IgM nephropathy in children: clinicopathologic analysis
Nefropatía IgM en niños: análisis clinicopatológico
Luis F. Ariasa, M.ª Claudia Pradab, M. Claudia Pradab, Catalina Vélez-Echeverric, Lina M. Serna-Higuitac, Ana K. Serrano-Gayubob, Carolina L. Ochoac, Juan J. Vanegas-Ruizc
a Departamento de Patología, Facultad de Medicina, Universidad de Antioquia y Hospital Universitario San Vicente de Paúl, Medellín, Antioquia, Colombia,
b Servicio de Nefrología, Facultad de Medicina, Universidad de Antioquia y Hospital Universitario San Vicente de Paúl, Medellín, Antioquia, Colombia,
c Servicio de Nefrología, Hospital Pablo Tobón Uribe, Medellín, Antioquia, Colombia,
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"apellidos" => "Vanegas-Ruiz" "referencia" => array:1 [ 0 => array:2 [ "etiqueta" => "<span class="elsevierStyleSup">c</span>" "identificador" => "affc" ] ] ] ] "afiliaciones" => array:3 [ 0 => array:3 [ "entidad" => "Departamento de Patología, Facultad de Medicina, Universidad de Antioquia y Hospital Universitario San Vicente de Paúl, Medellín, Antioquia, Colombia, " "etiqueta" => "<span class="elsevierStyleSup">a</span>" "identificador" => "affa" ] 1 => array:3 [ "entidad" => "Servicio de Nefrología, Facultad de Medicina, Universidad de Antioquia y Hospital Universitario San Vicente de Paúl, Medellín, Antioquia, Colombia, " "etiqueta" => "<span class="elsevierStyleSup">b</span>" "identificador" => "affb" ] 2 => array:3 [ "entidad" => "Servicio de Nefrología, Hospital Pablo Tobón Uribe, Medellín, Antioquia, Colombia, " "etiqueta" => "<span class="elsevierStyleSup">c</span>" "identificador" => "affc" ] ] ] ] "titulosAlternativos" => array:1 [ "es" => array:1 [ "titulo" => "Nefropatía IgM en niños: análisis clinicopatológico" ] ] "resumenGrafico" => array:2 [ "original" => 0 "multimedia" => array:8 [ "identificador" => "fig1" "etiqueta" => "Tab. 1" "tipo" => "MULTIMEDIAFIGURA" "mostrarFloat" => true "mostrarDisplay" => false "copyright" => "Elsevier España" "figura" => array:1 [ 0 => array:4 [ "imagen" => "11962_16025_48348_en_t11111962_02ing_maquetacin_1.jpg" "Alto" => 836 "Ancho" => 2177 "Tamanyo" => 406495 ] ] "descripcion" => array:1 [ "en" => "Demographic and clinical data" ] ] ] "textoCompleto" => "<p class="elsevierStylePara"><span class="elsevierStyleBold">INTRODUCTION</span></p><p class="elsevierStylePara"> </p><p class="elsevierStylePara">Two articles published in 1978 by independent groups,<span class="elsevierStyleSup">1,2</span> are considered by many authors to be the first descriptions of a glomerulopathy characterised by diffuse mesangial deposits of immunoglobulin M (IgM) in patients with severe proteinuria. However, four years earlier, a work had been published that described renal biopsies with glomerular deposits predominantly of IgM, but in patients with persistent or recurrent haematuria.<span class="elsevierStyleSup">3</span> Although controversial, IgM nephropathy (IgMN) is defined by its immunopathological characteristics: the presence of IgM as the only or dominant immunoglobulin, located in the mesangium and with global and diffuse distribution.<span class="elsevierStyleSup">1,2,4-18</span> Its histologic characteristics are highly variable, from a normal glomerular appearance, as in minimal change disease (MCD) to varying degrees of mesangial hypercellularity and focal segmental glomerulosclerosis (FSGS). Most recent publications on IgMN describe its clinical presentation as being characterised by nephrotic syndrome (NS) or severe proteinuria with varying prognosis and response to steroids;<span class="elsevierStyleSup">1,2,5,14,19-21</span> few authors describe cases of isolated haematuria.<span class="elsevierStyleSup">3,13,18</span></p><p class="elsevierStylePara">There has been considerable debate regarding the meaning or importance of mesangial IgM deposits. Some authors consider that these deposits are an epiphenomenon of little importance in the aetiology or clinical progression<span class="elsevierStyleSup">20,22-24 </span>while others view them as nephritogenic and consider IgMN to be a well-defined clinicopathological entity.