Changes in the spectrum of biopsy-proven renal diseases over 11 years: a single-center study in China.

BACKGROUND: There have been some shifts in the frequency and distribution of biopsy-proven renal diseases in China over recent years. The aim of the study was to investigate the changing spectrum of renal diseases from the view of kidney biopsy data in a single center of China. METHODS AND RESULTS: A total of 10,996 cases of native renal biopsies from patients aged ≥15 years old in Huashan Hospital, Fudan University, between 2008 and 2018 were analyzed retrospectively. The results showed that primary glomerular nephropathy (PGN) remained the most common biopsy-proven renal disease (69.42% of total), with IgA nephropathy (IgAN) accounting for 44.40% of PGN, membranous nephropathy (MN) for 28.55%, minimal change disease (MCD) for 13.26% and focal segmental glomerulosclerosis (FSGS) for 8.00%. During the study period, the proportion of MN in PGN appeared an increasing tendency, while that of IgAN and MCD remained stable and that of FSGS showed a decline. Secondary glomerular nephropathy (SGN) constituted 21.54% of total cases, among which the leading two diseases were lupus nephritis (LN) and Henoch-Schonlein purpura nephritis (HSN) which accounted for 41.08% and 19.11% respectively. CONCLUSIONS: The 11-year retrospective study revealed that PGN was the predominant histologic diagnosis among patients undergoing renal biopsy and the most frequent type of PGN remained to be IgAN, followed by MN which increased dramatically.

An Update on Viral Infection-Associated Collapsing Glomerulopathy.

The COVID-19 era has been a reminder to clinicians around the world of the important role that viral infections play in promoting glomerular disease. Several viral infections including human immunodeficiency virus (HIV), severe acute respiratory syndrome coronavirus 2, Epstein-Barr virus, cytomegalovirus, and parvovirus B19 can cause podocyte injury and present with a collapsing glomerulopathy (CG) variant of focal segmental glomerulosclerosis or minimal change disease. CG associated with COVID-19 has been termed COVID-19-associated nephropathy due to its striking resemblance to HIV-associated nephropathy. Host susceptibility is a major determinant of viral infection-associated CG, and the presence of two APOL1 risk variants explains most of the racial predilection to viral-associated CG observed in individuals of African ancestry. Interactions between APOL1 risk variants, viral genes, and the systemic inflammatory response to viral infection all contribute to kidney injury. This review will summarize our current knowledge of viral infection-associated CG, focusing primarily on the clinical presentation, histological features, mechanisms, and disease course of HIV-associated nephropathy and COVID-19-associated nephropathy.

[Diagnostic significance of C4d in membranous nephropathy]. / Importancia diagnóstica del C4d en la nefropatía membranosa.

INTRODUCTION: Membranous nephropathy (MN) is the most common cause of primary nephrotic syndrome in adults (20-30%). Light microscopy shows thickening of glomerular basement membrane with appearance of spikes. These histological findings are not evident in early forms, in which case the granular deposition pattern of IgG and/or C3 in the basement membrane by immunofluorescence (IF) constitutes the diagnostic tool that allows to differentiate it from minimal change disease (MCD). Complement system plays a key role in the pathophysiology of MN. C4d is a degradation product and a marker of the complement system activation. C4d labelling by immunohistochemical (HI) technique can help in the differential diagnosis between both glomerulopathies NM and MCD when the material for IF is insufficient and light microscopy is normal. Our objective was to explore the discrimination power of C4d to differentiate between MN and MCD in renal biopsy material. METHODS: Paraffin-embedded samples were recovered from renal biopsies with a diagnosis of MN and MCD performed between 1/1/2008 and 4/1/2019. IH staining was performed by immunoperoxidase technique using a rabbit anti-human C4d polyclonal antibody. RESULTS: In all cases with MN (n = 27, 15 males) with a median age of 63 (range: 18-87) years, C4d deposits were detected. In 21 cases with MCD (12 males) with a median age of 51 (range: 18-87) years, the C4d marking was negative in every samples. CONCLUSION: The results indicate that the marking of the renal biopsy with C4d is a useful tool for the differential diagnosis between NM and MCD.

