Administration of intravenous iron formulations induces complement activation in-vivo

Background: Intravenous (IV) iron is widely used to treat anemia in chronic kidney disease patients. Previously, iron formulations were shown to induce immune activation in-vitro. The current study aimed to investigate the effect of IV iron on complement activation in-vivo, and whether this subsequently induces inflammation and/or oxidative stress. Methods: Two distinct patient groups were included: 51 non-dialysis and 32 dialysis patients. The non-dialysis group received iron sucrose or ferric carboxymaltose, based on physicians’ choice. Plasma samples were collected prior to and 1 h after completion of IV iron infusion. The dialysis group received iron sucrose exclusively. Plasma samples were collected at the start and end of two consecutive hemodialysis sessions, one with and one without IV iron. Finally, plasma levels of MBL, C1q, properdin, factor D, sC5b-9, MPO, PTX3 were assessed by ELISA. Results: In the non-dialysis group, sC5b-9 levels significantly increased after IV iron by 32%, while levels of factor D and MBL significantly dropped. Subgroup analysis demonstrated that iron sucrose induced complement activation whereas ferric carboxymaltose did not. In the dialysis group, levels of sC5b-9 significantly increased by 46% during the dialysis session with IV iron, while factor D levels significantly fell. Furthermore, the relative decrease in factor D by IV iron correlated significantly with the relative increase in sC5b-9 by IV iron. MPO levels rose significantly during the dialysis session with IV iron, but not in the session without iron. Moreover, the relative increase in MPO and sC5b-9 by IV iron correlated significantly. PTX3 levels were not affected by IV iron. Conclusions: Iron sucrose but not ferric carboxymaltose, results in complement activation possibly via the lectin and alternative pathway partially mediating oxidative stress but not inflammation.Conflict of Interest Statement: CG received speaking fees and research funding from Vifor Pharma

Dilatation tracheoscopy for laryngeal and tracheal stenosis in patients with Wegener’s granulomatosis

Wegener’s granulomatosis (WG) frequently involves the subglottis and trachea and may compromise the upper airway. The objective of this study is to evaluate retrospectively the effect of treatment of subglottic stenosis (SGS) and tracheal stenosis (TS) by dilatation tracheoscopy (DT) in patients with WG. We performed a cohort study on all patients who underwent DT between February 2001 and September 2005 in our institution. From this cohort we identified a total of nine WG patients. In all patients, clinical, serological and histopathological data had been prospectively collected by a standardized protocol from the time point of diagnosis. In the nine patients that were identified with SGS or TS due to WG (eight women and one man), a total of 22 DT’s were performed. Two patients needed a tracheostoma (one temporarily). The mean follow-up after the first DT was 25.4 ± 14.1 months. Two patients did not experience a recurrence of SGS or TS. Six patients required a second DT without recurrence of local disease. The remaining patient underwent 8 DT's in a 4-year period. DT can offer a simple and repeatable solution to SGS and TS due to WG. Seven of the nine patients required more than one dilatation and some patients experience a functional restriction. One patient has a definitive tracheostoma

Oxalate clearance by haemodialysis - a comparison of seven dialysers

Background. In patients with primary hyperoxaluria (PH) and oliguric end-stage renal disease, oxalate removal is largely dependent on the clearance by dialysis. Data on the oxalate clearance of newer dialyser types are scarce or absent. Therefore, we measured oxalate clearances of seven dialysers in a single 52-year-old female patient with PH. Since haemodiafiltration (HDF) has been advocated to increase oxalate clearance, we also assessed the effect of different predilution flows. The goal of the study was to select the dialyser and pre-dilution flow combination with the highest oxalate clearance. Methods. Oxalate clearances were assessed by simultaneously taking afferent blood and efferent dialysate samples at 30, 60, 120 and 180 min after the start of haernodialysis. Blood flow and dialysate flow were 350 and 500 ml/min, respectively. All dialysers were tested at a pre-dilution flow of 2 I/h. Six dialysers were also tested at either a pre-dilution flow of 4.5 I/h or without HDF, depending on the ultrafiltration coefficient of the dialyser. Results. Oxalate clearances differed markedly between the tested dialysers, ranging from 144 +/- 10 to 220 +/- 12 ml/min. The highest oxalate clearances were achieved with HdF 100S (219 +/- 10 ml/min) and Sureflux FB-2 IOU (220 12 ml/min) at a pre-dilution flow of 2 I/h. Higher pre-dilution flows (2 l/h vs no HDF or 4.5 vs 2.0 l/h) yielded similar oxalate clearances. Conclusion. The highest oxalate clearances were achieved with a high-flux polysulfone and a cellulose triacetate dialyser with a large surface area. Higher pre-dilution flows did not augment oxalate clearance

Renal survival and prognostic factors in patients with PR3-ANCA associated vasculitis with renal involvement

Background. Severe renal disease is a feature of anti-neutrophil cytoplasmic antibodies (ANCA)-associated small-vessel vasculitis. We evaluated patient and renal survival and prognostic factors in patients with PR3-ANCA associated vasculitis with renal involvement at diagnosis during long-term follow-up. Methods. Eighty-five patients were diagnosed between 1982 and 1996 and followed until 2001 allowing greater than or equal to5 years of follow-up. All patients were treated with prednisolone and cyclophosphamide. Univariate and multivariate analyses with patient and renal survival as dependent variables were performed. Results. Of the 85 patients in this study, 17 (20%) died within one year after diagnosis. Of the 25 patients (29%) who were dialysis dependent at diagnosis, two remained dependent and two again became dialysis dependent after less than one year; nine died early without renal recovery. Risk factors for death occurring within one year in univariate analysis (RR, 95% CI) were age >65 years (6.5, 1.6-13.7) and dialysis dependency at diagnosis (3.6, 1.0-13). Twenty patients died beyond one year during the long-term follow-up. Male gender (4.7, 1.6-10) and developing dialysis dependency during follow-up (4.1, 1.4-12) were associated with poor outcome. Risk factor for renal failure within one year was dialysis dependency at diagnosis (29, 3.6-229). Of 64 patients dialysis independent one year after diagnosis, 12 patients became dialysis dependent during follow-up. A renal relapse was strongly associated with development of renal failure in long-term follow-up (17, 3.5-81). Conclusions.Early death and failure to recover renal function in P R3-ANCA associated vasculitis is associated with age >65 years and dialysis dependency at diagnosis. Long-term renal survival is determined by renal relapses during follow-up only. Slow, progressive renal failure without relapses is rarely observed in this group