Alternative C activation is involved in the pathogenesis of ANCA-associated vasculitis. However, glucocorticoids used as treatment contribute to the morbidity and mortality of vasculitis. We determined whether avacopan (CCX168), an orally administered, selective C5a receptor inhibitor, could replace oral glucocorticoids without compromising efficacy. In this randomized, placebo-controlled trial, adults with newly diagnosed or relapsing vasculitis received placebo plus prednisone starting at 60 mg daily (control group), avacopan (30 mg, twice daily) plus reduced-dose prednisone (20 mg daily), or avacopan (30 mg, twice daily) without prednisone. All patients received cyclophosphamide or rituximab. The primary efficacy measure was the proportion of patients achieving a ≥50% reduction in Birmingham Vasculitis Activity Score by week 12 and no worsening in any body system. We enrolled 67 patients, 23 in the control and 22 in each of the avacopan groups. Clinical response at week 12 was achieved in 14 of 20 (70.0%) control patients, 19 of 22 (86.4%) patients in the avacopan plus reduced-dose prednisone group (difference from control 16.4%; two-sided 90% confidence limit, -4.3% to 37.1%; =0.002 for noninferiority), and 17 of 21 (81.0%) patients in the avacopan without prednisone group (difference from control 11.0%; two-sided 90% confidence limit, -11.0% to 32.9%;=0.01 for noninferiority). Adverse events occurred in 21 of 23 (91%) control patients, 19 of 22 (86%) patients in the avacopan plus reduced-dose prednisone group, and 21 of 22 (96%) patients in the avacopan without prednisone group. In conclusion, C5a receptor inhibition with avacopan was effective in replacing high-dose glucocorticoids in treating vasculitis.

Summary Dysregulations concerning the composition and function of regulatory T cells (Tregs-Tregs. The suppressive activity of the total Treg cell pool was diminished in both patient collectives. Hence, our findings propose that pre-eclampsia and PL are characterized by homeostatic changes in the composition of the total Treg pool with distinct Treg subsets that were accompanied by a significant decrease of its suppressive activity.

Background and objectives Patients receiving hemodialysis are at high risk for both SARS-CoV-2 infection and severe COVID-19 disease. A life-saving vaccine is available, but sensitivity to vaccines is generally lower in dialysis patients. Little is yet known about antibody responses after COVID-19 vaccination in this vulnerable group. Design, setting, participants, and measurements In this prospective single-center study, we included 22 dialysis patients and 46 healthy controls from Heidelberg University Hospital between December 2020 and February 2021. We measured anti-S1 IgG with a threshold index for detection >1, neutralizing antibodies with a threshold for viral neutralization of ≥30% and antibodies against different SARS-CoV-2 fragments 17-22 days after the first and 18-22 days after the second dose of the mRNA vaccine BNT162b2. Results After the first vaccine dose, 4/22 (18%) dialysis patients compared with 43/46 (93%) healthy controls developed positive anti-S1 IgG, with a median (IQR) anti-S1 IgG index of 0.2 (0.1-0.7) compared with 9 (4-16), respectively. SARS-CoV-2 neutralizing antibodies exceeded the threshold for neutralization in 4/22 (18%) dialysis patients compared with 43/46 (93%) in healthy controls, with a median (IQR) percent inhibition of 11 (3-24) compared with 65 (49-75), respectively. After the second dose, 14/17 (82%) of dialysis patients developed neutralizing antibodies exceeding the threshold for viral neutralization and antibodies against the receptor-binding S1-domain of the spike protein, compared to 46/46 (100%) of healthy controls, respectively. The median (IQR) percent inhibition was 51 (32-86) compared to 98 (97-98) in healthy controls. Conclusions Patients receiving long-term hemodialysis show a reduced antibody response to the first and second doses of the mRNA vaccine BNT162b2. The majority (82%) develop neutralizing antibodies after the second dose, but at lower levels than healthy controls.

IntroductionAcute kidney injury (AKI) is associated with a high mortality of up to 60%. The mode of renal replacement therapy (intermittent versus continuous) has no impact on patient survival. Sustained low efficiency dialysis using a single-pass batch dialysis system (SLED-BD) has recently been introduced for the treatment of dialysis-dependent AKI. To date, however, only limited evidence is available in the comparison of SLED-BD versus continuous veno-venous hemofiltration (CVVH) in intensive care unit (ICU) patients with AKI.MethodsProspective, randomized, interventional, clinical study at a surgical intensive care unit of a university hospital. Between 1 April 2006 and 31 January 2009, 232 AKI patients who underwent renal replacement therapy (RRT) were randomized in the study. Follow-up was assessed until 30 August 2009. Patients were either assigned to 12-h SLED-BD or to 24-h predilutional CVVH. Both therapies were performed at a blood flow of 100 to 120 ml/min.Results115 patients were treated with SLED-BD (total number of treatments n = 817) and 117 patients with CVVH (total number of treatments n = 877).The primary outcome measure, 90-day mortality, was similar between groups (SLED: 49.6% vs. CVVH: 55.6%, P = 0.43). Hemodynamic stability did not differ between SLED-BD and CVVH, whereas patients in the SLED-BD group had significantly fewer days of mechanical ventilation (17.7 ± 19.4 vs. 20.9 ± 19.8, P = 0.047) and fewer days in the ICU (19.6 ± 20.1 vs. 23.7 ± 21.9, P = 0.04). Patients treated with SLED needed fewer blood transfusions (1,375 ± 2,573 ml vs. 1,976 ± 3,316 ml, P = 0.02) and had a substantial reduction in nursing time spent for renal replacement therapy (P < 0.001) resulting in lower costs.ConclusionsSLED-BD was associated with reduced nursing time and lower costs compared to CVVH at similar outcomes. In the light of limited health care resources, SLED-BD offers an attractive alternative for the treatment of AKI in ICU patients.Trial registrationClinicalTrials.gov NCT00322530