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Fabry disease is an X-linked lysosomal storage disorder caused by defective enzyme activity of α-galactosidase A and treated with enzyme replacement therapy (ERT) with recombinant α-galactosidase. ERT reduces left ventricular mass assessed by echocardiography or magnetic resonance imaging. However, electrocardiogram changes during ERT have not been fully elucidated. In the present case, ERT with agalsidase alfa for 4 years decreased QRS voltage and negative T depth along with a reduction of left ventricular mass and wall thickness and improvement of symptoms in a female patient with Fabry disease. Long-term observation of electrocardiogram changes might be useful for determining the efficacy of ERT in this case.
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Doença de Fabry , Humanos , Feminino , Doença de Fabry/complicações , Doença de Fabry/tratamento farmacológico , alfa-Galactosidase/uso terapêutico , Hipertrofia Ventricular Esquerda/tratamento farmacológico , Hipertrofia Ventricular Esquerda/etiologia , Terapia de Reposição de Enzimas , Eletrocardiografia , Resultado do TratamentoRESUMO
OBJECTIVES: To investigate the association between duration of consecutive presence of decoy cells on urine cytology and BK virus nephropathy after kidney transplantation. METHODS: In total, 121 kidney transplant recipients were retrospectively evaluated. The best duration of consecutive presence of decoy cells that could be used to predict BK virus nephropathy was analyzed using the area under the curve for each duration, and recipients were divided into two groups based on the best predictive performance. The effectiveness of SV40 immunostaining on urinary cytology was also analyzed. RESULTS: In total, 2534 urine specimens as well as SV40 immunostaining in 2241 urine specimens were analyzed. Six consecutive months of decoy cell positivity had the best predictive performance for BK virus nephropathy (area under the curve = 0.832). The incidence of BK virus nephropathy in recipients with positive decoy cells for 6 months or more consecutive months (5/44) was significantly higher than in those who had positive decoy cells for less than 6 months (0/77; P = 0.005). Decoy cell positivity had a sensitivity, specificity, positive predictive value, and negative predictive value for BK virus nephropathy of 100%, 66%, 11%, and 100% respectively. SV40 immunostaining provided slightly better specificity (68%) and positive predictive value (12%). CONCLUSIONS: The detection of decoy cells at 6 months or more on urine cytology had high predictive value for BK virus nephropathy in kidney transplant recipients. SV40 immunostaining on urine cytology added minimal diagnostic accuracy.
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Vírus BK , Nefropatias , Transplante de Rim , Infecções por Polyomavirus , Infecções Tumorais por Vírus , Humanos , Nefropatias/diagnóstico , Nefropatias/etiologia , Transplante de Rim/efeitos adversos , Infecções por Polyomavirus/diagnóstico , Infecções por Polyomavirus/epidemiologia , Estudos Retrospectivos , Transplantados , Infecções Tumorais por Vírus/diagnóstico , Infecções Tumorais por Vírus/epidemiologia , UrinaRESUMO
OBJECTIVES: To analyze the effect and impact of low-dose rituximab induction therapy on cytomegalovirus infection in living-donor renal transplantation. METHODS: A total of 92 recipients undergoing living-donor renal transplantation at Okayama University Hospital from May 2009 to August 2018 were evaluated retrospectively. Indications for preoperative rituximab (200 mg/body) were the following: (i) ABO major mismatch; (ii) ABO minor mismatch; (iii) donor-specific anti-human leukocyte antigen antibody-positive; and (iv) focal segmental glomerulosclerosis. We excluded four recipients who were followed <3 months, five who received >200 mg/body rituximab and seven who received prophylactic therapy for cytomegalovirus. RESULTS: There were 59 patients in the rituximab group and 17 in the non-rituximab group. Groups differed significantly in age (median age 53 vs 37 years, respectively; P = 0.04), but not in sex (male 64% vs 65%, P = 1.00), focal segmental glomerulosclerosis (3% vs 0%, P = 1.00) or percentage of cytomegalovirus-seronegative recipients of renal allografts from cytomegalovirus-seropositive donors (12% vs 18%, P = 0.68). The estimated glomerular filtration rate did not differ significantly between groups until 24 months after transplantation. Cytomegalovirus clinical symptoms (10% vs 24%, P = 0.22), including fever ≥38°C (5% vs 12%, P = 0.31) and gastrointestinal symptoms (5% vs 12%, P = 0.31), and the 5-year survival rates of death-censored graft loss (90% vs 83%, P = 0.43) did not differ significantly between groups. CONCLUSIONS: Low-dose rituximab induction therapy is effective in immunological high-risk recipients without increasing cytomegalovirus infection in the absence of valganciclovir prophylaxis.
