Nefropatía por IgA con microangiopatía trombótica / IgA nephropathy with thrombotic microangiopathy

INTRODUCTION: IgA nephropathy is the most common glomerulopathy in the world, it has a wide clinical expression, from asymptomatic to rapidly progressive glomerulonephritis. The definitive diagnosis is renal biopsy, within which the IgA pattern can be identified, including thrombotic microangiopathy. CLINICAL CASE: 28-year-old female patient, with a history of preeclampsia in the last pregnancy, presents high blood pressure, hematuria and proteinuria. Study begins with initially negative results. Renal biopsy confirms IgA nephropathy with thrombotic microangiopathy. DISCUSSION: Vascular damage is underestimated in IgA nephropathy. Thrombotic microangiopathy can be associated with various clinical manifestations, however when it is associated with IgA Nephropathy it is usually associated with proteinuria, arterial hypertension and elevation of creatinine. In the presence of microangiopathy, secondary causes must be ruled out. In general, there is no pathognomonic serological marker. Eventually patients could benefit from the use of eculizumab. CONCLUSION: IgA nephropathy is the most common glomerulopathy worldwide; there is a wide range of clinical presentations, among which thrombotic microangiopathy can be found. This presentation is associated with a higher risk of progression to end-stage renal disease.

INTRODUCCIÓN: La nefropatía por IgA es la glomerulopatía más frecuente en el mundo, tiene una amplia expresión clínica, desde asintomática hasta glomerulonefritis rápidamente progresivas. El diagnóstico definitivo es la biopsia renal, dentro de las cuales se puede identificar el patrón de la IgA, dentro de los cuales está la microangiopatía trombótica. CASO CLÍNICO: Paciente femenina 28 años, con antecedentes de preeclampsia en último embarazo, presenta hipertensión arterial, hematuria y proteinuria. Se inicia estudio con resultados inicialmente negativos. Biopsia renal confirma nefropatía por IgA con microangiopatía trombótica. DISCUSIÓN: En la nefropatía por IgA se subestima el daño vascular. La microangiopatía trombótica se puede asociar con varias manifestaciones clínicas, sin embargo, cuando está asociada a NIgA suele estar asociado con proteinuria, hipertensión arterial y elevación y creatinina. Ante la presencia de microangiopatía, se deben descartar causas secundarias de la misma. En general no existe un marcador serológico patognomónico. Eventualmente los pacientes se podrían beneficiar del uso de eculizumab. CONCLUSIÓN: La nefropatía por IgA es la glomerulopatía más frecuente a nivel mundial, existe una gran gama de presentaciones clínicas, dentro de las cuales se puede encontrar microangiopatía trombótica. Esta última presentación se asocia con mayor riesgo de progresión a enfermedad renal en etapa terminal.

Percutaneous kidney biopsies in children: a 24-year review in a tertiary center in northern Portugal.

INTRODUCTION: Percutaneous kidney biopsy (KB) is crucial to the diagnosis and management of several renal pathologies. National data on native KB in pediatric patients are scarce. We aimed to review the demographic and clinical characteristics and histopathological patterns in children who underwent native percutaneous KB over 24 years. METHODS: Retrospective observational study of patients undergoing native percutaneous KB in a pediatric nephrology unit between 1998 and 2021, comparing 3 periods: period 1 (1998-2005), period 2 (2006-2013), and period 3 (2014-2021). RESULTS: We found that 228 KB were performed, 78 (34.2%) in period 1, 91 (39.9%) in period 2, and 59 (25.9%) in period 3. The median age at KB was 11 (7-14) years. The main indications for KB were nephrotic syndrome (NS) (42.9%), hematuria and/or non-nephrotic proteinuria (35.5%), and acute kidney injury (13.2%). Primary glomerulopathies were more frequent (67.1%), particularly minimal change disease (MCD) (25.4%), IgA nephropathy (12.7%), and mesangioproliferative glomerulonephritis (GN) (8.8%). Of the secondary glomerulopathies, lupus nephritis (LN) was the most prevalent (11.8%). In group 1, hematuria and/or non-nephrotic proteinuria were the main reasons for KB, as opposed to NS in groups 2 and 3 (p < 0.01). LN showed an increasing trend (period 1-3: 2.6%-5.3%) and focal segmental glomerular sclerosis (FSGS) showed a slight decreasing trend (period 1-3: 3.1%-1.8%), without statistical significance. CONCLUSIONS: The main indication for KB was NS, which increased over time, justifying the finding of MCD as main histological diagnosis. LN showed an increase in incidence over time, while FSGS cases did not increase.