Introducción: La nefropatía membranosa (NM) es la causa más frecuente de síndrome nefrótico primario en adultos (20-30%). En la microscopia óptica se observa engrosamiento de membrana basal glomerular con aparición de espigas. Estos hallazgos histológicos no son evidentes en formas tempranas, en cuyo caso el patrón de depósito granular de IgG y/o C3 en la membrana basal por inmunofluorescencia (IF) permite diferenciarla de enfermedad por cambios mínimos (ECM). El sistema del complemento juega un papel central en la fisiopatología de la NM. C4d es producto de degradación y un marcador de la activación del complemento. La marcación con C4d en muestras de biopsias renales, por técnica de inmunohistoquímica (IH) puede colaborar en el diagnóstico diferencial entre ambas glomerulopatías. Nuestro objetivo fue explorar el poder de discriminación del C4d para diferenciar NM de ECM en material de biopsias renales. Métodos: Se recuperaron muestras en parafina de biopsias renales con diagnóstico de NM y ECM realizados entre 1/1/2008 y 1/4/2019. Se realizaron tinciones de IH por técnica de inmunoperoxidasa con C4d usando un anticuerpo policlonal antihumano de conejo. Resultados: En todos los casos con NM (n = 27, 15 hombres) con mediana de edad de 63 (rango: 18-86) años se detectaron depósitos de C4d. En los 21 casos con ECM (12 hombres) con mediana de edad de 51 (rango: 18-87) años la marcación de C4d fue negativa. Conclusión: Los resultados indican que la marcación de la biopsia renal con C4d es una herramienta útil para el diagnóstico diferencial entre NM y ECM.

Minimal Change Disease: Pathogenetic Insights from Glomerular Proteomics.

The mechanism underlying podocyte dysfunction in minimal change disease (MCD) remains unknown. This study aimed to shed light on the potential pathophysiology of MCD using glomerular proteomic analysis. Shotgun proteomics using label-free quantitative mass spectrometry was performed on formalin-fixed, paraffin-embedded (FFPE) renal biopsies from two groups of samples: control (CTR) and MCD. Glomeruli were excised from FFPE renal biopsies using laser capture microdissection (LCM), and a single-pot solid-phase-enhanced sample preparation (SP3) digestion method was used to improve yield and protein identifications. Principal component analysis (PCA) revealed a distinct separation between the CTR and MCD groups. Forty-eight proteins with different abundance between the two groups (p-value ≤ 0.05 and |FC| ≥ 1.5) were identified. These may represent differences in podocyte structure, as well as changes in endothelial or mesangial cells and extracellular matrix, and some were indeed found in several of these structures. However, most differentially expressed proteins were linked to the podocyte cytoskeleton and its dynamics. Some of these proteins are known to be involved in focal adhesion (NID1 and ITGA3) or slit diaphragm signaling (ANXA2, TJP1 and MYO1C), while others are structural components of the actin and microtubule cytoskeleton of podocytes (ACTR3 and NES). This study suggests the potential of mass spectrometry-based shotgun proteomic analysis with LCM glomeruli to yield valuable insights into the pathogenesis of podocytopathies like MCD. The most significantly dysregulated proteins in MCD could be attributable to cytoskeleton dysfunction or may be a compensatory response to cytoskeleton malfunction caused by various triggers.

Characterizing Glomerular Barrier Dysfunction with Patient-Derived Serum in Glomerulus-on-a-Chip Models: Unveiling New Insights into Glomerulonephritis.

Glomerulonephritis (GN) is characterized by podocyte injury or glomerular filtration dysfunction, which results in proteinuria and eventual loss of kidney function. Progress in studying the mechanism of GN, and developing an effective therapy, has been limited by the absence of suitable in vitro models that can closely recapitulate human physiological responses. We developed a microfluidic glomerulus-on-a-chip device that can recapitulate the physiological environment to construct a functional filtration barrier, with which we investigated biological changes in podocytes and dynamic alterations in the permeability of the glomerular filtration barrier (GFB) on a chip. We also evaluated the potential of GN-mimicking devices as a model for predicting responses to human GN. Glomerular endothelial cells and podocytes successfully formed intact monolayers on opposite sides of the membrane in our chip device. Permselectivity analysis confirmed that the chip was constituted by a functional GFB that could accurately perform differential clearance of albumin and dextran. Reduction in cell viability resulting from damage was observed in all serum-induced GN models. The expression of podocyte-specific marker WT1 was also decreased. Albumin permeability was increased in most models of serum-induced IgA nephropathy (IgAN) and membranous nephropathy (MN). However, sera from patients with minimal change disease (MCD) or lupus nephritis (LN) did not induce a loss of permeability. This glomerulus-on-a-chip system may provide a platform of glomerular cell culture for in vitro GFB in formation of a functional three-dimensional glomerular structure. Establishing a disease model of GN on a chip could accelerate our understanding of pathophysiological mechanisms of glomerulopathy.

Renal manifestations in adult-onset Still's disease: a systematic review.