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Infecções por Citomegalovirus , Transplante de Rim , Adulto , Infecções por Citomegalovirus/tratamento farmacológico , Infecções por Citomegalovirus/epidemiologia , Rejeição de Enxerto/epidemiologia , Rejeição de Enxerto/prevenção & controle , Sobrevivência de Enxerto , Humanos , Quimioterapia de Indução , Transplante de Rim/efeitos adversos , Masculino , Pessoa de Meia-Idade , Estudos Retrospectivos , Rituximab/uso terapêuticoRESUMO
AIM: Trefoil factor 3 (TFF3) is a small peptide that is involved in mucosal protection. TFF3 is widely expressed in multiple tissues including kidney tissue. Previous studies have reported that the levels of urinary TFF3 are significantly increased in patients with chronic kidney disease. The aim of this study is to detect the TFF3 mRNA in kidney and elucidate the relationship between renal TFF3 mRNA and tubulointerstitial fibrosis in IgA nephropathy (IgAN). METHODS: We investigated the renal mRNA expression of TFF3 by real-time PCR analysis in biopsy specimens from patients with IgAN, other glomerulonephritis (OGN) and minor glomerular abnormalities (MGA). We also determined the renal localization of TFF3 and the levels of urinary TFF3 by immunostaining and ELISA, respectively. RESULTS: The renal TFF3 mRNA expression was significantly associated with the urinary TFF3 secretion and the tubulointerstitial fibrosis score in the IgAN group alone. Immunostaining of the renal specimen of IgAN patients revealed that TFF3 is located in the renal tubular epithelial cells. The locations were almost the same as those that showed uromodulin positivity; specifically, the thick ascending limb (TAL) of the loop of Henle and the early portion of the distal tubule. The urinary TFF3 levels were positively correlated with the levels of urinary biomarkers of tubulointerstitial injury in such patients. CONCLUSION: Renal TFF3 mRNA is associated with renal tubulointerstitial fibrosis in IgAN patients. The TFF3 located in the renal tubular epithelial cells may play a role in the progression of tubulointerstitial fibrosis in IgAN patients.
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Glomerulonefrite por IGA/genética , Túbulos Renais/química , RNA Mensageiro/genética , Fator Trefoil-3/genética , Adulto , Idoso , Estudos de Casos e Controles , Progressão da Doença , Feminino , Fibrose , Glomerulonefrite por IGA/diagnóstico , Glomerulonefrite por IGA/urina , Humanos , Túbulos Renais/patologia , Masculino , Pessoa de Meia-Idade , Fator Trefoil-3/urina , Regulação para Cima , Adulto JovemRESUMO
BACKGROUND/AIMS: Bleeding is the most common complication after renal biopsy. Although numerous predictors of bleeding have been reported, it remains unclear whether arterial stiffness affects bleeding complications. METHOD: We performed an observational study of the renal biopsies performed in our division over an approximately 6-year period (May 2010 to May 2016). The clinical and laboratory factors were analyzed to reveal the risk factors associated with bleeding, with a focus on anemia (defined as a ≥10% decrease in hemoglobin [Hb] after biopsy). The brachial-ankle pulse wave velocity (baPWV) was measured to evaluate arterial stiffness. RESULTS: This study included 462 patients (male, n=244; female, n=218). Anemia (defined above) was observed in 54 patients (11.7%). The risk of anemia was higher in women, older patients, and patients with lower serum albumin, lower eGFR and lower diastolic blood pressure after biopsy. We then performed a further analysis of 187 patients whose baPWV data were available. Multivariate analysis revealed that a higher baPWV was an independent risk factor for anemia. ROC analysis for predicting anemia found that a baPWV value of 1839 cm/s had the best performance (AUC 0.689). CONCLUSION: An increased baPWV may be a more valuable predictor of bleeding than any of the other reported risk factors.
