We report five life-threatening anaphylactoid reactions occurring within the very first minutes of hemodialysis on polyacrylonitrile (AN69) capillary dialyzers in three patients receiving ACE inhibitors. Such reactions were not observed either in patients treated with ACE inhibitors but dialyzed on other membranes (N = 9), nor in patients on AN69 who did not receive ACE inhibitors (N = 19). These anaphylactoid reactions could be due to bradykinin accumulation, as a result of both increased synthesis--by interaction of blood with the AN69 polymer--and catabolism blockade by ACE inhibitors.

Over the past several years, considerable evidence has been obtained in support of the hypothesis that oxidants generated by the heme enzyme myeloperoxidase (MPO, EC1.11.2.2) play a key role in oxidation reaction of the artery wall. The enzyme, abundantly present in neutrophils and, to a lesser extent, in monocytes, is released during infl ammatory activation of immune cells. MPO produces hypochlorous acid (HOCl) by the reaction of hydrogen Abstract Oxidation of LDL by the myeloperoxidase (MPO)-H 2 O 2 -chloride system is a key event in the development of atherosclerosis. The present study aimed at investigating the interaction of MPO with native and modifi ed LDL and at revealing posttranslational modifi cations on apoB-100 (the unique apolipoprotein of LDL) in vitro and in vivo. Using amperometry, we demonstrate that MPO activity increases up to 90% when it is adsorbed at the surface of LDL. This phenomenon is apparently refl ected by local structural changes in MPO observed by circular dichroism. Using MS, we further analyzed in vitro modifi cations of apoB-100 by hypochlorous acid (HOCl) generated by the MPO-H 2 O 2 -chloride system or added as a reagent. A total of 97 peptides containing modifi ed residues could be identifi ed. Furthermore, differences were observed between LDL oxidized by reagent HOCl or HOCl generated by the MPO-H 2 O 2 -chloride system. Finally, LDL was isolated from patients with high cardiovascular risk to confi rm that our in vitro fi ndings are also relevant in vivo. We show that several HOCl-mediated modifi cations of apoB-100 identifi ed in vitro were also present on LDL isolated from patients who have increased levels of plasma MPO and MPO-modifi ed LDL. In conclusion, these data emphasize the specifi city of MPO to oxidize LDL. -Delporte,

Several studies support the hypothesis that bacterial contamination of the dialysate stimulates the inflammatory response to hemodialysis (HD) and increases the long-term morbidity of HD patients; this phenomenon could also be modulated by the nature of the HD membrane. Therefore, this study was designed to compare the effects of non-sterile (NSBD, mean endotoxin content +/- SEM 97 +/- 22 EU/ml) and ultrapure bicarbonate dialysate (UPBD, sterile and pyrogen-free, obtained by ultrafiltration through polyamide) on several aspects of the inflammatory reaction during in vitro HD. The HD sessions (7 in each experimental group) were performed using miniaturized new cuprophane (CU) and polyacrylonitrile (PAN) hollow fiber dialyzers, and closed dialysate and blood circuits (the latter filled with heparinized blood from healthy donors). Plasma C3aDesarg levels were significantly increased after 15 minutes (t1) and increased further after three hours (t2) of CU HD, while during PAN dialysis they decreased from t0 to t1 and t2; however, no difference appeared between experiments with NSBD and UPBD. Granulocyte (PMN) and monocyte (MNC) expression of LFA-1, Mac-1, and CD45 at the start (t0), t1 and t2 was quantitated by flow cytometry analysis, after staining of the cells with specific fluorescinated monoclonal antibodies. In contrast with published data of in vivo HD, LFA-1 was overexpressed at t1 and peaked at t2, which suggests that the leukocytes expressing more LFA-1 leave the systemic circulation during in vivo HD. During CU HD, Mac-1 and CD45 on PMN and MNC were significantly increased at t1, and still more at t2. During PAN HD, Mac-1 and CD45 remained unchanged at t1, but increased significantly at t2 on PMN as on MNC. Again, no significant difference was found between NSBD and UPBD in LFA-1, Mac-1 and CD45 expression on PMN and MNC, during both CU and PAN HD. AFter three hours of dialysis, plasma levels of TNF-alpha, but not of IL-6, were significantly increased with CU and PAN. Again, no difference appeared when NSBD and UPBD were compared. Moreover, the lack of influence of bacterial contamination of the dialysate on TNF-alpha production was confirmed when MNC were cultured up to 24 hours after the end of the HD session. We conclude that complement activation products, either in plasma (CU) of those adsorbed on the HD membrane (CU and PAN) play the major role in the overexpression of beta 2-integrins and CD45 by PMN and MNC during HD. Also, bacterial products (at the levels that can be found in clinical conditions) do not influence either beta 2-integrin overexpression or TNF-alpha production induced by the dialysis membrane.

Contrary to the manufacturer instructions, we found a significant decrease in tacrolimus exposure after switching to Advagraf. Therefore, the switch from Prograf to Advagraf should be performed under close medical supervision.

Screening for and treating asymptomatic bacteriuria are common in KTRs despite uncertainties around the benefits and harms. In an era of antimicrobial resistance, further studies are needed to address the diagnosis and management of asymptomatic bacteriuria in these patients.