OBJECTIVE: We aimed to review the literature on the clinical presentation, renal pathology, treatment, and outcome of renal manifestations in adult-onset Still's disease (AOSD). METHODS: We used PRISMA guidelines for our systematic review and included all English-language original articles from inception till September 15, 2023, on AOSD and kidney involvement in any form. Data on patient demographics, diagnostic criteria, clinical presentation, renal pathology, treatment employed including dialysis, outcome, cause of death were collected and analyzed. RESULTS: The median age at the diagnosis of renal issues was 37, with a higher prevalence among females (58.1%). Among the cases, 28 experienced renal problems after being diagnosed with AOSD, 12 had simultaneous diagnoses of renal issues and AOSD, and in 4 cases, renal problems appeared before AOSD diagnosis. Out of the 44 cases, 36 underwent renal biopsy, revealing various pathology findings including AA amyloidosis (25%), collapsing glomerulopathy (11.4%), thrombotic microangiopathy (TMA) (11.4%), IgA nephropathy (9.1%), minimal change disease (6.8%), and others. Some cases were clinically diagnosed with TMA, proximal tubular dysfunction, or macrophage activation syndrome-related acute kidney injury. Treatment approaches varied, but glucocorticoids were commonly used. Renal involvement was associated with increased mortality and morbidity, with 6 out of 44 patients passing away, 4 progressing to end-stage renal disease (ESRD), and data on 2 cases' outcomes not available. CONCLUSION: Renal manifestations in AOSD are diverse but rarely studied owing to the rarity of the disease. Studies with larger data would be essential to study further on the pathogenesis and implications.

Idiopathic nephrotic syndrome in Syrian children: clinicopathological spectrum, treatment, and outcomes.

BACKGROUND: Idiopathic nephrotic syndrome (INS) is the most common glomerular disease in children. We performed this study to report histopathological findings, the correlation between clinical and histopathological features, and the response to steroids and other immunosuppressive drugs and outcomes in Syrian children with INS. METHODS: A single-center retrospective observational cohort study was conducted at Children's University Hospital in Damascus, and included all patients aged 1-14 years, admitted from January 2013 to December 2022, with INS and who underwent kidney biopsy. RESULTS: The study included 109 patients, with a male/female ratio of 1.13:1, and a median age of 5 years with interquartile range (2.8-10). The main indication of kidney biopsy was steroid-resistant nephrotic syndrome (SRNS) (57.8%). The main histopathological patterns were minimal change disease (MCD) (45%) and focal segmental glomerulosclerosis (FSGS) (37.6%). FSGS was the most common histopathological pattern in SRNS (44.3%). In SRNS, we used calcineurin inhibitors to induce remission. Tacrolimus was used in 49 patients with response rate (complete remission of proteinuria) of 69.4% and cyclosporine in 20 patients with response rate of 50%. In steroid-dependent nephrotic syndrome (SDNS), we used mycophenolate mofetil (MMF) and cyclophosphamide to prevent relapses; MMF was used in 9 patients with response rate (maintaining sustained remission) of 89% and cyclophosphamide in 3 patients with response rate of 66.7%. Rituximab was used in four patients with FSGS, two SRNS patients and two SDNS patients, with sustained remission rate of 100%. Fifteen patients (13.7%) progressed to chronic kidney disease stage 5. Of them, 7 patients had FSGS and 8 patients had focal and global glomerulosclerosis;14 of them were steroid-resistant and one patient was steroid-dependent with persistent relapses. The most common outcome was sustained remission (47%) in MCD and frequent relapses (31.7%) in FSGS. CONCLUSIONS: FSGS was the most common histopathological pattern in idiopathic SRNS and had the worst prognosis. Calcineurin inhibitors could be an effective therapy to induce complete remission in SRNS. Rituximab may be an effective treatment to achieve sustained remission in SDNS and frequently relapsing NS and may have a potential role in SRNS with further studies required.

Management and Clinical Outcomes of Membranous Nephropathy, IgA Nephropathy, and Minimal Change Disease Two Years Post-Kidney Biopsy.

