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Background Immunoglobulin A (IgA) nephritis (IgAN) and renal IgA vasculitis (IgAV) show renal IgA deposits, but whether these two diseases are distinct entities or a spectrum of the same condition is under debate. In this study, we add perspective by contrasting the clinical course and histological presentation using the Oxford classification and the National Institutes of Health lupus nephritis activity index (LN-AI) and chronicity index (LN-CI) in IgAN and IgAV. Methods In this single-centre, retrospective study, kidney biopsies of 163 adult patients with IgAN and 60 adult patients with IgAV were compared according to the Oxford MEST-C score, LN-AI and LN-CI. At the time of biopsy, clinical presentation was compared in terms of age, arterial hypertension, diabetes mellitus, extrarenal manifestations, estimated glomerular filtration rate, proteinuria and urine sediment. IgAV patients and all IgAN patients with crescents received immunosuppressive treatment. After biopsy, kidney function was followed until patients reached end-stage renal disease (ESRD) or they died. Results The clinical course and kidney histology differ in IgAN and IgAV. IgAV patients showed more microhaematuria and nephritic sediment, while IgAN patients had a greater history of arterial hypertension, more proteinuria and a higher risk for ESRD. These clinical differences were associated with histological differences, as kidney biopsies of IgAN patients were characterized by glomerulosclerosis and tubular atrophy while kidney biopsies of IgAV patients were characterized by endocapillary hypercellularity and crescents. Overall, tubular atrophy and an LN-CI ≥4 were associated with a higher risk for ESRD in IgAN and IgAV. Conclusion Our study supports the notion that IgAN and IgAV follow distinct courses, suggesting that they require different treatment strategies. Moreover, we make a point that the Oxford classification and LN-CI can be useful in categorizing and predicting long-term prognosis not only in IgAN, but also in IgAV. [ABSTRACT FROM AUTHOR]

Copyright of Innere Medizin (2731-7080) is the property of Springer Nature and its content may not be copied or emailed to multiple sites or posted to a listserv without the copyright holder's express written permission. However, users may print, download, or email articles for individual use. This abstract may be abridged. No warranty is given about the accuracy of the copy. Users should refer to the original published version of the material for the full abstract. (Copyright applies to all Abstracts.)

Abstract Background IgA vasculitis (IgAV) is the most common form of systemic vasculitis in childhood and frequently involves the kidney. A minority of patients with IgA vasculitis nephritis (IgAVN), especially those presenting with heavy proteinuria and/or kidney failure at onset, are at risk of chronic end-stage kidney disease. For deciding upon treatment intensity, knowledge of the short-term clinical course of IgAVN is needed to improve treatment algorithms. Methods For this retrospective multicenter study, the medical records of 66 children with biopsy-proven IgAVN were reviewed. Age, gender, medical history and therapeutic interventions were recorded. Laboratory data included serum creatinine, albumin, urinary protein excretion (UPE) and glomerular filtration rate (eGFR). Threshold values were determined for each parameter, full remission was defined as no proteinuria and eGFR > 90 ml/min/1.73m2. Results Median age at onset of IgAVN was 8.9 years. 14.1% of the children presented with nephrotic syndrome, 50% had an eGFR below 90 ml/min/1.73 m2 and 51.5% showed cellular crescents in renal histology. The treatment regimens varied notably. Forty-four patients were treated with immunosuppression; 17 patients with crescents or nephrotic syndrome were treated with corticosteroid (CS) pulse therapy. After 6 months, UPE had decreased from 3.7 to 0.3 g/g creatinine and the proportion of patients with a decreased eGFR had fallen from 50.0% to 35.5%. Thirteen children (26.5%) achieved full remission within 6 months. Conclusions In most patients with IgAVN proteinuria decreases slowly and kidney function improves, but full remission is reached only in a minority after 6 months. Persistent heavy proteinuria in the first two months rarely developed into long-term proteinuria. Therefore, decisions for more intense treatment should take into account the course of UPE over time. For a comparison of treatment effects, patient numbers were too small. Prospective, randomized controlled trials are necessary to clarify risk factors and the effect of immunosuppressive therapies.

