia.pre2011.Dec.11154" "estado" => "S300" "subdocumento" => "" "abierto" => array:3 [ "ES" => true "ES2" => true "LATM" => true ] "gratuito" => true "lecturas" => array:1 [ "total" => 0 ] "idiomaDefecto" => "es" "EPUB" => "https://multimedia.elsevier.es/PublicationsMultimediaV1/item/epub/X021169951200068X?idApp=UINPBA000064" ] ] "EPUB" => "https://multimedia.elsevier.es/PublicationsMultimediaV1/item/epub/X2013251412000687?idApp=UINPBA000064" "url" => "/20132514/0000003200000002/v0_201502091616/X2013251412000687/v0_201502091617/en/main.assets" ] "en" => array:11 [ "idiomaDefecto" => true "titulo" => "C1q Nephropathy and Malignancy" "tieneTextoCompleto" => true "paginas" => array:1 [ 0 => array:2 [ "paginaInicial" => "270" "paginaFinal" => "272" ] ] "autores" => array:1 [ 0 => array:3 [ "autoresLista" => "Sofia Rocha, M. João Carvalho, Luísa Lobato, Josefina Santos, Guilherme Rocha, Ramón Vizcaíno, António Cabrita" "autores" => array:7 [ 0 => array:4 [ "nombre" => "Sofia" "apellidos" => "Rocha" "email" => array:1 [ 0 => "sofiarocha81@gmail.com" ] "referencia" => array:1 [ 0 => array:2 [ "etiqueta" => "<span class="elsevierStyleSup">a</span>" "identificador" => "affa" ] ] ] 1 => array:3 [ "nombre" => "M. João" "apellidos" => "Carvalho" "referencia" => array:1 [ 0 => array:2 [ "etiqueta" => "<span class="elsevierStyleSup">a</span>" "identificador" => "affa" ] ] ] 2 => array:3 [ "nombre" => "Luísa" "apellidos" => "Lobato" "referencia" => array:1 [ 0 => array:2 [ "etiqueta" => "<span class="elsevierStyleSup">a</span>" "identificador" => "affa" ] ] ] 3 => array:3 [ "nombre" => "Josefina" "apellidos" => "Santos" "referencia" => array:1 [ 0 => array:2 [ "etiqueta" => "<span class="elsevierStyleSup">a</span>" "identificador" => "affa" ] ] ] 4 => array:3 [ "nombre" => "Guilherme" "apellidos" => "Rocha" "referencia" => array:1 [ 0 => array:2 [ "etiqueta" => "<span class="elsevierStyleSup">a</span>" "identificador" => "affa" ] ] ] 5 => array:3 [ "nombre" => "Ramón" "apellidos" => "Vizcaíno" "referencia" => array:1 [ 0 => array:2 [ "etiqueta" => "<span class="elsevierStyleSup">b</span>" "identificador" => "affb" ] ] ] 6 => array:3 [ "nombre" => "António" "apellidos" => "Cabrita" "referencia" => array:1 [ 0 => array:2 [ "etiqueta" => "<span class="elsevierStyleSup">a</span>" "identificador" => "affa" ] ] ] ] "afiliaciones" => array:2 [ 0 => array:3 [ "entidad" => "Department of Nephrology, Hospital de Santo António, Centro Hospitalar do Porto, Porto, Portugal, " "etiqueta" => "<span class="elsevierStyleSup">a</span>" "identificador" => "affa" ] 1 => array:3 [ "entidad" => "Department of Pathology, Hospital de Santo António, Centro Hospitalar do Porto, Porto, Portugal, " "etiqueta" => "<span class="elsevierStyleSup">b</span>" "identificador" => "affb" ] ] ] ] "resumenGrafico" => array:2 [ "original" => 0 "multimedia" => array:8 [ "identificador" => "fig1" "etiqueta" => "Fig. 1" "tipo" => "MULTIMEDIAFIGURA" "mostrarFloat" => true "mostrarDisplay" => false "copyright" => "Elsevier España" "figura" => array:1 [ 0 => array:4 [ "imagen" => "11246_16025_23512_en_f1_11246.jpg" "Alto" => 1068 "Ancho" => 1392 "Tamanyo" => 1272556 ] ] "descripcion" => array:1 [ "en" => "Kidney biopsy specimen." ] ] ] "textoCompleto" => "<p class="elsevierStylePara"><span class="elsevierStyleBold">Dear Editor,</span></p><p class="elsevierStylePara">C1q nephropathy (C1qN) is an idiopathic glomerular disease characterized by extensive mesangial deposition of C1q with associated mesangial immune complexes, in the absence of evidence of systemic lupus erythematosus.