INTRODUCTION: This study evaluated the phenotypic and pathology characteristics of patients undergoing kidney biopsy at a single center, while also determining the frequency and factors associated with clinical outcomes. METHODS: The incidence and distribution of biopsy-proven kidney diseases in 2000-2019 were surveyed. Consecutive individuals diagnosed with membranous nephropathy (MN), immunoglobulin A nephropathy (IgAN), and minimal change disease (MCD) between August 2015 and December 2019 were enrolled in the prospective 2-year follow-up study. Outcomes included remission of proteinuria and kidney disease progression events. Multivariable-adjusted Cox proportional hazards model was applied. RESULTS: 4,550 kidney biopsies were performed in 2000-2019, showing a noticeable increase in the proportion of MN. 426 patients were enrolled in the follow-up cohort. 346 (81.2%) achieved remission of proteinuria, 39 (9.2%) suffered kidney disease progression and 51.3% of them were diagnosed with IgAN. Kidney pathological diagnosis (MN vs. MCD: hazard ratio [HR], 0.42; 95% confidence interval [95% CI], 0.31-0.57; IgAN vs. MCD: 0.58; 0.39-0.85), levels of 24-h urine protein at biopsy (1.04; 1.00-1.08) and presence of nodular mesangial sclerosis (0.70; 0.49-0.99) were significantly correlated with remission of proteinuria after adjusting for baseline variables. 24-h urine protein levels at biopsy (1.14; 1.04-1.25) and the presence of crescents (2.30; 1.06-4.95) were the independent risk factors for kidney disease progression events after adjusting for baseline variables. CONCLUSION: The increasing frequency of MN has been affirmed over the past 2 decades. The therapeutic status, clinical outcomes, and factors influencing these outcomes were presented in this single-center study for the three primary glomerular diseases.

Differences of clinicopathological characteristics and outcomes of IgA nephropathy patients with and without nephrotic syndrome.

PURPOSE: To evaluate the differences in clinicopathological features and outcomes of IgA nephropathy (IgAN) patients with and without nephrotic syndrome. METHODS: In this retrospective cohort study, IgAN patients from January 2006 to December 2011 in the First Affiliated Hospital of Sun Yat-sen University were enrolled and followed up to Dec 31, 2013. Logistic and Cox regression were conducted to evaluate the associated factors of nephrotic syndrome (NS) and its relation with outcomes of creatinine doubling and progression to end-stage kidney disease (ESKD). RESULTS: A total of 1413 patients with IgAN were enrolled in this study, 57 (4.0%) of whom exhibited NS. Meanwhile, 13 (22.8%) of NS IgAN patients had minimal change disease (MCD). Logistic regression showed that more presence of hypertension, less glomerular sclerosis, less tubular atrophy/interstitial fibrosis, and lower density of IgA deposition in mesangial region were significantly associated with NS IgAN that were independent of age and gender. In addition, a total of 921 patients (890 with non-NS IgAN and 31 with NS IgAN) were followed up to Dec 31, 2013. After adjusting for age, sex, baseline estimated glomerular rate, hypertension and hemoglobin, no significant difference was observed in outcomes of serum creatinine doubling and ESKD between patients with or without NS IgAN. CONCLUSIONS: Prevalence of NS IgAN patients was 4.0%, and 22.8% of them had MCD. Patients with NS IgAN had more severe clinical but less severe pathological features. However, outcomes of serum creatinine doubling and ESKD were not significantly different between patients with or without NS IgAN.

Analysis of glomerular deposition of IgM and C3 in patients with podocytopathies.

Minimal Change Disease (MCD) and Focal Segmental Glomerulosclerosis (FSGS) are the main causes of nephrotic syndrome in the world. The complement system appears to play an important role in the pathogenesis of these diseases. To evaluate the deposition of immunoglobulins and particles of the complement system in renal biopsies of patients with FSGS and MCD and relate to laboratory data, we selected 59 renal biopsies from patients with podocytopathies, 31 from patients with FSGS and 28 with MCD. Epidemiological, clinical, laboratory information and the prognosis of these patients were evaluated. Analysis of the deposition of IgM, IgG, C3, C1q and C4d in renal biopsies was performed. We related IgM and C3 deposition with laboratory parameters. Statistical analysis was performed using GraphPad Prism version 7.0. Glomerular deposition of IgM was significantly higher in the FSGS group, as was codeposition of IgM and C3. The clinical course of patients and laboratory data were also worse in cases of FSGS, with a higher percentage progressing to chronic kidney disease and death. Patients with C3 deposition had significantly higher mean serum creatinine and significantly lower eGFR, regardless of disease. Patients with FSGS had more IgM and C3 deposition in renal biopsies, worse laboratory data and prognosis than patients with MCD. C3 deposition, both in FSGS and MCD, appears to be related to worsening renal function.

Evaluation of C4d expression and staining patterns by immunohistochemistry in renal biopsy samples with focal segmental glomerulosclerosis and minimal change disease.