Background and objective: About 25% of patients with IgA nephropathy (IgAN) progress to stage 5 chronic kidney disease (CKD) after years of evolution. Various tools have been developed in recent years designed to predict which of the patients will had poorer outcomes. The value of circulating galactosyl-deficient IgA1 (Gd-IgA1) has been related to a worse evolution of IgAN in several studies. There are also some publications that relate higher APRIL values with a worse evolution. Recently, a new method has been developed that allows measuring the value of circulating Gd-IgA1 in a simpler way than those previously available. The objective of this study is to analyze the influence of circulating Gd-IgA1, measured by this method, on the progression of IgAN. Materials and methods: Forty-nine patients with a diagnosis of IgAN demonstrated by renal biopsy were selected in our center, without having received prior immunosuppressive treatment, for whom frozen serum was available. The median follow-up was 4 years. Gd-IgA1 was measured by lectin-independent ELISA with the monoclonal antibody KM55 (IgA1 kit Cat. No. 30111694. IBL Int., Hamburg, Germany). Likewise, APRIL levels were also measured in these patients. Results: 19 (38.8%) patients reached stage 5 CKD. The fourth quartile of circulating Gd-IgA1 was related to a higher cumulative risk of reaching stage 5 CKD in the Kaplan–Meier analysis (risk at the 5th year 39.4% vs. 24.3%, log rank p = 0.019). The Gd-IgA1 value was related to an increased risk of CKD stage 5 (HR 1.147, 95% CI 1.035–1.270, p = 0.009), regardless of glomerular filtration rate, proteinuria, the percentage of sclerosed glomeruli and the value of segmental sclerosis. We did not find significant differences in the APRIL values. Conclusions: The value of circulating Gd-IgA1 measured by the monoclonal antibody KM55 is related to a worse evolution of patients with IgAN independently of other variables, so it could be included in the study of patients to improve the prediction of the risk of disease progression. Resumen: Antecedentes y objetivo: En torno al 25% de los pacientes con nefropatía IgA (NIgA) progresa hacia el estadio 5 de la enfermedad renal crónica tras años de evolución. En los últimos años se han desarrollado diversas herramientas diseñadas para predecir qué pacientes evolucionan peor. El valor de IgA1 galactosil-deficiente (Gd-IgA1) circulante se ha relacionado con una peor evolución de la NIgA en algunos estudios. También hay varios trabajos que relacionan valores más elevados de APRIL con una peor evolución. Recientemente se ha desarrollado un método que permite medir el valor de Gd-IgA1 circulante de una manera más sencilla que los previamente disponibles. El objetivo de este estudio es analizar la influencia de la Gd-IgA1 circulante, medida por este método, en la progresión de la NIgA. Materiales y métodos: Se seleccionaron 49 pacientes con diagnóstico de NIgA demostrado mediante biopsia renal en nuestro centro, sin haber recibido tratamiento inmunosupresor previo, de los que se dispusiera de suero congelado. La mediana de seguimiento fue de cuatro años. Se midió Gd-IgA1 mediante ELISA independiente de lectina con el anticuerpo monoclonal KM55 (IgA1 kit Cat. No 30111694. IBL Int., Hamburgo, Alemania). Así mismo también se midieron los niveles de APRIL en estos pacientes. Resultados: 19 (38,8%) pacientes alcanzaron ERC estadio 5. El cuarto cuartil de Gd-IgA1 circulante se relacionaba con un mayor riesgo acumulado de llegar a ERC estadio 5 en el análisis de Kaplan–Meier (riesgo al 5 año 39,4% vs. 24,3%; log rank p = 0,019). El valor de Gd-IgA1 se relacionaba con un mayor riesgo de ERC estadio 5 (HR 1,147; IC 95%: 1,035–1,270; p = 0,009), independientemente del filtrado glomerular, la proteinuria, el porcentaje de glomérulos esclerosados y el valor de esclerosis segmentaria. No encontramos diferencias significativas en los valores de APRIL. Conclusiones: El valor de Gd-IgA1 circulante medido mediante el anticuerpo monoclonal KM55 se relaciona con una peor evolución de los pacientes con NIgA independientemente de otras variables, por lo que se podría incluir en el estudio de los pacientes para mejorar la predicción del riesgo de progresión de la enfermedad.

