Dataset Information

Validation of distinct pathogenic patterns in a cohort of membranoproliferative glomerulonephritis patients by cluster analysis.

ABSTRACT: 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.

SUBMITTER: Garam N

PROVIDER: S-EPMC7147314 | biostudies-literature | 2020 Apr

REPOSITORIES: biostudies-literature

ACCESS DATA

Publications

Validation of distinct pathogenic patterns in a cohort of membranoproliferative glomerulonephritis patients by cluster analysis.

Garam Nóra N Prohászka Zoltán Z Szilágyi Ágnes Á Aigner Christof C Schmidt Alice A Gaggl Martina M Sunder-Plassmann Gere G Bajcsi Dóra D Brunner Jürgen J Dumfarth Alexandra A Cejka Daniel D Flaschberger Stefan S Flögelova Hana H Haris Ágnes Á Hartmann Ágnes Á Heilos Andreas A Mueller Thomas T Rusai Krisztina K Arbeiter Klaus K Hofer Johannes J Jakab Dániel D Sinkó Mária M Szigeti Erika E Bereczki Csaba C Janko Viktor V Kelen Kata K Reusz György S GS Szabó Attila J AJ Klenk Nóra N Kóbor Krisztina K Kojc Nika N Knechtelsdorfer Maarten M Laganovic Mario M Lungu Adrian Catalin AC Meglic Anamarija A Rus Rina R Kersnik-Levart Tanja T Macioniene Ernesta E Miglinas Marius M Pawłowska Anna A Stompór Tomasz T Podracka Ludmila L Rudnicki Michael M Mayer Gert G Rysava Romana R Reiterova Jana J Saraga Marijan M Seeman Tomáš T Zieg Jakub J Sládková Eva E Szabó Tamás T Capitanescu Andrei A Stancu Simona S Tisljar Miroslav M Galesic Kresimir K Tislér András A Vainumäe Inga I Windpessl Martin M Zaoral Tomas T Zlatanova Galia G Csuka Dorottya D

Clinical kidney journal 20190621 2

<h4>Background</h4>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.<h4>Methods</h4>A total of 92 patients with clinical, histological, complement and genetic data were involved in the study, and hierarchical cluster ...[more]

PMID: 32296528

Similar Datasets

Project description:This review revises the reclassification of the membranoproliferative glomerulonephritis (MPGN) after the consensus conference that by 2015 reclassified all the glomerulonephritis basing on etiology and pathogenesis, instead of the histomorphological aspects. After reclassification, two types of MPGN are to date recognized: The immunocomplexes mediated MPGN and the complement mediated MPGN. The latter type is more extensively described in the review either because several of these entities are completely new or because the improved knowledge of the complement cascade allowed for new diagnostic and therapeutic approaches. Overall the complement mediated MPGN are related to acquired or genetic cause. The presence of circulating auto antibodies is the principal acquired cause. Genetic wide association studies and family studies allowed to recognize genetic mutations of different types as causes of the complement dysregulation. The complement cascade is a complex phenomenon and activating factors and regulating factors should be distinguished. Genetic mutations causing abnormalities either in activating or in regulating factors have been described. The diagnosis of the complement mediated MPGN requires a complete study of all these different complement factors. As a consequence, new therapeutic approaches are becoming available. Indeed, in addition to a nonspecific treatment and to the immunosuppression that has the aim to block the auto antibodies production, the specific inhibition of complement activation is relatively new and may act either blocking the C5 convertase or the C3 convertase. The drugs acting on C3 convertase are still in different phases of clinical development and might represent drugs for the future. Overall the authors consider that one of the principal problems in finding new types of drugs are both the rarity of the disease and the consequent poor interest in the marketing and the lack of large international cooperative studies.

Dataset Information

Validation of distinct pathogenic patterns in a cohort of membranoproliferative glomerulonephritis patients by cluster analysis.

Publications

Validation of distinct pathogenic patterns in a cohort of membranoproliferative glomerulonephritis patients by cluster analysis.

Similar Datasets

OmicsDI is part of the ELIXIR infrastructure

Tweets