INTRODUCTION: C4d is an activation product of lectin pathway of complement. Glomerular deposition of C4d is associated with poor prognosis in different types of immune-related glomerulonephritis. The present study was conducted to investigate expression level of C4d and its staining pattern in renal biopsy of patients with focal segmental glomerulosclerosis (FSGS) and minimal change disease (MCD) by immunohistochemistry method. MATERIALS AND METHODS: In this retrospective cross-sectional study, renal biopsy specimens from 46 samples of MCD, 47 samples of FSGS, and 15 samples without glomerular disease as the controls, were subjected to immunohistochemistry staining with C4d. Demographic characteristics and information obtained from light and electron microscopy (EM) of patients were also extracted from their files. RESULTS: C4d positive staining was observed in 97.9 % of FSGS and 43.5 % of MCD samples, which showed a statistically significant difference (P < 0.001). The sensitivity and specificity of C4d expression for diagnosing FSGS were 97.9 % and 56.5 %, respectively. There was no significant correlation between C4d expression and any of the light and electron microscopy findings, including presence of foam cells, mesangial matrix expansion, interstitial fibrosis and tubular atrophy, and basement membrane changes in MCD patients. Also, no significant correlation was observed between C4d expression and clinical symptoms of proteinuria or prolonged high level of creatinine in patients with MCD. DISCUSSION AND CONCLUSION: The expression of C4d marker had a good sensitivity and negative predictive value in the diagnosis of FSGS.

Anti-nephrin antibodies in recurrence of focal segmental glomerulosclerosis: closer to discovering the Holy Grail?

Recurrent forms of primary focal segmental glomerulosclerosis (FSGS) pose an unmet challenge to nephrologists, both in terms of understanding the underlying pathophysiology and in terms of identifying an effective management strategy of this disease, which frequently leads to kidney graft loss. In the past few decades, experimental observations both in patients and in animal models have led to the hypothesis of the existence of circulating factors driving the loss of integrity of the glomerular filtration barrier in FSGS. Although different circulating factor candidates have been postulated, none has been unequivocally shown to be pathogenic. In the current study, Shirai et al. propose a new candidate for this role by identifying circulating anti-nephrin autoantibodies in a cohort of patients with post-transplant recurrence of primary FSGS. Recent evidence by Watts et al. has also identified anti-nephrin autoantibodies in the circulation and in the kidney biopsies of patients with minimal change disease. If confirmed, the identification of these autoantibodies would both contribute to identifying the elusive circulating factor in FSGS and increase our understanding of the spectrum of proteinuric glomerular lesions, spanning from minimal change disease to FSGS. The quest for the Holy Grail is perhaps closer to completion.

Bicellular Localization of Tricellular Junctional Protein Angulin-3/ILDR2 Allows Detection of Podocyte Injury.

Podocytes serve as part of the renal filtration unit with slit diaphragms. Although the structure of slit diaphragms between two cells is well characterized, how the tricellular contact of podocytes is organized and how it changes in injured podocytes remains unknown. This study focused on a tricellular junction protein, angulin-3, and its localization in healthy podocytes, in developmental stages, and in pathologic conditions, using a newly established monoclonal antibody. Angulin-3 was confined at tricellular junctions of primordial podocytes, then transiently localized at bicellular junctions as foot process interdigitation developed and the intercellular junctions rearranged into slit diaphragm, and eventually distributed in a sparse punctate pattern on the foot processes of adult podocytes. In the rodent podocyte injury models, angulin-3 showed bicellular localization between the foot processes, and the localization turned from punctate to dashed linear pattern along the effaced foot processes with the progression of podocyte injury. Angulin-3 also accumulated between foot processes in a linear pattern in kidney biopsy samples of human nephrotic syndrome. Additionally, the line length of angulin-3 staining signal correlated with risk of relapse under glucocorticoid therapy in patients with minimal change nephrotic syndrome. This study proposes an image program to score the linearity of the accumulation pattern of angulin-3 to evaluate the relapse risk of patients with minimal change nephrotic syndrome.

Scaffold protein SH3BP2 signalosome is pivotal for immune activation in nephrotic syndrome.