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Anemia/etiologia , Nefropatias/complicações , Rigidez Vascular , Adolescente , Adulto , Idoso , Idoso de 80 Anos ou mais , Índice Tornozelo-Braço , Biópsia/efeitos adversos , Feminino , Hemoglobinas , Hemorragia , Humanos , Nefropatias/patologia , Masculino , Pessoa de Meia-Idade , Valor Preditivo dos Testes , Análise de Onda de Pulso , Estudos Retrospectivos , Fatores de Risco , Adulto JovemRESUMO
A 77-year-old female with renal dysfunction, hypercalcemia, and hypercalciuria was presented. Systemic investigations including renal biopsy showed that the patient had Fanconi syndrome secondary to renal sarcoidosis. Treatment with 25 mg per day of prednisolone was initiated and her condition improved. Complication of Fanconi syndrome in patients with sarcoidosis is extremely rare. Although the pathological mechanism is still unknown, corticosteroid therapy was effective for ameliorating proteinuria, glycosuria, hypercalciuria, and aminoaciduria.
Assuntos
Anti-Inflamatórios/uso terapêutico , Síndrome de Fanconi/tratamento farmacológico , Glucocorticoides/uso terapêutico , Prednisolona/uso terapêutico , Sarcoidose/complicações , Idoso , Anti-Inflamatórios/administração & dosagem , Síndrome de Fanconi/diagnóstico , Síndrome de Fanconi/etiologia , Feminino , Glucocorticoides/administração & dosagem , Humanos , Prednisolona/administração & dosagem , Sarcoidose/diagnóstico , Sarcoidose/tratamento farmacológicoRESUMO
Fabry disease (FD) is an X-linked disorder resulting in a deficiency of α-galactosidase A (GLA) activity. The R112H mutation of GLA is relatively common in Japanese FD patients, characterized by a late-onset phenotype, almost normal to mild lyso-Gb3 elevation, and mild clinical symptoms, despite low GLA activity. This is due to the structural features of the R112H GLA protein. We herein report the case of a 42-year-old male patient with late-onset FD with a R112H mutation. The patient exhibited only renal involvement with no other organ damage and was successfully treated with galactosidase beta and subsequent migalastat for approximately 10 years. Especially, migalastat was clinically effective in normalizing plasma lyso-Gb3 levels and inhibiting the progression of renal damage associated with FD. Therefore, the use of migalastat in the FD patients with R112H mutation is highly recommended based on this case report.
RESUMO
A 68-year-old woman was admitted to our hospital because of a rapid progression of renal dysfunction with positive myeloperoxidase antineutrophil cytoplasmic antibody and was diagnosed with rapidly progressive glomerulonephritis associated with microscopic polyangiitis (MPA). Severe right rectus sheath hematoma (RSH) bleeding from the inferior epigastric artery developed after starting hemodialysis, which required 4 transarterial embolizations due to recurrent bleeding. After additional treatment with methylprednisolone pulse therapy and rituximab, no rebleeding occurred. Although the giant hematoma reached the pelvis, it shrank spontaneously without any intervention. Nontraumatic RSH should therefore be considered when treating patients with multiple risk factors.
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BACKGROUND: IgA nephropathy (IgAN) is a major cause of chronic glomerulonephritis worldwide. T cell dysregulation has been reported to contribute to the pathogenesis of IgAN. Methods We measured a broad range of Th1, Th2 and Th17 cytokines in the serum of IgAN patients. We searched for significant cytokines, which were associated with clinical parameters and histological scores in IgAN patients. RESULTS: Among 15 cytokines, the levels of soluble CD40L (sCD40L) and IL-31 were higher in IgAN patients and were significantly associated with a higher estimated glomerular filtration rate (eGFR), a lower urinary protein to creatinine ratio (UPCR), and milder tubulointerstitial lesions (i.e., the early phase of IgAN). Multivariate analysis revealed that serum sCD40L was an independent determinant of a lower UPCR after adjustment for age, eGFR, and mean blood pressure (MBP). CD40, a receptor of sCD40L, has been reported to be upregulated on mesangial cells in IgAN. The sCD40L/CD40 interaction may directly induce inflammation in mesangial areas and may therefore be involved in the development of IgAN. CONCLUSIONS: The present study demonstrated the significance of serum sCD40L and IL-31 in the early phase of IgAN. Serum sCD40L may be a marker of the beginning of inflammation in IgAN.