[Frequency of glomerular diseases in an analysis of 550 kidney biopsies]. / Caracterización de enfermedades glomerulares: análisis de 22 años de biopsias renales.

BACKGROUND: The frequency of glomerular diseases is dynamic and varies according to geographic area. AIM: To evaluate the frequency of primary and secondary glomerulopathies, their demographic profile and main clinical characteristics. MATERIAL AND METHODS: Renal biopsies from native kidneys performed between 1999 and 2020 were retrospectively reviewed. Demographic characteristics, clinical presentation, most relevant laboratory tests, frequency of primary and secondary glomerulopathies were analyzed. RESULTS: We analyzed 550 kidney biopsies from patients with a median age of 48 years (64% females). Nephrotic syndrome was the main indication for renal biopsy. Primary and secondary glomerulopathies occurred with similar frequency. Within the primary glomerulopathies, membranous nephropathy (34.1%) was the most common, followed by IgA nephropathy (31.1%) and focal segmental glomerulosclerosis (14.1%). Among the secondary glomerulopathies, lupus nephropathy was the most common (41.7%), followed by pauciimmune glomerulonephritis (27.1%) and diabetic nephropathy (6.4%). When comparing the results with other regions, significant differences were observed with reported frequencies in United States, Europe, Asia and the rest of Latin America. CONCLUSIONS: The most common primary glomerulopathies were membranous nephropathy and IgA nephropathy. Among the secondary glomerulopathies lupus nephropathy and pauci-immune glomerulonephritis were the most common. Compared to international registries, we observed a high proportion of membranous nephropathy and pauci-immune glomerulonephritis.

Caracterización de enfermedades glomerulares: análisis de 22 años de biopsias renales / Frequency of glomerular diseases in an analysis of 550 kidney biopsies

BACKGROUND: The frequency of glomerular diseases is dynamic and varies according to geographic area. AIM: To evaluate the frequency of primary and secondary glomerulopathies, their demographic profile and main clinical characteristics. MATERIAL AND METHODS: Renal biopsies from native kidneys performed between 1999 and 2020 were retrospectively reviewed. Demographic characteristics, clinical presentation, most relevant laboratory tests, frequency of primary and secondary glomerulopathies were analyzed. RESULTS: We analyzed 550 kidney biopsies from patients with a median age of 48 years (64% females). Nephrotic syndrome was the main indication for renal biopsy. Primary and secondary glomerulopathies occurred with similar frequency. Within the primary glomerulopathies, membranous nephropathy (34.1%) was the most common, followed by IgA nephropathy (31.1%) and focal segmental glomerulosclerosis (14.1%). Among the secondary glomerulopathies, lupus nephropathy was the most common (41.7%), followed by pauciimmune glomerulonephritis (27.1%) and diabetic nephropathy (6.4%). When comparing the results with other regions, significant differences were observed with reported frequencies in United States, Europe, Asia and the rest of Latin America. CONCLUSIONS: The most common primary glomerulopathies were membranous nephropathy and IgA nephropathy. Among the secondary glomerulopathies lupus nephropathy and pauci-immune glomerulonephritis were the most common. Compared to international registries, we observed a high proportion of membranous nephropathy and pauci-immune glomerulonephritis.

Long-term follow-up of an IgA nephropathy cohort: outcomes and risk factors.

AIM: IgA nephropathy (IgAN), the most common glomerulopathy worldwide and in Uruguay, raised treatment controversies. The study aimed to analyze long-term IgAN outcomes and treatment. METHODS: A retrospective analysis of a Uruguayan IgAN cohort, enrolled between 1985 and 2009 and followed up until 2020, was performed. The Ethics Committee approved the study. The inclusion criteria were (a) biopsy-proven IgAN; (b) age ≥12 years; and (c) available clinical, histologic, and treatment data. The patients were divided into two groups, with immunosuppressive (IS) or without (NoIS) treatment. Outcomes (end-stage kidney disease/kidney replacement therapy [ESKD/KRT] or all-cause death) were obtained from mandatory national registries. RESULTS: The study population included 241 patients (64.7% men), median age 32 (19.5) years, baseline blood pressure <130/80 mmHg in 37%, and microhematuria in 67.5% of patients. Baseline proteinuria, glomerulosclerosis, and a higher crescent percentage were significantly more frequent in the IS group. Proteinuria improved in both groups. Renal survival at 20 years was 74.6% without difference between groups. In the overall population and in the NoIS group, bivariate Cox regression analysis showed that baseline proteinuria, endocapillary hypercellularity, tubule interstitial damage, and crescents were associated with a higher risk of ESKD/KRT or death, but in the IS group, proteinuria and endocapillary hypercellularity were not. In the multivariate Cox analysis, proteinuria in the NoIS group, crescents in the IS group and tubule interstitial damage in both groups were independent risk factors. CONCLUSION: The IS group had more severe risk factors than the NoIS group but attained a similar outcome.

