• MeSH
• anemie komplikace   farmakoterapie   MeSH
• deficit železa MeSH
• dialýza ledvin MeSH
• erythropoetin farmakologie   MeSH
• poruchy metabolismu železa MeSH
• renální insuficience MeSH
• železo farmakologie   terapeutické užití   MeSH

• Konspekt
• Patologie. Klinická medicína
• NLK Obory
• nefrologie
• hematologie a transfuzní lékařství

• MeSH
• arterioskleróza komplikace   MeSH
• chronické selhání ledvin etiologie   MeSH
• dialýza ledvin škodlivé účinky   MeSH
• dusík močoviny v krvi MeSH
• erytropoéza účinky léků   MeSH
• hyperhomocysteinemie terapie   MeSH
• uremie metabolismus   chemicky indukované   imunologie   MeSH
• Publikační typ
• kongresy MeSH

• Konspekt
• Patologie. Klinická medicína
• NLK Obory
• nefrologie

AIMS: Anderson-Fabry disease (AFD) is an uncommon X-linked disorder caused by deficient activity of the lysosomal enzyme alpha-galactosidase A. The Fabry Outcome Survey is a European database designed to monitor the long-term efficacy and safety of enzyme replacement therapy (ERT) with agalsidase alfa. The aim of this study was to determine the prevalence and characteristics of cardiac disease in AFD patients. METHODS AND RESULTS: Clinical and laboratory data were available in 714 patients from 11 countries (mean age 35 +/- 17 years, 369 women, 336 treated). The prevalence of angina was 23 vs. 22%; palpitations and arrhythmias 27 vs. 26%; exertional dyspnoea 23 vs. 23%; and syncope 2 vs. 4%, in women and men, respectively (all P = NS). The frequency of all cardiac symptoms was significantly higher in treated than in untreated patients. Gender, age, and glomerular filtration rate were independent determinants of echocardiographically assessed left ventricular hypertrophy (LVH). CONCLUSION: This study confirms the high prevalence of cardiac morbidity associated with AFD. The disease burden in treated women exceeds that of untreated men, suggesting that most women selected for ERT have advanced disease. The presence of LVH is associated with higher frequency of cardiac signs and symptoms and relates independently to gender, age, and renal function.

• MeSH
• alfa-galaktosidasa terapeutické užití   MeSH
• dospělí MeSH
• dyspnoe epidemiologie   etiologie   MeSH
• echokardiografie MeSH
• Fabryho nemoc farmakoterapie   komplikace   MeSH
• financování organizované MeSH
• hodnoty glomerulární filtrace MeSH
• hypertrofie levé komory srdeční epidemiologie   komplikace   MeSH
• izoenzymy terapeutické užití   MeSH
• lidé středního věku MeSH
• lidé MeSH
• nemoci srdce epidemiologie   komplikace   MeSH
• prevalence MeSH
• rizikové faktory MeSH
• synkopa epidemiologie   etiologie   MeSH
• výsledek terapie MeSH
• Check Tag
• dospělí MeSH
• lidé středního věku MeSH
• lidé MeSH
• mužské pohlaví MeSH
• ženské pohlaví MeSH
• Publikační typ
• multicentrická studie MeSH
• Geografické názvy
• Evropa MeSH

Background: A novel data-driven cluster analysis identified distinct pathogenic patterns in C3-glomerulopathies and immune complex-mediated membranoproliferative glomerulonephritis. Our aim was to replicate these observations in an independent cohort and elucidate disease pathophysiology with detailed analysis of functional complement markers. Methods: A total of 92 patients with clinical, histological, complement and genetic data were involved in the study, and hierarchical cluster analysis was done by Ward method, where four clusters were generated. Results: High levels of sC5b-9 (soluble membrane attack complex), low serum C3 levels and young age at onset (13 years) were characteristic for Cluster 1 with a high prevalence of likely pathogenic variations (LPVs) and C3 nephritic factor, whereas for Cluster 2-which is not reliable because of the small number of cases-strong immunoglobulin G staining, low C3 levels and high prevalence of nephritic syndrome at disease onset were observed. Low plasma sC5b-9 levels, decreased C3 levels and high prevalence of LPV and sclerotic glomeruli were present in Cluster 3, and patients with late onset of the disease (median: 39.5 years) and near-normal C3 levels in Cluster 4. A significant difference was observed in the incidence of end-stage renal disease during follow-up between the different clusters. Patients in Clusters 3-4 had worse renal survival than patients in Clusters 1-2. Conclusions: Our results confirm the main findings of the original cluster analysis and indicate that the observed, distinct pathogenic patterns are replicated in our cohort. Further investigations are necessary to analyse the distinct biological and pathogenic processes in these patient groups.

