Valor de los niveles urinarios de interleucina 6, factor de crecimiento epidérmico, proteína quimioatractante de monocitos de tipo 1 y factor de crecimiento transformante Beta1 para la predicción de la extensión de las lesiones de fibrosis en biopsias de enfermos con nefropatía IgA / Value of urinary levels of interleukin-6, epidermal growth factor, monocyte chemoattractant protein type1 and transforming growth factor Beta1 in predicting the extent of fibrosis lesions in kidney biopsies of patients with IgA nephropathy

Objetivo: Analizar las asociaciones entre el nivel urinario de IL-6, EGF, MCP-1 y TGFβ1 y las características clínicas, bioquímicas y anatomopatológicas en enfermos con nefropatía IgA primaria y determinar su capacidad para realizar una estimación de la extensión de las lesiones de esclerosis glomerular e intersticial. Pacientes y métodos: Se estudió a 58 enfermos con nefropatía IgA. Se determinaron los niveles urinarios de IL-6, EGF, MCP-1 y TGFβ1 en el momento del diagnóstico. Tras realizar un análisis de la extensión de las lesiones renales mediante morfometría cuantitativa y mediante los criterios de Oxford, se analizó la capacidad de dichas moléculas para estimar la extensión de las lesiones glomerulares e intersticiales de fibrosis. Resultados: La IL-6, MCP-1 y TGF-β1 se asociaron a glomeruloesclerosis focal y a la extensión de la fibrosis intersticial, pero no a la presencia de proliferación mesangial, intracapilar o extracapilar. EGF presentó una asociación negativa con la fibrosis intersticial. Al categorizar a los enfermos según la clasificación de Oxford, los enfermos con scores T1 y T2 presentaron niveles significativamente superiores de IL-6, MCP-1 y TGFβ1, y niveles de EGF significativamente inferiores que los enfermos con T0. Tanto mediante regresión múltiple como mediante regresión logística, los niveles de MCP-1, IL-6 y EGF fueron predictores independientes de la superficie de fibrosis, tras ajustar por edad y FGe. Conclusión: La determinación de la concentración urinaria de IL-6, EGF y MCP-1 proporciona una información adicional que mejora de forma significativa la estimación de la superficie de fibrosis intersticial (AU)

Objective: To analyse the associations between urinary levels of IL-6 EGF, MCP-1 and TGFβ1 and clinical, biochemical and histopathological characteristics in patients with primary IgA nephropathy and their ability to predict the extent of lesions of glomerular and/or interstitial sclerosis. Patients and methods: A total of 58 patients with IgA nephropathy were studied. We determined the urine levels of IL-6, EGF, MCP-1, and TGFβ1 at the time of diagnosis. The extent of glomerular and interstitial fibrosis was analyzed by quantitative morphometry and kidney biopsies were classified according to the Oxford criteria. We analysed the ability of these molecules to predict the extent of glomerular and interstitial fibrosis lesions. Results: IL-6, TGFβ1 and MCP-1 were associated with focal glomerulosclerosis and interstitial fibrosis extension but not with the presence of mesangial, extracapillary or endocapillary proliferation. EGF showed a negative association with interstitial fibrosis. By categorising patients according to the Oxford classification, patients with T1 and T2 scores had significantly higher levels of IL-6, MCP-1, TGF-β1 and significantly lower levels of EGF than patients with T0 scores. By multiple regression and logistic regression analyses, the levels of MCP-1, IL-6 and EGF were independent predictors of the fibrosis surface, after adjusting for age and eGFR. Conclusion: The urinary concentration of IL-6, EGF and MCP-1 provides additional information that significantly improves the estimation of the surface of interstitial fibrosis in patients with IgA nephropathy (AU)

Value of urinary levels of interleukin-6, epidermal growth factor, monocyte chemoattractant protein type1 and transforming growth factor ß1 in predicting the extent of fibrosis lesions in kidney biopsies of patients with IgA nephropathy. / Valor de los niveles urinarios de interleucina 6, factor de crecimiento epidérmico, proteína quimioatractante de monocitos de tipo 1 y factor de crecimiento transformante ß1 para la predicción de la extensión de las lesiones de fibrosis en biopsias de enfermos con nefropatía IgA.

