Glomerular diseases最新文献

Recent years have seen an explosion of interest in the pathogenesis and therapy of immunoglobulin A nephropathy (IgAN). Large cohort studies have facilitated improvements in disease classification and prognosis, including the establishment and validation of a standard pathological classification, the Oxford classification. Landmark treatment studies published in the past several years have solidified a basic therapeutic approach, emphasizing the value of adding immunomodulatory drugs to supportive care for aggressive disease. There are currently a large number of therapies with diverse mechanisms of action in active development for IgAN, promising at least to enhance our understanding of key pathogenic pathways and, at best, to eventually prove useful in slowing or stopping the progression of IgAN. In this cutting-edge feature, we use a clinical case to review and discuss the current standard of care in the diagnosis and treatment of IgAN, as well as to highlight emerging approaches to treatment.

Introduction: Anti-neutrophil cytoplasmic antibody (ANCA)-associated vasculitis (AAV) is a systemic condition usually affecting small blood vessels, commonly causing kidney disease. It has a reported incidence of around 20-25 per million per year. AAV includes both granulomatosis with polyangiitis (GPA) and microscopic polyangiitis (MPA). Here, we describe the epidemiology of this condition at our renal centre over a 23-year period, compare GPA and MPA and compare the overall cohort by era of diagnosis.

Methods: We identified all patients with AAV with renal involvement between January 2000 and December 2022 through our biopsy database and electronic patient record. The cohort after exclusions totaled 278. We collected demographic data, baseline laboratory values, treatment received and outcomes including progression to renal replacement therapy (RRT), relapse rates and mortality. We performed subgroup analysis comparing those with GPA and MPA, and created 4 groups by era of diagnosis.

Results: Median age of the cohort was 63.5 years (interquartile range [IQR] 52-72), 52.5% were male and 92.4% White. GPA was seen in 49.3% and MPA in 42.1%. There was advanced renal disease at presentation with median eGFR 18 mL/min/1.73 m² (IQR 9-38) and 54 (19.4%) required RRT at presentation. Relapse occurred in 23%, progression to RRT in 26.6% and 1-year mortality was 3.2%. Median follow-up duration was 54 months (IQR 22-98). Those with GPA were younger, had higher incidence of ENT disease at presentation, were more likely to relapse and had greater 1- and 5-year survival. Mortality rate per hundred person years improved from 2010 onwards.

Conclusions: This is one of the largest retrospective observational studies conducted on AAV. We demonstrate that there were more cases of GPA (49.2%) compared to MPA (42.1%) presenting to our centre; comorbidity rates were high; there was advanced renal disease at presentation and mortality rate appeared to improve in the more recent eras.

Introduction: Novel molecular tools have the potential to improve current clinical and histology-based risk classification systems for various medical renal diseases including glomerulonephritis (GN). We aimed to assess the utility of gene expression for improving biopsy-based risk prediction in patients with GN with and without crescent formation.

Methods: This retrospective case-control study used NanoString nCounter to measure the expression of 54 previously described inflammation, nephron injury, endothelium, and crescent-related genes in 335 archival, formalin-fixed paraffin-embedded native kidney biopsies, including a 288-biopsy discovery cohort representing a broad spectrum of crescentic GN subtypes, and an independent 47-biopsy validation cohort focused on ANCA-associated crescentic GN. Clinical, histologic, and gene expression data were compared.

Results: Discovery cohort analysis demonstrated increased expression of 13 genes in crescentic GN cases that developed end-stage renal disease (ESRD) versus those that did not (false discovery rate <0.05). Within the 75-biopsy subset of ANCA-associated crescentic GN cases in the discovery cohort, this 13-gene set was found to be independently predictive of ESRD in multivariate Cox proportional hazards regression analysis (p = 0.015), with significant differentiation of high and low risk patients in the Kaplan-Meier renal survival analysis (log-rank test, p = 0.002). However, validation cohort analysis did not demonstrate significant improvement in risk stratification with the 13-gene set when compared with established clinicopathologic models.

Conclusion: These results suggest that biopsy-based gene expression may provide the opportunity for improved risk stratification in crescentic GN; however, the genes evaluated in this study appear to have limited added clinical utility over existing risk scores.

Introduction: Membranous nephropathy (MN) is a leading cause of nephrotic syndrome in adults. NELL1 accounts for approximately 10% of MN cases and is emerging as a distinct subtype often linked to secondary conditions, such as malignancies and drugs. Here, we describe a case of MN in a patient with metastatic papillary thyroid carcinoma.