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INTRODUCTION: While chronic kidney disease (CKD) is one of the most important contributors to mortality from non-communicable diseases, the number of nephrologists is limited worldwide. Medical cooperation is a system of cooperation between primary care physicians and nephrological institutions, consisting of nephrologists and multidisciplinary care teams. Although it has been reported that multidisciplinary care teams contribute to the prevention of worsening renal functions and cardiovascular events, there are few studies on the effect of a medical cooperation system. METHODS: We aimed to evaluate the effect of medical cooperation on all-cause mortality and renal prognosis in patients with CKD. One hundred and sixty-eight patients who visited the one hundred and sixty-three clinics and seven general hospitals of Okayama city were recruited between December 2009 and September 2016, and one hundred twenty-three patients were classified into a medical cooperation group. The outcome was defined as the incidence of all-cause mortality, or renal composite outcome (end-stage renal disease or 50% eGFR decline). We evaluated the effects on renal composite outcome and pre-ESRD mortality while incorporating the competing risk for the alternate outcome into a Fine-Gray subdistribution hazard model. RESULTS: The medical cooperation group had more patients with glomerulonephritis (35.0% vs. 2.2%) and less nephrosclerosis (35.0% vs. 64.5%) than the primary care group. Throughout the follow-up period of 5.59 ± 2.78 years, 23 participants (13.7%) died, 41 participants (24.4%) reached 50% decline in eGFR, and 37 participants (22.0%) developed end-stage renal disease (ESRD). All-cause mortality was significantly reduced by medical cooperation (sHR 0.297, 95% CI 0.105-0.835, p = 0.021). However, there was a significant association between medical cooperation and CKD progression (sHR 3.069, 95% CI 1.225-7.687, p = 0.017). CONCLUSION: We evaluated mortality and ESRD using a CKD cohort with a long-term observation period and concluded that medical cooperation might be expected to influence the quality of medical care in the patients with CKD.
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BACKGROUND: Catalase is an important antioxidant enzyme that regulates the level of intracellular hydrogen peroxide and hydroxyl radicals. The effects of catalase deficiency on albuminuria and progressive glomerulosclerosis have not yet been fully elucidated. The adriamycin (ADR) nephropathy model is considered to be an experimental model of focal segmental glomerulosclerosis. A functional catalase deficiency was hypothesized to exacerbate albuminuria and the progression of glomerulosclerosis in this model. METHODS: ADR was intravenously administered to both homozygous acatalasemic mutant mice (C3H/AnLCs(b)Cs(b)) and control wild-type mice (C3H/AnLCs(a)Cs(a)). The functional and morphological alterations of the kidneys, including albuminuria, renal function, podocytic, glomerular and tubulointerstitial injuries, and the activities of catalase were then compared between the two groups up to 8 weeks after disease induction. Moreover, the presence of a mutation of the toll-like receptor 4 (tlr4) gene, which was previously reported in the C3H/HeJ strain, was investigated in both groups. RESULTS: The ADR-treated mice developed significant albuminuria and glomerulosclerosis, and the degree of these conditions in the ADR-treated acatalasemic mice was higher than that in the wild-type mice. ADR induced progressive renal fibrosis, renal atrophy and lipid peroxide accumulation only in the acatalasemic mice. In addition, the level of catalase activity was significantly lower in the kidneys of the acatalasemic mice than in the wild-type mice during the experimental period. The catalase activity increased after ADR injection in wild-type mice, but the acatalasemic mice did not have the ability to increase their catalase activity under oxidative stress. The C3H/AnL strain was found to be negative for the tlr4 gene mutation. CONCLUSIONS: These data indicate that catalase deficiency plays an important role in the progression of renal injury in the ADR nephropathy model.