Distribution of kidney diseases in Joinville, Santa Catarina: analysis of a kidney biopsy data bank between 2008 and 2019.

INTRODUCTION: Studies based on kidney biopsies are important for the epidemiological understanding of nephropathies. OBJECTIVE: To describe the main nephropathies diagnosed through renal biopsies, and compare them with regards to gender, time, healthcare insurance and age. METHODS: A population-based retrospective study that reviewed all kidney disease diagnoses obtained by biopsy of a native kidney from pathology services between 2008 and 2019 in Joinville, Brazil. RESULTS: Of 778 biopsies performed, 44.5% were primary nephropathies and 28.5% were secondary. The highest prevalence was focal segmental glomerulosclerosis (FSGS) [18.1%], followed by tubulointerstitial nephropathy (TIN) [15.9%] and IgA nephropathy (IgAN) [9.1%]. There was a growing increase in the prevalence of TIN among elderly and uninsured patients over the period. In the multivariate analysis, among the primary glomerulopathies, males had a higher risk for the occurrence of IgAN [OR=2.02; 95% CI 1.13-3.61; p=0.018], as well as being a protective factor for the occurrence of lupus glomerulonephritis (LGN) [OR=0.20, 95% CI 0.08-0.49; p<0.001]. Advancing age and dependence on a public healthcare decreased the likelihood of having a diagnosis of LGN [OR=0.91, 95% CI 0.88-0.94, p < 0.001 and OR=0.45, CI 95 % 0.21-0.96; p = 0.036, respectively]. Patients without private healthcare insurance were more likely to have TIN [OR=1.77, 95%CI 1.16-2.70; p = 0.008]. CONCLUSION: Sex, age and type of medical healthcare insurance may be related to the occurrence of some nephropathies. The increased risk of TIN in individuals without a private healthcare plan may be an indication of inequalities in health care.

Recurrence of IgA Nephropathy after Kidney Transplantation in Adults.

BACKGROUND AND OBJECTIVES: In patients with kidney failure due to IgA nephropathy, IgA deposits can recur in a subsequent kidney transplant. The incidence, effect, and risk factors of IgA nephropathy recurrence is unclear, because most studies have been single center and sample sizes are relatively small. DESIGN, SETTING, PARTICIPANTS, & MEASUREMENTS: We performed a multicenter, international, retrospective study to determine the incidence, risk factors, and treatment response of recurrent IgA nephropathy after kidney transplantation. Data were collected from all consecutive patients with biopsy-proven IgA nephropathy transplanted between 2005 and 2015, across 16 "The Post-Transplant Glomerular Disease" study centers in Europe, North America, and South America. RESULTS: Out of 504 transplant recipients with IgA nephropathy, recurrent IgA deposits were identified by kidney biopsy in 82 patients; cumulative incidence of recurrence was 23% at 15 years (95% confidence interval, 14 to 34). Multivariable Cox regression revealed a higher risk for recurrence of IgA deposits in patients with a pre-emptive kidney transplant (hazard ratio, 3.45; 95% confidence interval, 1.31 to 9.17) and in patients with preformed donor-specific antibodies (hazard ratio, 2.59; 95% confidence interval, 1.09 to 6.19). After kidney transplantation, development of de novo donor-specific antibodies was associated with subsequent higher risk of recurrence of IgA nephropathy (hazard ratio, 6.65; 95% confidence interval, 3.33 to 13.27). Immunosuppressive regimen was not associated with recurrent IgA nephropathy in multivariable analysis, including steroid use. Graft loss was higher in patients with recurrence of IgA nephropathy compared with patients without (hazard ratio, 3.69; 95% confidence interval, 2.04 to 6.66), resulting in 32% (95% confidence interval, 50 to 82) graft loss at 8 years after diagnosis of recurrence. CONCLUSIONS: In our international cohort, cumulative risk of IgA nephropathy recurrence increased after transplant and was associated with a 3.7-fold greater risk of graft loss.