<span class="elsevierStyleSup">1,2,4,5,13,14,17,18,21,25-28</span> Electron microscopy displays mesangial and paramesangial electron dense deposits, which are considered to be a confirmation of diagnosis, in spite of the fact that they are not always present in all cases of IgMN or that in other cases there are few and they are poorly defined.<span class="elsevierStyleSup">14,15,17</span></p><p class="elsevierStylePara">Its incidence varies, in accordance with different series, between 4.8% and 8.6% of all renal biopsies, affecting all ages and without predilection for gender.<span class="elsevierStyleSup">7,28-30</span> Some authors report a higher frequency of cortico-resistance or cortico-dependence with relatively few cases of complete remission.<span class="elsevierStyleSup">9,31,32</span> However, other authors have not found a long-term prognosis other than MCD.<span class="elsevierStyleSup">6,19,20,22-24,33-35</span></p><p class="elsevierStylePara">Its pathophysiology is unknown, but it has been reported that in some patients there is an increase in serum IgM immune complexes, which could be due to an abnormality in the normal function of T lymphocytes or an abnormality in the clearance of immune complexes by mesangial cells, thereby inducing mesangial activation and hypercellularity measured by IgM deposits which would lead to histological changes similar to those of MCD or FSGS.<span class="elsevierStyleSup">27</span></p><p class="elsevierStylePara">There are currently no precise therapeutic implications for patients with NS and single or predominant diffuse mesangial IgM deposits; however, it is important to determine the clinical and morphological characteristics of this finding to attempt to obtain clarity. Our aim was to conduct a clinicopathological description and assess the response to steroid treatment of paediatric patients diagnosed with NS and with diffuse and global mesangial IgM deposits: IgMN.</p><p class="elsevierStylePara"> </p><p class="elsevierStylePara"><span class="elsevierStyleBold">MATERIAL AND METHOD</span></p><p class="elsevierStylePara"> </p><p class="elsevierStylePara">Retrospective descriptive study. From the records of the authors’ institutions, all biopsies of paediatric patients (under 18 years of age) were reviewed between January 2005 and June 2011. We included all cases of patients with NS who were diffuse mesangial IgM positive on immunofluorescence, whether there was single or dominant positivity. The exclusion criteria were simultaneous deposits of various immunoglobins and C1q and C3 fractions of the complement, since this suggested the possibility of lupus erythematosus, the presence of other immunoglobulins or complement fraction with equal (co-dominance) or greater intensity than for IgM on immunofluorescence, and strong and diffuse deposits of IgM in glomerular capillary walls, as this suggests other immune complex mediated diseases, diagnosis of any systemic disease that would compromise the kidneys (secondary glomerulopathy) and biopsies from transplanted kidney. Patients with weak staining for C3 were included. Although the diagnosis of IgMN has historically been defined as a positive immunofluorescence for IgM with the presence of electron dense deposits, other authors have based their diagnosis solely on the presence of positive immunofluorescence for IgM.<span class="elsevierStyleSup">14, 15, 28.31</span> The latter was the criterion that we used for the diagnosis of IgMN in the study population.</p><p class="elsevierStylePara">For the diagnostic study in each case, renal tissue samples were divided and processed for light microscopy and immunofluorescence; of the biopsy tissue selected for conventional light microscopy, we obtained 2 micron thick sections for haematoxylin and eosin stain, Masson’s trichrome stain, periodic acid-Schiff stain and methenamine silver stain. Immunofluorescence (for IgA, IgG, IgM, C3, C1q, κ and λ) was essential for determining the presence of IgM deposits in the mesangium and ruling out other causes of NS.