OBJECTIVE: To analyse the associations between urinary levels of IL-6 EGF, MCP-1 and TGFß1 and clinical, biochemical and histopathological characteristics in patients with primary IgA nephropathy and their ability to predict the extent of lesions of glomerular and/or interstitial sclerosis. PATIENTS AND METHODS: A total of 58 patients with IgA nephropathy were studied. We determined the urine levels of IL-6, EGF, MCP-1, and TGFß1 at the time of diagnosis. The extent of glomerular and interstitial fibrosis was analyzed by quantitative morphometry and kidney biopsies were classified according to the Oxford criteria. We analysed the ability of these molecules to predict the extent of glomerular and interstitial fibrosis lesions. RESULTS: IL-6, TGFß1 and MCP-1 were associated with focal glomerulosclerosis and interstitial fibrosis extension but not with the presence of mesangial, extracapillary or endocapillary proliferation. EGF showed a negative association with interstitial fibrosis. By categorising patients according to the Oxford classification, patients with T1 and T2 scores had significantly higher levels of IL-6, MCP-1, TGF-ß1 and significantly lower levels of EGF than patients with T0 scores. By multiple regression and logistic regression analyses, the levels of MCP-1, IL-6 and EGF were independent predictors of the fibrosis surface, after adjusting for age and eGFR. CONCLUSION: The urinary concentration of IL-6, EGF and MCP-1 provides additional information that significantly improves the estimation of the surface of interstitial fibrosis in patients with IgA nephropathy.

Estudio de las variables asociadas a la activación local del complemento en la nefropatía IgA idiopática / Study of the variables associated with local complement activation in IgA nephropathy

Objetivos: 1) Identificar las variables que se asocian con los niveles urinarios de MBL, C4d y C5b-9 en enfermos con nefropatía IgA idiopática. 2) Analizar si los niveles urinarios de MBL o C4d son útiles para identificar la presencia de depósitos mesangiales de C4d/MBL. Pacientes y método: Se estudió a 96 enfermos con nefropatía IgA primaria. Se registraron las variables demográficas, clínicas y bioquímicas en el momento del diagnóstico. Las lesiones renales se cuantificaron mediante la clasificación de Oxford. En las biopsias, se realizaron tinciones inmunohistoquímicas para MBL, properdina, C4d, y C5b-9. En orina, se determinó el nivel de properdina, MBL, C4d y C5b-9. Resultados: Los predictores independientes de los niveles de C4d y MBL en orina fueron el depósito mesangial de cada una de ellas y, en menor grado, la proteinuria. Los predictores independientes de los niveles urinarios de C5b-9 fueron los niveles de MBL y properdina, y la proteinuria. La excreción urinaria de C4d tuvo una sensibilidad del 90% (IC 95%: 58,7-99) y una especificidad del 73% (IC 95%: 54-87) para la detección de depósitos mesangiales de C4d y el nivel de MBL tuvo una sensibilidad del 83,9% (IC 95%: 62-95) y una especificidad del 81,6% (IC 95%: 65-92) para identificar depósitos mesangiales de MBL. Conclusión: El principal predictor de la concentración urinaria de C4d y MBL es la presencia de depósitos mesangiales de ellas. La MBL podría contribuir a la activación del complemento en la luz tubular a través de la vía de las lectinas. Los niveles urinarios de MBL y C4d podrían ser biomarcadores sensibles y específicos para la identificación de los enfermos que presentan depósitos mesangiales de MBL o C4d (AU)

Objectives: 1. To identify the variables that are associated with urinary levels of properdin, MBL, C4d, and C5b-9 in patients with idiopathic IgA nephropathy. 2. To analyse whether urinary levels of MBL and/or C4d are useful for identifying the presence of mesangial deposits of C4d/MBL. Patients and method: A total of 96 patients with IgA nephropathy were studied. Demographic, clinical and biochemical variables were recorded at the time of diagnosis. Renal lesions were quantified using the Oxford classification. Immunohistochemical staining for MBL, MASP-2, properdin, C4d, and C5b-9 was performed in kidney biopsies, and in urine, the levels of properdin, MBL, C4d and C5b-9 were determined. Results: In multivariate analysis, the independent predictors of C4d and MBL levels in urine were the mesangial deposits of each protein and, to a lesser extent, the urinary protein excretion. The independent predictors of urinary levels of C5b-9 were MBL properdin and proteinuria. Urinary excretion of C4d had a sensitivity of 90% (95% CI: 58,7 to 99) and a specificity of 73% (95% CI: 54-87) for detecting mesangial C4d deposits, and the level of MBL had a sensitivity of 83.9% (95% CI: 62-95) and a specificity of 81.6% (95% CI: 65-92) for identifying mesangial deposits of MBL. Conclusion: The main predictor of urinary concentration of C4d and MBL was the presence of their respective mesangial deposits. Urine MBL may contribute to complement activation in the tubular luz through the lectin pathway. Urinary levels of MBL and C4d could be sensitive and specific biomarkers for the identification of patients with mesangial deposits of MBL and C4d (AU)

Study of the variables associated with local complement activation in IgA nephropathy. / Estudio de las variables asociadas a la activación local del complemento en la nefropatía IgA idiopática.

