Podocyturia in pediatric patients with Fabry disease

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"etiqueta" => "b" "identificador" => "aff0010" ] 1 => array:2 [ "etiqueta" => "c" "identificador" => "aff0015" ] ] ] 6 => array:3 [ "nombre" => "Federico" "apellidos" => "Ochoa" "referencia" => array:1 [ 0 => array:2 [ "etiqueta" => "b" "identificador" => "aff0010" ] ] ] 7 => array:3 [ "nombre" => "Graciela" "apellidos" => "Vallejo" "referencia" => array:1 [ 0 => array:2 [ "etiqueta" => "a" "identificador" => "aff0005" ] ] ] 8 => array:3 [ "nombre" => "Elsa" "apellidos" => "Zotta" "referencia" => array:2 [ 0 => array:2 [ "etiqueta" => "b" "identificador" => "aff0010" ] 1 => array:2 [ "etiqueta" => "c" "identificador" => "aff0015" ] ] ] ] "afiliaciones" => array:3 [ 0 => array:3 [ "entidad" => "Unidad de Nefrología, Hospital General de Niños Ricardo Gutiérrez, Buenos Aires, Argentina" "etiqueta" => "a" "identificador" => "aff0005" ] 1 => array:3 [ "entidad" => "Departamento de Ciencias Fisiológicas IFIBIO Houssay, CONICET, Facultad de Medicina, Universidad de Buenos Aires, Buenos Aires, Argentina" "etiqueta" => "b" "identificador" => "aff0010" ] 2 => array:3 [ "entidad" => "Cátedra de Fisiopatología, Facultad de Farmacia y Bioquímica, Universidad de Buenos Aires, Buenos Aires, Argentina" "etiqueta" => "c" "identificador" => "aff0015" ] ] "correspondencia" => array:1 [ 0 => array:3 [ "identificador" => "cor0005" "etiqueta" => "⁎" "correspondencia" => "Corresponding author." ] ] ] ] "titulosAlternativos" => array:1 [ "es" => array:1 [ "titulo" => "Podocituria en pacientes pediátricos con enfermedad de Fabry" ] ] "resumenGrafico" => array:2 [ "original" => 0 "multimedia" => array:7 [ "identificador" => "fig0010" "etiqueta" => "Fig. 2" "tipo" => "MULTIMEDIAFIGURA" "mostrarFloat" => true "mostrarDisplay" => false "figura" => array:1 [ 0 => array:4 [ "imagen" => "gr2.jpeg" "Alto" => 1759 "Ancho" => 2145 "Tamanyo" => 239259 ] ] "descripcion" => array:1 [ "en" => "Levels of podocyturia and albuminuria in urine of children with Fabry disease (black arrow) and in normal children. There is a subgroup of 4 patients with Fabry disease who have low levels of albuminuria and podocyturia." ] ] ] "textoCompleto" => "IntroductionFabry disease (FD) is a hereditary disorder caused by the reduced activity of the enzyme α-galactosidase A. It is transmitted linked to the X chromosome and affects more severely to men than women.These patients fully develop the disease around the fifth decade of life, however, its onset occurs during pediatric age, with specific symptoms such as acroparesthesia, angiokeratomas, corneal opacity and hypo- or anhidrosis.<a class="elsevierStyleCrossRef" href="#bib0110">1</a>In the kidney, the progressive accumulation of glycosphingolipids causes functional alterations of podocytes, endothelial cells, smooth muscle and tubular cells. The main manifestations of this nephropathy are proteinuria with progressive deterioration of renal function.<a class="elsevierStyleCrossRef" href="#bib0115">2</a>The treatment is based on enzyme replacement therapy and general treatment directed to reduce the progression of chronic kidney disease.<a class="elsevierStyleCrossRef" href="#bib0120">3</a>Despite knowing the natural history of the disease and, specifically, the anatomopathological changes in Fabry's nephropathy, the initial mechanism inducing pathological albuminuria and the consequent evolution toward chronic kidney disease are not yet clear.Although the glomerular basement membrane was always considered the main determinant of the filtration process, it is now evident that it is the visceral epithelium of the Bowman capsule that defines the characteristics of the ultrafiltrate.<a class="elsevierStyleCrossRef" href="#bib0125">4</a> Indeed, the podocyte has a complex structure, formed by a body and its prolongations or foot processes, which are in direct contact with the basement membrane of the glomerular capillary; the space between 2 foot processes constitutes the structure known as filtration diaphragm, with pores from 4 to 14nm.<a class="elsevierStyleCrossRef" href="#bib0120">3</a>Assuming that the detachment of podocytes from the glomerular basement membrane and its appearance in the urine (podocyturia) is a natural process that is increased in the presence of renal damage (for example, the presence of Gb3 deposits in the architecture of the podocyte) then we should accept the presence of minimal podocyturia in healthy individuals and a significant increase would represent an early finding of glomerular disease,<a class="elsevierStyleCrossRef" href="#bib0125">4</a> which leads to the release of podocytes, with their consequent appearance in urine.<a class="elsevierStyleCrossRef" href="#bib0130">5</a> Therefore, the identification of urinary podocytes potentially constitutes a biomarker that precedes the appearance of pathological albuminuria, both in primary and secondary glomerulopathies.<a class="elsevierStyleCrossRefs" href="#bib0135">6,7</a>The primary objective of our work was to analyze the urine of pediatric patients with FD, to quantify the presence of podocytes, comparing it with the value of podocyturia measured in healthy children. The secondary objectives were to determine in pediatric patients with FD if a greater podocyturia is related to the appearance of pathological albuminuria and what are potential risk factors that may be involved.MethodsStudy designThis is observational analytical study of cases and controls, with an unequal distribution of samples (A: 2, B: 1) in 2 groups according to the absence of disease (control group: healthy controls) or with the presence of disease (group Fabry: patients with FD).Patients and controls included in the study were between 5 and 17 years old, eutrophic and with glomerular filtration rate (GFR) greater than 90ml/min/1.73m2. All with the approved medical consent.Patients with diabetes, malnutrition with a Z score <2 SD, obesity, hyperparathyroidism, hyperthyroidism, primary alterations of metabolism, renal tubular acidosis and orthostatic proteinuria were excluded.The children who presented a GFR reduction greater than 20% from inclusion in the study and those who did not comply with the indications for the collection of the sample were withdrawn from the study.Variables analyzedWe identified as independent variables the absence of disease (control group), the presence of disease (FD), gender, and age of the patient at the time of admission. Dependent variables were the value of podocyturia, overt albuminuria (defined as albuminuria with values greater than 20μg/min), the time elapsed in months from the diagnosis of FD to the measurement of podocyturia. and the time elapsed from the diagnosis of FD to the appearance of overt albuminuria.Laboratory studiesIn the Fabry group, blood was determined: serum creatinine, creatinine clearance (Scwhartz method), electrolytes, urea.Twenty four hours urine was collected for measurement of albumin, creatinine, pH and urinary density.PodocyturiaThe urine collected (24h) was used for laboratory analysis of both healthy and children with Fabry.Samples were processed no more than 1h after emission, using a volume of 10ml to which 1ml of 10% formalin buffer was added in PB (pH 7.2–7.4). The samples were centrifuged at 1500rpm for 5min and the supernatant discarded. 10% formalin buffer was added to the sediment until it was covered and kept at room temperature until the study was completed.An extended urine sediment was performed in xylanized slides of each sample.Indirect immunofluorescence was performed in a humid chamber. First, the samples were incubated with a blockade serum for 30min at room temperature. Then, without washing, it was incubated with the primary antibody antisinaptopodin (1:100, ABCAM, Cambridge, UK) used as a podocyte marker overnight at 4°C. Subsequently, there were washed 3 times with PBS, 5min each and incubated with secondary antibody Alexa 488 IgG (1:200, ABCAM, Cambridge, UK) for 2h at room temperature. Then the sample underwent, 3 washes with PBS, 5min each, and were stained with DAPI (ABCAM, Cambridge, UK). Samples were observed in a Nikon Eclipse E-200 epifluorescence microscope. The number of cells positive for synaptopodin was quantified in 10 fields 200× for each double-blind sample (Image Pro Plus 5.1, Media Cybernetics, Silver Spring, MD, USA).Statistical analysisSample size calculation:<ul class="elsevierStyleList" id="lis0005"><li class="elsevierStyleListItem" id="lsti0005">a)Percentage of patients with FD in whom it ws estimated to detect podocituria (p) 50% and another 50% without the alteration (q)</li><li class="elsevierStyleListItem" id="lsti0010">b)CI: 10%</li><li class="elsevierStyleListItem" id="lsti0015">c)Alpha error: 0.05, p: 95% (1.96)</li><li class="elsevierStyleListItem" id="lsti0020">d)Standard error: CI/1.96</li></ul>Sample size: p×q 50×50=34ES2 72The quantitative determination of the variable podocyturia was made and the values were presented as continuous data, with its standard deviation in each group. Comparison of the mean quantitative differences of this continuous variable between the 2 groups was performed using with nonparametric test, the Mann–Whitney test.The relationship between the values of albuminuria and podocyturia was evaluated using the Pearson correlation coefficient. The risk of developing albuminuria (dichotomous variable yes/no) was analyzed in patients with and without podocyturia (dichotomous variable yes/no), according to the relative risk.Finally, for the association between potential risk factors and the appearance of pathological albuminuria, we used the Cox proportional hazards ratio. A p<0.05 value was established as a level of statistical significance.The programs used as statistical supports were EPIDAT 3 and GraphPad inStat.ResultsWe studied 31 patients, 11 with FD (5 female) and 20 controls (12 female), with an average age of 11.6 years.<a class="elsevierStyleCrossRefs" href="#bib0130">5–17</a>The mean time elapsed from the diagnosis of FD to the measurement of podocyturia (40 months) and to the appearance of overt albuminuria (34 months) was not significant (p=0.09).The presence of synaptopodin was detected in podocytes from patients with FD and from the control group (<a class="elsevierStyleCrossRef" href="#fig0005">Fig. 1</a>) and the mean quantitative differences between both podocyturias were statistically significant (p=0.001).