focal segmental glomerulosclerosis
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- MeSH
- cyklofosfamid terapeutické užití MeSH
- dospělí MeSH
- fokálně segmentální glomeruloskleróza diagnóza farmakoterapie patologie MeSH
- kreatinin krev MeSH
- lidé MeSH
- nefrotický syndrom MeSH
- proteinurie MeSH
- steroidy terapeutické užití MeSH
- Check Tag
- dospělí MeSH
- lidé MeSH
- mužské pohlaví MeSH
- ženské pohlaví MeSH
Fokálně segmentální glomeruloskleróza, FSGS, je progresivní onemocnění glomerulů různé etiologie, které vede u téměř 50 % pacientů k nezvratnému selhání ledvin. FSGS je podmíněna poškozením podocytů histologicky charakterizovaným parciální sklerotizací glomerulů, klinicky nejčastěji nefrotickou proteinurií či nefrotickým syndromem a neuspokojivou léčebnou odpovědí. Transplantace ledviny je u pacientů s FSGS spojena s vysokým rizikem rekurence a horšími dlouhodobými výsledky. Zásadní pro prognózu pacienta je včasná léčba, která se liší u jednotlivých forem FSGS (primární, sekundární, genetická).
Focal segmental glomerulosclerosis, FSGS, is a progressive glomerular disease of different ethiology that leads in almost 50 % of patients to end stage renal failure. FSGS is caused by damage of podocytes, histologically characterized by partial scarring of glomeruli, clinically by nephrotic-range proteinuria or nephrotic syndrome and unsatisfactory therapeutic response. Kidney transplantation in FSGS patients is associated with high risk of disease recurrence and worse long-term outcomes. Early treatment is essential for the patient's prognosis, which varies between different forms of FSGS (primary, secondary, genetic).
BACKGROUND AND OBJECTIVES: Pirfenidone is an orally available antifibrotic agent that has shown benefit in animal models of pulmonary and renal fibrosis and in clinical trials of pulmonary fibrosis, multiple sclerosis, and hepatic cirrhosis. Our objective was to determine whether pirfenidone slows the loss of renal function in focal segmental glomerulosclerosis. DESIGN, SETTING, PARTICIPANTS, & MEASUREMENTS: An open-label trial was performed to evaluate the safety and efficacy of pirfenidone in patients with idiopathic and postadaptive focal segmental glomerulosclerosis. The monthly change in estimated GFR, expressed as ml/min per 1.73 m2, was compared between the baseline period and the treatment period. During both periods, patients received angiotensin antagonist therapy if tolerated. Twenty-one patients were enrolled, and 18 patients completed a median of 13 mo of pirfenidone treatment. RESULTS: The monthly change in GFR improved from a median of -0.61 ml/min per 1.73 m2 (interquartile range -1.31 to -0.41) during the baseline period to -0.45 ml/min per 1.73 m2 (interquartile range -0.78 to -0.16) with pirfenidone therapy. This change represents a median of 25% improvement in the rate of decline (P < 0.01). Pirfenidone had no effect on BP or proteinuria. Adverse events attributed to therapy included dyspepsia, sedation, and photosensitive dermatitis. CONCLUSIONS: It is concluded that pirfenidone is an attractive candidate for placebo-controlled trials in patients with progressive chronic kidney disease.
