β₂-Microglobulin-associated amyloidosis has emerged as a major complication of long-term renal replacement therapy. The syndrome is confined to those patients on nontransplant modes of therapy. It does not occur in patients with a functioning renal transplant or, if already present, it does not progress any further in such patients. In the population of ESRD patients on dialysis, β₂-microglobulin-associated amyloidosis affects most patients treated for more than 15 years and is a cause of significant morbidity and in rare cases even mortality. The present review, which is based on the presentation of a typical case, discusses the current knowledge on the pathogenesis, clinical manifestations, diagnosis, prevention and therapy of β_2-microblobulin-associated amyloidosis.

Background Dialyzers shall be designed to efficiently eliminate uremic toxins during a dialysis treatment, given that the accumulation of small and middle molecular weight uremic solutes is associated with increased mortality risk of patients with end-stage renal disease. In the present study we investigated the novel FX CorAL dialyzer with a modified membrane surface for the performance during online-hemodiafiltration in a clinical setting. Methods comPERFORM was a prospective, open, controlled, multi-centric, interventional, cross-over study with randomized treatment sequences. It randomized stable patients receiving regular post-dilution online hemodiafiltration (HDF) to FX CorAL 600 (Fresenius Medical Care Deutschland GmbH), xevonta Hi 15 (B. Braun), and ELISIO 150H (Nipro), each for one week. The primary outcome was β2-microglobulin removal rate (ß2-m RR) during online-HDF. Secondary endpoints were RR and/or clearance of ß2-m and other molecules. Albumin removal over time was an exploratory endpoint. Non-inferiority and superiority of FX CorAL 600 vs. competitors were tested. Results 52 patients were included and analyzed. FX CorAL 600 showed the highest ß2-m RR (75.47%), followed by xevonta Hi 15 (74.01%) and ELISIO 150H (72.70%). Superiority to its competitors was statistically significant (P = 0.0216 and P < 0.0001, respectively). Secondary endpoints related to middle molecules affirmed these results. FX CorAL 600 demonstrated the lowest albumin removal up to 60 min, and its sieving properties changed less over time than with competitors. Conclusions FX CorAL 600 efficiently removed middle and small molecules and was superior to the two comparators in ß2-m RR. Albumin sieving kinetics point to a reduced formation of a secondary membrane.

Background: High-flux dialyzers shall effectively remove uremic toxins and be hemocompatible to minimize intradialytic humoral and cellular stimulation and long-term impact on patient outcomes. A new dialyzer with a modified membrane surface has been tested for performance and hemocompatibility. Methods: This multicenter, prospective, randomized, cross-over study applied for one week each the new polysulfone-based FX CorAL 600 (Fresenius Medical Care, Bad Homburg, Germany), the polyarylethersulfone-based Polyflux 170H (Baxter Healthcare Corporation, Deerfield, IL, USA) and the cellulose-triacetate-based SureFluxTM 17UX (Nipro Medical Europe, Mechelen, Belgium) to assess non-inferiority of removal rate of β2-microglobulin of the FX CorAL 600. Performance was assessed by removal rate and clearance of small and middle molecules. Hemocompatibility was assessed through markers of complement, cell activation, contact activation and coagulation. Results: Of 70 patients, 58 comprised the intention-to-treat population. The removal rate of β2-microglobulin of the FX CorAL 600 was non-inferior to both comparators (P<0.0001 vs SureFluxTM 17UX; P=0.0006 vs Polyflux 170H), and superior to SureFluxTM 17UX. The activation of C3a and C5a with FX CorAL 600 was significantly lower 15 min after treatment start than with SureFluxTM 17UX. The activation of sC5b-9 with FX CorAL 600 was significantly lower over the whole treatment than with SureFluxTM 17UX, and lower after 60 min than with Polyflux 170H. The treatments with FX CorAL 600 were well tolerated. Conclusions: FX CorAL 600 efficiently removed small and middle molecules, showed a favorable hemocompatibility profile and was associated with a low frequency of adverse events in the present study with a limited patient number and follow-up time. Further studies with longer observation times are warranted to provide further evidence supporting the use of the new dialyzer in a wide range of therapeutic options and long-term treatments of hemodialysis patients to minimize the potential impact on inflammatory processes.

In patients on continuous ambulant peritoneal dialysis (CAPD) treatment, the peritoneal membrane is continuously exposed to the high glucose concentration contained in the dialysate. This may lead to the local generation of advanced glycation end-products (AGEs). To test this hypothesis we evaluated the plasma and dialysate AGE concentrations in five CAPD patients. The dialysate was measured after a 1 h and after a 12 h dwell time. Additionally, in two patients an immunohistochemical investigation of the peritoneal membrane for AGE was performed. For the determination of AGE an ELISA using a polyclonal antibody against AGE bovine serum albumin was used; the immunohistochemical staining was performed using the streptavidin-biotin complex method. We found only low concentrations of AGE in the dialysate after a 1 h dwell time; after 12 h, however, the dialysate AGE was even greater than the plasma concentration. In both peritoneal specimens we found positive staining for AGE in the interstitium of the mesothelial layer. The dialysate AGE contained a high proportion of high-molecular-weight AGE proteins and low-molecular-weight AGE was found to be in the same concentration range as the total serum AGE. We conclude that there is local generation of AGE in the peritoneal membrane and a 'washing out' of AGE from the peritoneal membrane during longer dwell times. We speculate that the accumulation of AGE might lead to some of the functional and morphological alterations observed after long-term CAPD.

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