<span class="elsevierStyleSup">1</span></p><p class="elsevierStylePara">The prevalence of C1qN has been estimated from 0.2% to 16%.<span class="elsevierStyleSup">1-9</span> Light microscopy (LM) findings range from no glomerular abnormalities to mesangial proliferation<span class="elsevierStyleSup">1,6-9,11,12</span> or focal segmental glomerulosclerosis (FSG).<span class="elsevierStyleSup">2-4,6-8,13</span> Clinical presentations vary from asymptomatic urinary anomalies,<span class="elsevierStyleSup">5,7,8,11,13</span> and macroscopic hematuria,<span class="elsevierStyleSup">14</span> to nephritic syndrome<span class="elsevierStyleSup">3,15</span> and corticorresistent nephrotic syndrome (NS).<span class="elsevierStyleSup">1,2-4,6-8</span> Earlier reports found a poor response to steroids and a high risk of progression to end-stage renal disease (ESRD),<span class="elsevierStyleSup">1,3,6,12,15</span> particularly those with FSG. Patients presenting asymptomatic urinary anomalies have been found to have a good prognosis.<span class="elsevierStyleSup">2-5,7,8</span> The variability in the prevalence, clinical presentation and prognosis of C1qN has been attributed to different ages and ethnicities of the patients included in the series, and to different thresholds to perform a renal biopsy.</p><p class="elsevierStylePara">The association between NS and malignancy has been reported in various glomerulopathies, but not with C1qN. Recognition of malignancy-associated glomerulopathies is important to prevent ineffective and potentially harmful treatment.</p><p class="elsevierStylePara">A 56-year-old male was admitted to our Department with NS. He reported persistent peripheral edema lasting for two months. He was a smoker of 80 packs/year. He had exuberant edema of lower extremities and abdominal wall. Laboratory findings revealed hypoalbuminemia (1.1g/dL), proteinuria (10g/day) and microscopic hematuria; serum creatinine was 1.1mg/dL and urea: 48mg/dL. Hyperlipidemia (total-cholesterol: 326mg/dL) was also noted. HBs-antigen, HCV-antibody and HIV-antibody were all negative. Serum protein electrophoresis was unremarkable; complement levels, ANCA, ANA, cryoglobulins and anti-phospholipid antibodies were normal. Ultrassonography of the kidneys was unremarkable. Abdominal ultrassonography showed small volume ascites, and chest X-ray revealed small pleural effusions, without any other abnormal findings.</p><p class="elsevierStylePara">A renal biopsy was performed, whose histological findings are shown in Figure 1. Fifteen glomeruli were observed, showing segmental thickening of glomerular basement membranes (GBM) and mesangium by an eosinophilic Congo-red negative amorphous material. Spike formation or stippling of the GBM was absent in periodic-acid methenamine-silver staining. Immunofluorescence (IF) revealed predominant presence of comma-shaped C1q mesangial deposits.</p><p class="elsevierStylePara">We started prednisolone (1mg/Kg/day), cyclosporine (3mg/Kg/day) and acenocumarol. One month later, he had an acute pyelonephritis, with worsening renal function (creatinine: 1.6mg/dL). Prednisolone dose was reduced to 0.5mg/Kg/day.