<elsevierMultimedia ident="fig0005"></elsevierMultimedia>The mean values of the urine measurements of are shown in <a class="elsevierStyleCrossRef" href="#tbl0005">Table 1</a>.<elsevierMultimedia ident="tbl0005"></elsevierMultimedia>In the Fabry group, not all patients had overt albuminuria. In fact, in 4 of them it was normal (<a class="elsevierStyleCrossRef" href="#tbl0010">Table 2</a>).<elsevierMultimedia ident="tbl0010"></elsevierMultimedia>The relative risk to develop pathological albuminuria according to the values of podocyturia was 1.1 in the control group (95% CI: 0.883–1.112) and 3.9 in the Fabry group (95% CI: 3.110–4.485). The correlation coefficient between podocyturia and albuminuria in the Fabry group was 0.8354 (95% CI: 0.4341–0.9601) (<a class="elsevierStyleCrossRef" href="#fig0010">Fig. 2</a>).<elsevierMultimedia ident="fig0010"></elsevierMultimedia>Finally, the 2 risk factors associated with the development of pathological albuminuria found in the Cox regression model were podocyturia (OR 14, 95% CI: 1.1–20) and age >10 years (OR 18; 95%: 1.1–39). We found no significant risk in the GFR (OR 0.5, 95% CI: 0.2–11), or gender (OR 1.3, 95% CI: 0.13–13).During all controls, the average GFR remained within normal values (102ml/min/1.73m2).The 7 patients with pathological albuminuria were started on nephroprotective treatment (enalapril 0.2mg/kg/day).DiscussionThe present study evaluates 11 patients with FD and 20 controls. Our results indicate that in FD there is an early positive relationship between podocyturia and “overt” pathological albuminuria. To date, there are very few reports of FD in the pediatric population.<a class="elsevierStyleCrossRefs" href="#bib0145">8,9</a>In FD, the deficiency of the activity of the enzyme α-galactosidase A generates a progressive accumulation of lysosomas of glycosphingolipids and induces damage to the basement membrane with the consequent appearance of podocytes in urine.<a class="elsevierStyleCrossRef" href="#bib0155">10</a>Indeed, it is known that podocytes coated by a glycocalyx sialoprotein are the main regulators of the physiological passage of proteins through the glomerular filter.This filtration takes place through the diaphragm that links podocytes to each other and to the actin cytoskeleton.<a class="elsevierStyleCrossRefs" href="#bib0160">11–13</a> Many of the alterations in these structures are induced by the lysosomal accumulation of Gb3 and may result in pedicle effacement, detachment and development of pathological albuminuria.<a class="elsevierStyleCrossRefs" href="#bib0175">14,15</a> This sequence of events, at least initially, will justify, as proposed by Eng,<a class="elsevierStyleCrossRef" href="#bib0185">16</a> the search for podocyturia as an adequate biomarker to evaluate early glomerular involvement of the disease. Therefore, its quantification would have a relevant prognostic value, representing an early, non-invasive indicator of kidney damage that may even precede the presence of proteinuria. Control of podocyturia should be evaluated, especially in those relatives in whom a confirmatory enzyme diagnosis has been made and no other renal involvement has yet been detected. Tondel et al. describes podocyte effacement and its subsequent detachment in most children with FD, so that both histological markers have been categorized as pathophysiological stages of early podocyte damage.<a class="elsevierStyleCrossRef" href="#bib0190">17</a>Trimarchi et al. shows a high podocyturia with low proteinuria in patients without treatment. In our treated patients these findings seem to be reversed (with a more prolonged period of damage); this indicates a changing relationship between podocyturia and proteinuria as the disease progresses.<a class="elsevierStyleCrossRef" href="#bib0195">18</a>In general terms, we can state that the magnitude of podocyturia (correcting per urine creatinine concentration) in the pediatric population, compared with adults, seems to confirm the theory of progressive podocyte reduction, related to age and the possible existing nephropathy. Consistent with this hypothesis was our observation in the younger patients with Fabry disease of an initial association between podocyturia and albuminuria, possibly related to the period of time with the disease, most obvious in a younger pediatric population. Hughes et al. reported, a relationship between age and the risk of developing kidney damage.<a class="elsevierStyleCrossRef" href="#bib0200">19</a> In this same line, in FD patients the period of time elapsed between the detection of podocyturia and pathological albuminuria is similar, which support the assumption that a given time disease is required to see quantitative changes in pdocyturia and albuminuria.<a class="elsevierStyleCrossRef" href="#bib0205">20</a>Patients with albuminuria were started on progressive doses of enalapril and most patients responded with a reduction of albuminuria. This data is not included in the manuscript.The consensus among experts is the in patients with Fabry disease that enzyme replacement therapy should be started early; this may attenuate or prevent progressive nephropathy and other organic complications.<a class="elsevierStyleCrossRef" href="#bib0210">21</a> However, according to our data the time elapsed until the evaluation of 2 key pathophysiological parameters (podocyturia and albuminuria) was too prolonged. This should be corrected if the intention is to apply effective therapeutic intervention. Nevertheless, there is no unanimity about the optimal time to start treatment and there is no long-term data documented as to whether the enzymatic prescription would prevent the nephropathy in children. A non-invasive method such as evaluation of podocyturia as an early marker of glomerular damage could help to decide the initiation of treatment.The work has certain weaknesses, especially a reduced sample size and the impossibility of correlating the studies carried out with the pathological anatomy. However, the originality of the present work is the finding of an early positive association between 2 important variables such as podocyturia and albuminuria in pediatric patients. Our final aim, work in progress, is to establish the sequential relationship between both variables and determine the time interval of their successive appearances, so specific therapy is implemented early; this would be particularly beneficial in the Fabry population that has not yet developed the pathological albuminuria.In conclusion, our study shows that the detection of podocyturia in pediatric patients with Fabry disease could be used as an early marker of renal damage, which precedes and is directly proportional to the appearance of pathological albuminuria.Conflicts of interestsThe authors have no conflicts of interest to declare." "textoCompletoSecciones" => array:1 [ "secciones" => array:10 [ 0 => array:3 [ "identificador" => "xres1184175" "titulo" => "Abstract" "secciones" => array:5 [ 0 => array:2 [ "identificador" => "abst0005" "titulo" => "Introduction" ] 1 => array:2 [ "identificador" => "abst0010" "titulo" => "Objectives" ] 2 => array:2 [ "identificador" => "abst0015" "titulo" => "Methods" ] 3 => array:2 [ "identificador" => "abst0020" "titulo" => "Results" ] 4 => array:2 [ "identificador" => "abst0025" "titulo" => "Conclusion" ] ] ] 1 => array:2 [ "identificador" => "xpalclavsec1104543" "titulo" => "Keywords" ] 2 => array:3 [ "identificador" => "xres1184174" "titulo" => "Resumen" "secciones" => array:5 [ 0 => array:2 [ "identificador" => "abst0030" "titulo" => "Introducción" ] 1 => array:2 [ "identificador" => "abst0035" "titulo" => "Objetivos" ] 2 => array:2 [ "identificador" => "abst0040" "titulo" => "Métodos" ] 3 => array:2 [ "identificador" => "abst0045" "titulo" => "Resultados" ] 4 => array:2 [ "identificador" => "abst0050" "titulo" => "Conclusión" ] ] ] 3 => array:2 [ "identificador" => "xpalclavsec1104544" "titulo" => "Palabras clave" ] 4 => array:2 [ "identificador" => "sec0005" "titulo" => "Introduction" ] 5 => array:3 [ "identificador" => "sec0010" "titulo" => "Methods" "secciones" => array:5 [ 0 => array:2 [ "identificador" => "sec0015" "titulo" => "Study design" ] 1 => array:2 [ "identificador" => "sec0020" "titulo" => "Variables analyzed" ] 2 => array:2 [ "identificador" => "sec0025" "titulo" => "Laboratory studies" ] 3 => array:2 [ "identificador" => "sec0030" "titulo" => "Podocyturia" ] 4 => array:2 [ "identificador" => "sec0035" "titulo" => "Statistical analysis" ] ] ] 6 => array:2 [ "identificador" => "sec0040" "titulo" => "Results" ] 7 => array:2 [ "identificador" => "sec0045" "titulo" => "Discussion" ] 8 => array:2 [ "identificador" => "sec0050" "titulo" => "Conflicts of interests" ] 9 => array:1 [ "titulo" => "References" ] ] ] "pdfFichero" => "main.pdf" "tienePdf" => true "fechaRecibido" => "2018-02-13" "fechaAceptado" => "2018-05-14" "PalabrasClave" => array:2 [ "en" => array:1 [ 0 => array:4 [ "clase" => "keyword" "titulo" => "Keywords" "identificador" => "xpalclavsec1104543" "palabras" => array:5 [ 0 => "Fabry disease" 1 => "Podocyturia" 2 => "Albuminuria" 3 => "α-Galactosidase" 4 => "Renal damage" ] ] ] "es" => array:1 [ 0 => array:4 [ "clase" => "keyword" "titulo" => "Palabras clave" "identificador" => "xpalclavsec1104544" "palabras" => array:5 [ 0 => "Enfermedad de Fabry" 1 => "Podocituria" 2 => "Albuminuria" 3 => "α-galactosidasa" 4 => "Daño renal" ] ] ] ] "tieneResumen" => true "resumen" => array:2 [ "en" => array:3 [ "titulo" => "Abstract" "resumen" => "IntroductionFabry disease (FD) is a hereditary disorder caused by a deficiency of α-galactosidase A enzyme activity. The transmission of the disorder is linked to the X chromosome. ObjectivesThe objectives of the study were: 1. To quantify the presence of podocytes in pediatric patients with FD and compare them with the value of the measured podocyturia in healthy controls. 