Resumen: Antecedentes y objetivo: En torno al 25% de los pacientes con nefropatía IgA (NIgA) progresa hacia el estadio 5 de la enfermedad renal crónica tras años de evolución. En los últimos años se han desarrollado diversas herramientas diseñadas para predecir qué pacientes evolucionan peor. El valor de IgA1 galactosil-deficiente (Gd-IgA1) circulante se ha relacionado con una peor evolución de la NIgA en algunos estudios. También hay varios trabajos que relacionan valores más elevados de APRIL con una peor evolución. Recientemente se ha desarrollado un método que permite medir el valor de Gd-IgA1 circulante de una manera más sencilla que los previamente disponibles. El objetivo de este estudio es analizar la influencia de la Gd-IgA1 circulante, medida por este método, en la progresión de la NIgA. Materiales y métodos: Se seleccionaron 49 pacientes con diagnóstico de NIgA demostrado mediante biopsia renal en nuestro centro, sin haber recibido tratamiento inmunosupresor previo, de los que se dispusiera de suero congelado. La mediana de seguimiento fue de cuatro años. Se midió Gd-IgA1 mediante ELISA independiente de lectina con el anticuerpo monoclonal KM55 (IgA1 kit Cat. No 30111694. IBL Int., Hamburgo, Alemania). Así mismo también se midieron los niveles de APRIL en estos pacientes. Resultados: 19 (38,8%) pacientes alcanzaron ERC estadio 5. El cuarto cuartil de Gd-IgA1 circulante se relacionaba con un mayor riesgo acumulado de llegar a ERC estadio 5 en el análisis de Kaplan-Meier (riesgo al 5 año 39,4% vs. 24,3%; log rank p = 0,019). El valor de Gd-IgA1 se relacionaba con un mayor riesgo de ERC estadio 5 (HR 1,147; IC 95%: 1,035-1,270; p = 0,009), independientemente del filtrado glomerular, la proteinuria, el porcentaje de glomérulos esclerosados y el valor de esclerosis segmentaria. No encontramos diferencias significativas en los valores de APRIL. Conclusiones: El valor de Gd-IgA1 circulante medido mediante el anticuerpo monoclonal KM55 se relaciona con una peor evolución de los pacientes con NIgA independientemente de otras variables, por lo que se podría incluir en el estudio de los pacientes para mejorar la predicción del riesgo de progresión de la enfermedad. Abstract: Background and objective: About 25% of patients with IgA nephropathy (IgAN) progress to stage 5 chronic kidney disease (CKD) after years of evolution. Various tools have been developed in recent years designed to predict which of the patients will had poorer outcomes. The value of circulating galactosyl-deficient IgA1 (Gd-IgA1) has been related to a worse evolution of IgAN in several studies. There are also some publications that relate higher APRIL values with a worse evolution. Recently, a new method has been developed that allows measuring the value of circulating Gd-IgA1 in a simpler way than those previously available. The objective of this study is to analyze the influence of circulating Gd-IgA1, measured by this method, on the progression of IgAN. Materials and methods: Forty-nine patients with a diagnosis of IgAN demonstrated by renal biopsy were selected in our center, without having received prior immunosuppressive treatment, for whom frozen serum was available. The median follow-up was 4 years. Gd-IgA1 was measured by lectin-independent ELISA with the monoclonal antibody KM55 (IgA1 kit Cat. No. 30111694. IBL Int., Hamburg, Germany). Likewise, APRIL levels were also measured in these patients. Results: 19 (38.8%) patients reached stage 5 CKD. The fourth quartile of circulating Gd-IgA1 was related to a higher cumulative risk of reaching stage 5 CKD in the Kaplan–Meier analysis (risk at the 5th year 39.4% vs. 24.3%, log rank p = 0.019). The Gd-IgA1 value was related to an increased risk of CKD stage 5 (HR 1.147, 95% CI 1.035–1.270, p = 0.009), regardless of glomerular filtration rate, proteinuria, the percentage of sclerosed glomeruli and the value of segmental sclerosis. We did not find significant differences in the APRIL values. Conclusions: The value of circulating Gd-IgA1 measured by the monoclonal antibody KM55 is related to a worse evolution of patients with IgAN independently of other variables, so it could be included in the study of patients to improve the prediction of the risk of disease progression.

Introduction: IgA nephropathy (IgAN) is the most common primary glomerulonephritis (GN) in western countries and Henoch-Schönlein purpura nephritis (HSPN) is the most common form of vasculitis in childhood. Renal biopsy findings in both nephropathies are often similar and are characterized by mesangioproliferative GN with mesangial or mesangiocapillary IgA and C3c deposits. Objectives: The aim of this study was to investigate the significance of glomerular C4d-deposition as a discriminating factor between pediatric HSPN and IgAN. Patients and Methods: We retrospectively analyzed patient records and renal biopsies from 53 pediatric patients from one single center with a median age of 10.5 years (range 2.3-18 years). Twenty-two patients suffered from IgAN and 31 from HSPN. Work-up of all renal biopsies was performed using standard protocols including immunohistochemistry for C4d. Results: Pediatric IgAN patients presented significantly more often with gross hematuria, higher serum creatinine, lower glomerular filtration rate, lower serum C3 and proteinuria and on histology less endocapillary hypercellularity compared to HSPN patients. However, the rate of glomerular C4d-positivity was not different between IgAN (36%) and HSPN (42%). Comparing all cases with positive versus negative glomerular C4d-staining, pediatric patients with glomerular C4d-positivity showed significantly lesser gross hematuria and received significantly more often cyclophosphamide. This was in line with a tendency towards more proteinuria, hypertension and renal insufficiency at last follow-up in C4d-positive compared to C4d-negative patients. Conclusion: In conclusion, in our monocentric study glomerular C4d does not differ between pediatric HSPN and IgAN, but was associated with a tendency to a more severe course of the disease that needs to be confirmed in larger multicentric studies.