- MeSH
- dospělí MeSH
- fokálně segmentální glomeruloskleróza farmakoterapie patofyziologie MeSH
- hodnoty glomerulární filtrace účinky léků MeSH
- ledviny patofyziologie účinky léků MeSH
- lidé středního věku MeSH
- lidé MeSH
- pilotní projekty MeSH
- prospektivní studie MeSH
- pyridony terapeutické užití MeSH
- Check Tag
- dospělí MeSH
- lidé středního věku MeSH
- lidé MeSH
- mužské pohlaví MeSH
- ženské pohlaví MeSH
Nephrology, dialysis, transplantation, ISSN 0931-0509 vol. 18, suppl. 6, August 2003
vi86 s. : il., tab., grafy ; 28 cm
- MeSH
- fokálně segmentální glomeruloskleróza patologie MeSH
- nefrotický syndrom patofyziologie MeSH
- nefróza MeSH
- nemoci ledvin MeSH
- proteinurie MeSH
- Publikační typ
- kongresy MeSH
- sborníky MeSH
- Konspekt
- Patologie. Klinická medicína
- NLK Obory
- nefrologie
- urologie
The aim of the study was to characterize by molecular profiling two glomerular diseases: IgA nephropathy (IgAN) and focal segmental glomerulosclerosis (FSGS) and to identify potential molecular markers of IgAN and FSGS progression. The expressions of 90 immune-related genes were compared in biopsies of patients with IgAN (n=33), FSGS (n=17) and in controls (n=11) using RT-qPCR. To identify markers of disease progression, gene expression was compared between progressors and non-progressors in 1 year follow-up. The results were verified on validation cohort of patients with IgAN (n=8) and in controls (n=6) using laser-capture microdissection, that enables to analyze gene expression separately for glomeruli and interstitium. In comparison to controls, patients with both IgAN and FSGS, had lower expression of BAX (apoptotic molecule BCL2-associated protein) and HMOX-1 (heme oxygenase 1) and higher expression of SELP (selectin P). Furthermore, in IgAN higher expression of PTPRC (protein-tyrosine phosphatase, receptor-type C) and in FSGS higher expression of BCL2L1 (regulator of apoptosis BCL2-like 1) and IL18 compared to control was observed. Validation of differentially expressed genes between IgAN and controls on another cohort using laser-capture microdissection confirmed higher expression of PTPRC in glomeruli of patients with IgAN. The risk of progression in IgAN was associated with higher expression EDN1 (endothelin 1) (AUC=0.77) and FASLG (Fas ligand) (AUC=0.82) and lower expression of VEGF (vascular endothelial growth factor) (AUC=0.8) and in FSGS with lower expression of CCL19 (chemokine (C-C motif) ligand 19) (AUC=0.86). Higher expression of EDN1 and FASLG along with lower expression of VEGF in IgAN and lower expression of CCL19 in FSGS at the time of biopsy can help to identify patients at risk of future disease progression.
- MeSH
- dospělí MeSH
- fokálně segmentální glomeruloskleróza genetika patologie MeSH
- IgA nefropatie genetika patologie MeSH
- kohortové studie MeSH
- ledviny metabolismus patologie MeSH
- lidé středního věku MeSH
- lidé MeSH
- následné studie MeSH
- prospektivní studie MeSH
- senioři MeSH
- stanovení celkové genové exprese metody MeSH
- Check Tag
- dospělí MeSH
- lidé středního věku MeSH
- lidé MeSH
- mužské pohlaví MeSH
- senioři MeSH
- ženské pohlaví MeSH
- Publikační typ
- časopisecké články MeSH
- multicentrická studie MeSH
Metalloproteinase-2 (MMP-2) and metalloproteinase-9 (MMP-9) degrade type IV collagen, and represent important tissue remodeling enzymes in several kidney disorders. In this study, we measured urinary levels of MMP-2, MMP-9, and the tissue inhibitors of metalloproteinases (TIMP-1 and TIMP-2) in patients with steroid-sensitive nephrotic syndrome (SSNS, n = 18, median age 5) and focal segmental glomerulosclerosis (FSGS, n = 16, median age 15). We found that urinary concentrations of MMP-2, MMP-9, TIMP-1, and TIMP-2 were significantly elevated in FSGS patients as compared to SSNS in both relapse and remission (p < 0.002). Furthermore, urinary levels of these enzymes are increased early on in the FSGS disease process (chronic kidney disease stages 1 and 2). The findings from this pilot study suggest that MMPs and TIMPs have the potential to represent candidate, early non-invasive biomarkers for diagnosis and/or response to therapy. In addition, they may represent therapeutic targets for preventing chronic kidney disease progression in FSGS.
- MeSH
- biologické markery moč MeSH
- dítě MeSH
- ELISA MeSH
- fokálně segmentální glomeruloskleróza enzymologie moč MeSH
- lidé MeSH
- matrixová metaloproteinasa 2 moč MeSH
- matrixová metaloproteinasa 9 moč MeSH
- mladiství MeSH
- nefrotický syndrom moč MeSH
- pilotní projekty MeSH
- předškolní dítě MeSH
- tkáňový inhibitor metaloproteinasy 1 moč MeSH
- tkáňový inhibitor metaloproteinasy 2 moč MeSH
- Check Tag
- dítě MeSH
- lidé MeSH
- mladiství MeSH
- mužské pohlaví MeSH
- předškolní dítě MeSH
- ženské pohlaví MeSH
- Publikační typ
- časopisecké články MeSH
Primary forms of minimal change disease and focal segmental glomerulosclerosis are rare podocytopathies and clinically characterized by nephrotic syndrome. Glucocorticoids are the cornerstone of the initial immunosuppressive treatment in these two entities. Especially among adults with minimal change disease or focal segmental glomerulosclerosis, relapses, steroid dependence or resistance are common and necessitate re-initiation of steroids and other immunosuppressants. Effective steroid-sparing therapies and introduction of less toxic immunosuppressive agents are urgently needed to reduce undesirable side effects, in particular for patients whose disease course is complex. Rituximab, a B cell depleting monoclonal antibody, is increasingly used off-label in these circumstances, despite a low level of evidence for adult patients. Hence, critical questions concerning drug-safety, long-term efficacy and the optimal regimen for rituximab-treatment remain unanswered. Evidence in the form of large, multicenter studies and randomized controlled trials are urgently needed to overcome these limitations.