2. To determine whether a greater podocyturia is related to the onset of pathological albuminuria in patients with FD. 3. To determine the risk factors associated with pathological albuminuria. MethodsWe performed an analytical, observational study of Fabry and control subjects, which were separated into 2 groups in accordance with the absence of the disease (control group) or the presence of the disease (Fabry group). ResultsWe studied 31 patients, 11 with FD and 20 controls, with a mean age of 11.6 years.The difference between the mean time elapsed from the diagnosis of FD to the measurement of podocyturia (40 months) and the onset of pathological albuminuria (34 months) was not significant (p=0.09). Podocytes were identified by staining for the presence of synaptopodin and the mean quantitative differences between both podocyturias were statistically significant (p=0.001). Albuminuria was physiological in 4 of the patients with FD and the relative risk to develop pathological albuminuria according to podocyturia was 1.1 in the control group and 3.9 in the Fabry group, with a coefficient of correlation between podocyturia and albuminuria in the Fabry group of 0.8354. Finally, the 2 risk factors associated with the development of pathological albuminuria were podocyturia (OR: 14) and being aged over 10 years (OR: 18). We found no significant risk with regard to glomerular filtrate renal (GFR) (OR: 0.5) or gender (OR: 1.3). The mean GFR remained within normal values. ConclusionThe detection of podocyturia in pediatric patients with FD could be used as an early marker of renal damage, preceding and proportional to the occurrence of pathological albuminuria." "secciones" => array:5 [ 0 => array:2 [ "identificador" => "abst0005" "titulo" => "Introduction" ] 1 => array:2 [ "identificador" => "abst0010" "titulo" => "Objectives" ] 2 => array:2 [ "identificador" => "abst0015" "titulo" => "Methods" ] 3 => array:2 [ "identificador" => "abst0020" "titulo" => "Results" ] 4 => array:2 [ "identificador" => "abst0025" "titulo" => "Conclusion" ] ] ] "es" => array:3 [ "titulo" => "Resumen" "resumen" => "IntroducciónLa enfermedad de Fabry (EF) es un trastorno hereditario causado por una deficiencia de la actividad de la enzima α-galactosidasa A, cuya transmisión está relacionada con el cromosoma X. ObjetivosLos objetivos del estudio fueron: 1. Cuantificar la presencia de podocitos en pacientes pediátricos con EF y compararla con el valor de la podocituria medida en controles sanos. 2. Determinar en pacientes con EF si una mayor podocituria está relacionada con la albuminuria patológica. 3. Determinar los factores de riesgo asociados con la albuminuria patológica. MétodosImplementamos un estudio analítico observacional de casos y controles, separados en 2 grupos de acuerdo con la ausencia de enfermedad (grupo control) o con la presencia de enfermedad (grupo Fabry). ResultadosEstudiamos a 31 pacientes, 11 con EF y 20 controles, con una media de edad de 11,6 años. La diferencia entre el tiempo medio transcurrido desde el diagnóstico de EF hasta la medición de la podocituria (40 meses) y la aparición de la albuminuria patológica (34 meses) no fue significativa (p: 0,09). Los podocitos se identificaron mediante tinción para sinaptopodina y las diferencias medias cuantitativas entre ambas podociturias fueron estadísticamente significativas (p: 0,001). La albuminuria fue fisiológica en 4 de las pacientes Fabry y el riesgo relativo para desarrollar albuminuria patológica de acuerdo con la podocituria fue en el grupo control 1,1 y en el grupo Fabry 3,9, con un coeficiente de correlación entre la podocituria y la albuminuria en el grupo Fabry de 0,8354. Finalmente los 2 factores de riesgo asociados al desarrollo de albuminuria patológica fueron la podocituria (OR 14) y la edad mayor a 10 años (OR 18). No encontramos riesgo significativo ni en el filtrado glomerular (FG) (OR 0,5), ni en el género (OR 1,3). El FG medio se mantuvo dentro de valores normales. ConclusiónLa detección de podocituria en pacientes pediátricos con EF podría utilizarse como un marcador temprano de daño renal previo y relacionado con la albuminuria patológica." "secciones" => array:5 [ 0 => array:2 [ "identificador" => "abst0030" "titulo" => "Introducción" ] 1 => array:2 [ "identificador" => "abst0035" "titulo" => "Objetivos" ] 2 => array:2 [ "identificador" => "abst0040" "titulo" => "Métodos" ] 3 => array:2 [ "identificador" => "abst0045" "titulo" => "Resultados" ] 4 => array:2 [ "identificador" => "abst0050" "titulo" => "Conclusión" ] ] ] ] "NotaPie" => array:1 [ 0 => array:2 [ "etiqueta" => "☆" "nota" => "Please cite this article as: Liern M, Collazo A, Valencia M, Fainboin A, Isse L, Costales-Collaguazo C, et al. Podocituria en pacientes pediátricos con enfermedad de Fabry. Nefrologia. 2019;39:177–183." ] ] "multimedia" => array:4 [ 0 => array:7 [ "identificador" => "fig0005" "etiqueta" => "Fig. 1" "tipo" => "MULTIMEDIAFIGURA" "mostrarFloat" => true "mostrarDisplay" => false "figura" => array:1 [ 0 => array:4 [ "imagen" => "gr1.jpeg" "Alto" => 1179 "Ancho" => 1667 "Tamanyo" => 108669 ] ] "descripcion" => array:1 [ "en" => "Detection of podocyturia by indirect immunofluorescence. (A) Panoramic view of urinary sediment without synaptopodin (Control). (B) Urine sediment in patients with Fabry, positive synaptopodin is observed in podocytes. Magnification: (A) ×100; (B) ×400." ] ] 1 => array:7 [ "identificador" => "fig0010" "etiqueta" => "Fig. 2" "tipo" => "MULTIMEDIAFIGURA" "mostrarFloat" => true "mostrarDisplay" => false "figura" => array:1 [ 0 => array:4 [ "imagen" => "gr2.jpeg" "Alto" => 1759 "Ancho" => 2145 "Tamanyo" => 239259 ] ] "descripcion" => array:1 [ "en" => "Levels of podocyturia and albuminuria in urine of children with Fabry disease (black arrow) and in normal children. There is a subgroup of 4 patients with Fabry disease who have low levels of albuminuria and podocyturia." ] ] 2 => 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:2 [ "leyenda" => "SD: standard deviation; FD: Fabry disease; GFR, glomerular filtration rate." "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="" valign="top" scope="col" style="border-bottom: 2px solid black"> \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">Group A (control), n: 20 \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">Group B (Fabry disease), n: 11 \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">p \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">Mean age, years (range) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">1.1 (5–17) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">1.7 (5–17) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">0.09 \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">Gender, M/F \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">7/13 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">5/6 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">0.08 \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">Mean age in years at the diagnosis of FD (range) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="" valign="top"> \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">7.9 (5–11) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="" valign="top"> \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">Mean GFR (ml/1.73m2/min)(SD) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="" valign="top"> \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">102 (8) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="" valign="top"> \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">Proteinuria (mg/m2/h) (SD) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">1.5 (0.7) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">4.3 (0.5) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">0.05 \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">Albuminuria (ucg/min) (SD) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">10 (5.2) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">21 (12) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top"><0.01 \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">Pathological albuminuria (%) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">0 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">64% \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top"><0.001 \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">Podocyturia/Cr in urine (mg/dl) (SD) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">0.4 (0.3) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">1.5 (0.8) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top"><0.01 \t\t\t\t\t\t\n \t\t\t\t</td></tr></tbody></table> """ ] "imagenFichero" => array:1 [ 0 => "xTab2018697.png" ] ] ] ] "descripcion" => array:1 [ "en" => "Description of the measurements of urine parameters and other parameters in controls and patients with Fabry disease." ] ] 3 => array:8 [ "identificador" => "tbl0010" "etiqueta" => "Table 2" "tipo" => "MULTIMEDIATABLA" "mostrarFloat" => true "mostrarDisplay" => false "detalles" => array:1 [ 0 => array:3 [ "identificador" => "at2" "detalle" => "Table " "rol" => "short" ] ] "tabla" => array:2 [ "leyenda" => "n: 11 patients; FD: Fabry disease." "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">Gender \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 (years) \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">Podocyturia/Cr in urine (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">Time elapsed from the diagnosis of FD to the measurement of podocyturia (months) \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">Albuminuria (ucg/min) \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">Time elapsed since diagnosis of FD to the observation of pathological albuminuria (months) \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">Mutation \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 biopsy \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">Initiation and time on enzymatic treatment \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">Man \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">17 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">0.5 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">59 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">25 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">59 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">A292T \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="" valign="top"> \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">January 