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BACKGROUND: In the past three years, cases of gross hematuria (GH) after the vaccination for coronavirus disease 2019 (COVID-19) in IgA nephropathy (IgAN) patients have been frequently reported worldwide. However, the post-event renal prognosis of these patients, their clinical backgrounds, and underlying mechanisms remain unknown. Therefore, we conducted a nationwide multicenter prospective cohort study in Japan. METHODS: We analyzed laboratory findings at the time of the first presentation to the hospital, and 3 and 6 months after in patients with GH after the vaccination, and histopathological findings in their kidney biopsy specimens. Moreover, changes in pathological biomarkers of IgAN such as galactose-deficient IgA1 (Gd-IgA1) and its immune complexes (ICs) were also evaluated. RESULTS: During the study period, 127 newly presenting with GH after the vaccination were enrolled, with a clear female bias (73.2%). GH was observed after the second or subsequent vaccinations in most patients (92.9%). Of the 37 patients undergoing kidney biopsy prior to the vaccination, 36 patients had been diagnosed with IgAN/IgA vasculitis (IgAV). In remaining 90 patients, 69 of the 70 who newly underwent kidney biopsy were diagnosed with IgAN (N=67)/IgAV (N=2). Their histopathology did not show a high incidence of acute lesions such as endocapillary hypercellularity and crescentic lesions. Most cases showed a temporary increase in proteinuria, but no sustained worsening in renal function. Among the biomarkers measured, serum Gd-IgA1 and ICs were comparable throughout the observation period, however, only urinary Gd-IgA1 was increased at the time of GH. CONCLUSIONS: We found that GH after the vaccination is more likely to occur in IgAN/IgAV patients, with a female bias, but without progressive exacerbation of renal function. Although further investigation is needed regarding causal relationship between vaccination and GH, this study provides many insights into the molecular mechanisms of GH.
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Progressive multifocal leukoencephalopathy (PML), a severe demyelinating disease of the central nervous system, is caused by the reactivation of the polyomavirus JC virus (JCV). It favors the cerebrum and typically occurs in patients with immunodeficiencies, with a progressive course and fatal outcome in the majority of cases. However, the cerebellar form of PML, characterized by isolated posterior fossa lesions, such as those in the cerebellum or brainstem at disease onset, is rare, and reports of its occurrence in peritoneal dialysis (PD) patients are lacking. In this paper, we describe a rare case of a cerebellar form of PML in a PD patient. A 64-year-old man undergoing PD was referred to our hospital for anorexia, nausea, and vomiting in the past month. He had finger-to-nose test abnormalities, gaze-directed nystagmus, and scanning speech. He was diagnosed with the cerebellar form of PML based on his progressive cerebellar symptoms, the typical magnetic resonance imaging findings, and the presence of JCV-DNA in the cerebrospinal fluid polymerase chain reaction test. He developed nocturnal delirium, aggravated disquiet, and died of pneumonia on the 69th day. Clinicians should consider the cerebellar form of PML as a differential diagnosis if PD patients develop progressive cerebellar symptoms.
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Carbamazepine (CBZ) intoxication can occur due to various factors, including drug interactions and over-ingestion. Extracorporeal elimination, particularly through hemodialysis and hemoperfusion, is effective in treating severe carbamazepine intoxication. However, as the effectiveness of various modalities can differ, method selection may be based on a specific clinical situation. A 47-year-old woman who took CBZ for schizophrenia presented to our hospital with episodes of vomiting and consciousness disorder. As the CBZ concentration was > 20 µg/mL, she was admitted to the intensive care unit with a diagnosis of acute CBZ poisoning. She underwent one session of hemoperfusion for 2 h, and her CBZ level decreased from > 20 µg/mL to 6.4 µg/mL. However, she developed acute kidney and liver injuries 2 days after admission and underwent intermittent hemodialysis, plasma exchange, continuous hemodiafiltration (CHDF), and online HDF, depending on her condition. Her general condition improved, and she was transferred to the psychiatric department. To our knowledge, no case reports have described severe acute CBZ poisoning in a patient who developed multiorgan failure to date, which was successfully treated with multimodal blood purification therapy. When treating severe CBZ intoxication, blood purification therapy should be tailored to the changing pathophysiology of the condition.