Renal Morphology in Coronavirus Disease: A Literature Review.

Renal biopsy is useful to better understand the histological pattern of a lesion (glomerular, tubulointerstitial, and vascular) and the pathogenesis that leads to kidney failure. The potential impact of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) on the kidneys is still undetermined, and a variety of lesions are seen in the kidney tissue of coronavirus disease patients. This review is based on the morphological findings of patients described in case reports and a series of published cases. A search was conducted on MEDLINE and PubMed of case reports and case series of lesions in the presence of non-critical infection by SARS-CoV-2 published until 15/09/2020. We highlight the potential of the virus directly influencing the damage or the innate and adaptive immune response activating cytokine and procoagulant cascades, in addition to the genetic component triggering glomerular diseases, mainly collapsing focal segmental glomerulosclerosis, tubulointerstitial, and even vascular diseases. Kidney lesions caused by SARS-CoV-2 are frequent and have an impact on morbidity and mortality; thus, studies are needed to assess the morphological kidney changes and their mechanisms and may help define their spectrum and immediate or long-term impact.

Glomerular endothelial activation, C4d deposits and microangiopathy in immunoglobulin A nephropathy.

Immunoglobulin A nephropathy (IgAN) is considered as mesangiopathy since it initiates in the mesangium; however, other glomerular components are involved and the glomerular capillary wall offers the first contact to circulating macromolecular IgA1. Acute and active forms of IgAN are associated with endocapillary hypercellularity and vascular damage of various degrees, in severe cases with microangiopathy (MA) without or with thrombosis [thrombotic microangiopathy (TMA)]. Vascular damage activates complement and coagulation cascades. A defective complement regulation has recently been detected in active and progressive cases of IgAN. C4d deposits in renal biopsies have been found to be an early risk factor. These observations have raised interest in manifestation of MA and TMA in progressive cases of IgAN. MA-TMA lesions have been found in various percentages (2-53%) of patients with IgAN according to patients' selection and pathology definition of TMA. The association with hypertension (HTN) was so strong that it led to the hypothesis that MA/TMA in IgAN was a mere consequence of severe HTN. Old and new clinical and experimental data indicate that in IgAN the interaction of the glomerular capillary wall with immune reactants and complement uncontrolled activation leading to C4b deposits favours the development of MA-TMA, which plays a role in progression and renal function decline. The central role of complement activation is relevant also for the new therapeutic interventions offered by the pharma.

The implications of focal segmental glomerulosclerosis in children with IgA nephropathy.

Focal segmental glomerular sclerotic lesions in IgA nephropathy (IgAN), considered for years a chronic histologic feature related to proteinuria in remnant nephrons without any active role in the pathogenesis and progression of glomerular damage of IgAN, have been recently reconsidered. The Oxford classification of IgAN reported it as the "S" score and found it to be an independent risk factor for progression of IgAN. Its prognostic value was confirmed also in children. The identification of some histologic subvariants of the S lesion has produced interesting insights into different pathogenetic mechanisms of glomerular damage in IgAN. Tip lesion and podocyte hypertrophy are considered secondary to active podocytopathy and are correlated with higher levels of proteinuria and a faster decline in glomerular filtration rate. Moreover, endocapillary and mesangial hypercellularity might contribute in children with IgAN to formation and progression of S lesions. Considering the pathophysiology of these processes, children with some S features may benefit not only from nephroprotective measures but also from immunosuppression.

Temporal trends in biopsy proven glomerular disease in Uruguay, 1990-2014.