2012 \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">Man \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">16 \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="char" valign="top">85 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">33 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">85 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">A292T \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">(5 years of treatment) \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">Man \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="char" valign="top">2.3 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">29 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">39 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">29 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">L415P \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="" valign="top"> \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">January 2012 (5 years of treatment) \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">Woman \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">15 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">1.1 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">46 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">27 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">29 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">A292T \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">March 2015 (2 years of treatment) \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">Woman \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">12 \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="char" valign="top">35 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">26 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">23 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">T194I \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">February 2015 (2 years of treatment) \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">Woman \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">12 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">2.6 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">18 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">17 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">18 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">L415P \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="" valign="top"> \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">February 2017 (3 months of treatment) \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">Man \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="char" valign="top">1.6 \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="char" valign="top">31 \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">– \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="" valign="top"> \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">October 2017 (7 months of treatment) \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">Woman \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="char" valign="top">2.5 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">7 \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="char" valign="top">– \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="" valign="top"> \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">October 2016 (1 year of treatment) \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">Man \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">12 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">1.6 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">32 \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="char" valign="top">– \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">A292T \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="" valign="top"> \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="" valign="top"> \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">Man \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">12 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">1.1 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">46 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">11 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">– \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">A292T \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="" valign="top"> \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="" valign="top"> \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">Woman \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">8 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">1.9 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">8 \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="char" valign="top">– \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">A292T \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="" valign="top"> \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="" valign="top"> \t\t\t\t\t\t\n \t\t\t\t</td></tr></tbody></table> """ ] "imagenFichero" => array:1 [ 0 => "xTab2018696.png" ] ] ] ] "descripcion" => array:1 [ "en" => "Description of the variables collected in group B (Fabry disease)." ] ] ] "bibliografia" => array:2 [ "titulo" => "References" "seccion" => array:1 [ 0 => array:2 [ "identificador" => "bibs0015" "bibliografiaReferencia" => array:21 [ 0 => array:3 [ "identificador" => "bib0110" "etiqueta" => "1" "referencia" => array:1 [ 0 => array:2 [ "contribucion" => array:1 [ 0 => array:2 [ "titulo" => "Fabry disease: diagnosis and management, with emphasis on the renal manifestations" "autores" => array:1 [ 0 => array:2 [ "etal" => false "autores" => array:1 [ 0 => "D.J. 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Podocituria en pacientes pediátricos con enfermedad de Fabry

Miguel Lierna,

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jliern@yahoo.com

Corresponding author.

, Anabella Collazoa, Maylin Valenciaa, Alejandro Fainboina, Lorena Issea, Cristian Costales-Collaguazob,c, Federico Ochoab, Graciela Vallejoa, Elsa Zottab,c

a Unidad de Nefrología, Hospital General de Niños Ricardo Gutiérrez, Buenos Aires, Argentina

b Departamento de Ciencias Fisiológicas IFIBIO Houssay, CONICET, Facultad de Medicina, Universidad de Buenos Aires, Buenos Aires, Argentina

c Cátedra de Fisiopatología, Facultad de Farmacia y Bioquímica, Universidad de Buenos Aires, Buenos Aires, Argentina

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    "textoCompleto" => "<span class="elsevierStyleSections"><span id="sec0005" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0075">Introduction</span><p id="par0005" class="elsevierStylePara elsevierViewall">Fabry disease &#40;FD&#41; is a hereditary disorder caused by the reduced activity of the enzyme &#945;-galactosidase A&#46; It is transmitted linked to the X chromosome and affects more severely to men than women&#46;</p><p id="par0010" class="elsevierStylePara elsevierViewall">These patients fully develop the disease around the fifth decade of life&#44; however&#44; its onset occurs during pediatric age&#44; with specific symptoms such as acroparesthesia&#44; angiokeratomas&#44; corneal opacity and hypo- or anhidrosis&#46;<a class="elsevierStyleCrossRef" href="#bib0110"><span class="elsevierStyleSup">1</span></a></p><p id="par0015" class="elsevierStylePara elsevierViewall">In the kidney&#44; the progressive accumulation of glycosphingolipids causes functional alterations of podocytes&#44; endothelial cells&#44; smooth muscle and tubular cells&#46; The main manifestations of this nephropathy are proteinuria with progressive deterioration of renal function&#46;<a class="elsevierStyleCrossRef" href="#bib0115"><span class="elsevierStyleSup">2</span></a></p><p id="par0020" class="elsevierStylePara elsevierViewall">The treatment is based on enzyme replacement therapy and general treatment directed to reduce the progression of chronic kidney disease&#46;<a class="elsevierStyleCrossRef" href="#bib0120"><span class="elsevierStyleSup">3</span></a></p><p id="par0025" class="elsevierStylePara elsevierViewall">Despite knowing the natural history of the disease and&#44; specifically&#44; the anatomopathological changes in Fabry&#39;s nephropathy&#44; the initial mechanism inducing pathological albuminuria and the consequent evolution toward chronic kidney disease are not yet clear&#46;</p><p id="par0030" class="elsevierStylePara elsevierViewall">Although the glomerular basement membrane was always considered the main determinant of the filtration process&#44; it is now evident that it is the visceral epithelium of the Bowman capsule that defines the characteristics of the ultrafiltrate&#46;<a class="elsevierStyleCrossRef" href="#bib0125"><span class="elsevierStyleSup">4</span></a> Indeed&#44; the podocyte has a complex structure&#44; formed by a body and its prolongations or foot processes&#44; which are in direct contact with the basement membrane of the glomerular capillary&#59; the space between 2 foot processes constitutes the structure known as filtration diaphragm&#44; with pores from 4 to 14<span class="elsevierStyleHsp" style=""></span>nm&#46;<a class="elsevierStyleCrossRef" href="#bib0120"><span class="elsevierStyleSup">3</span></a></p><p id="par0035" class="elsevierStylePara elsevierViewall">Assuming that the detachment of podocytes from the glomerular basement membrane and its appearance in the urine &#40;podocyturia&#41; is a natural process that is increased in the presence of renal damage &#40;for example&#44; the presence of Gb3 deposits in the architecture of the podocyte&#41; then we should accept the presence of minimal podocyturia in healthy individuals and a significant increase would represent an early finding of glomerular disease&#44;<a class="elsevierStyleCrossRef" href="#bib0125"><span class="elsevierStyleSup">4</span></a> which leads to the release of podocytes&#44; with their consequent appearance in urine&#46;<a class="elsevierStyleCrossRef" href="#bib0130"><span class="elsevierStyleSup">5</span></a> Therefore&#44; the identification of urinary podocytes potentially constitutes a biomarker that precedes the appearance of pathological albuminuria&#44; both in primary and secondary glomerulopathies&#46;<a