</p><p class="elsevierStylePara">Fragments selected for immunofluorescence were frozen at -24 ° C in a medium suitable for tissue preservation (OCT Tissue-Tek<span class="elsevierStyleSup">®</span>, USA) and 3 micron thick sections were immediately made with cryostat for each immunoglobulin, complement fraction and light chain, these sections were fixed in acetone and frozen until the technique was carried out. For the latter, after the microscope slides were defrosted to room temperature, three washes were made with tris-buffered saline (TBS), each slide was incubated with the primary antibodies labelled with fluorescein isothiocyanate (Dako Carpinteria, USA) at a 1:20 dilution for 30 minutes, then three more washes were made with TBS and the coverslip was mounted with aqueous mounting medium: glycerine. Histological sections of all cases were reviewed to determine the percentage of overall glomerulosclerosis, the presence of segmental glomerular sclerosis and the approximate percentages of interstitial fibrosis and tubular atrophy.</p><p class="elsevierStylePara">All the cases included were classified as primary glomerular disease, since one of the exclusion criteria was another disease that could be the cause of glomerulopathy.</p><p class="elsevierStylePara">The clinical information and follow-up were recorded for analysis. All the information was obtained from the records of the Pathology Department or the Paediatric Nephrology Section of the authors’ institutions. The following information was recorded: age, sex, clinical presentation, renal function at diagnosis (by serum creatinine or creatinine clearance), disease progression time, systemic high blood pressure and subsequent progression on the basis of renal function (by serum creatinine or creatinine clearance) and 24-hour urine proteinuria.</p><p class="elsevierStylePara">The beginning of the disease or presentation was considered as the moment in which proteinuria was detected for the first time. Nephrotic range proteinuria was considered as values above 40mg/m<span class="elsevierStyleSup">2</span>/hour; complete remission was defined as proteinuria under 4mg/m<span class="elsevierStyleSup">2</span>/hour; partial remission was defined as proteinuria between 4 and 39mg/m<span class="elsevierStyleSup">2</span>/hour. Haematuria was defined as the presence of >3 red blood cells per high power field on urinalysis or by the presence of red cell casts in the urine sediment. Relapse was defined as the presence of proteinuria greater than 40mg/m<span class="elsevierStyleSup">2</span>/hour or three crosses in a urinary smear for three consecutive days after being in remission; cortico-resistance was defined as the presence of nephrotic proteinuria after eight weeks of treatment with steroids; cortico-dependent was when the patient had two consecutive relapses during the decrease of steroid treatment or relapse within 14 days of its discontinuation. The pharmacological treatment received was also recorded. The minimum follow-up period was six months.</p><p class="elsevierStylePara">The frequency data are presented as percentages; the values in which we determined dispersion measurements are presented as medians and minimum and maximum values, owing to the non-normal distribution of data.</p><p class="elsevierStylePara"> </p><p class="elsevierStylePara"><span class="elsevierStyleBold">RESULTS</span></p><p class="elsevierStylePara"> </p><p class="elsevierStylePara"><span class="elsevierStyleBold">Demographic and clinical data</span></p><p class="elsevierStylePara"> </p><p class="elsevierStylePara">Out of a total of 251 paediatric renal biopsies during the study period, 13 biopsies (5.17%) were found with NS diagnosis and diffuse IgMN mesangial deposits. Six of the cases correspond to females (46.15%); the median age was 2 years (range: 1 to 12). All patients were diagnosed with NS, of which 7 (53.8%) were categorised as frequent relapse patients, 5 (38.4%) cortico-resistant and one (7.7%) cortico-dependent. The median level of proteinuria at diagnosis was 78mg/m<span class="elsevierStyleSup">2</span>/hour (range: 38-321) (Table 1); all patients presented nephrotic range proteinuria at some time in the progression of their disease. There was haematuria in 4 of the 13 patients (30.7%), which was episodic microscopic in one of them and persistent microscopic in the three remaining patients. Two patients (15.3%) presented high levels of blood pressure at the time of diagnosis (blood pressure levels above the 95<span class="elsevierStyleSup">th</span> percentile for weight and height). The level of serum creatinine at the time of diagnosis was normal in 92.3% of patients (12/13). During the follow-up, 2 patients (15.3%) presented persistently high creatinine levels in the first year following diagnosis (non-end-stage chronic renal failure).