Valor diagnóstico de los niveles séricos del receptor soluble de la uroquinasa en adultos con síndrome nefrótico idiopático / Diagnostic value of soluble urokinase-type plasminogen activator receptor serum levels in adults with idiopathic nephrotic syndrome

Introducción: Estudios recientes sugieren que los niveles del receptor soluble de la uroquinasa (suPAR) podrían ser útiles para diferenciar la glomeruloesclerosis focal y segmentaria (GFS) idiopática de otras glomerulopatías causantes de síndrome nefrótico, pero estos datos no han sido confirmados en estudios independientes. El objetivo de nuestro estudio es analizar si los niveles circulantes de suPAR son útiles para identificar la enfermedad renal primaria en enfermos afectos de síndrome nefrótico secundario a GFS, enfermedad por cambios mínimos o nefropatía membranosa (NM) idiopática. Métodos: Se realizaron mediciones de niveles de suPAR circulante en el momento del diagnóstico en 60 pacientes con síndrome nefrótico secundario a GFS, enfermedad por cambios mínimos (ECM) y NM. Se analizaron las correlaciones entre niveles de suPAR y variables demográficas, clínicas y bioquímicas. La sensibilidad y la especificidad de suPAR para diferenciar a los enfermos con GFS se analizaron mediante curvas ROC. Resultados: Tras ajustar por edad y función renal, los niveles de suPAR fueron significativamente más elevados en enfermos con GFS que en ECM (p < 0,001), pero no hubo diferencias entre GFS y NM (p = 0,12). Un valor de suPAR ≥ 3452 pg/ml tuvo una sensibilidad del 73,7 % y una especificidad del 72,5 %, con un área bajo la curva (ABC) de 0,782 ± 0,124, p = 0,001, para identificar a los enfermos con GFS. Tras excluir a los enfermos con NM, un valor ≥ 3531 pg/ml tuvo una especificidad del 99,93 % para diferenciar entre ECM y GFS. Conclusiones: Los valores de suPAR por sí solos no diferencian entre los tres tipos de glomerulopatía. Sin embargo, tras excluir el diagnóstico de NM, un nivel de suPAR > 3531 pg/ml podría tener una elevada especificidad (pero baja sensibilidad) para el diagnóstico de GFS

Introduction: Recent studies suggest that soluble urokinase-type plasminogen activator receptor (suPAR) levels could be useful for distinguishing idiopathic focal segmental glomerulosclerosis (FSGS) from other glomerulopathies that cause nephrotic syndrome, but these data have not been confirmed in independent studies. The objective of our study is to analyse whether circulating levels of suPAR are useful for identifying primary kidney disease in patients with nephrotic syndrome secondary to FSGS, minimal change disease or idiopathic membranous nephropathy (MN). Methods: We measured circulating suPAR at diagnosis in 60 patients with nephrotic syndrome secondary to FSGS, minimal change disease (MCD) and membranous nephropathy (MN). The correlations between suPAR levels and demographic, clinical and biochemical variables were analysed. The sensitivity and specificity of suPAR in distinguishing FSGS patients were analysed by ROC curves. Results: After adjusting for age and renal function, suPAR levels were significantly higher in patients with FSGS than in those with MCD (p<.001), but there were no differences between FSGS and MN (P=.12). A suPAR value ≥3452pg/ml had a sensitivity of 73.7% and a specificity of 72.5%, with an area under the curve (AUC) of 0.782±0.124, p=.001, for identifying patients with FSGS. After excluding patients with MN, a value ≥3531pg/ml had a specificity of 99.93% for distinguishing between MCD and FSGS. Conclusions: suPAR values alone do not distinguish between the three types of glomerulopathy. Nevertheless, after excluding the diagnosis of MN, a suPAR level >3531pg/ml could have a high specificity (but a low sensitivity) in the diagnosis of FSGS

Valor de los niveles séricos del receptor soluble de la uroquinasa en el diagnóstico diferencial entre glomeruloesclerosis focal y segmentaria idiopática y secundaria / Value of soluble urokinase receptor serum levels in the differential diagnosis between idiopathic and secondary focal segmental glomerulosclerosis