Assuntos
Acatalasia/fisiopatologia , Albuminúria/induzido quimicamente , Albuminúria/fisiopatologia , Catalase/metabolismo , Doxorrubicina , Nefropatias/induzido quimicamente , Nefropatias/fisiopatologia , Acatalasia/complicações , Animais , Suscetibilidade a Doenças , Masculino , Camundongos , Camundongos Endogâmicos C3H , Camundongos KnockoutRESUMO
Human acatalasemia may be a risk factor for the development of diabetes mellitus. However, the mechanism by which diabetes is induced is still poorly understood. The impact of catalase deficiency on the onset of diabetes has been studied in homozygous acatalasemic mutant mice or control wild-type mice by intraperitoneal injection of diabetogenic alloxan. The incidence of diabetes was higher in acatalasemic mice treated with a high dose (180 mg/kg body weight) of alloxan. A higher dose of alloxan accelerated severe atrophy of pancreatic islets and induced pancreatic beta cell apoptosis in acatalasemic mice in comparison to wild-type mice. Catalase activity remained low in the acatalasemic pancreas without the significant compensatory up-regulation of glutathione peroxidase or superoxide dismutase. Furthermore, daily intraperitoneal injection of angiotensin II type 1 (AT1) receptor antagonist telmisartan (0.1 mg/kg body weight) prevented the development of alloxan-induced hyperglycemia in acatalasemic mice. This study suggests that catalase plays a crucial role in the defense against oxidative-stress-mediated pancreatic beta cell death in an alloxan-induced diabetes mouse model. Treatment with telmisartan may prevent the onset of alloxan-induced diabetes even under acatalasemic conditions.
Assuntos
Diabetes Mellitus Experimental/metabolismo , Acatalasia/metabolismo , Aloxano , Bloqueadores do Receptor Tipo 1 de Angiotensina II/uso terapêutico , Animais , Apoptose , Benzimidazóis/uso terapêutico , Benzoatos/uso terapêutico , Glicemia/efeitos dos fármacos , Glicemia/metabolismo , Peso Corporal , Catalase/metabolismo , Morte Celular , Diabetes Mellitus Experimental/genética , Diabetes Mellitus Experimental/prevenção & controle , Glutationa Peroxidase/metabolismo , Homozigoto , Hiperglicemia/enzimologia , Hiperglicemia/metabolismo , Células Secretoras de Insulina/efeitos dos fármacos , Células Secretoras de Insulina/enzimologia , Células Secretoras de Insulina/patologia , Células Secretoras de Insulina/fisiologia , Masculino , Camundongos , Camundongos Endogâmicos C3H , Camundongos Knockout , Camundongos Mutantes , Superóxido Dismutase/metabolismo , TelmisartanRESUMO
BACKGROUND: We investigated the association between ABO-incompatible (ABO-I) kidney transplantation and early graft function. METHODS: We retrospectively analyzed 95 patients who underwent living donor kidney transplantation between May 2009 and July 2019. It included 61 ABO-compatible (ABO-C) and 34 ABO-I transplantations. We extracted data on immunologic profile, sex, age, cold ischemic time, type of immunosuppression, and graft function. Two definitions were used for slow graft function (SGF) as follows: postoperative day (POD) 3 serum creatinine level >3 mg/dL and estimated glomerular filtration rate (eGFR) <20 mL/min/1.73 m2. Logistic regression analysis was performed to analyze the effect of ABO-I on the incidence of SGF. RESULTS: The characteristics between the ABO-C and ABO-I were not different. ABO-I received rituximab and plasma exchange. Patients also received tacrolimus and mycophenolate mofetil for 2 weeks and prednisolone for 1 week before transplantation as preconditioning. Of the 95 study patients, 19 (20%) and 21 (22%) were identified with SGF according to POD 3 serum creatinine level or eGFR, respectively. Multivariable analysis revealed that ABO-I significantly reduced the incidence of SGF (odds ratio, 0.15; 95% confidence interval, 0.03-0.7; P = .02), and cold ischemic time >150 min increased the incidence of SGF (odds ratio, 6.5; 95% confidence interval, 1.7-25; P = .006). Similar results were identified in POD 3 eGFR. Inferior graft function in patients with SGF was identified up to 6 months after transplantation. CONCLUSION: ABO-I reduces the incidence of SGF, which is associated with an inferior graft function up to 6 months.