Despite clinical use of immunosuppressive agents, the immunopathogenesis of minimal change disease (MCD) and focal segmental glomerulosclerosis (FSGS) remains unclear. Src homology 3-binding protein 2 (SH3BP2), a scaffold protein, forms an immune signaling complex (signalosome) with 17 other proteins, including phospholipase Cγ2 (PLCγ2) and Rho-guanine nucleotide exchange factor VAV2 (VAV2). Bioinformatic analysis of human glomerular transcriptome (Nephrotic Syndrome Study Network cohort) revealed upregulated SH3BP2 in MCD and FSGS. The SH3BP2 signalosome score and downstream MyD88, TRIF, and NFATc1 were significantly upregulated in MCD and FSGS. Immune pathway activation scores for Toll-like receptors, cytokine-cytokine receptor, and NOD-like receptors were increased in FSGS. Lower SH3BP2 signalosome score was associated with MCD, higher estimated glomerular filtration rate, and remission. Further work using Sh3bp2KI/KI transgenic mice with a gain-in-function mutation showed ~6-fold and ~25-fold increases in albuminuria at 4 and 12 weeks, respectively. Decreased serum albumin and unchanged serum creatinine were observed at 12 weeks. Sh3bp2KI/KI kidney morphology appeared normal except for increased mesangial cellularity and patchy foot process fusion without electron-dense deposits. SH3BP2 co-immunoprecipitated with PLCγ2 and VAV2 in human podocytes, underscoring the importance of SH3BP2 in immune activation. SH3BP2 and its binding partners may determine the immune activation pathways resulting in podocyte injury leading to loss of the glomerular filtration barrier.

Minimal change disease associated with type 1 and type 2 diabetes mellitus / Glomerulopatia de lesões mínimas associada ao diabetes melito do tipo 1 e do tipo 2

A 19-year-old female with type 1 diabetes for four years, and a 73-year-old female with type 2 diabetes for twenty years developed sudden-onset nephrotic syndrome. Examination by light microscopy, immunofluorescence, and electron microscopy (in one case) identified minimal change disease (MCD) in both cases. There was a potential causative drug (meloxicam) for the 73-year-old patient. Both patients were treated with prednisone and responded with complete remission. The patient with type 1 diabetes showed complete remission without relapse, and the patient with type 2 diabetes had two relapses; complete remission was sustained after associated treatment with cyclophosphamide and prednisone. Both patients had two years of follow-up evaluation after remission. We discuss the outcomes of both patients and emphasize the role of kidney biopsy in diabetic patients with an atypical proteinuric clinical course, because patients with MCD clearly respond to corticotherapy alone or in conjunction with other immunosuppressive agents.

Uma paciente de 19 anos de idade com diabetes tipo 1 durante quatro anos e uma paciente de 73 anos de idade com diabetes tipo 2 durante vinte anos desenvolveram quadro súbito de síndrome nefrótica. O exame histológico à microscopia de luz, imunofluorescência e microscopia eletrônica (em um caso) diagnosticou glomerulopatia de lesões mínimas (GLM) em ambos os casos. Na paciente de 73 anos de idade, houve uma associação com o uso de meloxicam. As duas pacientes foram tratadas com corticosteroides e responderam com remissão completa do quadro. A paciente de 19 anos com diabetes tipo 1 apresentou remissão completa sem recidivas, e a paciente de 73 anos com diabetes tipo 2 apresentou dois episódios de recidiva; a remissão completa foi conseguida após associação ao tratamento com ciclofosfamida. As duas pacientes foram seguidas dois anos após a remissão completa. Os casos descritos enfatizam o papel da biópsia renal em pacientes diabéticos com evolução atípica do aparecimento de proteinúria, pois pacientes com GLM respondem bem à corticoterapia como único tratamento ou associado a outro agente imunossupressor.

Clinicopathological features of atypical nephrotic syndrome in jamaican children / Características clínico-patológicas del síndrome nefrótico atípico en los niños jamaicanos

OBJECTIVES: To document the histopathological spectrum of atypical nephrotic syndrome in Jamaican children and to make clinicopathological correlations which will assist physicians in identifying patients needing nephrology consultation. METHODS: This was a retrospective review of renal biopsy data of Jamaican children who were referred to the University Hospital of the West Indies and the Bustamante Hospital for Children between January 1985 and December 2008. The study population consisted of children < 12 years old with atypical nephrotic syndrome. RESULTS: Biopsies were done in 157 children - 85 males and 72 females (mean age 8.91 ± 3.44 years). Indications for biopsy were steroid resistance (35%), frequent relapses (8.9%) and other atypical presentations (56.1%). Overall, mesangial proliferative glomerulonephritis (MesGN) was the commonest histology (49/157, 31.2%), followed by minimal change disease (MCD) (36/157, 22.9%) and diffuse proliferative glomerulonephritis (DPGN) (26/157, 16.6%). Infection was present in 38/157 (24%) cases. Diffuse proli ferative glomerulonephritis was the predominant type associated with streptococcal infection (52.9%) while Hepatitis B was seen in 83% ofcases ofmembranous nephropathy. CONCLUSION: Mesangial proliferative glomerulonephritis is the commonest histology seen in Jamaican children with atypical nephrotic syndrome. Most membranous nephropathy is Hepatitis B related. Hypertension with hypocomplementaemia, renal failure and anaemia are features ofmore serious renal disease (eg membranoproliferative glomerulonephritis and crescentic nephritis) rather than MCNS and should warrant urgent nephrology consultation for renal biopsy.