</p><p class="elsevierStylePara"> </p><p class="elsevierStylePara"><span class="elsevierStyleBold">Histological and immunopathological findings</span></p><p class="elsevierStylePara"> </p><p class="elsevierStylePara">The median total number of glomeruli per biopsy was 21 (range 7-34), the most frequent glomerular morphological finding was diffuse mesangial hypercellularity: in 46.1% of patients. In 30.8%, FSGS was found and in 23.1% there were no glomerular abnormalities (minimal glomerular changes). All biopsies had diffuse mesangial positivity for IgM and in two cases there were also focal and segmental deposits of the same immunoglobulin in some capillary walls. In one case, there was weak mesangial positivity for C3 (Table 2). Tubular atrophy was found in 3 patients (23.1%), which was mild (<25%) in all of them; in the 10 remaining cases, there were no tubulointerstitial or chronic vascular abnormalities (Figure 1 and Figure 2).</p><p class="elsevierStylePara"> </p><p class="elsevierStylePara"><span class="elsevierStyleBold">Clinical progression</span></p><p class="elsevierStylePara"> </p><p class="elsevierStylePara">During the follow-up, at six months we found that 7 patients (53.8%) continued with nephrotic range proteinuria, 2 maintained non-nephrotic range proteinuria and in 4 patients, proteinuria had disappeared. However, at the end of the follow-up, 7 patients were classified as having NS with frequent relapses (53.8%), five were cortico-resistant (38.5%) and one was cortico-dependent (7.7%).</p><p class="elsevierStylePara">100% of patients received steroids and antiproteinuric medication; in 4 of them (30.7%) this was the only medication they received; 3 out of 13 (23.1%) received cyclophosphamide, 5 (38.4 %) mycophenolate, 1 astemizole (7.7%) and 1 patient (7.7%) received cyclosporine.</p><p class="elsevierStylePara">On comparing the findings of the renal biopsy with the progression of the patients, we found that all patients with FSGS were cortico-resistant; however, in patients with diffuse mesangial hypercellularity, 83.3% (5/6) were classified as frequent relapse patients, and 16.6%, as cortico-resistant (Table 3). With regard to the treatment used on cortico-resistant patients, 1 received cyclosporine, 3 mycophenolate and 1 only steroids and enalapril; the latter patient presented a rapid loss of renal function, which may explain the non-use of a second immunosuppressant (Table 3).</p><p class="elsevierStylePara">Two patients (14.3%) presented deterioration in renal function (not terminal), one had a histological finding of FSGS and another was diagnosed with diffuse mesangial hypercellularity. The three hypertensive patients continued to have high blood pressure in spite of treatment.</p><p class="elsevierStylePara"> </p><p class="elsevierStylePara"><span class="elsevierStyleBold">DISCUSSION</span></p><p class="elsevierStylePara"> </p><p class="elsevierStylePara">According to the review of databases, this is the first study carried out in our country on clinical, histological and immunopathological characteristics of children with IgMN. Out of the total renal biopsies during the study period, IgMN corresponded to 5.17%, which is similar to that which had been reported in previous studies, where prevalence varies between 4.8-7.8%.<span class="elsevierStyleSup">7,28-30</span></p><p class="elsevierStylePara">The characteristics of our patients suggest that IgMN usually presents with cortico-resistance or cortico-dependence. However, there is a bias inherent in the indications for carrying out a renal biopsy in paediatric patients with NS: only those who have atypical clinical features, cortico-dependence, frequent relapses or cortico-resistance are biopsied. Therefore, it is not possible to know with certainty how many patients with NS and response to treatment have diffuse mesangial IgM deposits (IgMN). However, clinical follow-ups of many years, comparing patients with a biopsy that shows MCD or FSGS without IgM deposits and patients with IgMN would allow the importance of mesangial deposits of this immunoglobulin to be determined in response to steroids and the long-term prognosis.