OBJECTIVES: 1. To identify the variables that are associated with urinary levels of properdin, MBL, C4d, and C5b-9 in patients with idiopathic IgA nephropathy. 2. To analyse whether urinary levels of MBL and/or C4d are useful for identifying the presence of mesangial deposits of C4d/MBL. PATIENTS AND METHOD: A total of 96 patients with IgA nephropathy were studied. Demographic, clinical and biochemical variables were recorded at the time of diagnosis. Renal lesions were quantified using the Oxford classification. Immunohistochemical staining for MBL, MASP-2, properdin, C4d, and C5b-9 was performed in kidney biopsies, and in urine, the levels of properdin, MBL, C4d and C5b-9 were determined. RESULTS: In multivariate analysis, the independent predictors of C4d and MBL levels in urine were the mesangial deposits of each protein and, to a lesser extent, the urinary protein excretion. The independent predictors of urinary levels of C5b-9 were MBL properdin and proteinuria. Urinary excretion of C4d had a sensitivity of 90% (95% CI: 58,7 to 99) and a specificity of 73% (95% CI: 54-87) for detecting mesangial C4d deposits, and the level of MBL had a sensitivity of 83.9% (95% CI: 62-95) and a specificity of 81.6% (95% CI: 65-92) for identifying mesangial deposits of MBL. CONCLUSION: The main predictor of urinary concentration of C4d and MBL was the presence of their respective mesangial deposits. Urine MBL may contribute to complement activation in the tubular luz through the lectin pathway. Urinary levels of MBL and C4d could be sensitive and specific biomarkers for the identification of patients with mesangial deposits of MBL and C4d.

Insuficiencia renal aguda relacionada con medicamentos en pacientes hospitalizados / Drug-related acute renal failure in hospitalised patients

Antecedentes: La información sobre la incidencia de insuficiencia renal aguda (IRA) intrahospitalaria relacionada con medicamentos y las características de los pacientes es escasa. Objetivo: Estimar la incidencia de IRA relacionada con medicamentos en pacientes hospitalizados y comparar sus características con las de los pacientes con IRA relacionada con otras causas. Métodos: Cohorte prospectiva de pacientes con IRA intrahospitalaria (julio de 2010-julio de 2011). Se recogió información sobre características y antecedentes de los pacientes, factores de riesgo y gravedad de la IRA según la clasificación RIFLE, y medicación durante la hospitalización. El análisis de la imputabilidad de los fármacos y la evaluación de la relación causal se realizó siguiendo los métodos y el algoritmo del Sistema Español de Farmacovigilancia. Resultados: Un total de 194 casos presentaron un episodio de IRA intrahospitalaria. La edad mediana de los pacientes fue de 72 años (RI 20); el 60% eran hombres. La incidencia de IRA intrahospitalaria fue de 9,6 por cada 1.000 ingresos. Un 77,8% de los casos presentaron riesgo o daño renal según la clasificación RIFLE. En 105 (54,1%) casos, la IRA se relacionó con medicamentos; principalmente diuréticos, medicamentos que actúan sobre el sistema renina-angiotensina, inmunosupresores, bloqueadores β-adrenérgicos, bloqueantes de los canales de calcio, medios de contraste y antiinflamatorios no esteroideos. La morbilidad cardiovascular fue mayor y la frecuencia de factores de riesgo de IRA y la mortalidad menores en los pacientes con IRA relacionada con medicamentos. Conclusiones: La mitad de los episodios de IRA intrahospitalaria se relacionaron con medicamentos. Los pacientes con IRA relacionada con medicamentos presentaron más antecedentes patológicos cardiovasculares, pero menos factores de riesgo de IRA y una menor mortalidad (AU)