OBJETIVOS: Documentar el espectro histopatológico del síndrome nefrótico atípico en los niños jamaicanos y hacer correlaciones clínico-patológicas que ayuden a los médicos a identificar pacientes que necesitan la consulta de nefrología.. MÉTODOS: Se trata de un estudio retrospectivo de datos de biopsias renales de niños jamaicanos remitidos al Hospital Universitario de West Indies y al Hospital Pediátrico Bustamante, entre enero de 1985 y diciembre de 2008. La población del estudio consistió en niños < 12 años de edad que padecían el síndrome nefrótico atípico. RESULTADOS: Se realizaron biopsias a 157 niños - 85 varones y 72 hembras (edad promedio 8.91 + 3.44 años). Las indicaciones para la biopsia se debieron a resistencia a los esteroides (35%), recaídas frecuentes (8.9%) y otras manifestaciones atípicas (56.1%). En general, la glomerulonefritis proliferativa mesangial (GNMes) fue la histología más común con 49/157 (31.2%), seguida por la enfermedad de cambio mínimo (ECM) con 36/157(22.9%) y la glomerulonefritis proliferativa difusa (GNPD) con 26/157 (16.6%). La infección estuvo presente en 38/157 (24%) de los casos. La glomerulonefritis proliferativa difusa fue el tipo predominante asociado con la infección estreptocóccica (52.9%), mientras que Hepatitis B fue observada en el 83% de los casos de nefropatía membranosa. CONCLUSIÓN: La glomerulonefritis proliferativa mesangial es la histología que con mayor frecuencia se observa en los niños jamaicanos que padecen el síndrome nefrótico atípico. La mayoría de los casos de nefropatía membranosa guardan relación con la hepatitis B. La hipertensión con hipocomplementemia, la insuficiencia renal y la anemia son rasgos más bien de enfermedades renales más serias (p.ej, glomerulonefritis membranoproliferativa, nefritis crescéntica) que del síndrome nefrótico de cambios mínimos (SNCM) y debe asegurarse la consulta urgente con el nefrólogo para se realice una biopsia renal.

Renal histological findings in adults in Jamaica / Hallazgos histológicos renales en adultos en Jamaica

BACKGROUND: In 2006, it was reported that Focal and Segmental Glomerulosclerosis (FSGS), Minimal Change Disease (MCD) and Membranous Glomerulonephritis (MGN) were the commonest primary glomerular diseases identified from percutaneous kidney biopsies done in Jamaica for that year (n = 76). The sample size was thought to be small and might have affected the reported findings. So a threeyear review of percutaneous kidney biopsies in Jamaica was carried out. METHODS: Histology reports and clinical data were reviewed for percutaneous kidney biopsies performed from January 2005 to December 2007. Demographic data (age, gender), laboratory investigations such as serum urea, serum creatinine, proteinuria, haematuria, 24-hour urinary protein, and creatinine clearance, and clinical diagnosis were collected from the histology requisition form. RESULTS: There was a total of 224 native kidney biopsies performed. There were 91 males (40.6%) and 133 females (59.4%). Age distribution showed a total number of 25 paediatric cases (11.2%) and 199 adult cases (88.8%). Proteinuria was present in 171 cases (76.3%) and haematuria in 86 cases (38.4%). Of the total biopsies done, 78 cases (39.2%) had primary glomerular diseases, 110 cases (55.3%) had secondary glomerular diseases and 11 (5.5%) biopsies were reported as either normal or inadequate for histological diagnosis. The most common reasons indicated for percutaneous kidney biopsy were proteinuria, haematuria and staging of lupus nephritis. Most common histological findings for primary glomerular disease after percutaneous kidney biopsy were FSGS (n = 34), MGN (n = 15) and MCD (n = 12). In secondary glomerular diseases (n = 110), there were more females (70.8%) than males. Systemic lupus erythematosus was present in 63.3%. Histology of lupus nephritis according to the International Society of Nephrologists classification shows Membranous Lupus Nephritis [MLN] (40.2%), Diffuse Lupus Nephritis [DLN] (19.5%) and Minimal Mesangial Lupus Nephritis [MMLN] (14.3%) as the common histological types. CONCLUSIONS: The most common histological finding for primary glomerular disease following percutaneous kidney biopsy was FSGS, MCD and MGN. Membranous Lupus Nephritis was the commonest histological type for lupus nephritis in this series.