</p><p class="elsevierStylePara">Two months later, his clinical condition deteriorated, with asthenia, anorexia and anasarca. Laboratory findings revealed a serum creatinine of 3.9mg/d, with proteinuria (39g/day) and hypoalbuminemia (1.1g/dL); trough levels of cyclosporine were 176ng/mL. In an attempt to reduce proteinuria, non-steroidal anti-inflammatory drugs were tried, without response. Cyclosporine was stopped and a right nephrectomy was performed. FSG was noted in all of the 15 glomeruli, with persistence of mesangial C1q deposits. It is plausible that the first biopsy was not representative, or maybe this findings represented the rapid course of the disease.</p><p class="elsevierStylePara">In the post-operative period, the patient developed signs of hyperhydration and started haemodialysis. Hypoalbuminemia and signs of hyperhidration gradually improved, but he maintained severe proteinuria. When clinical euvolemia was achieved, a right pleural effusion persisted. A CT scan was performed, revealing a disseminated neoplasm (Figure 2). A pleural exudate without malignant cells was drained. Tumor markers Ca 19.9 (95.2U/L, normal <27U/L) and neuron specific enolase (NSE) (96.6U/L, normal <15.2U/L) were elevated.</p><p class="elsevierStylePara">The patient’s general condition rapidly deteriorated with marked cachexy and, later on, respiratory failure. Invasive investigation was not possible, as the patient was not fit. A week later, he died with a nosocomial respiratory infection. Histological characterization of the neoplasm was not possible, as the patient’s family refused an autopsy.</p><p class="elsevierStylePara">C1qN can present with NS, typically with histological phenotype of either MCD or FSG. In a report of 15 pediatric patients with C1qN, 9 children had corticorresistent NS. FSG was diagnosed in four cases with poor outcome.<span class="elsevierStyleSup">3</span> Markowitz et al.<span class="elsevierStyleSup">2</span> reported 19 patients with C1qN, 79% of which with nephrotic proteinuria. Renal biopsy disclosed FSG in 17 patients and MCD in two. Four patients with FSG had progressive renal insufficiency and two developed ESRD within 27 months. In a report of 20 pediatric patients, 70% presented nephrotic range proteinuria.<span class="elsevierStyleSup">4</span> The most common histological phenotypes were FSG (40%) and MCD (30%). Patients with FSG had poor prognosis, with half progressing to ESRD in 3 years. In the report of Vizjak et al.<span class="elsevierStyleSup">7</span> comprising 72 kidney biopsies with C1qN, FSG was found in 11 patients with NS, 33% which progressed to ESRD within 2.9 years. Hisano et al.<span class="elsevierStyleSup">8</span> reported a lower prevalence of NS (41%) among 61 Japanese patients with C1qN. The prevalence of MCD in the nephrotic group was 92%, while FSG corresponded only to 8% of the cases. The majority of the patients in nephrotic group were frequent relapsers, but only 4% progressed to ESRD.</p><p class="elsevierStylePara">A paraneoplastic syndrome is usually inferred when glomerular proteinuria develops in the six months before or after the diagnosis of malignancy. In our patient, initial evaluation didn’t provide any clue to an underlying diagnosis of malignancy. His systemic manifestations were attributed to severe protein loss, as well as to prolonged periods of hospitalization. Five months after the diagnosis of NS, a right pleural effusion persisted after achievement of euvolemia, and a CT was performed showing a disseminated neoplasm. The patient’s clinical condition had markedly deteriorated and he died of sepsis and respiratory failure within a week.