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Incompatibilidade de Grupos Sanguíneos/imunologia , Função Retardada do Enxerto/epidemiologia , Função Retardada do Enxerto/imunologia , Sobrevivência de Enxerto/imunologia , Transplante de Rim/efeitos adversos , Sistema ABO de Grupos Sanguíneos/imunologia , Adulto , Feminino , Taxa de Filtração Glomerular , Humanos , Terapia de Imunossupressão/métodos , Imunossupressores/uso terapêutico , Incidência , Transplante de Rim/métodos , Doadores Vivos , Masculino , Pessoa de Meia-Idade , Razão de Chances , Troca Plasmática , Plasmaferese , Estudos RetrospectivosRESUMO
We evaluated the impact of vonoprazan on blood concentrations of tacrolimus via a retrospective analysis of 52 renal transplant recipients who took tacrolimus and converted from rabeprazole to vonoprazan between August 2018 and September 2019. We compared tacrolimus trough levels upon conversion among groups that were classified based on cytochrome P450 (CYP) gene polymorphisms. CYP3A5 groups were heterozygous or homozygous for CYP3A5∗1 and CYP3A5∗3 alleles. CYP2C19 genotypes were classified as extensive (∗1/∗1), intermediate (∗1/∗2 and ∗1/∗3) or poor metabolizers (∗2/∗2, ∗2/∗3 and ∗3/∗3). Tacrolimus trough levels increased only 0.3 ng/mL upon conversion in the CYP3A5∗3/∗3 group: 5.8 [3.4-7.2] vs 6.1 [3.8-7.9]; p = 0.06. No statistically significance changes in tacrolimus levels also occurred in the CYP3A5∗1/∗1 or CYP3A5∗1/∗3 groups. Subgroup analyses of CYP3A5∗3/∗3 demonstrated low changes for all three CYP2C19 subgroups: 5.2 [4.3-6.5] vs 6.2 [4.3-7.9]; p = 0.07, 6.1 [3.4-7.2] vs 6.7 [4.6-7.9]; p = 0.12 and 5.4 [3.6-6.5] vs 4.7 [3.8-6.3]; p = 1.00, respectively. Conversion to vonoprazan thus resulted in little increase of tacrolimus trough levels, even in the group predicted to be most susceptible (CYP3A5∗3/∗3 and 2C19∗1/∗1), thus supporting the safety of concomitant use of vonoprazan with tacrolimus.
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Transplante de Rim , Tacrolimo , Citocromo P-450 CYP3A/genética , Sistema Enzimático do Citocromo P-450/genética , Genótipo , Imunossupressores , Polimorfismo Genético/genética , Pirróis , Rabeprazol , Estudos Retrospectivos , SulfonamidasRESUMO
Aberrant O-glycosylation of serum and tonsillar IgA1 is one of the main pathogeneses of IgA nephropathy (IgAN). However, the synthesis of underglycosylated IgA1 in tonsils has not yet been characterized. This study examined tonsillar B lymphocytes of IgAN (n=34) using tonsils derived from patients with chronic tonsillitis (n=24) and sleep apnea syndrome (n=14) as a control. Gene expression of beta1,3-galactosyltransferase (beta3GalT), and the core 1 beta3GalT-specific molecular chaperone, Cosmc, UDP-N-acetyl-alpha-D-galactosamine: polypeptide N-acetylgalactosaminyl-transferase 2, were significantly decreased in tonsillar CD19-positive B lymphocytes from IgAN patients compared to control tonsillar tissues as determined by real-time RT-PCR. Tonsillar B cell beta3GalT gene expression significantly correlated with estimated GFR and negatively correlated with proteinuria and histological injury score. Western blotting showed the protein expression of beta3GalT in the tonsils to significantly decrease in IgAN in comparison to the controls. These data suggest the downregulation of beta3GalT in tonsillar B lymphocytes to be closely associated with the clinical characteristics of IgAN.