Our aim is to describe variations in the incidence rates of glomerular disease diagnosed by renal biopsies performed in Uruguay over the last 25 years in relation to sex, age, clinical presentation and histological diagnosis. We analyzed all renal biopsies performed in Uruguay during the 25 years period and estimated incidence rates per million people per year (pmp/yr) for the population older than 14 years. Mann Kendall's trend analysis was used to assess incidence trends. In order to identify changes in trends, we compared annual incidence rates with the Joinpoint method. From 1990 to 2014, 3390 biopsies of native kidneys corresponding to glomerular disease were performed in patients older than 14 years. The average biopsy rate was 58 per pmp/yr. The glomerular disease incidence rate increased progressively over the period (p<0.05). Trends analysis over five-year periods demonstrated a progressive increase of IgA nephropathy (3.08 pmp/yr 1990-1994 to 12.53 pmp/yr 2010-2014 p<0.05), membranous nephropathy (2.38 pmp/yr 1990-1994 to 8.04 pmp/yr 2010-2014 p< 0.05) and lupus nephritis (4,23 pmp/yr 1990-1994 to 7,81 pmp/yr 2010-2014 p<0.05). There was a change in the trend of focal segmental glomerular sclerosis (FSGS) which increased until 1996 and decreased afterwards. The incidence rates of glomerular disease have doubled globally in the last quarter of a century in Uruguay, mainly related to the increase of IgA nephropathy, membranous nephropathy and lupus nephritis. There was a change in the slope of the incidence rate of FSGS.

Renal outcome in IgA nephropathy according to Oxford classification and ultrastructural analysis in a Brazilian center
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AIMS: Correlate clinical and histologic features with renal outcome in patients with biopsy-proven IgA nephropathy (IgAN). MATERIALS AND METHODS: Retrospective analysis of records and renal tissue of IgAN patients. Histology was revised according to MEST score of Oxford classification. Focal segmental glomerulosclerosis (FSGS) features were assessed by light microscopy. Electron microscopy review searched for podocyte effacement. RESULTS: 67 patients were included, 56.7% men, mean age 34.5 ± 12.5 years, mean arterial pressure (MAP) 106 ± 18 mmHg, estimated glomerular filtration rate (eGFR) 63.32 ± 43.07 mL/min/1.73m2 and proteinuria 3.1 ± 2.2 g/24 h. M1 was seen in 38 patients (56.7%), E1 in 12 (17.9%), S1 in 49 (73.1%), T1 in 18 (26.8%), and T2 in 17 (25.3%). Mean effacement index (EI) was 0.81 ± 0.18 and did not correlate with proteinuria. 27 patients (40.2%) had end-stage renal disease (ESRD) which correlated with MAP (p = 0.002), eGFR (p = 0.0003), T1 (p = 0.0008) and T2 (p = 0.0001), follow-up MAP (p = 0.02) and follow-up proteinuria (p = 0.01 for 1.0 - 4.0 g/24 h and p = 0.005 for ≥ 4.0 g/24 h). T score correlated with MAP and proteinuria at baseline (p = 0.0001 and 0.0097, respectively) and during follow-up (p = 0.0001 and < 0.0001, respectively). Podocyte hypertrophy correlated with MAP at baseline and during follow-up (p = 0.0046 and 0.0295, respectively). Tip lesion correlated with MAP at baseline (p = 0.0228). There was no correlation between FSGS features or EI with proteinuria or ESRD. CONCLUSIONS: Our data corroborate eGFR, proteinuria, MAP and T score as risk factors for ESRD in IgAN. Most patients had diffuse podocyte effacement, probably secondary to factors unrelated to proteinuria.
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The Oxford Classification predictors of chronic kidney disease in pediatric patients with IgA nephropathy / Preditores da doença renal crônica segundo a Classificação de Oxford em pacientes pediátricos com nefropatia por IgA

Abstract Objective: The Oxford Classification for Immunoglobulin A nephropathy (IgAN) identifies pathological variables that may predict the decline of renal function. This study aimed to evaluate the Oxford Classification variables as predictors of renal dysfunction in a cohort of Brazilian children and adolescents with IgAN. Methods: A total of 54 patients with IgAN biopsied from 1982 to 2010 were assessed. Biopsies were re-evaluated and classified according to the Oxford Classification. Multivariate analysis of laboratory and pathological data was performed. The primary outcomes were decline of baseline estimated glomerular filtration rate (eGFR) greater than or equal to 50%. Results: Mean follow-up was 7.6 ± 5.0 years. Mean renal survival was 13.5 ± 0.8 years and probability of decline ≥50% in baseline eGFR was 8% at five years of follow-up and 15% at ten years. Ten children (18.5%) had a decline of baseline eGFR ≥ 50% and five (9.3%) evolved to end-stage renal disease. Kaplan-Meier analysis showed that baseline proteinuria, proteinuria during follow-up, endocapillary proliferation, and tubular atrophy/interstitial fibrosis were associated with the primary outcome. Multivariate Cox analysis showed that only baseline proteinuria (HR, 1.73; 95% CI, 1.20-2.50, p = 0.003) and endocapillary hypercellularity (HR, 37.18; 95% CI, 3.85-358.94, p = 0.002) were independent predictors of renal dysfunction. No other pathological variable was associated with eGFR decline in the multivariate analysis. Conclusion: This is the first cohort study that evaluated the predictive role of the Oxford Classification in pediatric patients with IgAN from South America. Endocapillary proliferation was the unique pathological feature that independently predicted renal outcome.

