Navegando por Palavras-chave "Glomerulopathies"
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- ItemAcesso aberto (Open Access)Butirato, produto da microbiota intestinal, previne dano aos podócitos via mecanismos epigenéticos e dependentes de receptores acoplados a proteína G(Universidade Federal de São Paulo (UNIFESP), 2017-07-31) Felizardo, Raphael Jose Ferreira [UNIFESP]; Camara, Niels Olsen Saraiva [UNIFESP]; http://lattes.cnpq.br/8098379714093877; http://lattes.cnpq.br/9834749309169873; Universidade Federal de São Paulo (UNIFESP)Introduction: Chronic Kidney Disease (CKD) is characterized by structural abnormalities and progressive decrease of kidney function until complete loss of filtration capacity. Damages to podocytes, specialized cells involved on filtration process, are one of the major causes that lead to a CKD. The literature comprises a large number of experimental attempts that focus on mitigating the damage to the podocytes. In recent years, many studies point to the gut microbiota as a modulator of intestinal and extraintestinal diseases through the generation of short chain fatty acids (SCFA). It is already known that chronic kidney patients have an imbalanced gut microbiota and lower production of SCFA. Thus, we have explored the role of butyrate, an AGCC able to regulate epigenetic processes and activate G protein coupled receptors (GPR), during the progression of experimental nephropathy induced by adriamycin, focusing mainly on the protection of podocytes. Methods: Wild type mice in a Balb/c background, Gpr109a-/- mice and Gpr109a-/-.Gpr43-/- mice were induced to develop glomerulopathy by a single dose of adriamycin and treated with butyrate. Results: Wild type mice treated with butyrate showed improvement of renal function, associated to a preserved podocyte layer in the glomerular basement membrane and reduction of pro-inflammatory and pro-fibrotic markers in the kidneys. Particularly, butyrate modulated the activity of enzymes involved on epigenetic modifications in the kidneys and changed the frequency of histone markers (H3K9Ac, H3K4me3 and H3K9me3) in the promoter region of the genes encoding synaptopodin, podocin and NEPH-1 in the podocytes. Concomitantly, treatment with butyrate was not sufficient to improve the renal function of Gpr109a -/- mice and Gpr109a-/-.Gpr43-/-mice. Activation of the receptors was associated with the regulations of small GTPases activity Rac1 and Cdc42 and maintenance of the organization of actin filaments in the podocytes grown in vitro. Conclusion: Our results demonstrate that butyrate exerts important effects on podocyte homeostasis during experimental nephropathy through epigenetic and GPR109a receptors-mediated mechanisms.
- ItemAcesso aberto (Open Access)Estudo do eixo intestino-rim: as alterações na microbiota intestinal em um modelo experimental de nefropatia induzida pela adriamicina(Universidade Federal de São Paulo (UNIFESP), 2018-04-28) Silva, Denis Goncalves [UNIFESP]; Camara, Niels Olsen Saraiva [UNIFESP]; http://lattes.cnpq.br/8098379714093877; http://lattes.cnpq.br/1625763026411693Introduction: Kidney diseases are a global epidemic, with a high economic burden for global health systems. Recently, the gut-kidney axis is gaining strength as organs that influence each other, however little is known on how glomerulopathies, as Focal segmental glomerulosclerosis (FSGS), can modify and affect the composition of the gut microbiota and metabolites. The progressive loss of podocytes is a major cause of chronic kidney disease (CKD), with a high prevalence rate and limited current etiological knowledge. Objective: Explore the interrelationship between the renal injury caused by glomerular dysfunction and changes in gut microbiota. Methods: Wild type Balb/c mice were chemically-induced to develop glomerulopathy (Adriamycin, ADR) and were evaluated for 30 days. In parallel, 14 days before receiving ADR, a group of Balb/c mice underwent microbiota depletion, administering broad spectrum antibiotics (ampicillin, metronidazole, neomycin, vancomycin) in autoclaved drinking water and then they were induced the same way to develop glomerulopathy. Results: ADR caused renal histopathological lesions, such as glomerular collapse, decreased number of podocytes per glomerulus, glomerular barrier dysfunction and uremia. In addition, ADR-induced animals showed histological changes in gut colon, with increased levels in amorphous cell mass and a decrease in claudin-1 expression. Structural changes in intestinal colon were also associated with gut microbiota dysbiosis, with reduced Bacteroidetes phylum and less gut mucus. Disease-induced animals that had previously depleted gut microbiota exhibited better glomerular barrier function, with lower levels of protein and albumin in the urine. Conclusion: Our results shows, for the first time in literature, that the development of ADR-induced glomerulopathy promotes changes in the structure of the colon and in the proportion of gut bacterial phyla. Interestingly, initial results showed that depletion of gut microbiota conferred protection to the loss of glomerular barrier function.