Case presentation: A 78-year-old man with metastatic papillary thyroid carcinoma and a distant history of treated syphilis presented with nephrotic syndrome. A renal biopsy revealed segmental MN with positive NELL1 staining, while the thyroid carcinoma tissue also demonstrated NELL1 staining at weak to moderate intensity. The patient was managed conservatively without immunosuppression due to the lack of oncologic treatment options and syphilis was treated with doxycycline due to positive serologies, though active infection was not suspected. Follow-up showed stabilization of renal function and marked reduction in proteinuria.

Conclusion: NELL1-positive MN is increasingly recognized for its association with malignancy. The patient achieved partial remission with supportive, non-immunosuppressive therapy. Clinicians should maintain a high index of suspicion for secondary conditions when NELL1-positive MN is encountered. This case report reviews secondary NELL1 associations and underscores the diagnostic challenges in MN when multiple potential secondary causes exist.

Introduction: Sickle cell disease (SCD), an autosomal recessive disorder caused by hemoglobin S, leads to red blood cell sickling and multiorgan damage, including sickle cell nephropathy (SCN). While SCN histopathological changes are well described, data from the Middle East region, where the Arab-Indian (AI) haplotype is common, are limited. We hypothesized that SCN in patients in Saudi Arabia shows histopathological features similar to those in other regions, reflecting a shared renal injury mechanism.

Methods: This single-center retrospective study analyzed kidney biopsies from adults with SCD in the Eastern Province of Saudi Arabia from 2012 to 2023. Histological specimens were examined using hematoxylin and eosin, periodic acid-Schiff stain, Masson trichrome stain, Jones silver stain, and immunofluorescence. Haplotype genotyping was performed using a nuclease allelic discrimination assay with target-specific primers and TaqMan probes labeled with VIC and FAM. Clinical and biochemical data were collected at the time of biopsy and at the last follow-up.

Results: Twelve biopsies were included in the study (median age 44 years, 50% female). Median serum creatinine was 91.5 µmol/L (interquartile range [IQR] 59-130), and 24-h urinary protein was 3,300 mg (IQR 1,181-5,725). Of 9 patients tested, seven had homozygous AI haplotype, one had heterozygous AI, and one had BEN/CAR/CAM. Histopathology showed tubular hemosiderosis (92%), global sclerosis (75%), glomerular hypertrophy (75%), sickled red blood cells (58%), focal segmental glomerulosclerosis (42%), and glomerular basement membrane duplication (33%). These findings mirror SCN patterns in other haplotypes.

Conclusions: In Saudi patients with SCD with predominant AI haplotype, SCN histopathological features align with those reported globally, suggesting a consistent renal pathogenesis across haplotypes. This study improves our understanding of SCN in the AI haplotype, supporting standardized treatment methods and further research into preventing progression.

Introduction: Membranoproliferative glomerulonephritis (MPGN) is a rare pattern of glomerular injury that may be immune complex-mediated (ICM), most often secondary to infections, autoimmune disorders, or hematologic or less often solid tumor malignancies. Infections with Haemophilus, Aggregatibacter, Cardiobacterium, Eikenella, Kingella (HACEK) organisms are a well-known but rare cause of infective endocarditis (IE), which may be difficult to detect. Bacterial infections are more common in patients with cirrhosis, which may complicate the interpretation of clinical findings.

Case presentation: The patient is a 44-year-old male with alcoholic cirrhosis who presented with hematuria, proteinuria, and acute kidney injury (AKI), with negative blood cultures. Kidney biopsy revealed ICM-MPGN, with no underlying etiology identified. His clinical course was complicated by recurrent fluid overload with AKI requiring dialysis. Following corticosteroid therapy for ICM-MPGN, he developed Aggregatibacter bacteremia associated with worsening mitral regurgitation but without vegetations. After antibiotic therapy, the mitral valve was replaced and showed healed endocarditis. Following prolonged antibiotic therapy and successful surgical intervention, his kidney function improved and he remains dialysis independent.

Conclusion: This case highlights the role of HACEK organisms causing subclinical and difficult to diagnose IE, the increased risk of infection in patients with cirrhosis, and the need for a thorough evaluation for infectious etiologies in patients with ICM-MPGN prior to immunosuppressive therapy.

Introduction: We report a rare case of class III lupus nephritis presenting as crescentic pauci-immune glomerulonephritis - an unusual biopsy finding not captured in the current International Society of Nephrology/Renal Pathology Society classification, highlighting a diagnostic and therapeutic challenge.

Case presentation: A 24-year-old woman with systemic lupus erythematosus presented with preserved renal function, microscopic hematuria, nephritic-range proteinuria, elevated anti-dsDNA levels, negative antineutrophil cytoplasmic antibody serologies, and a kidney biopsy demonstrating focal crescentic pauci-immune glomerulonephritis with mesangial, subendothelial, and subepithelial electron-dense deposits, consistent with a rare histopathologic variant of class III LN.

