General prognostic models may neglect vulnerable subgroups in ANCA-associated vasculitis.

BACKGROUND: ANCA-associated vasculitis is an organ and life-threatening disease with the highest incidence in elderly patients. However, few studies have focussed on characteristics and treatment outcomes in a direct comparison of elderly and younger patients. METHODS: In a retrospective, single-centre, renal biopsy-cohort, patients were dichotomized by age ≥ 65 years to analyse baseline clinical, histological, laboratory and immunological characteristics and outcome differences in elderly and younger patients as regard to mortality, renal recovery from dialysis and eGFR after two years. RESULTS: In the biopsy registry, n = 774 patients were identified, of whom 268 were ≥ 65 years old. Among them, ANCA-associated vasculitis was the most prevalent kidney disease (n = 54 ≈ 20%). After a follow-up of 2 years, overall mortality was 13.4%, with 19% and 4% in patients ≥ and < 65 years of age, respectively. While 41% of elderly and 25% of younger patients were dialysis-dependent at the time of biopsy, renal recovery was achieved in 41% and 57% of patients, respectively. The accuracy of prediction differed significantly between the whole cohort and elderly patients as regard to mortality (sensitivity 46% vs. 90%, respectively) and between younger and elderly patients as regard to eGFR (r2 = 0.7 vs. 0.46, respectively). Age-group-wise analysis revealed patients above 80 years of age to have particularly dismal renal outcome and survival. CONCLUSION: In our cohort, ANCA-associated vasculitis is the single most frequent histopathological diagnosis among the elderly patients in our cohort. Elderly and younger patients have comparable chances of recovering from dialysis-dependent renal failure, with comparable residual independent kidney function after two years. This study suggests (1) relevant predictors differ between age groups and hence (2) models involving all patients with ANCA-associated vasculitis neglect important features of vulnerable subgroups, i.e., patients above 80 years old.

Efficacy of Double Membrane Filtration Immunoadsorption in Severe C1q-Binding Donor-Specific Antibody-Positive Acute Humoral Kidney Allograft Rejection: A Case Series.

INTRODUCTION: Acute antibody-mediated rejection (ABMR) is an important threat to renal allograft survival in the early transplant period and the major single cause of graft loss in the first postoperative year. Semi-selective immunoadsorption (IA) remains one of the commonly applied treatments in ABMR, reducing allo-reactive antibody load. Adding double filtration plasmapheresis (DFPP) to IA might enhance therapeutic efficacy by also addressing innate humoral effectors like complement factors. METHODS: Four patients with ABMR were treated with DFPP + IA. Clinical, histological, and immunological data and adverse events were retrospectively collected. RESULTS: Here we present four high-risk treatment-refractory ABMR cases with C1q-binding donor-specific antibodies and histology of humoral rejection under treatment with DFPP + IA. While the earlier cases (within the first year after transplantation) showed marked reduction in ABMR severity and improvement of kidney function, the later cases did not respond accordingly. Late ABMR patient 1 stabilized, whereas late ABMR patient 2 did not respond to treatment. CONCLUSIONS: Our data support the consideration of DFPP + IA as a rescue treatment option in early, severe, high-risk ABMR cases in which other treatments failed.

Phenprocoumon based anticoagulation is an underestimated factor in the pathogenesis of calciphylaxis.

BACKGROUND: Calciphylaxis is a life threatening complication in renal patients. Of great importance is the identification of concomitant factors for calciphylaxis. Due to the variability of clinical presentation the evaluation of such factors may be obscured when calciphylaxis diagnosis is based just on clinical features. We aimed to characterize associated factors only in patients with calciphylaxis proven by histomorphological parameters in addition to clinical presentation. METHODS: In a single center retrospective study we analyzed 15 patients in an 8 year period from 2008 to 2016. Only patients with clinical features and histomorphological proof of calciphylaxis were included. Criteria for histological diagnosis of calciphylaxis were intimal hyperplasia, micro thrombi or von Kossa stain positive media calcification. RESULTS: The mean age of patients was 64.8 years. Nine patients (60%) were female; 12 (80%) were obese with a Body-Mass-Index (BMI) > 30 kg/m2; 3 (20%) had no renal disease; 12 (80%) had CKD 4 or 5 and 10 (66.7%) had end-stage renal disease (ESRD). One-year mortality in the entire cohort was 73.3%. With respect to medication history, the majority of patients (n = 13 (86.7%)) received vitamin K antagonists (VKA); 10 (66.7%) were treated with vitamin D; 6 (40%) had oral calcium supplementation; 5 (33.3%) had been treated with corticosteroids; 12 (80%) were on proton pump inhibitors (PPI); 13 (86.7%) patients had a clinical proven hyperparathyroidism. Ten (66.7%) patients presented with hypoalbuminemia at diagnosis. CONCLUSIONS: The evaluation of biopsy proven calciphylaxis demonstrates that especially treatment with vitamin K antagonists and liver dysfunction are most important concomitant factors in development of calciphylaxis. As progression and development of calciphylaxis are chronic rather than acute processes, early use of DOACs instead of VKA might be beneficial and reduce the incidence of calciphylaxis.

Real-life effectiveness of canakinumab in cryopyrin-associated periodic syndrome.

OBJECTIVE: Cryopyrin-associated periodic syndrome (CAPS) is a heterogeneous group of diseases characterized by excessive IL-1ß release resulting in severe systemic and organ inflammation. Canakinumab targets IL-1ß and is approved at standard dose for children and adults with all CAPS phenotypes. Limited data are available for the real-life effectiveness of canakinumab in patients living with CAPS. Therefore the aim of the study was to evaluate the real-life dosing and effectiveness of canakinumab in CAPS. METHODS: A multi-centre study of consecutive children and adults with CAPS treated with canakinumab was performed. Demographics, CAPS phenotype and disease activity, inflammatory markers and canakinumab treatment strategy were recorded. Treatment response was assessed using CAPS disease activity scores, CRP and/or serum amyloid A levels. Comparisons between age groups, CAPS phenotypes and centres were conducted. RESULTS: A total of 68 CAPS patients at nine centres were included. All CAPS phenotypes were represented. Thirty-seven (54%) patients were females, the median age was 25 years and 27 (40%) were children, and the median follow-up was 28 months. Overall, complete response (CR) was seen in 72% of CAPS patients, significantly less often in severe (14%) than in mild CAPS phenotypes (79%). Only 53% attained CR on standard dose canakinumab. Dose increase was more commonly required in children (56%) than in adults (22%). Centres with a treat-to-target approach had significantly higher CR rates (94 vs 50%). CONCLUSION: Real-life effectiveness of canakinumab in CAPS was significantly lower than in controlled trials. Treat-to-target strategies may improve the outcome of children and adults living with CAPS.