Resumo Objetivo: A Classificação Oxford para a Nefropatia por Imunoglobulina A (IgAN) identificou variáveis patológicas de risco para disfunção renal. O presente estudo teve como objetivo avaliar as variáveis da Classificação de Oxford como preditores de disfunção renal em crianças brasileiras com IgAN. Métodos: Foram analisados 54 pacientes com diagnóstico de IgAN entre 1982-2010. As biópsias renais foram reavaliadas pela Classificação de Oxford. Foram feitas análises uni e multivariada das variáveis clínicas e patológicas. O desfecho primário foi queda da taxa de filtração glomerular (TFG) ≥ 50% da filtração basal. Resultados: O acompanhamento médio foi de 7,6 ± 5,0 anos. A sobrevida renal média foi de 13,5 ± 0,8 anos e a probabilidade de atingir o desfecho primário foi de 8% em cinco anos e 15% em 10 anos de seguimento. Dez crianças (18,5%) apresentaram queda na TFG basal ≥ 50% e cinco (9,3%) evoluíram para doença renal crônica terminal. A análise de Kaplan-Meier mostrou que a proteinúria basal e de seguimento, a proliferação endocapilar e a atrofia tubular/fibrose intersticial foram associadas com o desfecho primário. A análise multivariada de Cox mostrou que a proteinúria basal (HR = 1,73; IC95% 1,20-2,50, p = 0,003) e a proliferação endocapilar (HR = 37,18; IC95% 3,85-358,94, p = 0,002) foram preditores independentes de disfunção renal. Nenhuma outra variável patológica foi associada com declínio da TFG na análise multivariada. Conclusão: Este é o primeiro estudo brasileiro que avaliou a Classificação Oxford em crianças com IgAN. A proliferação endocapilar foi a única característica patológica capaz de predizer independentemente o declínio da função renal.

Evaluation of TGF-ß1 and MCP-1 expression and tubulointerstitial fibrosis in children with Henoch-Schönlein purpura nephritis and IgA nephropathy: A clinical correlation.

OBJECTIVES:: Henoch-Schönlein purpura nephritis and immunoglobulin A nephropathy are two diseases with similar clinical presentations but very different prognoses. Transforming growth factor ß1 and monocyte chemoattractant protein-1 have been associated with the development of tissue fibrosis. We examined the development of tubulointerstitial fibrosis and its relationship with Transforming growth factor ß1 and monocyte chemoattractant protein-1 expression in these patients. METHODS:: Renal tissue samples were collected by renal biopsy from 50 children with Henoch-Schönlein purpura nephritis and 50 children with immunoglobulin A nephropathy. Hematoxylin and eosin and Masson's trichrome-stained tissues were examined using light microscopy. Tubulointerstitial fibrosis was graded using the method described by Bohle et al. (1). The immunohistochemical detection of Transforming growth factor ß1 and monocyte chemoattractant protein-1 expression was correlated with the tubulointerstitial fibrosis grade. Clinical Trial registration number: ZJCH-2012-0105. RESULTS:: Transforming growth factor ß1 and monocyte chemoattractant protein-1 expression in the renal tissues was significantly greater in the patients with immunoglobulin A nephropathy than in the patients with Henoch-Schönlein purpura nephritis (both p<0.001). The immunoglobulin A nephropathy patients had a higher tubulointerstitial fibrosis grade than the Henoch-Schönlein purpura nephritis patients (p<0.001). The tubulointerstitial fibrosis grade was in accordance with the Transforming growth factor ß1 and monocyte chemoattractant protein-1 expression levels in both diseases (both p<0.001). CONCLUSION:: Transforming growth factor ß1 and monocyte chemoattractant protein-1 expression was associated with the development of immunoglobulin A nephropathy and Henoch-Schönlein purpura nephritis. Further studies are needed to better evaluate this association.

Mesangial C4d deposition may predict progression of kidney disease in pediatric patients with IgA nephropathy.

