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Cluster Analysis Identifies Distinct Pathogenetic Patterns in C3 Glomerulopathies/Immune Complex-Mediated Membranoproliferative GN

Iatropoulos, Paraskevas ; Daina, Erica ; Curreri, Manuela ; Piras, Rossella ; Valoti, Elisabetta ; Mele, Caterina ; Bresin, Elena ; Gamba, Sara ; Alberti, Marta ; Breno, Matteo ; Perna, Annalisa ; Bettoni, Serena ; Sabadini, Ettore ; Murer, Luisa ; Vivarelli, Marina ; Noris, Marina ; Remuzzi, Giuseppe

Journal of the American Society of Nephrology, 2018-01, Vol.29 (1), p.283-294 [Periódico revisado por pares]

United States: American Society of Nephrology

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  • Título:
    Cluster Analysis Identifies Distinct Pathogenetic Patterns in C3 Glomerulopathies/Immune Complex-Mediated Membranoproliferative GN
  • Autor: Iatropoulos, Paraskevas ; Daina, Erica ; Curreri, Manuela ; Piras, Rossella ; Valoti, Elisabetta ; Mele, Caterina ; Bresin, Elena ; Gamba, Sara ; Alberti, Marta ; Breno, Matteo ; Perna, Annalisa ; Bettoni, Serena ; Sabadini, Ettore ; Murer, Luisa ; Vivarelli, Marina ; Noris, Marina ; Remuzzi, Giuseppe
  • Assuntos: Clinical Research
  • É parte de: Journal of the American Society of Nephrology, 2018-01, Vol.29 (1), p.283-294
  • Notas: ObjectType-Article-1
    SourceType-Scholarly Journals-1
    ObjectType-Feature-2
    content type line 23
  • Descrição: Membranoproliferative GN (MPGN) was recently reclassified as alternative pathway complement-mediated C3 glomerulopathy (C3G) and immune complex-mediated membranoproliferative GN (IC-MPGN). However, genetic and acquired alternative pathway abnormalities are also observed in IC-MPGN. Here, we explored the presence of distinct disease entities characterized by specific pathophysiologic mechanisms. We performed unsupervised hierarchical clustering, a data-driven statistical approach, on histologic, genetic, and clinical data and data regarding serum/plasma complement parameters from 173 patients with C3G/IC-MPGN. This approach divided patients into four clusters, indicating the existence of four different pathogenetic patterns. Specifically, this analysis separated patients with fluid-phase complement activation (clusters 1-3) who had low serum C3 levels and a high prevalence of genetic and acquired alternative pathway abnormalities from patients with solid-phase complement activation (cluster 4) who had normal or mildly altered serum C3, late disease onset, and poor renal survival. In patients with fluid-phase complement activation, those in clusters 1 and 2 had massive activation of the alternative pathway, including activation of the terminal pathway, and the highest prevalence of subendothelial deposits, but those in cluster 2 had additional activation of the classic pathway and the highest prevalence of nephrotic syndrome at disease onset. Patients in cluster 3 had prevalent activation of C3 convertase and highly electron-dense intramembranous deposits. In addition, we provide a simple algorithm to assign patients with C3G/IC-MPGN to specific clusters. These distinct clusters may facilitate clarification of disease etiology, improve risk assessment for ESRD, and pave the way for personalized treatment.
  • Editor: United States: American Society of Nephrology
  • Idioma: Inglês
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