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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PLOS ONE / Survival analysis of conservative vs. dialysis treatment of elderly patients with CKD stage 5

Elderly patients represent a growing population among people suffering from ESRD. So far only limited data on actual survival benefits of elderly adults initiating dialysis have been published. Besides the high burden of preexisting comorbidities, dialysis treatment itself may be associated with a further deterioration in functional status in this population. We retrospectively analyzed the Austrian Dialysis and Transplant Registry and identified 8,622 patients who started maintenance hemodialysis after the age of 65 years between 2002 and 2009. We compared this data set to a cohort of 174 patients aged over 65 years with CKD stage 5 who progressed to an eGFR < 10ml/min/ and were managed conservatively in the same era. All patients who died of malignant disease were excluded from this analysis. The risk of mortality was analyzed using multivariable Cox proportional hazards models. Furthermore, a parametric model of time to event analysis was used for visualization of changing risk over time and precise calculation of time to equal risk assuming a Weibull distribution. Hemodialysis treatment was associated with a decreased risk for death with a HR of 0.23 (95% CI 0.18 to 0.29; p<0.001) compared to conservative treatment. The time to event analysis however showed, that although survival was initially superior in the hemodialysis group, hazards crossed thereafter. Time to equal risk was 2.9 months and 1.9 months for female and male patient aged 65, respectively, and decreased to one month in the very elderly aged 95. Elderly patients with ERSD did benefit from initiation of hemodialysis, as the conservative group showed a very high initial mortality rate. This survival benefit of dialysis treatment however did not persist beyond the first two months compared to survivors of the conservative group.(VLID)487411

Months to equal risk compared between dialysis treatment and conservative management.

<p>Months to equal risk compared between dialysis treatment and conservative management.</p

Hazard ratios (HR) and confidence intervals (CI) for death based on the multivariable Cox proportional hazards model.

<p>Hazard ratios (HR) and confidence intervals (CI) for death based on the multivariable Cox proportional hazards model.</p

Demographics.

<p>Values are presented as mean (standard deviation) or as percentage.</p

Months to equal risk compared between dialysis treatment and conservative management.

<p>Months to equal risk compared between dialysis treatment and conservative management.</p

Patient survival stratified by dialysis treatment (HD) vs. conservative management (N) including 95% equal precisions bands.

<p>Patient survival stratified by dialysis treatment (HD) vs. conservative management (N) including 95% equal precisions bands.</p

Survival probability modeled by Weibull distribution and stratified by treatment.

<p>Dialysis treatment vs. conservative management for a female patient aged 70 years. <i>E</i> marks the time to equal risk (the slopes of the two survival curves are the same).</p