</p><p class="elsevierStylePara">Previous immunossupressive therapy may have triggered tumor cells, and promote the rapid and inexorable outcome. The patient was a heavy smoker, a known risk factor for several types of neoplasm, including lung and gastrointestinal tract carcinomas, the most frequently associated with paraneoplastic glomerulopathies. He also had high levels of NSE and Ca 19.9, which can be found in gastrointestinal and lung cancers.</p><p class="elsevierStylePara">Failure to recognize paraneoplastic glomerulonephritis can subject patients to ineffective and potentially harmful therapy. It is important to highlight the possible association between C1qN and malignancy. Before refractory NS associated with C1qN, an underlying malignancy should be suspected.</p><p class="elsevierStylePara"> </p><p class="elsevierStylePara"><span class="elsevierStyleBold">Conflict of interest</span></p><p class="elsevierStylePara">The authors declare that there is no conflict of interest associated with this manuscript.</p><p class="elsevierStylePara"><a href="grande/11246_16025_23512_en_f1_11246.jpg" class="elsevierStyleCrossRefs"><img src="11246_16025_23512_en_f1_11246.jpg" alt="Kidney biopsy specimen."></img></a></p><p class="elsevierStylePara">Figure 1. Kidney biopsy specimen.</p><p class="elsevierStylePara"><a href="grande/11246_16025_23513_en_f2_11246.jpg" class="elsevierStyleCrossRefs"><img src="11246_16025_23513_en_f2_11246.jpg" alt="CT scan"></img></a></p><p class="elsevierStylePara">Figure 2. CT scan</p>" "pdfFichero" => "P1-E534-S3460-A11246-EN.pdf" "tienePdf" => true "multimedia" => array:2 [ 0 => array:8 [ "identificador" => "fig1" "etiqueta" => "Fig. 1" "tipo" => "MULTIMEDIAFIGURA" "mostrarFloat" => true "mostrarDisplay" => false "copyright" => "Elsevier España" "figura" => array:1 [ 0 => array:4 [ "imagen" => "11246_16025_23512_en_f1_11246.jpg" "Alto" => 1068 "Ancho" => 1392 "Tamanyo" => 1272556 ] ] "descripcion" => array:1 [ "en" => "Kidney biopsy specimen." ] ] 1 => array:8 [ "identificador" => "fig2" "etiqueta" => "Fig. 2" "tipo" => "MULTIMEDIAFIGURA" "mostrarFloat" => true "mostrarDisplay" => false "copyright" => "Elsevier España" "figura" => array:1 [ 0 => array:4 [ "imagen" => "11246_16025_23513_en_f2_11246.jpg" "Alto" => 612 "Ancho" => 1395 "Tamanyo" => 367789 ] ] "descripcion" => array:1 [ "en" => "CT scan" ] ] ] "bibliografia" => array:2 [ "titulo" => "Bibliography" "seccion" => array:1 [ 0 => array:1 [ "bibliografiaReferencia" => array:15 [ 0 => array:3 [ "identificador" => "bib1" "etiqueta" => "1" "referencia" => array:1 [ 0 => array:3 [ "referenciaCompleta" => "Jennette JC, Hipp CG. 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| Year/Month | Html | Total | |
|---|---|---|---|
| 2024 November | 9 | 9 | 18 |
| 2024 October | 100 | 35 | 135 |
| 2024 September | 63 | 36 | 99 |
| 2024 August | 84 | 51 | 135 |
| 2024 July | 66 | 30 | 96 |
| 2024 June | 43 | 34 | 77 |
| 2024 May | 57 | 29 | 86 |
| 2024 April | 45 | 36 | 81 |
| 2024 March | 39 | 18 | 57 |
| 2024 February | 39 | 35 | 74 |