</p><p class="elsevierStylePara">The contradictory results in the literature with regard to the clinical importance of IgM deposits need to be analysed with caution due to the relatively short follow-up period in many studies; most patients with MCD or FSGS who develop chronic kidney disease do so after many years. The persistent increase in serum creatinine levels in two of our cases suggests that IgM could be important in the progression of the disease. However, one of these patients presented histological disorders of FSGS, a lesion that has demonstrated that it has an adverse prognosis for renal function. Thus far, the rigorous review of literature has not allowed us to draw objective conclusions on the long term prognosis of IgM.</p><p class="elsevierStylePara">Zeis et al.<span class="elsevierStyleSup">28</span> compared patients with presence or not of IgM in the renal biopsy and found a greater progression to FSGS on carrying out a second renal biopsy in patients with mesangial IgM, which suggests the possibility of histological transition from MCD or mesangial hypercellularity to FSGS. The authors consider the possibility of IgM being a pathogenic factor involved in a higher degree of glomerular damage and suggest that it may be a severity marker with a higher probability of requiring a second line of immunosuppressant treatment. Other authors did not find in their work that IgMN would involve a worse and statistically significant prognosis.<span class="elsevierStyleSup">6,19,20,22-24,33-35</span></p><p class="elsevierStylePara">The presence of haematuria, which is an uncommon finding in patients with NS due to MCD, was common in our patients (50%), which is similar to that found in some previous studies;<span class="elsevierStyleSup">7,9,10,25</span> nevertheless, we cannot determine if mesangial IgM has a direct relationship with or is the cause of this haematuria; in fact, in the other 50% of patients with IgMN, haematuria was not found. In most series, patients present complete NS or variable proteinuria; only some authors include cases with isolated haematuria.<span class="elsevierStyleSup">3,13,18</span> In our centre, we did not find cases of patients with isolated haematuria (without proteinuria) and IgMN immunopathological characteristics.</p><p class="elsevierStylePara">In conclusion, this study demonstrates that the presence of diffuse mesangial IgM in patients with nephrotic syndrome is not a very uncommon finding; its clinical presentation has been associated with a lower response to steroids and more aggressive behaviour. Nevertheless, its long-term prognosis is still unknown and comparative studies with a greater follow-up period are required for clear conclusions to be obtained.</p><p class="elsevierStylePara"> </p><p class="elsevierStylePara"><span class="elsevierStyleBold">Conflicts of interest</span></p><p class="elsevierStylePara"> </p><p class="elsevierStylePara">The authors declare that they have no conflicts of interest related to the contents of this article.</p><p class="elsevierStylePara"><a href="grande/11962_16025_48348_en_t11111962_02ing_maquetacin_1.jpg" class="elsevierStyleCrossRefs"><img src="11962_16025_48348_en_t11111962_02ing_maquetacin_1.jpg" alt="Demographic and clinical data"></img></a></p><p class="elsevierStylePara">Table 1. Demographic and clinical data</p><p class="elsevierStylePara"><a href="grande/11962_16025_48349_en_t21111962_02ing_maquetacin_1.jpg" class="elsevierStyleCrossRefs"><img src="11962_16025_48349_en_t21111962_02ing_maquetacin_1.jpg" alt="Histological and immunopathological findings"></img></a></p><p class="elsevierStylePara">Table 2. Histological and immunopathological findings</p><p class="elsevierStylePara"><a href="grande/11962_16025_48350_en_t31111962_02ing_maquetacin_1.jpg" class="elsevierStyleCrossRefs"><img src="11962_16025_48350_en_t31111962_02ing_maquetacin_1.jpg" alt="Histological findings and treatment received"></img></a></p><p class="elsevierStylePara">Table 3. Histological findings and treatment received</p><p class="elsevierStylePara"><a href="grande/11962_16025_48351_en_f11111962_02ing_maquetacin_1.jpg" class="elsevierStyleCrossRefs"><img