Conclusion: This case underscores the importance of kidney biopsy in atypical lupus presentations as histopathological findings may not always align with serological or clinical features, and can significantly influence diagnosis, prognosis, and management.

Introduction: The present study aimed to describe the clinical and demographic characteristics of nephrotic syndrome in children from a large, highly genetically admixed Latin American country and to identify key challenges in managing pediatric nephrotic syndrome in Brazil.

Methods: This observational, multicenter study included a patient sample from 21 pediatric nephrology centers. Descriptive statistics were employed to analyze the outcomes.

Results: Data were collected from 597 patients; 333 (56%) were male, with a median age of 3.5 years (interquartile range [IQR], 2.2-6.0) at disease onset. There was no consensus among centers regarding initial treatment duration, criteria of response to treatment, although all patients received corticosteroids. After a median follow-up of 4.3 years (IQR, 2.0-7.4), 423 (71.0%) patients were classified as steroid-sensitive, and 172 (28.9%) as steroid-resistant. Progressive kidney dysfunction (chronic kidney disease [CKD] stages 4/5) was observed in 35 (5.9%) patients. Despite 224 patients undergoing kidney biopsy and 172 being classified as steroid-resistant, only 8 (1.3%) children underwent genetic testing. Electron microscopy was performed in only 19 kidney biopsies.

Conclusion: Despite the inherent limitations of observational studies, this investigation presents valuable clinical and demographic data on nephrotic syndrome from a previously underrepresented region. It highlights significant unmet medical needs in Brazil, including the need for consensus on treatment protocols and standardized definitions of responses to treatment. In addition, the near absence of genetic testing in steroid-resistant nephrotic syndrome represents a critical gap that requires prompt intervention.

Introduction: Streptococcus pneumoniae infections are a preventable cause of morbidity and mortality in individuals with glomerular disease. There is limited immunogenicity data to inform the effectiveness of vaccination in this high-risk patient population.

Methods: We conduct a scoping review of studies evaluating pneumococcal vaccine immunogenicity in adults and children with idiopathic nephrotic syndrome, focal segmental glomerulosclerosis, IgA vasculitis, or systemic lupus erythematosus with nephritis. We summarize patient characteristics, serotypes assessed, and rates of seroprotection and/or seroconversion. We then use the Merative MarketScan® Commercial Claims and Encounters database to describe rates of adequate, partial, and inadequate pneumococcal vaccination (PCV13 and/or PPSV23) within 12 months of incident glomerular disease diagnosis from 2010 to 2018.

Results: A total of 879 citations were screened, of which 63 studies were reviewed for inclusion criteria. A final analytic set included 19 studies. Most studies reported clinically meaningful rates of seroprotection, though definitions varied widely across studies. In the analysis of commercial healthcare claims data, 1,343 children aged 2-11 years and 19,987 individuals aged 12 to <65 years with incident of GD were identified. Of those inadequately vaccinated prior to GD diagnosis, 4.0% (38/947) of the 2-11-year group and 6.8% (797/11,646) of those in the 12 to <65-year group were partially or adequately vaccinated within 12 months of diagnosis. Demographic and clinical factors more commonly identified in those with pneumococcal vaccination included sex, age, region, and prior influenza vaccination.

Conclusion: There is limited literature describing pneumococcal vaccine immunogenicity in patients with glomerular disease. Metrics of reporting seroprotection and seroconversion to pneumococcal vaccines would benefit from standardization. Healthcare claims for pneumococcal vaccines following a diagnosis of glomerular disease suggest that efforts to improve timely vaccination are needed.

Introduction: Preeclampsia, a leading cause of morbidity during pregnancy, is associated with glomerular endotheliosis, fibrin deposition, and thrombotic microangiopathy and is characterized by edema, proteinuria, and acute kidney injury. Preeclampsia has been described on a background of glomerular disease membranous nephropathy, IgA nephropathy, and focal segmental glomerulosclerosis, but biopsy studies have also described the de novo diagnosis of glomerulopathy as thrombotic microangiopathy, endotheliosis or collapsing glomerulopathy in the setting of preeclampsia.

Case presentations: We report 3 cases of preeclampsia-associated collapsing focal and segmental glomerulosclerosis in the third trimester of gestation, two of which were previously healthy and one with a history of chronic hypertension that presented with nephrotic-range proteinuria without secondary causes detected. It was decided to begin with antiproteinuric treatment after delivery, resulting in a complete response without the need for immunosuppressant drugs. The outcomes of these cases suggest that a favorable evolution is expected once preeclampsia had resolved and therefore the glomerular changes had been reversed.

Conclusion: A subgroup of pregnant patients can be managed without exposing the mother-child pair to adverse effects related to immunosuppression when preeclampsia is detected in the third trimester of gestation.