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The combination of systemic amyloid A (AA) amyloidosis and xanthogranulomatous pyelonephritis (XGP) resulting from a chronic urinary tract infection is extremely rare. We herein report a case of systemic AA amyloidosis secondary to XGP for which clinical remission developed after nephrectomy. To our knowledge, this is the first case report describing the clinical improvement of systemic AA amyloidosis secondary to XGP after nephrectomy in Japan. Clinicians should be aware of this uncommon combination and search for amyloid depositions in cases of XGP.
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Amiloidose , Pielonefrite Xantogranulomatosa , Infecções Urinárias , Humanos , Pielonefrite Xantogranulomatosa/complicações , Pielonefrite Xantogranulomatosa/diagnóstico por imagem , Pielonefrite Xantogranulomatosa/cirurgia , Amiloidose/complicações , Amiloidose/diagnóstico , Nefrectomia/efeitos adversos , Infecções Urinárias/complicações , Proteína Amiloide A SéricaRESUMO
BACKGROUND/AIMS: Our previous comprehensive analysis of the genes expressed in kidneys with anti-glomerular basement membrane (GBM) nephritis using DNA microarrays showed that SM22alpha was one of the highly expressed genes. SM22alpha is a 22-kDa cytoskeletal protein that is exclusively expressed in smooth muscle cells. We investigated the localization of SM22alpha at mRNA and protein levels, and its pathological significance in anti-GBM nephritis kidneys. METHODS: Northern blot analysis, in situ hybridization, immunohistochemistry and double immunofluorescence studies were performed. The specific antibody (Ab) against SM22alpha was obtained by immunization of rabbits with recombinant rat SM22alpha protein. RESULTS: SM22alpha mRNA expression was upregulated in kidneys and inducibly expressed in the parietal and visceral glomerular epithelial cells in anti-GBM nephritis kidneys. Immunohistochemistry with anti-SM22alpha Ab showed that SM22alpha protein was localized in the same series of cells. Double immunofluorescence with anti-SM22alpha and anti-glomerular cell markers demonstrated that SM22alpha might be expressed in epithelial cells of injured glomeruli. In visceral epithelial cells, SM22alpha might be expressed in cells in which podocyte specific markers, podocalyxin and nephrin were lost. CONCLUSION: The injured glomerular epithelial cells in anti-GBM nephritis might undergo structural and functional alterations, including the expression of a smooth muscle marker, SM22alpha.
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Membrana Basal/imunologia , Células Epiteliais/metabolismo , Glomerulonefrite/metabolismo , Glomérulos Renais/metabolismo , Proteínas dos Microfilamentos/metabolismo , Proteínas Musculares/metabolismo , Animais , Biomarcadores/metabolismo , Modelos Animais de Doenças , Células Epiteliais/patologia , Regulação da Expressão Gênica , Glomerulonefrite/induzido quimicamente , Glomerulonefrite/patologia , Imunoglobulina G , Glomérulos Renais/patologia , Masculino , Proteínas de Membrana/genética , Proteínas de Membrana/metabolismo , Proteínas dos Microfilamentos/genética , Proteínas Musculares/genética , Análise de Sequência com Séries de Oligonucleotídeos , Fenótipo , RNA Mensageiro/genética , RNA Mensageiro/metabolismo , Distribuição Aleatória , Ratos , Ratos Endogâmicos WKY , Sialoglicoproteínas/genética , Sialoglicoproteínas/metabolismoRESUMO
AIM: The diagnostic approach for renal diseases with the electrophoretic pattern of urinary protein on cellulose acetate (CA) membrane differentiates the causes of proteinuria. However, this method has not been used routinely because of its difficulty in obtaining a clear image. This study was performed in order to re-evaluate this method with an improved system. METHODS: Using the newly developed system of CA membrane electrophoresis and its visualization, we examined fresh urine from patients (n = 100) who subsequently underwent renal biopsy and compared the results with the histological findings. RESULTS: The improved method of urine electrophoresis with CA membrane provided clear images and was sensitive enough for urine samples to be applied without concentration. The profiles of proteinuria were clearly classified into three patterns: glomerular, tubular or mixed. The profiles exhibited a good agreement with the histological findings of renal biopsy. CONCLUSION: The recognition of damaged portions in kidney through the profiles of proteinuria by this system could be practically effective for understanding the kidney disease at bedside.