• Publikační typ
• časopisecké články MeSH

BACKGROUND: Acquired or genetic abnormalities of the complement alternative pathway are the primary cause of C3glomerulopathy(C3G) but may occur in immune-complex-mediated membranoproliferative glomerulonephritis (IC-MPGN) as well. Less is known about the presence and role of C4nephritic factor(C4NeF) which may stabilize the classical pathway C3-convertase. Our aim was to examine the presence of C4NeF and its connection with clinical features and with other pathogenic factors. RESULTS: One hunfe IC-MPGN/C3G patients were enrolled in the study. C4NeF activity was determined by hemolytic assay utilizing sensitized sheep erythrocytes. Seventeen patients were positive for C4NeF with lower prevalence of renal impairment and lower C4d level, and higher C3 nephritic factor (C3NeF) prevalence at time of diagnosis compared to C4NeF negative patients. Patients positive for both C3NeF and C4NeF had the lowest C3 levels and highest terminal pathway activation. End-stage renal disease did not develop in any of the C4NeF positive patients during follow-up period. Positivity to other complement autoantibodies (anti-C1q, anti-C3) was also linked to the presence of nephritic factors. Unsupervised, data-driven cluster analysis identified a group of patients with high prevalence of multiple complement autoantibodies, including C4NeF. CONCLUSIONS: In conclusion, C4NeF may be a possible cause of complement dysregulation in approximately 10-15% of IC-MPGN/C3G patients.

• MeSH
• autoprotilátky imunologie   metabolismus   MeSH
• dospělí MeSH
• komplement C3 nefritický faktor metabolismus   MeSH
• komplement metabolismus   MeSH
• lidé MeSH
• membranoproliferativní glomerulonefritida imunologie   metabolismus   MeSH
• mladiství MeSH
• mladý dospělý MeSH
• nemoci ledvin imunologie   metabolismus   MeSH
• Check Tag
• dospělí MeSH
• lidé MeSH
• mladiství MeSH
• mladý dospělý MeSH
• mužské pohlaví MeSH
• ženské pohlaví MeSH
• Publikační typ
• časopisecké články MeSH
• práce podpořená grantem MeSH

Background: Factor H-related protein 5 (FHR-5) is a member of the complement Factor H protein family. Due to the homology to Factor H, the main complement regulator of the alternative pathway, it may also be implicated in the pathomechanism of kidney diseases where Factor H and alternative pathway dysregulation play a role. Here, we report the first observational study on CFHR5 variations along with serum FHR-5 levels in immune complex-mediated membranoproliferative glomerulonephritis (IC-MPGN) and C3 glomerulopathy (C3G) patients together with the clinical, genetic, complement, and follow-up data. Methods: A total of 120 patients with a histologically proven diagnosis of IC-MPGN/C3G were enrolled in the study. FHR-5 serum levels were measured in ELISA, the CFHR5 gene was analyzed by Sanger sequencing, and selected variants were studied as recombinant proteins in ELISA and surface plasmon resonance (SPR). Results: Eight exonic CFHR5 variations in 14 patients (12.6%) were observed. Serum FHR-5 levels were lower in patients compared to controls. Low serum FHR-5 concentration at presentation associated with better renal survival during the follow-up period; furthermore, it showed clear association with signs of complement overactivation and clinically meaningful clusters. Conclusions: Our observations raise the possibility that the FHR-5 protein plays a fine-tuning role in the pathogenesis of IC-MPGN/C3G.

• MeSH
• aktivace komplementu MeSH
• alely MeSH
• biologické markery * MeSH
• dospělí MeSH
• ELISA MeSH
• genetická predispozice k nemoci MeSH
• genetická variace * MeSH
• imunokomplex imunologie   MeSH
• jednonukleotidový polymorfismus MeSH
• komplement C3 imunologie   MeSH
• komplement genetika   metabolismus   MeSH
• lidé MeSH
• management nemoci MeSH
• membranoproliferativní glomerulonefritida krev   diagnóza   etiologie   mortalita   MeSH
• mladiství MeSH
• mladý dospělý MeSH
• náchylnost k nemoci MeSH
• prognóza MeSH
• ROC křivka MeSH
• studie případů a kontrol MeSH
• určení symptomu MeSH
• vyšetření funkce ledvin MeSH
• Check Tag
• dospělí MeSH
• lidé MeSH
• mladiství MeSH
• mladý dospělý MeSH
• mužské pohlaví MeSH
• ženské pohlaví MeSH
• Publikační typ
• časopisecké články MeSH
• práce podpořená grantem MeSH