BACKGROUND: Data on the risk factors for chronic kidney disease in children with immunoglobulin A nephropathy (IgAN) are scarce. This study was aimed at investigating whether glomerular C4d immunostaining is a prognostic marker in pediatric IgAN. METHODS: In this retrospective cohort study, 47 patients with IgAN biopsied from 1982 to 2010 were evaluated. Immunohistochemistry for C4d was performed in all cases. For analysis, patients were grouped according to positivity or not for C4d in the mesangial area. Primary outcome was a decline in baseline estimated glomerular filtration rate (eGFR) by 50% or more. RESULTS: Median follow-up was 8.3 years. Median renal survival was 13.7 years and the probability of a 50% decline in eGFR was 13% over 10 years. Nine children exhibited the primary outcome and 4 developed end-stage renal disease (ESRD). Compared with C4d-negative patients (n = 37), C4d-positive patients (n = 10) presented higher baseline proteinuria (1.66 ± 0.68 vs 0.47 ± 0.19 g/day/1.73 m2, p < 0.001), a progressive decline in eGFR (−10.04 ± 19.38 vs 1.70 ± 18.51 ml/min/1.73 m2/year; p = 0.045), and more frequently achieved the primary outcome (50.0 vs 10.8%, p = 0.013), and ESRD (30.0 vs 2.7%, p = 0.026). No difference was observed in Oxford classification variables. Baseline proteinuria, endocapillary hypercellularity and mesangial C4d deposition were associated with primary outcome in univariate analysis. Proteinuria and mesangial C4d deposition at baseline independently predicted the decline in eGFR. Renal survival was significantly reduced in C4d-positive patients (8.6 vs 15.1 years in C4d-negative patients, p < 0.001). CONCLUSIONS: In this exclusively pediatric cohort, positivity for C4d in the mesangial area was an independent predictor of renal function deterioration in IgAN.

Evaluation of TGF-beta1 and MCP-1 expression and tubulointerstitial fibrosis in children with Henoch-Schönlein purpura nephritis and IgA nephropathy: A clinical correlation

OBJECTIVES: Henoch-Schönlein purpura nephritis and immunoglobulin A nephropathy are two diseases with similar clinical presentations but very different prognoses. Transforming growth factor β1 and monocyte chemoattractant protein-1 have been associated with the development of tissue fibrosis. We examined the development of tubulointerstitial fibrosis and its relationship with Transforming growth factor β1 and monocyte chemoattractant protein-1 expression in these patients. METHODS: Renal tissue samples were collected by renal biopsy from 50 children with Henoch-Schönlein purpura nephritis and 50 children with immunoglobulin A nephropathy. Hematoxylin and eosin and Masson's trichrome-stained tissues were examined using light microscopy. Tubulointerstitial fibrosis was graded using the method described by Bohle et al. (1). The immunohistochemical detection of Transforming growth factor β1 and monocyte chemoattractant protein-1 expression was correlated with the tubulointerstitial fibrosis grade. Clinical Trial registration number: ZJCH-2012-0105. RESULTS: Transforming growth factor β1 and monocyte chemoattractant protein-1 expression in the renal tissues was significantly greater in the patients with immunoglobulin A nephropathy than in the patients with Henoch-Schönlein purpura nephritis (both p<0.001). The immunoglobulin A nephropathy patients had a higher tubulointerstitial fibrosis grade than the Henoch-Schönlein purpura nephritis patients (p<0.001). The tubulointerstitial fibrosis grade was in accordance with the Transforming growth factor β1 and monocyte chemoattractant protein-1 expression levels in both diseases (both p<0.001). CONCLUSION: Transforming growth factor β1 and monocyte chemoattractant protein-1 expression was associated with the development of immunoglobulin A nephropathy and Henoch-Schönlein purpura nephritis. Further studies are needed to better evaluate this association.

The Oxford Classification predictors of chronic kidney disease in pediatric patients with IgA nephropathy.