class="elsevierStyleCrossRefs" href="#bib0135"><span class="elsevierStyleSup">6&#44;7</span></a></p><p id="par0040" class="elsevierStylePara elsevierViewall">The primary objective of our work was to analyze the urine of pediatric patients with FD&#44; to quantify the presence of podocytes&#44; comparing it with the value of podocyturia measured in healthy children&#46; The secondary objectives were to determine in pediatric patients with FD if a greater podocyturia is related to the appearance of pathological albuminuria and what are potential risk factors that may be involved&#46;</p></span><span id="sec0010" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0080">Methods</span><span id="sec0015" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0085">Study design</span><p id="par0045" class="elsevierStylePara elsevierViewall">This is observational analytical study of cases and controls&#44; with an unequal distribution of samples &#40;A&#58; 2&#44; B&#58; 1&#41; in 2 groups according to the absence of disease &#40;control group&#58; healthy controls&#41; or with the presence of disease &#40;group Fabry&#58; patients with FD&#41;&#46;</p><p id="par0050" class="elsevierStylePara elsevierViewall">Patients and controls included in the study were between 5 and 17 years old&#44; eutrophic and with glomerular filtration rate &#40;GFR&#41; greater than 90<span class="elsevierStyleHsp" style=""></span>ml&#47;min&#47;1&#46;73<span class="elsevierStyleHsp" style=""></span>m<span class="elsevierStyleSup">2</span>&#46; All with the approved medical consent&#46;</p><p id="par0055" class="elsevierStylePara elsevierViewall">Patients with diabetes&#44; malnutrition with a <span class="elsevierStyleItalic">Z</span> score &#60;2 SD&#44; obesity&#44; hyperparathyroidism&#44; hyperthyroidism&#44; primary alterations of metabolism&#44; renal tubular acidosis and orthostatic proteinuria were excluded&#46;</p><p id="par0060" class="elsevierStylePara elsevierViewall">The children who presented a GFR reduction greater than 20&#37; from inclusion in the study and those who did not comply with the indications for the collection of the sample were withdrawn from the study&#46;</p></span><span id="sec0020" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0090">Variables analyzed</span><p id="par0065" class="elsevierStylePara elsevierViewall">We identified as independent variables the absence of disease &#40;control group&#41;&#44; the presence of disease &#40;FD&#41;&#44; gender&#44; and age of the patient at the time of admission&#46; Dependent variables were the value of podocyturia&#44; overt albuminuria &#40;defined as albuminuria with values greater than 20<span class="elsevierStyleHsp" style=""></span>&#956;g&#47;min&#41;&#44; the time elapsed in months from the diagnosis of FD to the measurement of podocyturia&#46; and the time elapsed from the diagnosis of FD to the appearance of overt albuminuria&#46;</p></span><span id="sec0025" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0095">Laboratory studies</span><p id="par0070" class="elsevierStylePara elsevierViewall">In the Fabry group&#44; blood was determined&#58; serum creatinine&#44; creatinine clearance &#40;Scwhartz method&#41;&#44; electrolytes&#44; urea&#46;</p><p id="par0075" class="elsevierStylePara elsevierViewall">Twenty four hours urine was collected for measurement of albumin&#44; creatinine&#44; pH and urinary density&#46;</p></span><span id="sec0030" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0100">Podocyturia</span><p id="par0080" class="elsevierStylePara elsevierViewall">The urine collected &#40;24<span class="elsevierStyleHsp" style=""></span>h&#41; 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for each double-blind sample &#40;Image Pro Plus 5&#46;1&#44; Media Cybernetics&#44; Silver Spring&#44; MD&#44; USA&#41;&#46;</p></span><span id="sec0035" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0105">Statistical analysis</span><p id="par0100" class="elsevierStylePara elsevierViewall">Sample size calculation&#58;<ul class="elsevierStyleList" id="lis0005"><li class="elsevierStyleListItem" id="lsti0005"><span class="elsevierStyleLabel">a&#41;</span><p id="par0105" class="elsevierStylePara elsevierViewall">Percentage of patients with FD in whom it ws estimated to detect podocituria &#40;<span class="elsevierStyleItalic">p</span>&#41; 50&#37; and another 50&#37; without the alteration &#40;<span class="elsevierStyleItalic">q</span>&#41;</p></li><li class="elsevierStyleListItem" id="lsti0010"><span class="elsevierStyleLabel">b&#41;</span><p id="par0110" class="elsevierStylePara elsevierViewall">CI&#58; 10&#37;</p></li><li class="elsevierStyleListItem" id="lsti0015"><span class="elsevierStyleLabel">c&#41;</span><p id="par0115" class="elsevierStylePara elsevierViewall">Alpha error&#58; 0&#46;05&#44; <span class="elsevierStyleItalic">p</span>&#58; 95&#37; &#40;1&#46;96&#41;</p></li><li class="elsevierStyleListItem" id="lsti0020"><span class="elsevierStyleLabel">d&#41;</span><p id="par0120" class="elsevierStylePara elsevierViewall">Standard error&#58; CI&#47;1&#46;96</p></li></ul></p><p id="par0125" class="elsevierStylePara elsevierViewall">Sample size&#58; <span class="elsevierStyleItalic">p</span><span class="elsevierStyleHsp" style=""></span>&#215;<span class="elsevierStyleHsp" style=""></span><span class="elsevierStyleItalic">q</span> 50<span class="elsevierStyleHsp" style=""></span>&#215;<span class="elsevierStyleHsp" style=""></span>50<span class="elsevierStyleHsp" style=""></span>&#61;<span class="elsevierStyleHsp" style=""></span>34</p><p id="par0130" class="elsevierStylePara elsevierViewall">ES<span class="elsevierStyleSup">2</span> 72</p><p id="par0135" class="elsevierStylePara elsevierViewall">The quantitative determination of the variable podocyturia was made and the values were presented as continuous data&#44; with its standard deviation in each group&#46; Comparison of the mean quantitative differences of this continuous variable between the 2 groups was performed using with nonparametric test&#44; the Mann&#8211;Whitney test&#46;</p><p id="par0140" class="elsevierStylePara elsevierViewall">The relationship between the values of albuminuria and podocyturia was evaluated using the Pearson correlation coefficient&#46; The risk of developing albuminuria &#40;dichotomous variable yes&#47;no&#41; was analyzed in patients with and without podocyturia &#40;dichotomous variable yes&#47;no&#41;&#44; according to the relative risk&#46;</p><p id="par0145" class="elsevierStylePara elsevierViewall">Finally&#44; for the association between potential risk factors and the appearance of pathological albuminuria&#44; we used the Cox proportional hazards ratio&#46; A <span class="elsevierStyleItalic">p</span><span class="elsevierStyleHsp" style=""></span>&#60;<span class="elsevierStyleHsp" style=""></span>0&#46;05 value was established as a level of statistical significance&#46;</p><p id="par0150" class="elsevierStylePara elsevierViewall">The programs used as statistical supports were EPIDAT 3 and GraphPad inStat&#46;</p></span></span><span id="sec0040" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0110">Results</span><p id="par0155" class="elsevierStylePara elsevierViewall">We studied 31 patients&#44; 11 with FD &#40;5 female&#41; and 20 controls &#40;12 female&#41;&#44; with an average age of 11&#46;6 years&#46;<a class="elsevierStyleCrossRefs" href="#bib0130"><span class="elsevierStyleSup">5&#8211;17</span></a></p><p id="par0160" class="elsevierStylePara elsevierViewall">The mean time elapsed from the diagnosis of FD to the measurement of podocyturia &#40;40 months&#41; and to the appearance of overt albuminuria &#40;34 months&#41; was not significant &#40;<span class="elsevierStyleItalic">p</span><span class="elsevierStyleHsp" style=""></span>&#61;<span class="elsevierStyleHsp" style=""></span>0&#46;09&#41;&#46;</p><p id="par0165" class="elsevierStylePara elsevierViewall">The presence of synaptopodin was detected in podocytes from patients with FD and from the control group &#40;<a class="elsevierStyleCrossRef" href="#fig0005">Fig&#46; 1</a>&#41; and the mean quantitative differences between both podocyturias were statistically significant &#40;<span class="elsevierStyleItalic">p</span><span class="elsevierStyleHsp" style=""></span>&#61;<span class="elsevierStyleHsp" style=""></span>0&#46;001&#41;&#46;</p><elsevierMultimedia ident="fig0005"></elsevierMultimedia><p id="par0170" class="elsevierStylePara elsevierViewall">The mean values of the urine measurements of are shown in <a class="elsevierStyleCrossRef" href="#tbl0005">Table 1</a>&#46;</p><elsevierMultimedia ident="tbl0005"></elsevierMultimedia><p id="par0175" class="elsevierStylePara elsevierViewall">In the Fabry group&#44; not all patients had overt albuminuria&#46; In fact&#44; in 4 of them it was normal &#40;<a class="elsevierStyleCrossRef" href="#tbl0010">Table 2</a>&#41;&#46;</p><elsevierMultimedia ident="tbl0010"></elsevierMultimedia><p id="par0180" class="elsevierStylePara elsevierViewall">The relative risk to develop pathological albuminuria according to the values of podocyturia was 1&#46;1 in the control group &#40;95&#37; CI&#58; 0&#46;883&#8211;1&#46;112&#41; and 3&#46;9 in the Fabry group &#40;95&#37; CI&#58; 3&#46;110&#8211;4&#46;485&#41;&#46; The correlation coefficient between podocyturia and albuminuria in the Fabry group was 0&#46;8354 &#40;95&#37; CI&#58; 0&#46;4341&#8211;0&#46;9601&#41; &#40;<a class="elsevierStyleCrossRef" href="#fig0010">Fig&#46; 2</a>&#41;&#46;</p><elsevierMultimedia ident="fig0010"></elsevierMultimedia><p id="par0185" class="elsevierStylePara elsevierViewall">Finally&#44; the 2 risk factors associated with the development of pathological albuminuria found in the Cox regression model were podocyturia &#40;OR 14&#44; 95&#37; CI&#58; 1&#46;1&#8211;20&#41; and age &#62;10 years &#40;OR 18&#59; 95&#37;&#58; 1&#46;1&#8211;39&#41;&#46; We found no significant risk in the GFR &#40;OR 0&#46;5&#44; 95&#37; CI&#58; 0&#46;2&#8211;11&#41;&#44; or gender &#40;OR 1&#46;3&#44; 95&#37; CI&#58; 0&#46;13&#8211;13&#41;&#46;</p><p id="par0190" class="elsevierStylePara elsevierViewall">During all controls&#44; the average GFR remained within normal values &#40;102<span class="elsevierStyleHsp" style=""></span>ml&#47;min&#47;1&#46;73<span