ANTECEDENTES: En 2006, se reportó que la Glomeruloesclerosis Segmentaria y Focal (GESF), la Enfermedad de Cambios Mínimos (ECM) y la Glomerulonefritis Membranosa (GNM) fueron las enfermedades glomerulares primarias más comunes identificadas a partir de las biopsias renales percutáneas realizadas en Jamaica ese año (n = 76). El tamaño de la muestra se consideró pequeño y pudo haber afectado los hallazgos reportados. De manera que se realizó un examen de tres años, de las biopsias renales percutáneas en Jamaica. MÉTODOS: Se revisaron los reportes de histología y los datos clínicos correspondientes a las biopsias renales percutáneas realizadas desde enero de 2005 a diciembre de 2007. RESULTADOS: Hubo un total de 224 biopsias de riñón nativo. Se realizaron 74, 78 y 72 biopsias renales en 2005, 2006 y 2007 respectivamente. Hubo 91 varones (40.6%) y 133 hembras (59.4%). La distribución por edades mostró un total de 25 casos pediátricos (11.2%) y 119 casos de adultos (88.8%). La proteinuria estuvo presente en 171 casos (76.3%) y la hematuria en 86 casos (38.4%). Del total de biopsias realizadas, 78 casos (39.2%) tenían enfermedades glomerulares primarias, 110 casos (55.3%) tenían enfermedades glomerulares secundarias y 11 (5.5%) biopsias fueron reportadas como normales, o como inadecuadas para el diagnóstico histológico. Las razones más comunes señaladas para la biopsia renal percutánea fueron la proteinuria, la hematuria y la estadificación de la nefritis por lupuso nefritis lúpica. Los hallazgos histológicos más comunes para la enfermedad glomerular primaria tras la biopsia renal percutánea fueron GESF (n = 34), GNM (n = 15) y ECM (n = 12). En relación con las enfermedades glomerulares secundarias (n = 110), hubo más hembras (70.8%) que varones. El lupus eritematoso sistémico estuvo presente en 63.3%. De acuerdo con la clasificación de la Sociedad Internacional de Nefrología, la histología de la nefritis por lupus muestra la nefritis lúpica membranosa (NLM) [40.2%], la nefritis lúpica difusa (NLD) [19.5%], y la nefritis lúpica mesangial mínima (NLMM) [14.3%], como los tipos histológicos más comunes. CONCLUSIÓN: Los hallazgos histológicos más comunes para la enfermedad glomerular primaria tras la biopsia renal percutánea, fueron GESF, ECM y GNM. La nefritis lúpica membranosa fue el tipo de histología más común para la nefritis por lupus en esta serie.

Mudança de padräo histológico em síndrome nefrótica idiopática (SNI) na infância: estudo de 41 casos / Change of histological standard in idiopathic nephrotic syndrome in childhood

Foram estudadas 41 crianças portadoras de síndrome nefrótica idiopática (SNI) com biópsia renal incial compatível com lesäo histológica mínima (LHM). Em funçäo de um resposta insatisfatória à corticoterapia, essas crianças foram submetidaas a uma segunda biópsia renal, onde constatou-se mudança de padräo histopatológico como lesäo esclerosante focal (LEF) em 19 pacientes. A partir de tal achado, foi feita revisäo da biópsia renal inicial, na tentativa de estabelecer dados histopatológcios que pudessem sugerir, já na primeira biópsia, os achados do segundo exame. Observou-se a presença de LHM associada à proliferaçäo mesangial (PM) e/ou fibrose intersticial (FI) naqueles pacientes que evoluiram para LEF

Lesión glomerular mínima / Minimal glomerular lesion

Se consideran la presentación clínica, la evolución, el tratamiento y el pronóstico de la lesión glomerular mínima (LGM) en el adulto y se analizan 43 pacientes con sindrome nefrótico idiopático por LGM. Se describen las alteraciones histológicas que la caracterizan; glomérulos normales en microscopía óptica y fusión de los pedicelios de las células epiteliales en microscopía electrónica. Se discute la etiopatogenia y se refiere como probable mecanismo patogénico una disfunción de las células T, con producción de linfokinas, que disminuiría la carga negativa de la membrana basal glomerular, con producción de proteinuria. Se refiere que clinicamente se presenta como un sindrome nefrótico con excelente respuesta al tratamiento corticoideo, que en 80 por ciento de los casos evoluciona con empujes y recaídas y sin deterioro de la función renal. Se discuten los resultados del tratamiento, la iatrogenia corticoidea en los pacientes recaedores frecuentes y corticodependientes y los beneficios de la asociación de drogas citotóxicas