Introduction: The information available on the incidence and the characteristics of patients with acute renal failure (ARF) related to drugs is scarce. Objectives: To estimate the incidence of drug-related ARF in hospitalised patients and to compare their characteristics with those of patients with ARF due to other causes. Material and methods: We selected a prospective cohort of patients with ARF during hospital admission (July 2010-July 2011). Information on patients’ demographics, medical antecedents, ARF risk factors, ARF severity according to the RIFLE classification and hospital drug administration was collected. We analysed the relationship of drugs with the ARF episodes using Spanish Pharmacovigilance System methods and algorithm. Results: A total of 194 cases had an episode of hospital-acquired ARF. The median age of patients was 72 years [IQR 20]; 60% were men. The ARF incidence during hospitalization was 9.6 per 1,000 admissions. According to the RIFLE classification, a risk of kidney damage or kidney injury was present in 77.8% of cases. In 105 (54.1%) cases, ARF was drug-related; the drugs most frequently involved were diuretics, agents acting on the renin-angiotensin system, immunosuppressants, β-blocking agents, calcium channel blockers, contrast media and non-steroid anti-inflammatory drugs. Patients with drug-related ARF had more multi-morbidity, fewer ARF risk factors and lower mortality. Conclusions: Half of ARF episodes during hospitalisation were drug related. Patients with drug-related ARF had higher cardiovascular morbidity than those with ARF related to other causes, but they had a lower frequency of ARF risk factors and mortality (AU)

Drug-related acute renal failure in hospitalised patients.

INTRODUCTION: The information available on the incidence and the characteristics of patients with acute renal failure (ARF) related to drugs is scarce. OBJECTIVES: To estimate the incidence of drug-related ARF in hospitalised patients and to compare their characteristics with those of patients with ARF due to other causes. MATERIAL AND METHODS: We selected a prospective cohort of patients with ARF during hospital admission (July 2010-July 2011). Information on patients' demographics, medical antecedents, ARF risk factors, ARF severity according to the RIFLE classification and hospital drug administration was collected. We analysed the relationship of drugs with the ARF episodes using Spanish Pharmacovigilance System methods and algorithm. RESULTS: A total of 194 cases had an episode of hospital-acquired ARF. The median age of patients was 72 years [IQR 20]; 60% were men. The ARF incidence during hospitalization was 9.6 per 1,000 admissions. According to the RIFLE classification, a risk of kidney damage or kidney injury was present in 77.8% of cases. In 105 (54.1%) cases, ARF was drug-related; the drugs most frequently involved were diuretics, agents acting on the renin-angiotensin system, immunosuppressants, ß-blocking agents, calcium channel blockers, contrast media and non-steroid anti-inflammatory drugs. Patients with drug-related ARF had more multi-morbidity, fewer ARF risk factors and lower mortality. CONCLUSIONS: Half of ARF episodes during hospitalisation were drug related. Patients with drug-related ARF had higher cardiovascular morbidity than those with ARF related to other causes, but they had a lower frequency of ARF risk factors and mortality.

Tratamiento de la glomeruloesclerosis focal y segmentaria idiopática: opciones en caso de resistencia a corticosteroides y anticalcineurínicos / Treatment of idiopathic focal segmental glomerulosclerosis: options in the event of resistance to corticosteroids and calcineurin inhibitors

La mitad de los enfermos con síndrome nefrótico causado por glomeruloesclerosis focal y segmentaria (GFS) primaria presentan resistencia al tratamiento con esteroides. En caso de corticorresistencia, la mejor opción basada en la evidencia ha sido clásicamente el tratamiento con inhibidores de calcineurina, aunque estudios recientes indican que micofenolato podría tener una eficacia similar. En los enfermos con resistencia a anticalcineurínicos, no existe ninguna opción capaz de modificar el curso clínico de la enfermedad, avalada por ensayos clínicos de diseño apropiado, aunque en estudios observacionales se ha sugerido la posible utilidad de micofenolato, sirolimus, rituximab, aféresis o altas dosis de galactosa como opciones terapéuticas. En las GFS de origen idiopático, resistentes a esteroides y anticalcineurínicos, antes de tomar la decisión de ensayar o no otros fármacos inmunosupresores, podría ser apropiado realizar un análisis sistemático que contemplara: 1) considerar si la dosis y el tiempo de tratamiento con esteroides y anticalcineurínicos fueron adecuados; 2) analizar el nivel de expresión de la glicoproteína P en los linfocitos; 3) considerar realizar una nueva biopsia renal en caso de que en la primera no se disponga de estudio de microscopía electrónica; 4) en enfermos jóvenes, considerar un estudio genético para descartar la presencia de la variante p.R229Q de la podocina en combinación con mutaciones heterozigotas en NPHS2, y 4) considerar la gravedad y dificultad de manejo del síndrome nefrótico y la probabilidad de pérdida progresiva de la función renal. En la actualidad, hay múltiples vías de estudio para intentar identificar los mecanismos patogénicos causantes de la lesión podocitaria y hay también en curso varios estudios para analizar la eficacia de fármacos como adalimumab, fresolimumab, rosiglitazona, ACTH (corticotropina) o galactosa a altas dosis, cuyos resultados preliminares han generado expectativas que requieren ser confirmadas en estudios clínicos a mayor escala. En un futuro, es posible que el mejor conocimiento de la vía o vías patogénicas causantes de GFS permita diferenciar entre las formas inmunomodulables y las que no lo son, pero, hoy por hoy, este desafío continúa plenamente vigente