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Eletroforese em Acetato de Celulose , Nefropatias/complicações , Nefropatias/diagnóstico , Rim/patologia , Proteinúria/urina , Urinálise/métodos , Biópsia , Glomerulonefrite por IGA/complicações , Glomerulonefrite por IGA/diagnóstico , Glomerulonefrite por IGA/patologia , Glomerulonefrite por IGA/urina , Humanos , Nefropatias/patologia , Nefropatias/fisiopatologia , Nefropatias/urina , Nefrite/complicações , Nefrite/diagnóstico , Nefrite/patologia , Nefrite/urina , Valor Preditivo dos Testes , Proteinúria/etiologia , Reprodutibilidade dos Testes , Sensibilidade e Especificidade , Compostos de Prata , Coloração e Rotulagem/métodosRESUMO
BACKGROUND: Monocyte chemoattractant protein (MCP)-1 is closely related to the pathogenesis of the progression of various chronic renal diseases, including IgA nephropathy (IgAN), through its chemoattractant effect on macrophages. However, the correlation of MCP-1 gene polymorphism with the long-term prognosis of Japanese patients with IgAN has not been clearly determined yet. METHODS: We investigated 277 Japanese patients diagnosed with IgAN based on renal biopsy to clarify the association between the progression of IgAN and MCP-1 gene polymorphism at position A-2518G, which regulates the transcription of the MCP-1 gene. RESULTS: The incidence of endstage renal disease was significantly higher in patients with the AA genotype (47.1%) compared to those with the AG (24.1%) or GG (27.4%) genotype (P = 0.024). Moreover, Kaplan-Meier analysis revealed that the AA genotype significantly facilitated the progression of renal disease (log rank; P = 0.0029), and Cox proportional hazards regression model analysis showed that the AA genotype represented a 2.058-fold risk for the progression of renal disease (P = 0.026) compared to the AG/GG genotype. However, when the patients were treated with angiotensin-converting enzyme inhibitor and/or angiotensin receptor blocker, or corticosteroid, homozygosity for the -2518A allele was not associated with a higher rate of incidence of endstage renal disease. Serum MCP-1 levels were higher although not significantly so, in the patients with IgAN possessing the AA genotype. CONCLUSIONS: The AA genotype at MCP-1 -2518 was an independent risk factor for the progression of renal disease in Japanese patients with IgAN, and was closely associated with renal survival.
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Quimiocina CCL2/genética , Glomerulonefrite por IGA/genética , Glomerulonefrite por IGA/mortalidade , Polimorfismo Genético , Adulto , Feminino , Genótipo , Humanos , Incidência , Japão/epidemiologia , Falência Renal Crônica/genética , Falência Renal Crônica/mortalidade , Masculino , Prognóstico , Fatores de Risco , Análise de SobrevidaRESUMO
BACKGROUND: The immunoregulatory activity of ligands for peroxisome proliferator-activated receptors (PPARs) has been recently paid attention. The regulatory effect of bezafibrate (BZF), a ligand for PPARalpha on glomerulonephritis was investigated using a rat anti-glomerular basement membrane (GBM) glomerulonephritis model. METHODS: The effect on development of anti-GBM glomerulonephritis was examined by treatment with BZF from day -7 to day 7 after intravenous injection of rabbit anti-GBM serum into Wistar Kyoto (WKY) rats. The therapeutic efficacy after onset of the glomerulonephritis was also checked by treatment with BZF from day 3 to 7. On day 7, the condition was evaluated histologically. The expression of a tissue injury molecule, macrophage metalloesterase (MME), was measured by Northern blot analysis. The suppressive effect on immune cells was assessed by proliferation assay with mitogen-stimulated rat spleen cells. RESULTS: Histopathologic changes induced by anti-GBM in rats treated with BZF (day -7 to day 7) were markedly suppressed in a dose-dependent fashion. Infiltration of ED-1+ macrophages in glomeruli, proteinuria, and mRNA expression of MME in kidneys were diminished in parallel with histologic improvement. Moreover, the disease activity was also attenuated even by the treatment after onset of the glomerulonephritis (day 3 to 7). The mitogen-induced proliferation of spleen cells was down-regulated at concentrations of BZF, which were equivalent to those in sera of BZF-treated rats. CONCLUSION: BZF markedly suppresses the activity of rat anti-GBM crescentic glomerulonephritis. Fibrates might serve as a therapeutic option for crescentic glomerulonephritis.