- ItemSomente MetadadadosMycophenolate mofetil in children with steroid/cyclophosphamide-resistant nephrotic syndrome(Springer, 2010-03-01) Mello, Valderez Raposo de; Rodrigues, Maira Tinte; Mastrocinque, Tais Helena; Laranjo Martins, Simone Paiva; Braga de Andrade, Olberes Vitor; Medeiros Guidoni, Eliana Biondi; Scheffer, Daniel Kashiwamura; Martini Filho, Dino; Toporovski, Julio; Benini, Vanda; Universidade Federal de São Paulo (UNIFESP); Santa Casa São PauloThe purpose of this study was to assess the results of therapy with mycophenolate mofetil (MMF) in children with idiopathic nephrotic syndrome (INS) who were both steroid- and cyclophosphamide-resistant. Treatment lasted a minimum of 6 months, and follow-up data were collected over a 2-year period. the children were divided into two groups: Group 1 (n = 34) comprised patients who had received cyclosporine A (CsA) before the initiation of MMF therapy; Group 2 (n = 18) comprised patients who received only MMF. Among the 34 patients of Group 1, complete and partial remission were achieved in seven (20.6%) and 13 patients (38.6%), respectively; there was no response in 14 patients (41.2%). Among the 18 patients in Group 2, complete and partial remission occurred in five (27.8%) and six (33.3%) patients, respectively; there was no response in seven patients (38.9%). Eight patients developed chronic kidney disease. the main side-effects were gastrointestinal complaints (n = 11, 21%), recurring severe infections (n = 1, 1.9%), and mild thrombocytopenia/leucopenia (n = 1, 1.9%). MMF proved to be therapeutically effective in 59.5% of the cases. These beneficial effects need to be confirmed in studies with a long-term follow-up after discontinuation of the treatment. Our statistical analysis of the results of therapy with MMF did not reveal any significant difference between its use alone or following CsA administration.
- ItemAcesso aberto (Open Access)Níveis de vitamina D em indivíduos brasileiros com glomerulopatias(Universidade Federal de São Paulo (UNIFESP), 2017-10-26) Augusto, Frederico Knupp [UNIFESP]; Kirsztajn, Gianna Mastroianni [UNIFESP]; Carvalho, Aluízio Barbosa de [UNIFESP]; http://lattes.cnpq.br/7909431111187945; http://lattes.cnpq.br/5744106277657588; http://lattes.cnpq.br/9497938274582982; Universidade Federal de São Paulo (UNIFESP)INTRODUCTION: Patients with glomerulopathies have different levels of proteinuria and among the proteins lost there is the vitamin D binding protein. However, little is known about the levels of 25-hydroxyvitamin D [25(OH)D] and its relation to proteinuria in this population. OBJECTIVES: To evaluate possible associations between blood levels of 25(OH)D and those of 24-hour proteinuria, as well as between 25(OH)D levels and demographic, clinical and laboratory parameters, main medications and renal function decline. PATIENTS AND METHODS: in the present prospective cohort study, we evaluated 175 adult or elderly patients diagnosed with glomerulopathy, levels of 25(OH)D, calcium, phosphorus, PTH, urinalysis, serum creatinine, estimated glomerular filtration rate (eGFR), clinical and laboratory parameters, in collections performed between the months of August to October. RESULTS: In our sample, the mean age was 44.5 years ± 14.9, 62.9% were female and 50% white. The mean Body Mass Index (BMI) was 28 ± 5.1 kg/m2, proteinuria was 1.48 ± 2.18 g/24h, the eGFR was 75.9 ± 32.9 mL/min., and the follow-up of 1102 ± 494 days. We identified a high frequency of 25(OH)D deficiency and deficiency and an inverse relationship between its levels and those of proteinuria, regardless of the stage of chronic kidney disease (p < 0.001). Most patients were overweight or obese. BMI was significantly associated with reduced levels of 25(OH)D (p = 0.024). Among patients with more than 1 year of follow-up, levels of 25(OH)D < 15 ng/mL were associated with a higher rate of decline in eGFR (p = 0.017). CONCLUSIONS: There is an inverse association between vitamin D and proteinuria levels, regardless of the eGFR. Reduced levels of 25(OH)D were associated with high BMI, but not with age, gender and ethnicity or GFR. Levels of 25(OH)D < 15 ng/mL were associated with a faster decline in renal function. These findings suggest that vitamin D deficiency or insufficiency may have consequences on the progression of glomerulopathies and their progression to more advanced stages of chronic kidney disease.
- ItemSomente MetadadadosRelative Contribution of Morphometric and Functional Indicators of Tubulointerstitial Lesion to Glomerular Diseases Prognosis(Karger, 2008-01-01) De Deus, Rogério Barbosa [UNIFESP]; Teixeira, Vicente de Paulo Castro [UNIFESP]; Kirsztajn, Gianna Mastroianni [UNIFESP]; Universidade Federal de São Paulo (UNIFESP)Background: Early diagnosis of proximal tubular lesions can be achieved by detecting abnormal levels of low molecular weight proteins in urine. Material and Methods: 100 cases of glomerulopathies were retrospectively studied to establish the profile of urinary levels of retinol-binding protein (urRBP) and their correlation with histological markers of tubulointerstitial lesions in renal biopsies. the histological study included staining with picrosirius red. Results: Non-proliferative glomerulopathies, male sex, white race and young adults were predominant. the chance of abnormal urRBP occurring was higher among patients with a predominant proliferative component, baseline serum creatinine >1.2 mg/dl (p = 0.008), creatinine clearance <70 ml/min (p = 0.006), and severe interstitial fibrosis (p = 0.042). in multivariate analysis, only serum creatinine and creatinine clearance were independently associated to urRBP, and only urRBP was a time-independent prognostic factor for survival without renal failure ( risk of renal failure: 9 !). Conclusion: Our study suggests that urRBP determination is prognostically relevant in the progression of glomerulopathies; on the other hand, the evaluated morphometric markers correlated poorly with the clinical outcome of these patients. Consequently, urRBP determination, as a functional marker of tubulointerstitial damage, was more appropriate for determining the prognosis of glomerular diseases than the morphometric analysis of renal biopsies. Copyright (C) 2008 S. Karger AG, Basel