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Linfócitos B/imunologia , Linfócitos B/metabolismo , Glomerulonefrite por IGA/genética , Glomerulonefrite por IGA/imunologia , Adolescente , Adulto , Sequência de Bases , Estudos de Casos e Controles , Criança , Pré-Escolar , Primers do DNA/genética , Feminino , Galactosiltransferases/genética , Expressão Gênica , Glomerulonefrite por IGA/fisiopatologia , Glicosilação , Humanos , Imunoglobulina A/química , Imunoglobulina A/metabolismo , Rim/imunologia , Rim/fisiopatologia , Masculino , Pessoa de Meia-Idade , Chaperonas Moleculares/genética , N-Acetilgalactosaminiltransferases/genética , Tonsila Palatina/imunologia , Proteinúria/genética , Proteinúria/imunologia , Adulto Jovem , Polipeptídeo N-AcetilgalactosaminiltransferaseAssuntos
Doenças Autoimunes/complicações , Nefrose Lipoide/complicações , Pancreatite/complicações , Idoso de 80 Anos ou mais , Doenças Autoimunes/diagnóstico , Doenças Autoimunes/tratamento farmacológico , Doenças Autoimunes/imunologia , Biomarcadores/sangue , Glucocorticoides/uso terapêutico , Humanos , Imunoglobulina G/sangue , Masculino , Nefrose Lipoide/diagnóstico , Nefrose Lipoide/imunologia , Nefrose Lipoide/terapia , Pancreatite/diagnóstico , Pancreatite/tratamento farmacológico , Pancreatite/imunologia , Diálise Renal , Fatores de Tempo , Resultado do TratamentoRESUMO
Autophagy is a cellular mechanism involved in the bulk degradation of proteins and turnover of organelle. Several studies have shown the significance of autophagy of the renal tubular epithelium in rodent models of tubulointerstitial disorder. However, the role of autophagy in the regulation of human glomerular diseases is largely unknown. The current study aimed to demonstrate morphological evidence of autophagy and its association with the ultrastructural changes of podocytes and clinical data in patients with idiopathic nephrotic syndrome, a disease in which patients exhibit podocyte injury. The study population included 95 patients, including patients with glomerular disease (minimal change nephrotic syndrome [MCNS], n = 41; idiopathic membranous nephropathy [IMN], n = 37) and 17 control subjects who underwent percutaneous renal biopsy. The number of autophagic vacuoles and the grade of foot process effacement (FPE) in podocytes were examined by electron microscopy (EM). The relationships among the expression of autophagic vacuoles, the grade of FPE, and the clinical data were determined. Autophagic vacuoles were mainly detected in podocytes by EM. The microtubule-associated protein 1 light chain 3 (LC3)-positive area was co-localized with the Wilms tumor 1 (WT1)-positive area on immunofluorescence microscopy, which suggested that autophagy occurred in the podocytes of patients with MCNS. The number of autophagic vacuoles in the podocytes was significantly correlated with the podocyte FPE score (r = -0.443, p = 0.004), the amount of proteinuria (r = 0.334, p = 0.033), and the level of serum albumin (r = -0.317, p = 0.043) in patients with MCNS. The FPE score was a significant determinant for autophagy after adjusting for the age in a multiple regression analysis in MCNS patients (p = 0.0456). However, such correlations were not observed in patients with IMN or in control subjects. In conclusion, the results indicated that the autophagy of podocytes is associated with FPE and severe proteinuria in patients with MCNS. The mechanisms underlying the activation of autophagy in association with FPE in podocytes should be further investigated in order to elucidate the pathophysiology of MCNS.