- MeSH
- dospělí MeSH
- fokálně segmentální glomeruloskleróza * farmakoterapie MeSH
- imunologické faktory terapeutické užití MeSH
- imunosupresiva škodlivé účinky MeSH
- lidé MeSH
- lipoidní nefróza * farmakoterapie MeSH
- nefrotický syndrom MeSH
- recidiva MeSH
- rituximab terapeutické užití MeSH
- Check Tag
- dospělí MeSH
- lidé MeSH
- Publikační typ
- časopisecké články MeSH
- přehledy MeSH
Progresia nefropatíí je komplexný proces, určovaný; (a) Glomerulosklerózou zahrňujúcou lokálnu proliferáciu mezangiálnych, glomerulárnych epitelových a endotelových buniek v súhre s trombocytami a monocytami zo systémového riečiska. Zmnoženie mezangiálnej matrix v konečnej fáze vedie ku glomeruloskleróze. Glomeruloskleróza je reverzibilná, daná rovnováhou sklerotlzuiúclch a proteolytických procesov, (b) Intersticiálnou fibrózou s hromadením flbrobiastov najprv v perivoskulárnej adventícíi, zmenou ich fenotypu na myofibroblasty, ktoré produkujú kolagén I a III, aktín (β-SMA) a ďalšie bielkoviny. Na fibróze sa podieľajú aj monocyty/fagocyty, T- lymfocyty o tubulárne bunky. Zmnoženie intersticiálnej matrix znižuje prekrvenie interstícia s ischémiou tubulárnych buniek. Ich zánikom až vznikom atubulárnych glomerulov. Veľkosť flbrózy koreluje s poklesom renálnych funkcií. Myofibroblasty sa dostávajú „dierami" v parietálnej stene do glomerulu a v glomerule spúštajú, prípadne akcelerujú glomerulosklerózu. Poznanie molekulárnej biológie tychto zmien zásadne prehĺbilo naše poznatky o progresii nefropatií, čo je základným predpokladom ich racionálneho ovplyvnenia.
Progression of nephropathies is a comprehensive process determined by (a) glomerulosclerosis involving local proliferation of mesangiol, glomerular, epithelial and endothelial cells in conjunction with platelets and monocytes from the systemic vascular bed. Proliferation of mesangial matrices in the end stage results in glomerulosclerosis. The glomerulosclerosis Is reversible and dependent on the balance of sclerotizing and proteolytic processes; (b) lnterstitial fibrosis and fibroblast accumulation. Initially In the perivascular adventitium, a modification of their phenotype to myofibroblasts producing collagen I and III, actin (alpha-SMA), and other proteins. A role in fibrosis is also played by monocytes/phagocytes, T-lymphocytes, and tubular cells. The interstitial matrix proliferation diminishes interstitial perfusion with ischemia of tubular cells, their death up to the development of otubular glomeruli. The severity of fibrosis correlaies with the decrease in renal function. Myofibroblasts enter the glomerulus via „holes" in the parietal wall triggering or, possibly, accelerating glomerulosclerosis in the glomerulus. Molecular biology has unraveled these changes thereby helping improve our understanding of progression of nephropathies, which is a basic prerequisite for their rational control.
- MeSH
- fibróza MeSH
- fokálně segmentální glomeruloskleróza MeSH
- ledviny patofyziologie patologie MeSH
- molekulární struktura MeSH
- Publikační typ
- přehledy MeSH
- MeSH
- chromozomální delece MeSH
- dospělí MeSH
- fokálně segmentální glomeruloskleróza diagnóza patologie MeSH
- geny Wilmsova nádoru patologie MeSH
- lidé MeSH
- nádory ledvin patologie MeSH
- proteinurie patologie MeSH
- syndrom WAGR diagnóza genetika patologie MeSH
- Check Tag
- dospělí MeSH
- lidé MeSH
- mužské pohlaví MeSH
- Publikační typ
- kazuistiky MeSH