Half of patients with nephrotic syndrome caused by primary focal segmental glomerulosclerosis (FSGS) have resistance to treatment with steroids. In the case of corticosteroid resistance, the best evidence-based option has classically been treatment with calcineurin inhibitors, although recent studies indicate that mycophenolate may have similar efficacy. In patients with resistance to calcineurin inhibitors, there is no option that allows the clinical course of the disease to be modified, and this is supported by appropriately designed clinical trials, although observational studies have suggested the potential usefulness of mycophenolate, sirolimus, rituximab, apheresis or high galactose doses as treatment options. In FSGS of idiopathic origin, resistant to steroids and calcineurin inhibitors, before taking the decision whether or not to test other immunosuppressive drugs, it might be appropriate to conduct a systematic analysis that considers: 1) evaluating whether the dose and duration of treatment with steroids and calcineurin inhibitors were suitable, 2) analysing the level of P-glycoprotein expression in lymphocytes, 3) performing a new renal biopsy if there is no electron microscopic study available for the first, 4) in young patients, considering a genetic study to rule out the presence of the podocin variant pR229Q in combination with heterozygous mutations in NPHS2, and 5) evaluating the seriousness and difficulty of managing the nephrotic syndrome and the likelihood of progressive loss of renal function. Currently, there are multiple study avenues that attempt to identify the pathogenic mechanisms that cause podocyte injury and there are also several studies underway to analyse the efficacy of drugs such as adalimumab, fresolimumab, rosiglitazone, ACTH (corticotropin) or galactose at high doses, whose preliminary results have generated expectations that require confirmation in larger-scale clinical studies. In the future, it is possible that a better understanding of the pathogenic pathway or pathways that cause FSGS may allow differentiation between immunomodulable and non-immunomodulable forms, however, this continues to be a challenge for today

Treatment of idiopathic focal segmental glomerulosclerosis: options in the event of resistance to corticosteroids and calcineurin inhibitors.

Half of patients with nephrotic syndrome caused by primary focal segmental glomerulosclerosis (FSGS) have resistance to treatment with steroids. In the case of corticosteroid resistance,  the best evidence-based option has classically been treatment with calcineurin inhibitors,  although recent studies indicate that mycophenolate may have similar efficacy. In patients with resistance to calcineurin inhibitors,  there is no option that allows the clinical course of the disease to be modified, and this is supported by appropriately designed clinical trials, although observational studies have suggested the potential usefulness of mycophenolate, sirolimus, rituximab, apheresis or high galactose doses as treatment options. In FSGS of idiopathic origin, resistant to steroids and calcineurin inhibitors, before taking the decision whether or not to test other immunosuppressive drugs, it might be appropriate to conduct a systematic analysis that considers: 1) evaluating whether the dose and duration of treatment with steroids and calcineurin inhibitors were suitable, 2) analysing the level of P-glycoprotein expression in lymphocytes, 3) performing a new renal biopsy if there is no electron microscopic study available for the first, 4) in young patients,  considering a genetic study to rule out the presence of the podocin variant pR229Q in combination with heterozygous mutations in NPHS2,  and 5) evaluating the seriousness and difficulty of managing the nephrotic syndrome and the likelihood of progressive loss of renal function. Currently, there are multiple study avenues that attempt to identify the pathogenic mechanisms that cause podocyte injury and there are also several studies underway to analyse the efficacy of drugs such as adalimumab, fresolimumab, rosiglitazone, ACTH (corticotropin) or galactose at high doses, whose preliminary results have generated expectations that require confirmation in larger-scale clinical studies.  In the future, it is possible that a better understanding of the pathogenic pathway or pathways that cause FSGS may allow differentiation between immunomodulable and non-immunomodulable forms,  however, this continues to be a challenge currently.