src="11962_16025_48351_en_f11111962_02ing_maquetacin_1.jpg" alt="Renal biopsy findings"></img></a></p><p class="elsevierStylePara">Figure 1. Renal biopsy findings</p><p class="elsevierStylePara"><a href="grande/11962_16025_48352_en_f21111962_02ing_maquetacin_1.jpg" class="elsevierStyleCrossRefs"><img src="11962_16025_48352_en_f21111962_02ing_maquetacin_1.jpg" alt="Renal biopsy findings"></img></a></p><p class="elsevierStylePara">Figure 2. Renal biopsy findings</p>" "pdfFichero" => "P1-E557-S4288-A11962-EN.pdf" "tienePdf" => true "PalabrasClave" => array:2 [ "es" => array:5 [ 0 => array:4 [ "clase" => "keyword" "titulo" => "Palabras clave" "identificador" => "xpalclavsec440265" "palabras" => array:1 [ 0 => "Síndrome nefrótico" ] ] 1 => array:4 [ "clase" => "keyword" "titulo" => "Palabras clave" "identificador" => "xpalclavsec440267" "palabras" => array:1 [ 0 => "Nefropatía IgM" ] ] 2 => array:4 [ "clase" => "keyword" "titulo" => "Palabras clave" "identificador" => "xpalclavsec440269" "palabras" => array:1 [ 0 => "Enfermedad de cambios mínimos" ] ] 3 => array:4 [ "clase" => "keyword" "titulo" => "Palabras clave" "identificador" => "xpalclavsec440271" "palabras" => array:1 [ 0 => "Enfermedades glomerulares" ] ] 4 => array:4 [ "clase" => "keyword" "titulo" => "Palabras clave" "identificador" => "xpalclavsec440273" "palabras" => array:1 [ 0 => "Glomeruloesclerosis focal y segmentaria" ] ] ] "en" => array:5 [ 0 => array:4 [ "clase" => "keyword" "titulo" => "Keywords" "identificador" => "xpalclavsec440266" "palabras" => array:1 [ 0 => "Nephrotic syndrome" ] ] 1 => array:4 [ "clase" => "keyword" "titulo" => "Keywords" "identificador" => "xpalclavsec440268" "palabras" => array:1 [ 0 => "IgM nephropathy" ] ] 2 => array:4 [ "clase" => "keyword" "titulo" => "Keywords" "identificador" => "xpalclavsec440270" "palabras" => array:1 [ 0 => "Minimal change disease" ] ] 3 => array:4 [ "clase" => "keyword" "titulo" => "Keywords" "identificador" => "xpalclavsec440272" "palabras" => array:1 [ 0 => "Glomerular diseases" ] ] 4 => array:4 [ "clase" => "keyword" "titulo" => "Keywords" "identificador" => "xpalclavsec440274" "palabras" => array:1 [ 0 => "Focal segmental glomeruloesclerosis" ] ] ] ] "tieneResumen" => true "resumen" => array:2 [ "es" => array:1 [ "resumen" => "<p class="elsevierStylePara"><span class="elsevierStyleBold">Introducción</span><span class="elsevierStyleBold">:</span> La nefropatía IgM (NIgM) es una glomerulonefritis caracterizada por depósitos mesangiales difusos de inmunoglobulina M (IgM), que suele manifestarse con proteinuria en rango nefrótico y que, según algunos trabajos previos, se presenta más frecuentemente en pacientes que son resistentes o dependientes del tratamiento con esteroides. <span class="elsevierStyleBold">Objetivo:</span> Realizar una descripción clínica, histológica e inmunopatológica, y evaluar la respuesta al tratamiento esteroideo de los pacientes pediátricos con diagnóstico de síndrome nefrótico y depósitos mesangiales y difusos de IgM. <span class="elsevierStyleBold">Métodos</span><span class="elsevierStyleBold">:</span> Estudio descriptivo, retrospectivo, realizado en dos centros hospitalarios, donde se analizaron los registros clínicos de pacientes pediátricos con diagnóstico de NIgM y se revaluaron los cortes histológicos. <span class="elsevierStyleBold">Resultados: </span>Trece niños fueron incluidos en el presente estudio. La NIgM correspondió al 5,17 % de todas las biopsias renales pediátricas. La edad de los pacientes estuvo entre 1 y 12 años (mediana: 2 años); el 46,7 % fueron mujeres. El hallazgo morfológico más frecuente fue hipercelularidad mesangial difusa (46,1 %), seguido de glomeruloesclerosis focal y segmentaria (30,8 %) y cambios glomerulares mínimos (23,1 %). Todos los pacientes recibieron esteroides, en 4 de ellos (30,7 %) como el único medicamento inmunosupresor; 3 (23,1 %) recibieron además ciclofosfamida, 5 (38,4 %) micofenolato y 1 (7,7 %) ciclosporina. Siete pacientes (53,8 %) presentaron recaídas frecuentes, 5 (38,5 %) fueron corticorresistentes y 1 (7,7 %) corticodependiente. Dos pacientes (15,38 %) presentaron alteración crónica de la función renal. <span class="elsevierStyleBold">Conclusión</span><span class="elsevierStyleBold">:</span> La presencia de IgM mesangial difusa en pacientes pediátricos con síndrome nefrótico no es un hallazgo muy infrecuente, su presentación clínica se ha asociado con menor respuesta a esteroides. Sin embargo, su pronóstico a largo plazo aún no se conoce.