Antecedentes: Se ha descrito que el nivel circulante del receptor soluble de la uroquinasa (suPAR) podría ser útil para diferenciar la glomeruloesclerosis focal y segmentaria idiopática de las formas secundarias, pero los resultados publicados son discordantes. En el presente estudio, se analiza la variabilidad intraindividual, las variables clínicas y anatomopatológicas asociadas con los niveles de suPAR y si los niveles circulantes de suPAR permiten diferenciar las formas de glomeruloesclerosis focal y segmentaria (GFS) idiopáticas de las GFS secundarias, independientemente de la presencia de síndrome nefrótico y de la fase de actividad. Métodos: Se estudiaron 35 pacientes afectos de GFS idiopática y 48 con GFS secundaria (83 en total). Se realizaron mediciones de suPAR circulante en el momento del diagnóstico y/o tras la remisión y se analizaron las correlaciones entre niveles de suPAR y variables demográficas, clínicas y bioquímicas. La capacidad de suPAR para diferenciar entre ambas formas de GFS se analizó mediante curvas ROC y análisis de regresión logística. Resultados: En ambas formas de GFS, los niveles de suPAR fueron independientes de la proteinuria y del subtipo histopatológico de GFS y se asociaron significativamente a la edad y a la función renal. Tras ajustar por ambas variables, los niveles de suPAR fueron significativamente superiores en los enfermos con GFS idiopática, tanto en fase de síndrome nefrótico como en situación de remisión parcial o total. El nivel de suPAR con mayor sensibilidad (80 %) y mayor especificidad (73 %) para discriminar entre formas idiopáticas y secundarias fue de 3443,6 pg/ml (área bajo la curva [ABC] 0,78 ± 0,083, p < 0,001). En el análisis de regresión logística, tras ajustar por edad, función renal y presencia de síndrome nefrótico, los niveles de suPAR se asociaron de forma independiente con el diagnóstico de GFS idiopática, pero el modelo tuvo un mal ajuste para categorías de riesgo bajas, en las que tendió a clasificar las formas primarias como secundarias (χ 2 = 11,2 p = 0,027). Conclusiones: Los niveles de suPAR carecen de sensibilidad para diferenciar entre GFS idiopática y secundaria. Sin embargo, valores de suPAR superiores a 4000 ng/ml son altamente específicos de GFS primaria, por lo que, ante un patrón morfológico de GFS asociado a proteinuria no nefrótica, indicarían una baja probabilidad de GFS secundaria (AU)

Background: It has been reported that the circulating level of the soluble urokinase receptor (suPAR) could be useful for distinguishing idiopathic from secondary focal segmental glomerulosclerosis, but the results published are conflicting. In this study, we analyse the intraindividual variability and clinical and anatomopathological variables associated with the suPAR levels and if circulating suPAR levels allow the different forms of focal segmental glomerulosclerosis (FSGS) to be distinguished, i.e., idiopathic forms from secondary FSGS, regardless of the presence of nephrotic syndrome and the activity phase. Method: We studied 35 patients affected by idiopathic FSGS and 48 with secondary FSGS (83 in total). We carried out measurements of circulating suPAR at the time of diagnosis and/or after remission and we analysed correlations between suPAR levels and demographic, clinical and biochemical variables. The ability of suPAR to distinguish between both forms of FSGS was analysed by ROC curves and logistic regression analysis. Results: In both forms of FSGS, suPAR levels were independent of proteinuria and the histopathological subtype of FSGS and they were significantly associated with age and renal function. After adjusting for both variables, suPAR levels were significantly higher in patients with idiopathic FSGS, both in the nephrotic syndrome phase and in partial or complete remission. The most sensitive suPAR level (80%) and the most specific (73%) for discriminating between idiopathic and secondary forms was 3443.6pg/ml (area below curve [ABC] 0.78±0.083, P<.001). In the logistic regression analysis, after adjusting for age, renal function and presence of nephrotic syndrome, suPAR levels were independently associated with the diagnosis of idiopathic FSGS, but the model was poorly adjusted for low risk categories in which it tended to classify primary forms as secondary forms (χ 2 = 11.2 p=.027). Conclusions: SuPAR levels lack sensitivity for differentiating between idiopathic and secondary FSGS. However, suPAR values greater than 4000ng/ml are highly specific to primary FSGS, and as such, with a morphological FSGS pattern associated with non-nephrotic proteinuria, they would indicate a low probability of secondary FSGS (AU)

[Diagnostic value of soluble urokinase-type plasminogen activator receptor serum levels in adults with idiopathic nephrotic syndrome]. / Valor diagnóstico de los niveles séricos del receptor soluble de la uroquinasa en adultos con síndrome nefrótico idiopático.