| 2024 January | 29 | 30 | 59 |
| 2023 December | 20 | 22 | 42 |
| 2023 November | 43 | 39 | 82 |
| 2023 October | 39 | 35 | 74 |
| 2023 September | 36 | 33 | 69 |
| 2023 August | 37 | 12 | 49 |
| 2023 July | 42 | 33 | 75 |
| 2023 June | 51 | 25 | 76 |
| 2023 May | 65 | 32 | 97 |
| 2023 April | 30 | 11 | 41 |
| 2023 March | 68 | 22 | 90 |
| 2023 February | 35 | 21 | 56 |
| 2023 January | 34 | 21 | 55 |
| 2022 December | 58 | 38 | 96 |
| 2022 November | 47 | 35 | 82 |
| 2022 October | 38 | 40 | 78 |
| 2022 September | 49 | 30 | 79 |
| 2022 August | 47 | 40 | 87 |
| 2022 July | 34 | 38 | 72 |
| 2022 June | 33 | 31 | 64 |
| 2022 May | 29 | 32 | 61 |
| 2022 April | 41 | 53 | 94 |
| 2022 March | 45 | 46 | 91 |
| 2022 February | 32 | 46 | 78 |
| 2022 January | 37 | 28 | 65 |
| 2021 December | 57 | 45 | 102 |
| 2021 November | 38 | 41 | 79 |
| 2021 October | 27 | 48 | 75 |
| 2021 September | 45 | 39 | 84 |
| 2021 August | 48 | 35 | 83 |
| 2021 July | 29 | 38 | 67 |
| 2021 June | 34 | 21 | 55 |
| 2021 May | 53 | 32 | 85 |
| 2021 April | 106 | 62 | 168 |
| 2021 March | 56 | 34 | 90 |
| 2021 February | 52 | 17 | 69 |
| 2021 January | 42 | 17 | 59 |
| 2020 December | 33 | 11 | 44 |
| 2020 November | 31 | 15 | 46 |
| 2020 October | 27 | 11 | 38 |
| 2020 September | 29 | 7 | 36 |
| 2020 August | 30 | 12 | 42 |
| 2020 July | 45 | 11 | 56 |
| 2020 June | 50 | 12 | 62 |
| 2020 May | 59 | 8 | 67 |
| 2020 April | 36 | 16 | 52 |
| 2020 March | 49 | 14 | 63 |
| 2020 February | 48 | 18 | 66 |
| 2020 January | 51 | 22 | 73 |
| 2019 December | 61 | 25 | 86 |
| 2019 November | 45 | 21 | 66 |
| 2019 October | 30 | 10 | 40 |
| 2019 September | 57 | 19 | 76 |
| 2019 August | 33 | 12 | 45 |
| 2019 July | 33 | 21 | 54 |
| 2019 June | 37 | 10 | 47 |
| 2019 May | 40 | 11 | 51 |
| 2019 April | 78 | 32 | 110 |
| 2019 March | 49 | 28 | 77 |
| 2019 February | 28 | 21 | 49 |
| 2019 January | 32 | 16 | 48 |
| 2018 December | 78 | 29 | 107 |
| 2018 November | 118 | 19 | 137 |
| 2018 October | 69 | 10 | 79 |
| 2018 September | 66 | 24 | 90 |
| 2018 August | 52 | 12 | 64 |
| 2018 July | 57 | 15 | 72 |
| 2018 June | 50 | 11 | 61 |
| 2018 May | 59 | 13 | 72 |
| 2018 April | 56 | 10 | 66 |
| 2018 March | 74 | 14 | 88 |
| 2018 February | 59 | 12 | 71 |
| 2018 January | 61 | 11 | 72 |
| 2017 December | 75 | 11 | 86 |
| 2017 November | 35 | 2 | 37 |
| 2017 October | 38 | 10 | 48 |
| 2017 September | 28 | 8 | 36 |
| 2017 August | 39 | 7 | 46 |
| 2017 July | 45 | 14 | 59 |
| 2017 June | 44 | 12 | 56 |
| 2017 May | 54 | 16 | 70 |
| 2017 April | 29 | 9 | 38 |
| 2017 March | 30 | 28 | 58 |
| 2017 February | 28 | 37 | 65 |
| 2017 January | 25 | 27 | 52 |
| 2016 December | 65 | 10 | 75 |
| 2016 November | 71 | 20 | 91 |
| 2016 October | 88 | 24 | 112 |
| 2016 September | 136 | 6 | 142 |
| 2016 August | 198 | 8 | 206 |
| 2016 July | 191 | 14 | 205 |
| 2016 June | 112 | 0 | 112 |
| 2016 May | 149 | 0 | 149 |
| 2016 April | 109 | 0 | 109 |
| 2016 March | 96 | 0 | 96 |
| 2016 February | 126 | 0 | 126 |
| 2016 January | 114 | 0 | 114 |
| 2015 December | 130 | 0 | 130 |
| 2015 November | 98 | 0 | 98 |
| 2015 October | 86 | 0 | 86 |
| 2015 September | 74 | 0 | 74 |
| 2015 August | 63 | 0 | 63 |
| 2015 July | 57 | 0 | 57 |
| 2015 June | 26 | 0 | 26 |
| 2015 May | 38 | 0 | 38 |
| 2015 April | 7 | 0 | 7 |
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