El depósito de C3 en la glomerulonefritis extracapilar de tipo IIIcondiciona un mal pronóstico / C3 deposits worsens the prognosis in type III extracapillary glomerulonephritis

Introducción: La glomerulonefritis extracapilar (GNEC) pauciinmune o de tipo III es una de las causas más comunes de glomerulonefritis rápidamente progresiva y suele estar asociada con la presencia de anticuerpos antineutrófilos citoplasmáticos (ANCA). Están reportándose evidencias sobre la importancia de la activación del complemento en la patogénesis de la GNEC. El objetivo de nuestro estudio fue evaluar el papel pronóstico del depósito de C3 en las GNEC de tipo III. Métodos: Se estudió a pacientes diagnosticados de GNEC de tipo IIIentre 1995 y 2015 (n=72). Comparamos a pacientes con tinción positiva para C3 en el estudio de inmunofluorescencia con aquellos con tinción negativa. Se analizaron variables clínicas e histológicas y se relacionaron con progresión a enfermedad renal terminal. Resultados: Se encontró tinción positiva para C3 en 22 pacientes de un total de 72 (30,5%). Basalmente los pacientes con depósitos de C3 tenían peor función renal que aquellos sin depósitos (creatinina sérica 5 vs. 3,85mg/dl; p=0,050). La supervivencia renal a los 10 años fue del 36,9% en los pacientes con tinción positiva para C3 frente al 64,4% en los pacientes con tinción negativa (p=0,005). La supervivencia a los 10 años fue peor en los pacientes con depósitos de C3 (77 vs. 49,3%). Conclusiones: Nuestro estudio revela que la presencia de depósito de C3 en la GNEC de tipo III se asocia a un peor pronóstico renal y de la supervivencia del paciente. Estos resultados son compatibles con la hipótesis de que la activación de la vía alternativa del complemento contribuye al daño renal asociado a la GNEC de tipo III (AU)

Introduction: Type III extracapillary glomerulonephritis (PEGN) is a common cause of rapidly progressive glomerulonephritis and it is usually associated with circulating anti-neutrophil cytoplasmic antibodies (ANCAs). Recent evidence points to complement activation as an important factor in the pathogenesis of PEGN. The aim of the present study was to assess the value of C3 deposits in the prognosis of PEGN. Methods: All patients diagnosed of PEGN from 1995 to 2015 (n=72) were included in this study. Progression of renal disease in patients with positive staining for C3 by immunofluorescence was compared with those with negative staining. Mean follow up was 73 months. Progression to end-stage renal disease in relation to clinical and histological variables was analyzed. Results: Positive staining for C3 was observed in 22 out of the 72 patients (30.5%). At the time of diagnosis, patients with C3 deposits had higher serum creatinine concentration than those without C3 staining (5.00 vs. 3.85mg/dl, P=0.050). Renal survival at 10 years was 36.9% in patients with positive C3 staining vs. 64.4% in patients with negative staining (P=0.005). Mortality at 10 years was higher in patients with C3 deposits than in patients without deposits (77 vs. 49.3%). Conclusions: Thus, our study shows that PEGN with deposits of C3 is associated with worse renal prognosis and greater mortality. These results would support the hypothesis that activation of the alternative pathway complement may play an important role in the generation of renal injury associated with PEGN (AU)

C3 deposits worsens the prognosis in type iii extracapillary glomerulonephritis. / El depósito de C3 en la glomerulonefritis extracapilar de tipo iii condiciona un mal pronóstico.

INTRODUCTION: Type iii extracapillary glomerulonephritis (PEGN) is a common cause of rapidly progressive glomerulonephritis and it is usually associated with circulating anti-neutrophil cytoplasmic antibodies (ANCAs). Recent evidence points to complement activation as an important factor in the pathogenesis of PEGN. The aim of the present study was to assess the value of C3 deposits in the prognosis of PEGN. METHODS: All patients diagnosed of PEGN from 1995 to 2015 (n=72) were included in this study. Progression of renal disease in patients with positive staining for C3 by immunofluorescence was compared with those with negative staining. Mean follow up was 73 months. Progression to end-stage renal disease in relation to clinical and histological variables was analyzed. RESULTS: Positive staining for C3 was observed in 22 out of the 72 patients (30.5%). At the time of diagnosis, patients with C3 deposits had higher serum creatinine concentration than those without C3 staining (5.00 vs. 3.85mg/dl, P=0.050). Renal survival at 10 years was 36.9% in patients with positive C3 staining vs. 64.4% in patients with negative staining (P=0.005). Mortality at 10 years was higher in patients with C3 deposits than in patients without deposits (77 vs. 49.3%). CONCLUSIONS: Thus, our study shows that PEGN with deposits of C3 is associated with worse renal prognosis and greater mortality. These results would support the hypothesis that activation of the alternative pathway complement may play an important role in the generation of renal injury associated with PEGN.