class="elsevierStyleHsp" style=""></span>m<span class="elsevierStyleSup">2</span>&#41;&#46;</p><p id="par0195" class="elsevierStylePara elsevierViewall">The 7 patients with pathological albuminuria were started on nephroprotective treatment &#40;enalapril 0&#46;2<span class="elsevierStyleHsp" style=""></span>mg&#47;kg&#47;day&#41;&#46;</p></span><span id="sec0045" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0115">Discussion</span><p id="par0200" class="elsevierStylePara elsevierViewall">The present study evaluates 11 patients with FD and 20 controls&#46; Our results indicate that in FD there is an early positive relationship between podocyturia and &#8220;overt&#8221; pathological albuminuria&#46; To date&#44; there are very few reports of FD in the pediatric population&#46;<a class="elsevierStyleCrossRefs" href="#bib0145"><span class="elsevierStyleSup">8&#44;9</span></a></p><p id="par0205" class="elsevierStylePara elsevierViewall">In FD&#44; the deficiency of the activity of the enzyme &#945;-galactosidase A generates a progressive accumulation of lysosomas of glycosphingolipids and induces damage to the basement membrane with the consequent appearance of podocytes in urine&#46;<a class="elsevierStyleCrossRef" href="#bib0155"><span class="elsevierStyleSup">10</span></a></p><p id="par0210" class="elsevierStylePara elsevierViewall">Indeed&#44; it is known that podocytes coated by a glycocalyx sialoprotein are the main regulators of the physiological passage of proteins through the glomerular filter&#46;</p><p id="par0215" class="elsevierStylePara elsevierViewall">This filtration takes place through the diaphragm that links podocytes to each other and to the actin cytoskeleton&#46;<a class="elsevierStyleCrossRefs" href="#bib0160"><span class="elsevierStyleSup">11&#8211;13</span></a> Many of the alterations in these structures are induced by the lysosomal accumulation of Gb3 and may result in pedicle effacement&#44; detachment and development of pathological albuminuria&#46;<a class="elsevierStyleCrossRefs" href="#bib0175"><span class="elsevierStyleSup">14&#44;15</span></a> This sequence of events&#44; at least initially&#44; will justify&#44; as proposed by Eng&#44;<a class="elsevierStyleCrossRef" href="#bib0185"><span class="elsevierStyleSup">16</span></a> the search for podocyturia as an adequate biomarker to evaluate early glomerular involvement of the disease&#46; Therefore&#44; its quantification would have a relevant prognostic value&#44; representing an early&#44; non-invasive indicator of kidney damage that may even precede the presence of proteinuria&#46; Control of podocyturia should be evaluated&#44; especially in those relatives in whom a confirmatory enzyme diagnosis has been made and no other renal involvement has yet been detected&#46; Tondel et al&#46; describes podocyte effacement and its subsequent detachment in most children with FD&#44; so that both histological markers have been categorized as pathophysiological stages of early podocyte damage&#46;<a class="elsevierStyleCrossRef" href="#bib0190"><span class="elsevierStyleSup">17</span></a></p><p id="par0220" class="elsevierStylePara elsevierViewall">Trimarchi et al&#46; shows a high podocyturia with low proteinuria in patients without treatment&#46; In our treated patients these findings seem to be reversed &#40;with a more prolonged period of damage&#41;&#59; this indicates a changing relationship between podocyturia and proteinuria as the disease progresses&#46;<a class="elsevierStyleCrossRef" href="#bib0195"><span class="elsevierStyleSup">18</span></a></p><p id="par0225" class="elsevierStylePara elsevierViewall">In general terms&#44; we can state that the magnitude of podocyturia &#40;correcting per urine creatinine concentration&#41; in the pediatric population&#44; compared with adults&#44; seems to confirm the theory of progressive podocyte reduction&#44; related to age and the possible existing nephropathy&#46; Consistent with this hypothesis was our observation in the younger patients with Fabry disease of an initial association between podocyturia and albuminuria&#44; possibly related to the period of time with the disease&#44; most obvious in a younger pediatric population&#46; Hughes et al&#46; reported&#44; a relationship between age and the risk of developing kidney damage&#46;<a class="elsevierStyleCrossRef" href="#bib0200"><span class="elsevierStyleSup">19</span></a> In this same line&#44; in FD patients the period of time elapsed between the detection of podocyturia and pathological albuminuria is similar&#44; which support the assumption that a given time disease is required to see quantitative changes in pdocyturia and albuminuria&#46;<a class="elsevierStyleCrossRef" href="#bib0205"><span class="elsevierStyleSup">20</span></a></p><p id="par0230" class="elsevierStylePara elsevierViewall">Patients with albuminuria were started on progressive doses of enalapril and most patients responded with a reduction of albuminuria&#46; This data is not included in the manuscript&#46;</p><p id="par0235" class="elsevierStylePara elsevierViewall">The consensus among experts is the in patients with Fabry disease that enzyme replacement therapy should be started early&#59; this may attenuate or prevent progressive nephropathy and other organic complications&#46;<a class="elsevierStyleCrossRef" href="#bib0210"><span class="elsevierStyleSup">21</span></a> However&#44; according to our data the time elapsed until the evaluation of 2 key pathophysiological parameters &#40;podocyturia and albuminuria&#41; was too prolonged&#46; This should be corrected if the intention is to apply effective therapeutic intervention&#46; Nevertheless&#44; there is no unanimity about the optimal time to start treatment and there is no long-term data documented as to whether the enzymatic prescription would prevent the nephropathy in children&#46; A non-invasive method such as evaluation of podocyturia as an early marker of glomerular damage could help to decide the initiation of treatment&#46;</p><p id="par0240" class="elsevierStylePara elsevierViewall">The work has certain weaknesses&#44; especially a reduced sample size and the impossibility of correlating the studies carried out with the pathological anatomy&#46; However&#44; the originality of the present work is the finding of an early positive association between 2 important variables such as podocyturia and albuminuria in pediatric patients&#46; Our final aim&#44; work in progress&#44; is to establish the sequential relationship between both variables and determine the time interval of their successive appearances&#44; so specific therapy is implemented early&#59; this would be particularly beneficial in the Fabry population that has not yet developed the pathological albuminuria&#46;</p><p id="par0245" class="elsevierStylePara elsevierViewall">In conclusion&#44; our study shows that the detection of podocyturia in pediatric patients with Fabry disease could be used as an early marker of renal damage&#44; which precedes and is directly proportional to the appearance of pathological albuminuria&#46;</p></span><span id="sec0050" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0120">Conflicts of interests</span><p id="par0250" class="elsevierStylePara elsevierViewall">The authors have no conflicts of interest to declare&#46;</p></span></span>"
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        "resumen" => "<span id="abst0005" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0010">Introduction</span><p id="spar0005" class="elsevierStyleSimplePara elsevierViewall">Fabry disease &#40;FD&#41; is a hereditary disorder caused by a deficiency of &#945;-galactosidase A enzyme activity&#46; The transmission of the disorder is linked to the X chromosome&#46;</p></span> <span id="abst0010" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0015">Objectives</span><p id="spar0010" class="elsevierStyleSimplePara elsevierViewall">The objectives of the study were&#58; 1&#46; To quantify the presence of podocytes in pediatric patients with FD and compare them with the value of the measured podocyturia in healthy controls&#46; 2&#46; To determine whether a greater podocyturia is related to the onset of pathological albuminuria in patients with FD&#46; 3&#46; To determine the risk factors associated with pathological albuminuria&#46;</p></span> <span id="abst0015" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0020">Methods</span><p id="spar0015" class="elsevierStyleSimplePara elsevierViewall">We performed an analytical&#44; observational study of Fabry and control subjects&#44; which were separated into 2 groups in accordance with the absence of the disease &#40;control group&#41; or the presence of the disease &#40;Fabry group&#41;&#46;</p></span> <span id="abst0020" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0025">Results</span><p id="spar0020" class="elsevierStyleSimplePara elsevierViewall">We studied 31 patients&#44; 11 with FD and 20 controls&#44; with a mean age of 11&#46;6 years&#46;</p><p id="spar0025" class="elsevierStyleSimplePara elsevierViewall">The difference between the mean time elapsed from the diagnosis of FD to the measurement of podocyturia &#40;40 months&#41; and the onset of pathological albuminuria &#40;34 months&#41; was not significant &#40;<span class="elsevierStyleItalic">p</span><span class="elsevierStyleHsp" style=""></span>&#61;<span class="elsevierStyleHsp" style=""></span>0&#46;09&#41;&#46; Podocytes were identified by staining for the presence of synaptopodin and the mean quantitative differences between both podocyturias were statistically significant &#40;<span class="elsevierStyleItalic">p</span><span class="elsevierStyleHsp" style=""></span>&#61;<span class="elsevierStyleHsp" style=""></span>0&#46;001&#41;&#46; Albuminuria was physiological in 4 of the patients with FD and the relative risk to develop pathological albuminuria according to podocyturia was 1&#46;1 in the control group and 3&#46;9 in the Fabry group&#44; with a coefficient of correlation between podocyturia and albuminuria in the Fabry group of 0&#46;8354&#46; Finally&#44; the 2 risk factors associated with the development of pathological albuminuria were podocyturia &#40;OR&#58; 14&#41; and being aged over 10 years &#40;OR&#58; 18&#41;&#46; We found no significant risk with regard to glomerular filtrate renal &#40;GFR&#41; &#40;OR&#58; 0&#46;5&#41; or gender &#40;OR&#58; 1&#46;3&#41;&#46; The mean GFR remained within normal values&#46;</p></span> <span id="abst0025" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0030">Conclusion</span><p id="spar0030" class="elsevierStyleSimplePara elsevierViewall">The detection of podocyturia in pediatric patients with FD could be used as an early marker of renal damage&#44; preceding and proportional to the occurrence of pathological albuminuria&#46;</p></span>"