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Proteínas Associadas aos Microtúbulos/metabolismo , Nefrose Lipoide/patologia , Podócitos/citologia , Proteinúria/metabolismo , Vacúolos/metabolismo , Proteínas WT1/metabolismo , Adulto , Idoso , Autofagia , Biópsia , Estudos de Casos e Controles , Feminino , Glomerulonefrite Membranosa/metabolismo , Glomerulonefrite Membranosa/patologia , Humanos , Masculino , Pessoa de Meia-Idade , Nefrose Lipoide/metabolismo , Podócitos/metabolismo , Adulto JovemRESUMO
We report a case of immunotactoid glomerulopathy (ITG) with cerebral hemorrhage and hypocomplementemia, with successful therapeutic outcome following the corticosteroids and antihypertensive treatment. A 70-year-old man presented with facial edema in October 2006. One day prior to his referral, he experienced speech disturbance, headache, and vomiting, and on the next day he was referred to our hospital. The laboratory examination revealed massive proteinuria (11.3 g/day) and hematuria. The total serum hemolytic complement (CH50) was decreased to 23 U/ml and C4 component was decreased to 7.5 mg/dl, whereas C3 component remained within normal limits (82 mg/dl). Brain computed tomography scan showed high-density lesions in the left parieto-occipital area suggesting subcortical cerebral hemorrhage. Renal biopsy revealed diffuse subendothelial PAS-positive depositions. Immunofluorescence studies revealed intensive deposition of IgG, IgA, C3, C1q, Fibrinogen, and kappa light chain with granular pattern in the capillary and mesangial area. Electron microscopic examination revealed regularly arranged microtubular deposits, appearing as 21-33 nm in diameter. Based on these findings, this patient was diagnosed as ITG complicated with cerebral hemorrhage and hypocomplementemia. He received oral prednisolone (30 mg/day), resulting in reduction of proteinuria, improvement of hypocomplementemia, and prevention of renal functional deterioration. This case demonstrates that accurate diagnosis of ITG may result in successful therapeutic outcome.
Assuntos
Corticosteroides/uso terapêutico , Anti-Hipertensivos/uso terapêutico , Glomerulonefrite Membranoproliferativa/tratamento farmacológico , Rim/efeitos dos fármacos , Síndrome Nefrótica/tratamento farmacológico , Administração Oral , Corticosteroides/administração & dosagem , Idoso , Biópsia , Hemorragia Cerebral/tratamento farmacológico , Hemorragia Cerebral/imunologia , Quimioterapia Combinada , Edema/tratamento farmacológico , Edema/imunologia , Glomerulonefrite Membranoproliferativa/imunologia , Glomerulonefrite Membranoproliferativa/patologia , Hematúria/tratamento farmacológico , Hematúria/imunologia , Humanos , Rim/imunologia , Rim/patologia , Imageamento por Ressonância Magnética , Masculino , Síndrome Nefrótica/imunologia , Síndrome Nefrótica/patologia , Prednisolona/uso terapêutico , Proteinúria/tratamento farmacológico , Proteinúria/imunologia , Tomografia Computadorizada por Raios X , Resultado do TratamentoRESUMO
BACKGROUND: Alterations in DNA methylation may be involved in disease progression in patients with chronic kidney disease (CKD). Recent studies have suggested that 5-methyl-2'-deoxycytidine (5MedC) may be a marker of hypermethylation of DNA. Currently, there is no information available regarding the urine levels of 5MedC and its association with the progression of CKD. METHOD: We examined the urine levels of 5MedC in spot urine samples from 308 patients with CKD (median age: 56 years, male: 53.2%, and glomerulonephritis: 51.0%) using a competitive enzyme-linked immunosorbent assay and investigated the relationships among urine 5MedC, urine albumin, urine α1-microglobulin (α1MG), and the laboratory parameters associated with CKD. The patients were followed for three years to evaluate renal endpoints in a prospective manner. RESULTS: The urine 5MedC level was significantly increased in the later stages of CKD compared to the early to middle stages of CKD. In multiple logistic regression models, urine 5MedC was significantly associated with the prediction of later CKD stages. Urine 5MedC (median value, 65.9 µmol/gCr) was significantly able to predict a 30% decline in the estimated GFR or a development of end-stage renal disease when combined with macroalbuminuria or an increased level of urine α1MG (median value, 5.7 mg/gCr). CONCLUSION: The present data demonstrate that the urine 5MedC level is associated with a reduced renal function and can serve as a novel and potent biomarker for predicting the renal outcome in CKD patients. Further studies will be necessary to elucidate the role of urine DNA methylation in the progression of CKD.