Copyright of Nefrologia is the property of Revista Nefrologia and its content may not be copied or emailed to multiple sites or posted to a listserv without the copyright holder's express written permission. However, users may print, download, or email articles for individual use. This abstract may be abridged. No warranty is given about the accuracy of the copy. Users should refer to the original published version of the material for the full abstract. (Copyright applies to all Abstracts.)

Chronic tonsillitis has been attracted attention as a source of abnormal immune responses and a possible trigger of autoimmune diseases such as IgA nephritis, IgA vasculitis, palmoplantar pustulosis, psoriasis, rheumatoid arthritis, Behçet’s disease, and myositis. Here we present the first report of anti–signal recognition particle antibody–associated necrotizing myopathy (anti-SRP myopathy) with IgA nephropathy and chronic tonsillitis in which the therapeutic response to intravenous immunoglobulin (IVIG) treatment was dramatically improved after tonsillectomy and accompanied by a rapid increase in ΔIgG, defined as the change in serum IgG levels 2 weeks after the start of IVIG treatment relative to pre-treatment levels. Moreover, serum anti-SRP antibody titers became undetectable after tonsillectomy even though the resected tonsils did not produce anti-SRP antibodies. Tonsillectomy should be considered when chronic tonsillitis is observed in patients with autoimmune diseases showing poor response to treatment, including anti-SRP myopathy.

Abstract Background The nucleotide oligomerization domain-like receptor subfamily C5 (NLRC5) is primarily expressed in the adaptive and innate immune systems. NLRC5 was recently discovered to regulate immunity and inflammatory responses. Abnormal immune and inflammatory responses are considered critical pathogenesis in IgA nephritis (IgAN). However, the role of NLRC5 in IgAN is unknown. We previously showed that NLRC5 can be detected in patients with IgAN; herein, we further examined the pathophysiological significance of NLRC5 in the serum and renal deposits of patients with IgAN. This study is the first to find that NLRC5 is closely correlated with IgAN. Methods IgAN patients (n = 50) who were diagnosed by renal biopsy provided blood and renal biopsy tissue, and age-matched healthy control subjects (blood donators n = 22; tissue donators n = 5) were included. Renal biopsies were diagnosed, and blood biochemical parameters were tested. Serum creatinine, urea, proteinuria, haematuria, albumin, and immunoglobulin A levels were recorded. Serum NLRC5 concentrations were detected by enzyme-linked immunosorbent assay, and tissue NLRC5 expression in kidney tissue was detected by immunohistochemical analysis. ROC curve analysis was used to evaluate the diagnostic value of the serum NLRC5 concentration in IgAN. Results Serum NLRC5 concentration was significantly decreased in the IgAN group compared to that in the healthy control group (P

Chronic tonsillitis has been attracted attention as a source of abnormal immune responses and a possible trigger of autoimmune diseases such as IgA nephritis, IgA vasculitis, palmoplantar pustulosis, psoriasis, rheumatoid arthritis, Behçet's disease, and myositis. Here we present the first report of anti–signal recognition particle antibody–associated necrotizing myopathy (anti-SRP myopathy) with IgA nephropathy and chronic tonsillitis in which the therapeutic response to intravenous immunoglobulin (IVIG) treatment was dramatically improved after tonsillectomy and accompanied by a rapid increase in ΔIgG, defined as the change in serum IgG levels 2 weeks after the start of IVIG treatment relative to pre-treatment levels. Moreover, serum anti-SRP antibody titers became undetectable after tonsillectomy even though the resected tonsils did not produce anti-SRP antibodies. Tonsillectomy should be considered when chronic tonsillitis is observed in patients with autoimmune diseases showing poor response to treatment, including anti-SRP myopathy. [ABSTRACT FROM AUTHOR]