</p>" ] "en" => array:1 [ "resumen" => "<p class="elsevierStylePara"><span class="elsevierStyleBold"><span class="elsevierStyleItalic">Introduction:</span></span><span class="elsevierStyleItalic"> IgM nephropathy (IgMN) is a glomerulonephritis characterised by diffuse mesangial immunoglobulin M (IgM) deposits. It usually presents with nephrotic range proteinuria and, according to some previous work, it occurs most often in patients who are resistant to or dependent on steroid treatment.<span class="elsevierStyleBold"> Objective:</span> To perform a clinical, histological and immunopathological description and assess the response to steroid treatment of paediatric patients diagnosed with nephrotic syndrome and diffuse mesangial IgM deposits.<span class="elsevierStyleBold"> Method:</span> This is a descriptive, retrospective study carried out in two hospitals, where the clinical records of paediatric patients with IgMN were analysed and the histological sections were re-assessed. <span class="elsevierStyleBold">Results:</span> thirteen children were included in this study. IgMN corresponded to 5.17% of all paediatric renal biopsies. The age of patients ranged from 1 year to 12 years (median: 2 years), 46.7% were women. The most common morphological finding was diffuse mesangial hypercellularity (46.1%), followed by focal segmental glomerulosclerosis (30.8%) and minimal glomerular changes (23.1%). All patients received steroids; in 4 cases (30.7%) as the only immunosuppressant medication, 3 (23.1%) also received cyclophosphamide, 5 (38.4%) mycophenolate, and 1 (7.7%) cyclosporine. Seven patients (53.8%) had frequent relapses, 5 (38.5%) were cortico-resistant and 1 (7.7%) cortico-dependent. Two patients (15.38%) had chronic impairment of renal function. <span class="elsevierStyleBold">Conclusion:</span> The presence of diffuse mesangial IgM in paediatric patients with nephrotic syndrome is not a very uncommon finding; its clinical presentation has been associated with lower response to steroids. However, the long-term prognosis of these patients is still unknown.</span></p>" ] ] "multimedia" => array:5 [ 0 => array:8 [ "identificador" => "fig1" "etiqueta" => "Tab. 1" "tipo" => "MULTIMEDIAFIGURA" "mostrarFloat" => true "mostrarDisplay" => false "copyright" => "Elsevier España" "figura" => array:1 [ 0 => array:4 [ "imagen" => "11962_16025_48348_en_t11111962_02ing_maquetacin_1.jpg" "Alto" => 836 "Ancho" => 2177 "Tamanyo" => 406495 ] ] "descripcion" => array:1 [ "en" => "Demographic and clinical data" ] ] 1 => array:8 [ "identificador" => "fig2" "etiqueta" => "Tab. 2" "tipo" => "MULTIMEDIAFIGURA" "mostrarFloat" => true "mostrarDisplay" => false "copyright" => "Elsevier España" "figura" => array:1 [ 0 => array:4 [ "imagen" => "11962_16025_48349_en_t21111962_02ing_maquetacin_1.jpg" "Alto" => 771 "Ancho" => 2169 "Tamanyo" => 348233 ] ] "descripcion" => array:1 [ "en" => "Histological and immunopathological findings" ] ] 2 => array:8 [ "identificador" => "fig3" "etiqueta" => "Tab. 3" "tipo" => "MULTIMEDIAFIGURA" "mostrarFloat" => true "mostrarDisplay" => false "copyright" => "Elsevier España" "figura" => array:1 [ 0 => array:4 [ "imagen" => "11962_16025_48350_en_t31111962_02ing_maquetacin_1.jpg" "Alto" => 928 "Ancho" => 2177 "Tamanyo" => 465759 ] ] "descripcion" => array:1 [ "en" => "Histological findings and treatment received" ] ] 3 => array:8 [ "identificador" => "fig4" "etiqueta" => "Fig. 1" "tipo" => "MULTIMEDIAFIGURA" "mostrarFloat" => true "mostrarDisplay" => false "copyright" => "Elsevier España" "figura" => array:1 [ 0 => array:4 [ "imagen" => "11962_16025_48351_en_f11111962_02ing_maquetacin_1.jpg" "Alto" => 859 "Ancho" => 2121 "Tamanyo" => 534909 ] ] "descripcion" => array:1 [ "en" => "Renal biopsy findings" ] ] 4 => array:8 [ "identificador" => "fig5" "etiqueta" => "Fig. 2" "tipo" => "MULTIMEDIAFIGURA" "mostrarFloat" => true "mostrarDisplay" => false "copyright" => "Elsevier España" "figura" => array:1 [ 0 => array:4 [ "imagen" => "11962_16025_48352_en_f21111962_02ing_maquetacin_1.jpg" "Alto" => 836 "Ancho" => 2117 "Tamanyo" => 746099 ] ] "descripcion" => array:1 [ "en" => "Renal biopsy findings" ] ] ] "bibliografia" => array:2 [ "titulo" => "Bibliography" "seccion" => array:1 [ 0 => array:1 [ "bibliografiaReferencia" => array:32 [ 0 => array:3 [ "identificador" => "bib1" "etiqueta" => "1" "referencia" => array:1 [ 0 => array:3 [ "referenciaCompleta" => "Cohen A, Border W, Glassock R. 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| Year/Month | Html | Total | |