        "secciones" => array:5 [
          0 => array:2 [
            "identificador" => "abst0005"
            "titulo" => "Introduction"
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          1 => array:2 [
            "identificador" => "abst0010"
            "titulo" => "Objectives"
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          2 => array:2 [
            "identificador" => "abst0015"
            "titulo" => "Methods"
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        "resumen" => "<span id="abst0030" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0040">Introducci&#243;n</span><p id="spar0035" class="elsevierStyleSimplePara elsevierViewall">La enfermedad de Fabry &#40;EF&#41; es un trastorno hereditario causado por una deficiencia de la actividad de la enzima &#945;-galactosidasa A&#44; cuya transmisi&#243;n est&#225; relacionada con el cromosoma X&#46;</p></span> <span id="abst0035" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0045">Objetivos</span><p id="spar0040" class="elsevierStyleSimplePara elsevierViewall">Los objetivos del estudio fueron&#58; 1&#46; Cuantificar la presencia de podocitos en pacientes pedi&#225;tricos con EF y compararla con el valor de la podocituria medida en controles sanos&#46; 2&#46; Determinar en pacientes con EF si una mayor podocituria est&#225; relacionada con la albuminuria patol&#243;gica&#46; 3&#46; Determinar los factores de riesgo asociados con la albuminuria patol&#243;gica&#46;</p></span> <span id="abst0040" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0050">M&#233;todos</span><p id="spar0045" class="elsevierStyleSimplePara elsevierViewall">Implementamos un estudio anal&#237;tico observacional de casos y controles&#44; separados en 2 grupos de acuerdo con la ausencia de enfermedad &#40;grupo control&#41; o con la presencia de enfermedad &#40;grupo Fabry&#41;&#46;</p></span> <span id="abst0045" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0055">Resultados</span><p id="spar0050" class="elsevierStyleSimplePara elsevierViewall">Estudiamos a 31 pacientes&#44; 11 con EF y 20 controles&#44; con una media de edad de 11&#44;6 a&#241;os&#46; La diferencia entre el tiempo medio transcurrido desde el diagn&#243;stico de EF hasta la medici&#243;n de la podocituria &#40;40 meses&#41; y la aparici&#243;n de la albuminuria patol&#243;gica &#40;34 meses&#41; no fue significativa &#40;p&#58; 0&#44;09&#41;&#46; Los podocitos se identificaron mediante tinci&#243;n para sinaptopodina y las diferencias medias cuantitativas entre ambas podociturias fueron estad&#237;sticamente significativas &#40;p&#58; 0&#44;001&#41;&#46; La albuminuria fue fisiol&#243;gica en 4 de las pacientes Fabry y el riesgo relativo para desarrollar albuminuria patol&#243;gica de acuerdo con la podocituria fue en el grupo control 1&#44;1 y en el grupo Fabry 3&#44;9&#44; con un coeficiente de correlaci&#243;n entre la podocituria y la albuminuria en el grupo Fabry de 0&#44;8354&#46; Finalmente los 2 factores de riesgo asociados al desarrollo de albuminuria patol&#243;gica fueron la podocituria &#40;OR 14&#41; y la edad mayor a 10 a&#241;os &#40;OR 18&#41;&#46; No encontramos riesgo significativo ni en el filtrado glomerular &#40;FG&#41; &#40;OR 0&#44;5&#41;&#44; ni en el g&#233;nero &#40;OR 1&#44;3&#41;&#46; El FG medio se mantuvo dentro de valores normales&#46;</p></span> <span id="abst0050" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0060">Conclusi&#243;n</span><p id="spar0055" class="elsevierStyleSimplePara elsevierViewall">La detecci&#243;n de podocituria en pacientes pedi&#225;tricos con EF podr&#237;a utilizarse como un marcador temprano de da&#241;o renal previo y relacionado con la albuminuria patol&#243;gica&#46;</p></span>"
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        "nota" => "<p class="elsevierStyleNotepara" id="npar0005">Please cite this article as&#58; Liern M&#44; Collazo A&#44; Valencia M&#44; Fainboin A&#44; Isse L&#44; Costales-Collaguazo C&#44; et al&#46; Podocituria en pacientes pedi&#225;tricos con enfermedad de Fabry&#46; Nefrologia&#46; 2019&#59;39&#58;177&#8211;183&#46;</p>"
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          "en" => "<p id="spar0060" class="elsevierStyleSimplePara elsevierViewall">Detection of podocyturia by indirect immunofluorescence&#46; &#40;A&#41; Panoramic view of urinary sediment without synaptopodin &#40;Control&#41;&#46; &#40;B&#41; Urine sediment in patients with Fabry&#44; positive synaptopodin is observed in podocytes&#46; Magnification&#58; &#40;A&#41; &#215;100&#59; &#40;B&#41; &#215;400&#46;</p>"
        ]
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      1 => array:7 [
        "identificador" => "fig0010"
        "etiqueta" => "Fig&#46; 2"
        "tipo" => "MULTIMEDIAFIGURA"
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        "descripcion" => array:1 [
          "en" => "<p id="spar0065" class="elsevierStyleSimplePara elsevierViewall">Levels of podocyturia and albuminuria in urine of children with Fabry disease &#40;black arrow&#41; and in normal children&#46; There is a subgroup of 4 patients with Fabry disease who have low levels of albuminuria and podocyturia&#46;</p>"
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      2 => array:8 [
        "identificador" => "tbl0005"
        "etiqueta" => "Table 1"
        "tipo" => "MULTIMEDIATABLA"
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          "leyenda" => "<p id="spar0075" class="elsevierStyleSimplePara elsevierViewall">SD&#58; standard deviation&#59; FD&#58; Fabry disease&#59; GFR&#44; glomerular filtration rate&#46;</p>"
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                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="" valign="top" scope="col" style="border-bottom: 2px solid black">&nbsp;\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">Group A &#40;control&#41;&#44; <span class="elsevierStyleItalic">n</span>&#58; 20&nbsp;\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">Group B &#40;Fabry disease&#41;&#44; <span class="elsevierStyleItalic">n</span>&#58; 11&nbsp;\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"><span class="elsevierStyleItalic">p</span>&nbsp;\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">Mean age&#44; years &#40;range&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">1&#46;1 &#40;5&#8211;17&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">1&#46;7 &#40;5&#8211;17&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="char" valign="top">0&#46;09&nbsp;\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">Gender&#44; M&#47;F&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">7&#47;13&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">5&#47;6&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="char" valign="top">0&#46;08&nbsp;\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">Mean age in years at the diagnosis of FD &#40;range&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="" valign="top">&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">7&#46;9 &#40;5&#8211;11&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="" valign="top">&nbsp;\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">Mean GFR &#40;ml&#47;1&#46;73<span class="elsevierStyleHsp" style=""></span>m<span class="elsevierStyleSup">2</span>&#47;min&#41;&#40;SD&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="" valign="top">&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">102 &#40;8&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="" valign="top">&nbsp;\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">Proteinuria &#40;mg&#47;m<span class="elsevierStyleSup">2</span>&#47;h&#41; &#40;SD&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">1&#46;5 &#40;0&#46;7&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">4&#46;3 &#40;0&#46;5&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="char" valign="top">0&#46;05&nbsp;\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">Albuminuria &#40;ucg&#47;min&#41; &#40;SD&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">10 &#40;5&#46;2&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">21 &#40;12&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="char" valign="top">&#60;0&#46;01&nbsp;\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">Pathological albuminuria &#40;&#37;&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">0&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">64&#37;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="char" valign="top">&#60;0&#46;001&nbsp;\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">Podocyturia&#47;Cr in urine &#40;mg&#47;dl&#41; &#40;SD&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">0&#46;4 &#40;0&#46;3&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">1&#46;5 &#40;0&#46;8&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="char" valign="top">&#60;0&#46;01&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr></tbody></table>
                  """
              ]
              "imagenFichero" => array:1 [
                0 => "xTab2018697.png"
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        ]
        "descripcion" => array:1 [
          "en" => "<p id="spar0070" class="elsevierStyleSimplePara elsevierViewall">Description of the measurements of urine parameters and other parameters in controls and patients with Fabry disease&#46;</p>"
        ]
      ]
      3 => array:8 [
        "identificador" => "tbl0010"
        "etiqueta" => "Table 2"
        "tipo" => "MULTIMEDIATABLA"
        "mostrarFloat" => true
        "mostrarDisplay" => false
        "detalles" => array:1 [
          0 => array:3 [
            "identificador" => "at2"