Background: This study correlates the clinical presentation of Henoch-Schönlein purpura nephritis (HSPN) with findings on initial renal biopsy. Methods: Data from 202 pediatric patients enrolled in the HSPN registry of the German Society of Pediatric Nephrology reported by 26 centers between 2008 and 2014 were analyzed. All biopsy reports were re-evaluated for the presence of cellular crescents or chronic pathological lesions (fibrous crescents, glomerular sclerosis, tubular atrophy >5%, and interstitial fibrosis >5%). Results: Patients with HSPN with cellular glomerular crescents were biopsied earlier after onset of nephritis (median 24 vs 36 days, p = 0.04) than those without, whereas patients with chronic lesions were biopsied later (57 vs 19 days, p < 0.001) and were older (10.3 vs 8.6 years, p = 0.01) than those without. Patients biopsied more than 30 days after the onset of HSPN had significantly more chronic lesions (52 vs 22%, p < 0.001), lower eGFR (88 vs 102 ml/min/1.73m, p = 0.01), but lower proteinuria (2.3 vs 4.5 g/g, p < 0.0001) than patients biopsied earlier. Children above 10 years of age had lower proteinuria (1.98 vs 4.58 g/g, p < 0.001), lower eGFR (86 vs 101 ml/min/1.73m, p = 0.002) and were biopsied significantly later after onset of nephritis (44 vs 22 days, p < 0.001) showing more chronic lesions (45 vs 30%, p = 0.03). Proteinuria and renal function at presentation decreased with age. Conclusions: In summary, we find an age-dependent presentation of HSPN with a more insidious onset of non-nephrotic proteinuria, impaired renal function, longer delay to biopsy, and more chronic histopathological lesions in children above the age of 10 years. Thus, HSPN presents more like Immunoglobulin A (IgA) nephritis in older than in younger children. [ABSTRACT FROM AUTHOR]

Background: A pathergy reaction is defined as a hyperreactivity of the skin in response to minimal trauma, which is important in the diagnosis of Behçet's disease (BD). However, a pathergy reaction may not be restricted to the skin, and little is known about whether an invasive medical procedure can induce the reaction. Here we present a pathergy reaction induced by renal biopsy, an invasive procedure.Case Presentation: A 46-year-old man who was diagnosed with IgA vasculitis (IgAV) at the age of 38 was treated with prednisolone and mizoribine. However, complications such as common carotid arteritis or recurrent oral ulcer suggested the possibility of another pathophysiology. Later, increasing urine protein developed, suggesting disease aggravation. However, renal biopsy showed arteriosclerotic changes caused mainly by hypertension, negating exacerbation. After renal biopsy, his renal dysfunction and body temperature fluctuated, and detailed examinations revealed recurrent oral and genital ulcers and a folliculitis-like rash on his scrotum. Later, he complained of myodesopsia caused by hemorrhage in the ocular fundus due to occlusive vasculitis. Complete BD was diagnosed after development of the symptoms, and he was treated with prednisolone and colchicine.Conclusion: Co-occurrence of BD with IgAV is very rare and may be associated with immune disorders. Interestingly, a renal biopsy revealed BD, which was masked by the presence of IgAV, and elucidated the etiology of the unexplainable symptoms. To the best of our knowledge, this is the first report of renal pathergy. This case enlightens clinicians to the fact that not only a needle stimulation but also an invasive procedure can cause a pathergy reaction. [ABSTRACT FROM AUTHOR]

Henoch-Schönlein purpura (HSP) is the one of most common types of systemic vasculitis in childhood. Glomerulonephritis (HSPN) occurs in 30-50 % of HSP patients, mostly in a mild form but a small percentage of patients present with nephrotic syndrome or renal failure. HSPN is caused by the glomerular deposition of immunoglobulin A1 (IgA1)-containing immune complexes in the mesangium, the subepithelial and the subendothelial space. Formation of the IgA1 immune complex is thought to be the consequence of aberrantly glycosylated IgA1 molecules secreted into the circulation and their subsequent recognition by IgG specific for galactose-deficient IgA1. Mesangial proliferation and renal damage are triggered by the deposited immune complexes, which likely require activation of the complement system. Whereas other organ manifestations of HSP are mostly benign and self-limiting, HSPN might lead to chronic renal disease and end stage renal failure, thereby justifying immunosuppressive treatment. Long-term renal outcome correlates to the severity of the initial clinical presentation and the extent of renal biopsy changes, both of which are used to decide upon a possible treatment. As there are no evidence-based treatment options for severe HSPN, a large variety of therapeutic regimens are used. Prospective randomized controlled treatment studies are needed, but the low incidence of severe HSPN renders such studies difficult. [ABSTRACT FROM AUTHOR]