Análisis de las hospitalizaciones por bacteriemia relacionada con el catéter de hemodiálisis / Analysis of hospitalizations due to bacteraemia related to the haemodialysis catheter

El uso de catéteres venosos centrales para hemodiálisis se ha incrementado de tal forma, que actualmente en nuestro país, el 30%, de los pacientes son portadores de este acceso vascular. No obstante su duración es limitada y presentan con frecuencia complicaciones, como por ejemplo bacteriemias relacionadas con el catéter de hemodiálisis. Esta, es una complicación con elevada morbimortalidad en los pacientes en tratamiento renal sustitutivo crónico. El objetivo de este análisis fue conocer la incidencia de hospitalizaciones, identificar los gérmenes más frecuentemente relacionados en nuestra población y analizar los factores demográficos y clínicos asociados. Se realizó un estudio observacional prospectivo en el que se analizaron todos los ingresos por bacteriemia relacionada con el catéter de hemodiálisis durante el año 2011. Se recogieron los datos clínicos de los pacientes, demográficos y comorbilidad. El número total de ingresos por bacteriemias relacionadas con el catéter fue de 45 en 35 pacientes, con una edad media de 69.9 años. Los gérmenes más frecuentemente aislados fueron cocos gram positivos (Staphilococcus aureus mecitilin resistente y Staphilococcus aureus meticilin sensible). La mortalidad fue de 14% (5 pacientes). A la vista de nuestros resultados, podemos concluir que la bacteriemia relacionada con el catéter es una complicación grave en los pacientes en hemodiálisis. Representa casi el 50% de los ingresos durante 2011 de los pacientes en hemodiálisis. Está asociada con una elevada morbilidad y consumo de recursos(AU)

The use of central venous catheters for haemodialysis has increased to such an extent that in our country 30% of patients now have this vascular access. However their duration is limited and they frequently present complications, such as bacteraemia related to the haemodialysis catheter. This is a complication with high morbimortality in patients undergoing chronic renal replacement therapy. The aim of this analysis was to determine the incidence of hospitalizations, identify the germs most frequently found in our population and analyse the associated demographic and clinical factors. A prospective observational study was carried out in which all hospital admissions during 2011 for bacteraemia related to the haemodialysis catheter were analysed. Clinical, demographic and comborbility data of the patients were compiled. The total number of admissions for catheter-related bacteraemia was 45 in 35 patients, with a mean age of 69.9 years. The most frequently isolated germs were gram-positive cocci (Methicillin-Resistant Staphylococcus Aureus and Methicillin-Sensitive Staphylococcus Aureus). Mortality was 14% (5 patients). In light of our results, we may conclude that catheter- related bacteraemia is a serious complication in haemodialysis patients. It represents almost 50% of hospital admissions in 2011 of haemodialysis patients. It is associated to high morbility and consumption of resources(AU)

C4d como herramienta diagnóstica en la nefropatía membranosa / C4d as a diagnostic tool in membranous nephropathy