            "detalle" => "Table "
            "rol" => "short"
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        "tabla" => array:2 [
          "leyenda" => "<p id="spar0085" class="elsevierStyleSimplePara elsevierViewall"><span class="elsevierStyleItalic">n</span>&#58; 11 patients&#59; FD&#58; Fabry disease&#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="table-head  " align="left" valign="top" scope="col" style="border-bottom: 2px solid black">Gender&nbsp;\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 &#40;years&#41;&nbsp;\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">Podocyturia&#47;Cr in urine &#40;mg&#47;dl&#41;&nbsp;\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">Time elapsed from the diagnosis of FD to the measurement of podocyturia &#40;months&#41;&nbsp;\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">Albuminuria &#40;ucg&#47;min&#41;&nbsp;\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">Time elapsed since diagnosis of FD to the observation of pathological albuminuria &#40;months&#41;&nbsp;\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">Mutation&nbsp;\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 biopsy&nbsp;\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">Initiation and time on enzymatic treatment&nbsp;\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">Man&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="char" valign="top">17&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="char" valign="top">0&#46;5&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="char" valign="top">59&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="char" valign="top">25&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="char" valign="top">59&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">A292T&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="" valign="top">&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">January 2012&nbsp;\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">Man&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="char" valign="top">16&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="char" valign="top">0&#46;8&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="char" valign="top">85&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="char" valign="top">33&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="char" valign="top">85&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">A292T&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">yes&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">&#40;5 years of treatment&#41;&nbsp;\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">Man&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="char" valign="top">10&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="char" valign="top">2&#46;3&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="char" valign="top">29&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="char" valign="top">39&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="char" valign="top">29&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">L415P&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="" valign="top">&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">January 2012 &#40;5 years of treatment&#41;&nbsp;\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">Woman&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="char" valign="top">15&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="char" valign="top">1&#46;1&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="char" valign="top">46&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="char" valign="top">27&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="char" valign="top">29&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">A292T&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">yes&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">March 2015 &#40;2 years of treatment&#41;&nbsp;\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">Woman&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="char" valign="top">12&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="char" valign="top">2&#46;2&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="char" valign="top">35&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="char" valign="top">26&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="char" valign="top">23&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">T194I&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">yes&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">February 2015 &#40;2 years of treatment&#41;&nbsp;\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">Woman&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="char" valign="top">12&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="char" valign="top">2&#46;6&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="char" valign="top">18&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="char" valign="top">17&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="char" valign="top">18&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">L415P&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="" valign="top">&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">February 2017 &#40;3 months of treatment&#41;&nbsp;\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">Man&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="char" valign="top">10&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="char" valign="top">1&#46;6&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="char" valign="top">9&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="char" valign="top">31&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="char" valign="top">9&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">&#8211;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="" valign="top">&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">October 2017 &#40;7 months of treatment&#41;&nbsp;\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">Woman&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="char" valign="top">5&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="char" valign="top">2&#46;5&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="char" valign="top">7&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="char" valign="top">4&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="char" valign="top">&#8211;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">&#8211;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="" valign="top">&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">October 2016 &#40;1 year of treatment&#41;&nbsp;\t\t\t\t\t\t\n
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                  \t\t\t\t</td><td class="td" title="table-entry  " align="char" valign="top">32&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="char" valign="top">6&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="char" valign="top">&#8211;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">A292T&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="" valign="top">&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="" valign="top">&nbsp;\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">Man&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="char" valign="top">12&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="char" valign="top">1&#46;1&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="char" valign="top">46&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="char" valign="top">11&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="char" valign="top">&#8211;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">A292T&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="" valign="top">&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="" valign="top">&nbsp;\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">Woman&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="char" valign="top">8&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="char" valign="top">1&#46;9&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="char" valign="top">8&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="char" valign="top">3&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="char" valign="top">&#8211;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">A292T&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="" valign="top">&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="" valign="top">&nbsp;\t\t\t\t\t\t\n
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Article information

ISSN: 20132514
Original language: English

DOI:10.1016/j.nefroe.2019.03.001

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Year/Month	Html	Pdf	Total

2024 November	11	7	18
2024 October	69	48	117
2024 September	59	23	82
2024 August	80	62	142
2024 July	35	20	55
2024 June	57	33	90
2024 May	72	42	114
2024 April	54	35	89
2024 March	50	40	90
2024 February	40	51	91
2024 January	60	66	126
2023 December	49	23	72
2023 November	50	46	96
2023 October	36	34	70
2023 September	30	30	60
2023 August	31	29	60
2023 July	32	26	58
2023 June	33	28	61
2023 May	50	39	89
2023 April	29	21	50
2023 March	62	20	82
2023 February	43	19	62
2023 January	26	29	55
2022 December	51	26	77
2022 November	71	36	107
2022 October	63	37	100
2022 September	41	39	80
2022 August	31	45	76
2022 July	29	50	79
2022 June	36	41	77
2022 May	34	45	79
2022 April	43	49	92
2022 March	77	61	138
2022 February	39	44	83
2022 January	35	37	72
2021 December	33	37	70
2021 November	38	31	69
2021 October	73	47	120
2021 September	34	35	69
2021 August	52	47	99
2021 July	34	35	69
2021 June	45	38	83
2021 May	39	61	100
2021 April	57	75	132
2021 March	40	35	75
2021 February	60	35	95
2021 January	27	23	50
2020 December	42	23	65
2020 November	27	19	46
2020 October	27	21	48
2020 September	25	14	39
2020 August	23	16	39
2020 July	25	11	36
2020 June	14	16	30
2020 May	34	7	41
2020 April	21	17	38
2020 March	28	12	40
2020 February	42	24	66
2020 January	30	25	55
2019 December	45	29	74
2019 November	30	14	44
2019 October	45	15	60
2019 September	33	19	52
2019 August	38	27	65
2019 July	27	33	60
2019 June	31	25	56
2019 May	32	31	63
2019 April	72	32	104
2019 March	4	3	7

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