IgA nephritis (IgAN) is an autoimmune disease characterized by deposits of IgA in the glomerular mesangium. Clinically, the disease may be punctuated by episodes of macroscopic haematuria often associated with pharingotonsillitis or may be oligosyntomatic with microscopic haematuria and mild proteinuria. The natural course of IgAN may be indolent and benign; however, some 30–50% of patients may progress to end-stage renal disease when follow-up is extended to ≥20 years. In patients with IgAN, circulating IgA1 molecules have an aberrant structure of O-glycans in the hinge region, which is characterized by abbreviated glycans composed of N-acetylgalactosamine, with or without sialic acid. These aberrant IgA1 trigger the production of autoantibodies, with formation of immune complexes that deposit in the mesangium causing inflammation and production of extracellular matrix. A number of experimental and clinical data outlined a possible pathogenetic role of tonsillitis. As a consequence, tonsillectomy has been frequently performed in Japan. Observational studies, made in patients with normal renal function and mild proteinuria, reported that tonsillectomy could reduce the episodes of macrohaematuria as well as the entity of microhaematuria and proteinuria. However, the available studies had short-term follow-up and could not asses the role of tonsillectomy in protecting from renal function deterioration. In a longitudinal retrospective study, Isseki et al. compared the outcome of tonsillectomized patients with IgAN with that of IgAN patients who did not receive tonsillectomy. Tonsillectomized patients had a higher number of remissions and a better slope of glomerular filtration rate in comparison with controls. These data are interesting and suggest that tonsillectomy may prevent renal dysfunction in patients with IgAN and normal renal function. However, the retrospective nature of the study and the presence of some confounding factors require further investigations to confirm these promising data. [ABSTRACT FROM PUBLISHER]

Objective: The prevalence of primary glomerulonephritis in Singapore is compared with that of 28 other countries to review changing trends in the evolution of primary glomerulonephritis in Asia and other countries. Method: 2,586 renal biopsies in Singapore over the past 3 decades were reviewed and compared with data from 28 other countries. Results: In the 1st decade most Asian countries have mesangial proliferative glomerulonephritis as the most common form of primary glomerulonephritis, and in the 3rd decade there has been a dramatic increase in focal and segmental glomerulosclerosis reflecting aging and obesity in keeping with more developed countries. IgA nephritis remains the commonest glomerulonephritis in many countries. Membranous glomerulonephritis continues to be more prevalent in Western countries while mesangial proliferative glomerulonephritis remains prevalent in many Asian countries. Conclusion: Apart from geographical and genetic influences, socioeconomic factors may play a role in the evolution of the biopsy pattern in some countries. Worldwide, the prevalence of focal segmental glomerulosclerosis continues to increase. In third world countries some of the commoner forms of glomerulonephritis are related to infections, in contrast to developed countries where the antigenic exposure may be related to diet, allergens and other industrial agents. Copyright © 2010 S. Karger AG, Basel [ABSTRACT FROM AUTHOR]

Our aim was to report the effect of two treatment regimens in 43 cases of severe Henoch–Schönlein nephritis (HSN) and immunoglobulin A nephritis (IgAN) (24 HSN, 19 IgAN). Group A, 11 HSN and 7 IgAN, 88% with an International Study of Kidney Disease in Children (ISKDC) biopsy grade ≥ III and severe clinical features, were treated with corticosteroids, cyclophosphamide (CYC-P) and angiotensin-converting enzyme inhibitor/angiotensin receptor blocker (ACEi/ARB). Group B, 12 HSN and 13 IgAN, 72% with biopsy findings as above and 52% with severe clinical features, were treated with ACEi/ARB ± corticosteroids. The outcome classification was: (a) healthy; (b) mild proteinuria, normal glomerular filtration rate (GFR); (c) active renal disease; (d) chronic renal failure. Twenty-six patients had a good outcome (a + b). The 17 children with poor outcome (c + d) had lower GFR at onset and at follow-up, higher albumin excretion at follow-up, and higher percentage of segmental glomerulosclerosis in the renal biopsy, than those with good outcome. Treatment with corticosteroids, CYC-P and ACEi/ARB was effective in increasing GFR, reducing proteinuria and decreasing the disease activity index. The proteinuria had decreased at follow-up in both groups. In group A, GFR increased and histopathological activity index declined after treatment. The outcome did not differ between groups A and B. The effects of treatment did not differ between HSN and IgAN. [ABSTRACT FROM AUTHOR]