Introducción: La nefropatía membranosa (NM) es la causa más frecuente de síndrome nefrótico en adultos. El diagnóstico se basa en los hallazgos típicos observados con el microscopio electrónico (ME) y el estudio de inmunofluorescencia (IF). En algunas ocasiones, sólo se dispone de tejido para estudio de microscopio óptico (MO); en estos casos puede ser complicado diferenciar entre una NM y una enfermedad por cambios mínimos (ECM). Recientemente se está extendiendo el estudio con C4d por inmunohistoquímica. Existe muy poca información sobre el depósito de C4d en la NM. Nuestro estudio consistió en analizar si el depósito de C4d realizado en la muestra en parafina podría ser útil en el diagnóstico de NM. Material y métodos: Estudio retrospectivo que incluyó a todos los pacientes diagnosticados de NM mediante biopsia renal en nuestra unidad entre enero de 2001 y octubre de 2008. Se incluyeron sólo adultos con un diagnóstico certero de NM y ECM idiopática que dispusieran de estudios con MO, IF y ME. En octubre de 2008, secciones de 3 µm de tejido renal fijado en formaldehído fueron deparafinadas y rehidratadas. Después se tiñeron mediante inmunohistoquímica con C4d usando un anticuerpo policlonal antihumano obtenido de conejo. Resultados: Se incluyeron finalmente 19 pacientes con ECM y 21 con NM. Ningún depósito de C4d fue observado en ninguno de los glomérulos de los pacientes con ECM y el 100% de estos pacientes fueron clasificados como negativos. Sin embargo, el depósito de C4d se detectó en el 100% de los pacientes con NM y en todos los glomérulos con una distribución uniforme y granular dibujando todas las asas capilares. Conclusiones: El depósito de C4d mediante inmunohistoquímica es una herramienta muy útil en el diagnóstico de NM (AU)

Introduction: membranous nephropathy (MN) is the most common cause of nephrotic syndrome in adults. The diagnosis is based on typical findings observed using electron microscope (EM) and immunofluorescence (IF) studies. On some occasions, tissues are only available for analysis using an optical microscope (OM); in these cases, it can be difficult to differentiate between MN and minimal change disease (MCD). Recently, the use of C4d immunohistochemical staining has spread. Very little information is available regarding C4d deposits in MN. Our study consisted of analysing whether C4d staining of samples embedded in paraffin could be useful for diagnosing MN. Material and Method: Ours was a retrospective study including all patients diagnosed with MN by renal biopsy in our unit between January 2001 and October 2008. We only included adult patients with a definitive diagnosis of MN or idiopathic MCD by OM, IF, and ME studies. In October 2008, 3µm sections of renal tissue fixed in formaldehyde were removed from paraffin and rehydrated. The samples were then stained for C4d immunohistochemical analysis using anti-human polyclonal antibodies obtained from rabbits. Results: Our study included a final sample of 19 patients with MCD and 21 with MN. No C4d deposits were observed in any of the glomeruli in patients with MCD, and 100% of these patients were classified as negative. However, C4d deposits were detected in 100% of patients with MN, and were observable in all glomeruli with a uniform granular distribution, demarcating all capillary loops. Conclusions: C4d immunohistochemical staining is a very useful tool for diagnosing MN (AU)

C4d as a diagnostic tool in membranous nephropathy.

INTRODUCTION: membranous nephropathy (MN) is the most common cause of nephrotic syndrome in adults. The diagnosis is based on typical findings observed using electron microscope (EM) and immunofluorescence (IF) studies. On some occasions, tissues are only available for analysis using an optical microscope (OM); in these cases, it can be difficult to differentiate between MN and minimal change disease (MCD). Recently, the use of C4d immunohistochemical staining has spread. Very little information is available regarding C4d deposits in MN. Our study consisted of analysing whether C4d staining of samples embedded in paraffin could be useful for diagnosing MN. MATERIAL AND METHOD: Ours was a retrospective study including all patients diagnosed with MN by renal biopsy in our unit between January 2001 and October 2008. We only included adult patients with a definitive diagnosis of MN or idiopathic MCD by OM, IF, and ME studies. In October 2008, 3µm sections of renal tissue fixed in formaldehyde were removed from paraffin and rehydrated. The samples were then stained for C4d immunohistochemical analysis using anti-human polyclonal antibodies obtained from rabbits. RESULTS: Our study included a final sample of 19 patients with MCD and 21 with MN. No C4d deposits were observed in any of the glomeruli in patients with MCD, and 100% of these patients were classified as negative. However, C4d deposits were detected in 100% of patients with MN, and were observable in all glomeruli with a uniform granular distribution, demarcating all capillary loops. CONCLUSIONS: C4d immunohistochemical staining is a very useful tool for diagnosing MN.

Significance of preimplantation analysis of kidney biopsies from expanded criteria donors in long-term outcome.