|---|---|---|---|
| 2024 November | 8 | 9 | 17 |
| 2024 October | 62 | 76 | 138 |
| 2024 September | 78 | 50 | 128 |
| 2024 August | 83 | 76 | 159 |
| 2024 July | 71 | 45 | 116 |
| 2024 June | 95 | 55 | 150 |
| 2024 May | 94 | 69 | 163 |
| 2024 April | 120 | 60 | 180 |
| 2024 March | 109 | 45 | 154 |
| 2024 February | 66 | 61 | 127 |
| 2024 January | 88 | 41 | 129 |
| 2023 December | 58 | 38 | 96 |
| 2023 November | 80 | 57 | 137 |
| 2023 October | 52 | 51 | 103 |
| 2023 September | 71 | 49 | 120 |
| 2023 August | 66 | 45 | 111 |
| 2023 July | 98 | 77 | 175 |
| 2023 June | 61 | 55 | 116 |
| 2023 May | 104 | 55 | 159 |
| 2023 April | 69 | 33 | 102 |
| 2023 March | 73 | 38 | 111 |
| 2023 February | 80 | 28 | 108 |
| 2023 January | 79 | 37 | 116 |
| 2022 December | 94 | 59 | 153 |
| 2022 November | 102 | 39 | 141 |
| 2022 October | 73 | 51 | 124 |
| 2022 September | 55 | 52 | 107 |
| 2022 August | 68 | 46 | 114 |
| 2022 July | 49 | 47 | 96 |
| 2022 June | 49 | 41 | 90 |
| 2022 May | 56 | 32 | 88 |
| 2022 April | 66 | 53 | 119 |
| 2022 March | 77 | 48 | 125 |
| 2022 February | 52 | 41 | 93 |
| 2022 January | 59 | 49 | 108 |
| 2021 December | 105 | 44 | 149 |
| 2021 November | 59 | 36 | 95 |
| 2021 October | 75 | 52 | 127 |
| 2021 September | 58 | 52 | 110 |
| 2021 August | 66 | 47 | 113 |
| 2021 July | 54 | 43 | 97 |
| 2021 June | 78 | 28 | 106 |
| 2021 May | 57 | 35 | 92 |
| 2021 April | 196 | 75 | 271 |
| 2021 March | 106 | 29 | 135 |
| 2021 February | 113 | 22 | 135 |
| 2021 January | 79 | 23 | 102 |
| 2020 December | 79 | 33 | 112 |
| 2020 November | 53 | 17 | 70 |
| 2020 October | 81 | 24 | 105 |
| 2020 September | 48 | 12 | 60 |
| 2020 August | 47 | 12 | 59 |
| 2020 July | 56 | 11 | 67 |
| 2020 June | 61 | 18 | 79 |
| 2020 May | 77 | 31 | 108 |
| 2020 April | 60 | 23 | 83 |
| 2020 March | 67 | 25 | 92 |
| 2020 February | 82 | 23 | 105 |
| 2020 January | 81 | 33 | 114 |
| 2019 December | 72 | 35 | 107 |
| 2019 November | 50 | 28 | 78 |
| 2019 October | 47 | 19 | 66 |
| 2019 September | 71 | 22 | 93 |
| 2019 August | 45 | 17 | 62 |
| 2019 July | 76 | 26 | 102 |
| 2019 June | 43 | 21 | 64 |
| 2019 May | 60 | 22 | 82 |
| 2019 April | 112 | 45 | 157 |
| 2019 March | 68 | 30 | 98 |
| 2019 February | 46 | 20 | 66 |
| 2019 January | 47 | 22 | 69 |
| 2018 December | 117 | 45 | 162 |
| 2018 November | 81 | 23 | 104 |
| 2018 October | 86 | 23 | 109 |
| 2018 September | 85 | 35 | 120 |
| 2018 August | 75 | 27 | 102 |
| 2018 July | 47 | 26 | 73 |
| 2018 June | 51 | 19 | 70 |
| 2018 May | 45 | 18 | 63 |
| 2018 April | 55 | 16 | 71 |
| 2018 March | 54 | 13 | 67 |
| 2018 February | 56 | 10 | 66 |
| 2018 January | 42 | 8 | 50 |
| 2017 December | 47 | 15 | 62 |
| 2017 November | 57 | 27 | 84 |
| 2017 October | 66 | 28 | 94 |
| 2017 September | 51 | 13 | 64 |
| 2017 August | 37 | 15 | 52 |
| 2017 July | 42 | 14 | 56 |
| 2017 June | 49 | 17 | 66 |
| 2017 May | 53 | 15 | 68 |
| 2017 April | 36 | 17 | 53 |
| 2017 March | 41 | 20 | 61 |
| 2017 February | 46 | 38 | 84 |
| 2017 January | 29 | 16 | 45 |
| 2016 December | 71 | 24 | 95 |
| 2016 November | 86 | 18 | 104 |
| 2016 October | 127 | 28 | 155 |
| 2016 September | 146 | 16 | 162 |
| 2016 August | 248 | 17 | 265 |
| 2016 July | 247 | 15 | 262 |
| 2016 June | 169 | 0 | 169 |
| 2016 May | 155 | 0 | 155 |
| 2016 April | 139 | 0 | 139 |
| 2016 March | 115 | 0 | 115 |
| 2016 February | 116 | 0 | 116 |
| 2016 January | 135 | 0 | 135 |
| 2015 December | 141 | 0 | 141 |
| 2015 November | 108 | 0 | 108 |
| 2015 October | 108 | 0 | 108 |
| 2015 September | 86 | 0 | 86 |
| 2015 August | 69 | 0 | 69 |
| 2015 July | 68 | 0 | 68 |
| 2015 June | 39 | 0 | 39 |
| 2015 May | 53 | 0 | 53 |
| 2015 April | 5 | 0 | 5 |
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