Ji S, Liu M, Chen J, Yin L, Sha G, Chen H, Liu Z, Li L. The fate of glomerular mesangial IgA deposition in the donated kidney after allograft transplantation. Clin Transplant 2004 DOI: 10.1111/j.1399-0012.2004.00206.x © Blackwell Munksgaard, 2004 To investigate the fate of the mesangial IgA deposits in the donor kidney after allograft transplantation. Routine pre-transplant cadaveric donor kidney biopsy and repeated renal biopsies were performed at months 1, 3, and 6 after renal transplantation. The patients, 342 in number, were divided into IgA positive deposition kidney group (group A, n = 83) and non-IgA deposition kidney group (group B, n = 259). There were no significant differences between the two groups’ sex, age, time of hemodialysis, warm ischemia time, cold ischemia time, complement-dependent cytotoxicity, level of panel-reactive assay, and the distribution of original disease. Recipients in group A received donor kidney with glomerular mesangial proliferation and marked diffuse granular IgA deposition. All of them showed edema, nephrotic range protienuria, microhematuria, hypoalbuminemia, hypertension, and delayed graft function. Borderline change was higher in group A than in group B, 37.3 and 16.2% (p < 0.001), respectively. Acute allograft rejection was higher in group A than in group B, 31.3 and 19.3% (p < 0.001), respectively. The glomerular mesangial IgA deposits gradually disappeared from the mesangial regions in grafts of acute rejection. Graft survival in both groups was not significant, being 93.8 and 95.6% in 1 yr, and 86.7 and 88.3% in 3 yr. Clinical features of the recipients which received from donor kidney with glomerular mesangial proliferation and marked diffuse granular IgA deposition: edema, proteinuria, microhematuria, hypoalbuminemia, hypertension, and delayed graft function. The presence of IgA deposits on donated kidney, by a possible increase of the immunogenicity of these kidneys, might be a cause of increased rejection. There were no significant differences between the two groups on long-term allograft survival. [ABSTRACT FROM AUTHOR]

Ponticelli C, Traversi L, Banfi G. Renal transplantation in patients with IgA mesangial glomerulonephritis. Pediatr Transplantation 2004: 8: 334–338. © 2004 Blackwell Munksgaard Most patients with IgA nephritis are suitable candidates for renal transplantation. In about 33% of patients the disease may recur after transplantation, although there are differences in the various series because of the different criteria for biopsy, the different length of follow-up and the different ethnicities. Living donation, genetic factors and time of progression of original disease have been found to be related with the risk of recurrence by some investigators, but these associations were not confirmed by other studies. The graft survival in patients with IgA nephritis is similar or even better than that observed with other renal diseases. The available data indicate that recurrence has a little impact on the 10-yr graft survival. However, a minority of patients may show a rapid progressive course after recurrence. Little information is available on the impact of recurrence in the very long term. There is no established treatment for preventing or treating the recurrence of IgA nephritis. [ABSTRACT FROM AUTHOR]

IgA nephropathy (IgAN) is characterized by a variable clinical course and multifaceted pathophysiology. There is substantial evidence to suggest that complement activation plays a pivotal role in the pathogenesis of the disease. Therefore, complement inhibition using the humanized anti-C5 monoclonal antibody eculizumab could be a rational treatment. We report here a 16-year-old male with the vasculitic form of IgAN who failed to respond to aggressive conventional therapy including high-dose steroids, cyclophosphamide and plasma exchange and who was treated with four weekly doses of 900 mg eculizumab followed by a single dose of 1200 mg. He responded rapidly to this treatment and has had a stable creatinine around 150 μmol/L (1.67 mg/dL) for >6 months. However, proteinuria was unabated on maximal conventional anti-proteinuric treatment, and a repeat renal biopsy 11 months after presentation revealed severe chronic changes. We believe this case provides proof of principle that complement inhibition may be beneficial in IgAN but also that development of chronicity may be independent of complement. [ABSTRACT FROM AUTHOR]

A 30-year-old white male presented with hematuria, proteinuria and normal renal function following a flu-like illness. IgA was mildly elevated but C3 and C4 levels were normal in serum. Renal biopsy showed a mesangial proliferative nephritis with immunohistochemical features of IgA nephritis but with an unusual pattern and distribution of deposits in glomerular, tubular and Bowman’s capsular basement membranes. [ABSTRACT FROM AUTHOR]

Histopathological analysis was performed with reference to the progression of IgA nephritis. (1) The disease was found to progress to glomerular sclerosis from acute intraglomerular and/or extracapillary injuries initiated by damage to extracellular matrix. (2) These injuries tended to occur segmentally and recur in the chronic clinical course. (3) The addition of these segmental lesions accelerated the sclerotic process in IgA nephritis. (4) Matricial damage was found to be recoverable in childhood, but much less so when older. The development of a histological activity index using such findings should prove to be useful for the selection of therapy for IgA nephritis. [ABSTRACT FROM AUTHOR]

Alagille syndrome (arteriohepatic dysplasia) is a major cause of intrahepatic cholestasis in infancy. The present report describes a patient with Alagille syndrome who presented with hematuria and IgA nephritis 7 years after an orthotopic liver transplantation and immunosuppression. This patient suggests that glomerular lipidosis is not an inherent feature of the Alagille syndrome, and that IgA nephritis may develop in spite of ongoing immunosuppressive treatment. [ABSTRACT FROM AUTHOR]

