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

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

C4 nephritic factor in patients with immune-complex-mediated membranoproliferative glomerulonephritis and C3-glomerulopathy

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Prognosis of Dialysed Patients after Kidney Transplant Failure

Background/Aims: Patients with a failed kidney transplant represent a unique, high-risk chronic kidney disease population that is increasing in number, and may be sub-optimally managed. Our aim was to compare the survival of patients with failed allografts to patients with native kidney failure and to assess whether their survival is affected by the graft resection. Methods: Kaplan-Meier and Cox-regression survival analyses were performed on the data of 57 patients with graft failure and of 123 transplant-naive haemodialysed patients. Results: After adjustment for age and gender, there was no statistically significant difference in the mortality of patients in the two groups. The 43 patients, who had a transplanted kidney nephrectomy had a statistically not significant survival benefit over non-nephrectomised patients (age and gender adjusted hazard ratio: 0.56 95 % confidence interval: 0.24-1.58, p-value: 0.18). Conclusion: Elective graft resection is a safe, effective alternative for both the treatment and the prevention of the chronic inflammatory state associated with a failed kidney transplant