INTRODUCTION: Recent studies suggest that soluble urokinase-type plasminogen activator receptor (suPAR) levels could be useful for distinguishing idiopathic focal segmental glomerulosclerosis (FSGS) from other glomerulopathies that cause nephrotic syndrome, but these data have not been confirmed in independent studies. The objective of our study is to analyse whether circulating levels of suPAR are useful for identifying primary kidney disease in patients with nephrotic syndrome secondary to FSGS, minimal change disease or idiopathic membranous nephropathy (MN). METHODS: We measured circulating suPAR at diagnosis in 60 patients with nephrotic syndrome secondary to FSGS, minimal change disease (MCD) and membranous nephropathy (MN). The correlations between suPAR levels and demographic, clinical and biochemical variables were analysed. The sensitivity and specificity of suPAR in distinguishing FSGS patients were analysed by ROC curves. RESULTS: After adjusting for age and renal function, suPAR levels were significantly higher in patients with FSGS than in those with MCD (p<.001), but there were no differences between FSGS and MN (P=.12). A suPAR value ≥3452 pg/ml had a sensitivity of 73.7% and a specificity of 72.5%, with an area under the curve (AUC) of 0.782 ± 0.124, p=.001, for identifying patients with FSGS. After excluding patients with MN, a value ≥3531 pg/ml had a specificity of 99.93% for distinguishing between MCD and FSGS. CONCLUSIONS: suPAR values alone do not distinguish between the three types of glomerulopathy. Nevertheless, after excluding the diagnosis of MN, a suPAR level >3531 pg/ml could have a high specificity (but a low sensitivity) in the diagnosis of FSGS.

[Value of soluble urokinase receptor serum levels in the differential diagnosis between idiopathic and secondary focal segmental glomerulosclerosis]. / Valor de los niveles séricos del receptor soluble de la uroquinasa en el diagnóstico diferencial entre glomeruloesclerosis focal y segmentaria idiopática y secundaria.

BACKGROUND: It has been reported that the circulating level of the soluble urokinase receptor (suPAR) could be useful for distinguishing idiopathic from secondary focal segmental glomerulosclerosis, but the results published are conflicting. In this study, we analyse the intraindividual variability and clinical and anatomopathological variables associated with the suPAR levels and if circulating suPAR levels allow the different forms of focal segmental glomerulosclerosis (FSGS) to be distinguished, i.e., idiopathic forms from secondary FSGS, regardless of the presence of nephrotic syndrome and the activity phase. METHOD: We studied 35 patients affected by idiopathic FSGS and 48 with secondary FSGS (83 in total). We carried out measurements of circulating suPAR at the time of diagnosis and/or after remission and we analysed correlations between suPAR levels and demographic, clinical and biochemical variables. The ability of suPAR to distinguish between both forms of FSGS was analysed by ROC curves and logistic regression analysis. RESULTS: In both forms of FSGS, suPAR levels were independent of proteinuria and the histopathological subtype of FSGS and they were significantly associated with age and renal function. After adjusting for both variables, suPAR levels were significantly higher in patients with idiopathic FSGS, both in the nephrotic syndrome phase and in partial or complete remission. The most sensitive suPAR level (80%) and the most specific (73%) for discriminating between idiopathic and secondary forms was 3443.6 pg/ml (area below curve [ABC] 0.78 ± 0.083, P<.001). In the logistic regression analysis, after adjusting for age, renal function and presence of nephrotic syndrome, suPAR levels were independently associated with the diagnosis of idiopathic FSGS, but the model was poorly adjusted for low risk categories in which it tended to classify primary forms as secondary forms (χ(2) = 11.2 p=.027). CONCLUSIONS: SuPAR levels lack sensitivity for differentiating between idiopathic and secondary FSGS. However, suPAR values greater than 4000 ng/ml are highly specific to primary FSGS, and as such, with a morphological FSGS pattern associated with non-nephrotic proteinuria, they would indicate a low probability of secondary FSGS.