Inflammatory cells in tubulointerstitial lesions were investigated electron microscopically in 6 cases of IgA nephritis and 4 cases of drug-induced nephropathy. Urinary beta 2 microglobulin and N-acethyl-glucosaminidase values were higher in the drug-induced nephropathy group. Both nephropathy groups had the same inflammatory cell composition in the interstitium in which T lymphocytes and macrophages were dominant. By electron microscopy these inflammatory cells were observed to infiltrate into renal tubules through the tubular basement membrane. Inflammated tubules showed various epithelial injuries. These findings suggest that inflammatory cells were actively involved in the epithelial injuries of IgA nephritis possibly through a cellular immune mechanism. [ABSTRACT FROM AUTHOR]

Background: The nucleotide oligomerization domain-like receptor subfamily C5 (NLRC5) is primarily expressed in the adaptive and innate immune systems. NLRC5 was recently discovered to regulate immunity and inflammatory responses. Abnormal immune and inflammatory responses are considered critical pathogenesis in IgA nephritis (IgAN). However, the role of NLRC5 in IgAN is unknown. We previously showed that NLRC5 can be detected in patients with IgAN; herein, we further examined the pathophysiological significance of NLRC5 in the serum and renal deposits of patients with IgAN. This study is the first to find that NLRC5 is closely correlated with IgAN.Methods: IgAN patients (n = 50) who were diagnosed by renal biopsy provided blood and renal biopsy tissue, and age-matched healthy control subjects (blood donators n = 22; tissue donators n = 5) were included. Renal biopsies were diagnosed, and blood biochemical parameters were tested. Serum creatinine, urea, proteinuria, haematuria, albumin, and immunoglobulin A levels were recorded. Serum NLRC5 concentrations were detected by enzyme-linked immunosorbent assay, and tissue NLRC5 expression in kidney tissue was detected by immunohistochemical analysis. ROC curve analysis was used to evaluate the diagnostic value of the serum NLRC5 concentration in IgAN.Results: Serum NLRC5 concentration was significantly decreased in the IgAN group compared to that in the healthy control group (P < 0.0001), especially in S1 (Oxford classification) patients (P < 0.0001). Furthermore, serum NLRC5 concentration had a negative correlation with Lee's grade (r = 0.3526, P = 0.0060) and proteinuria levels (r = 0.4571, P = 0.0004). Tissue NLRC5 expression was significantly increased in the IgAN group compared to that in the healthy control group (P < 0.0001); a more significant increase was identified in the S1 group (P < 0.05) and had a positive correlation with Lee's grade (r = 0.497, P < 0.0001). We proposed a cut-off value of 1415 pg/ml for serum NLRC5 concentration, which was able to predict IgAN with 77.27% sensitivity and 87.5% specificity.Conclusions: Serum NLRC5 concentrations in IgAN are significantly decreased, and tissue NLRC5 expression is significantly increased in IgAN renal tissue, which is consistent with pathological severity. This finding suggests that NLRC5 could potentially be a diagnostic index and represents a prognostic factor in IgAN patients. [ABSTRACT FROM AUTHOR]

Thirteen paediatric nephrology units contributed to a retrospective review of 1447 kidney biopsies which were performed on children under 15 years of age from 1972 to 1986 and were examined by immunofluorescence and light microscopy. The histological studies were grouped into three 5-year periods: (1) 1972-1976 (248 biopsies), (2) 1977-1981 (607 biopsies), and (3) 1982-1986 (592 biopsies). The incidence of membranoproliferative glomerulonephritis (MPGN) was significantly lower during periods 2 (6.6%) and 3 (5.4%) than in period 1 (10.9%, P<0.05 and <0.01 respectively). The reasons for the significant decrease in the incidence of MPGN in Spanish children cannot be determined, but the observation agrees with those from French, Italian and Spanish studies involving adult patients. [ABSTRACT FROM AUTHOR]

Abstract: The second most common cause of chronic renal failure is glomerulonephritis, which is a collective term used for numerous diseases with the common denominator of histological renal inflammation emanating from the glomerular tuft. Whether all forms of glomerulonephritis should be considered as autoimmune disease is debatable, but immune mechanisms are important in all of them. This review focuses on four relatively well delineated forms of primary glomerulonephritis: Goodpastures or anti-GBM disease, IgA nephritis, membranous nephropathy and membranoproliferative glomerulonephritis. The autoantibodies are directed either to molecules within the glomeruli, such as the glomerular basement membrane in anti-GBM disease and to the podocytes in membranous glomerulonephritis, or to components of the immune system such as C3 convertase in membranoproliferative glomerulonephritis and IgA in IgA nephritis. Differences in diagnostic practices and classification controversies obscure comparative epidemiological studies, but there seem to be huge differences between incidence rates between countries and over time, both genetic factors and infections seem to matter but strong indications for a role of other environmental factors are still lacking. [Copyright &y& Elsevier]