BACKGROUND: The shortage of organs has led to expanding the criteria for donors. Histologic evaluations before transplantation may enable the identification of organs unsuitable for single implantation. The aim of this study was to evaluate the histologic findings as prognostic factors of allograft survival from expanded criteria donors (ECDs). METHODS: We included a cohort of 136 single transplantations with kidneys from ECD and correlated the preimplantation pathologic findings with graft failure. Renal structures from ECD older (n=104) or younger (n=32) than 60 years were evaluated histologically for renal senescence and rated with a total histologic score. A multivariate Cox analysis was performed to identify predictors of graft failure. RESULTS: Glomerulosclerosis was the most prevalent lesion in biopsies from donors older and younger than 60 years (P=0.002); interstitial fibrosis was more severe in biopsies from older donors (P=0.001); older donors showed a higher prevalence of tubular atrophy (P=0.022), and vascular compartment showed no significant differences. Kidney biopsy-based scoring system ranged from 0 to 15 points, indicating the presence of changes in the renal parenchyma. Biopsies with total histologic scores less than or equal to 5 showed significantly better 5-year graft survival than those with scores more than 5 (P<0.001). A preimplantation score more than 5 points remained an independent predictor of graft failure (hazard ratio 6.95; 95% confidence interval 1.57-30). CONCLUSIONS: Histologic analysis of kidney biopsies before transplantation is a valuable tool for facilitating the selection of viable grafts from ECD donors. When the total score is more than 5, single kidney transplantation from ECD should not be recommended for patients similar to this study population.

Darbepoetin-α treatment enhances glomerular regenerative process in the Thy-1 glomerulonephritis model.

Recent studies have demonstrated that erythropoietin (EPO) and its analogs induce cytoprotective effects on many nonerythroid cells. In this study, we examined whether darbepoetin-α might prevent glomerular lesions in the Thy-1.1 model of glomerulonephritis (Thy-1-GN). GN was induced in Wistar rats by a single injection of monoclonal anti-Thy-1.1 antibody. Rats were killed at 24 h, 72 h, 7 days, 10 days, or 15 days after antibody injection. Kidneys were removed for histological analysis, and proteinuria was measured. Because at day 7 the maximal degree of renal damage and proteinuria was found, the effect of darbepoetin-α was tested at day 7 and two different protocols of administration were used; After anti-Thy-1.1 injection, rats received two doses of darbepoetin-α or vehicle at days 0 and 4 or at days 4 and 6. At day 7, proteinuria, plasma creatinine concentration, and renal morphology analysis were performed. Also, α-actin, desmin, caspase-3, and Ki67 protein expression were evaluated by immunohistochemistry. Our results showed that in both protocols of administration, darbepoetin-α treatment decreased proteinuria in Thy-1-GN rats and this effect correlated with the improvement in renal morphology. Glomerular lesions, α-actin, and caspase-3 protein expression, observed in most glomeruli of Thy-1-GN rats, were significantly reduced in darbepoetin-α-treated rats, while cell proliferation was significantly enhanced. The results indicate that darbepoetin-α treatment promotes glomerular recovery.

Mesangial C4d deposition: a new prognostic factor in IgA nephropathy.

BACKGROUND: It has been shown that patients with IgA nephropathy can be divided into two groups on the basis of the pattern of complement activation. Activation of the lectin pathway of complement is associated with more severe renal disease. Glomerular deposition of C4d is a marker of activation of the lectin pathway of complement. The aim of our study was to determine whether C4d staining at the time of the renal biopsy could identify patients with a different long-term prognosis in IgA nephropathy. METHODS: This retrospective cohort study included all patients with IgA nephropathy who underwent renal biopsy at our centre from January 1992 to December 2006. We evaluated baseline age, sex, presence of macroscopic haematuria, hypertension, serum creatinine and glomerular filtration rate (GFR), urine protein, mesangial C4d staining, glomerulosclerosis, interstitial fibrosis and extracapillary proliferation. Kaplan-Meier survival and Cox proportional hazards analyses were performed, with end-stage renal disease (ESRD) being defined as onset of dialysis or transplantation. RESULTS: Nineteen patients (32.2%) were C4d positive and 40 patients (67.8%) C4d negative. Age, hypertension, absence of macroscopic haematuria, serum creatinine levels, GFR, glomerular sclerosis, interstitial fibrosis and C4d-positive staining were all univariately associated with evolution to ESRD. Renal survival at 10 years was 43.9% in C4d-positive patients versus 90.9% in C4d-negative patients (log-rank, P = 0.0005). CONCLUSION: Negative mesangial C4d staining in glomeruli in patients with IgA nephropathy helps to identify patients with a good long-term prognostic for whom aggressive treatments are not justified.