OBJECTIVE: The Oxford Classification for Immunoglobulin A nephropathy (IgAN) identifies pathological variables that may predict the decline of renal function. This study aimed to evaluate the Oxford Classification variables as predictors of renal dysfunction in a cohort of Brazilian children and adolescents with IgAN. METHODS: A total of 54 patients with IgAN biopsied from 1982 to 2010 were assessed. Biopsies were re-evaluated and classified according to the Oxford Classification. Multivariate analysis of laboratory and pathological data was performed. The primary outcomes were decline of baseline estimated glomerular filtration rate (eGFR) greater than or equal to 50%. RESULTS: Mean follow-up was 7.6±5.0 years. Mean renal survival was 13.5±0.8 years and probability of decline ≥50% in baseline eGFR was 8% at five years of follow-up and 15% at ten years. Ten children (18.5%) had a decline of baseline eGFR≥50% and five (9.3%) evolved to end-stage renal disease. Kaplan-Meier analysis showed that baseline proteinuria, proteinuria during follow-up, endocapillary proliferation, and tubular atrophy/interstitial fibrosis were associated with the primary outcome. Multivariate Cox analysis showed that only baseline proteinuria (HR, 1.73; 95% CI, 1.20-2.50, p=0.003) and endocapillary hypercellularity (HR, 37.18; 95% CI, 3.85-358.94, p=0.002) were independent predictors of renal dysfunction. No other pathological variable was associated with eGFR decline in the multivariate analysis. CONCLUSION: This is the first cohort study that evaluated the predictive role of the Oxford Classification in pediatric patients with IgAN from South America. Endocapillary proliferation was the unique pathological feature that independently predicted renal outcome.

An update on pathology of IgA nephropathy.

IgA Nephropathy (IgAN) is the commonest of the glomerular diseases in the world. Its progression rate of 30-40% of the cases em 20-30 years makes IgAN an important healthcare issue in Nephrology. Diagnosis of IgAN depends on biopsy findings, particularly at immunofluorescence microscopy. The frequence of IgAN diagnosis is variable in different populations and depends on screening and biopsy indication policies. IgAN pathogenesis is considered multifactorial; its primordial defect is the production of galactosis-deficient IgA molecules. This review paper discusses the most uptodate aspects of the pathogenesis, pathological classification and clinical implications of IgAN.

An update on pathology of IgA nephropathy / Atualização em nefropatia da IgA

Abstract IgA Nephropathy (IgAN) is the commonest of the glomerular diseases in the world. Its progression rate of 30-40% of the cases em 20-30 years makes IgAN an important healthcare issue in Nephrology. Diagnosis of IgAN depends on biopsy findings, particularly at immunofluorescence microscopy. The frequence of IgAN diagnosis is variable in different populations and depends on screening and biopsy indication policies. IgAN pathogenesis is considered multifactorial; its primordial defect is the production of galactosis-deficient IgA molecules. This review paper discusses the most uptodate aspects of the pathogenesis, pathological classification and clinical implications of IgAN.

Resumo A Nefropatia da IgA (IgAN) é a mais comum das doenças glomerulares no mundo. Sua taxa de progressão de 30-40% em 20-30 anos torna a IgAN uma importante preocupação em saúde pública na area da Nefrologia. O diagnóstico da IgAN depende dos achados de biópsia, particularmente de microscopia de imunofluorescência. A frequência do diagnóstico é variável em diferentes populações e depende do rastreamento de hematúria e da indicação de biopsia. A IgAN é uma doença multifatorial: o defeito primordial é a produção de moléculas de IgA deficientes em galactose. Esta revisão discute aspectos atualizados da patogênese e classificação patológica da IgAN e suas implicações clínicas.

Immunoglobulin a nephropathy: Pathological markers of renal survival in paediatric patients.

IgA nephropathy (IgAN) is one of the leading causes of glomerulonephritis characterized by the findings of IgA and IgG immune deposits in the mesangium of kidney biopsies from patients with persistent microscopic haematuria. IgAN is frequently detected among adolescents and young adults. IgAN presents a highly variable course that includes a spectrum from a very mild disease to end-stage renal disease (ESRD). There are several clinical and histological factors that strongly determined the final outcome of patients with IgAN. Pathological variables associated with unfavorable outcomes are mesangial hypercellularity, segmental glomerulosclerosis, endocapillary hypercellularity and interstitial fibrosis/tubular atrophy, according to the Oxford classification. Moreover, some studies also suggest a role for complement activation in the pathogenesis of IgAN. In this regard, staining for C4d may be an independent risk factor for the development of ESRD in IgAN. Despite the growing number of studies assessing IgAN risk factors, this kind of investigation in paediatric patients is still very limited. The aim of this article is to revise pathological markers related to deterioration of renal function in paediatric patients with IgAN, particularly those that can independently affect renal survival.