Patient and graft outcome in current era of immunosuppression: a single centre pilot study.

OBJECTIVES: The present single centre study aims at analyzing the impact on renal allograft outcome of the important changes which occurred in the transplant population and immunosuppressive therapy during the last two decades. METHODS: From 2000 to 2013, 779 single kidney transplantations were performed on 635 patients who all received on an intent-to-treat basis steroids, a calcineurin inhibitor, mycophenolate mofetil and an induction therapy with either antithymocyte globulin or an antagonist directed to the interleukin (IL)-2 receptor. Uni- and multivariate analyses of patient and immunologic graft survival were conducted. RESULTS: The sole factor predicting patient survival is recipient's age: 10-year survival rates are 94·7, 81·6 and 57·9% for the <45, 45-60 and >60 years age groups, respectively (P<0·001). Peak (>50% panel reactive antibodies) anti-human leucocyte antigens (HLA) sensitization, cold ischaemia time and HLA-B and -DR mismatches (MM) influence graft outcome: at 10 years, the difference in 10-year survival rates is 5·9% between grafts from sensitized and not sensitized patients (90·9 vs 96·8%, P = 0·002), 3·8% between grafts with <18 and ≧18 hours cold ischaemia (96·6 vs 92·8%, P = 0·003), 7·3% between grafts with no MM and either B or DR MM versus those with B and DR MM (96·8 vs 89·5%, P = 0·002). CONCLUSION: In our single centre experience, graft survival was most strongly determined by HLA matching, offering excellent long term graft outcome to most patients.

ANCA-negative associated vasculitis initially presenting with pulmonary embolism.

Antineutrophil-cytoplasm antibodies (ANCA)-associated vasculitis are severe inflammatory pathologies that, although rare, may induce significant morbidity or death. Their impact on multiple organ systems implies an important variability in their clinical presentation, which might delay the diagnosis. In this setting we report on a case of ANCA-negative-associated vasculitis, initially presenting as pulmonary embolism with severe pulmonary infarction and digestive involvement. Literature is then discussed on these complications and their implications for therapy.

[Thrombocytopenia and acute kidney injury]. / Thrombopénie et insuffisance rénale aiguë.

A 31-year old man is addressed to the emergency department for fever, abdominal pain and vomiting. Laboratory tests reveal an inflammatory syndrome, thrombocytopenia, acute kidney injury associated with major proteinuria (more than 3 g/24 h). Evaluation will conclude to an acute interstitial nephritis and the serology is positive for Hantavirus. This clinical case illustrates differential diagnosis of acute renal failure and reminds the theory of hemorrhagic fever with renal syndrome : usual clinical presentation is "flu"-like symptoms, thrombocytopenia and acute renal failure. Hantavirus is endemic in some area in Europe and in Belgium. This clinical presentation should suggest the diagnosis if the patient has stayed in an endemic area.

[Experience about more than 2000 renal transplantations at the university of Brussels]. / A propos de 2000 greffes rénales a l'U.L.B.: le parcours d'un patient transplanté rénal en 2007.

Since 1965, more than 2000 renal transplantations (including more than 100 living-donor transplantations) have been performed at the University of Brussels. An end-stage renal disease patient candidate to renal transplantation will be therefore followed from his enrolment on the waiting list to the long-term post-transplant period. Improvement in the outcome of renal transplantation is achieved due to better knowledge in many fields of medicine, such as immunology, infectious disease, metabolic diseases (hyperlipemia, diabetes mellitus), pharmacology, use of immunosuppressive regimen, a more adequate cardiovascular prevention and treatment. If the best results were achieved with kidneys from living donors, the graft survival rate at the University of Brussels was nearly 80% for the last period (2000-2006). Unfortunately, renal transplantation cannot cure certain comorbid conditions and even may promote them: infectious diseases, neoplasia, metabolic disorders (e.a diabetes mellitus, hyperlipemia). Many efforts have to be done to develop less toxic and more immune selective therapeutic strategies. Living donation and extension of the pool of cadaveric donors will reduce the length of time spent on the waiting list and will significantly impact on mortality and morbidity after kidney transplantation.

Effects of ultrapure and non-sterile dialysate on the inflammatory response during in vitro hemodialysis.

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.

Adhesion molecules and leukocyte common antigen on monocytes and granulocytes during hemodialysis.

As contact of blood with artificial membranes may activate cell adhesiveness, we investigated in 5 patients the expression of several adhesion-promoting molecules on monocytes and granulocytes during hemodialysis on cuprophane (CU), cellulose acetate (CA), and polyacrylonitrile (PAN) membranes. After staining with specific fluorescent monoclonal antibodies, flow cytometric analysis was performed to evaluate the expression of CD11b (= Mac 1, CR3, or C3bi receptor), CD11a (= leukocyte function antigen 1 or LFA-1, or gp 180/95), CD54 (= intercellular adhesion molecule 1 or ICAM 1), and CD45 (= leukocyte common antigen) on circulating leukocytes. Granulocytopenia occurred at 15 minutes with CU and CA but not with PAN; significant monocytopenia occurred on the contrary with all 3 membranes. The drop in monocyte counts was maximal at 15 minutes on CU and CA, and at 180 minutes on PAN; it was also more important with CU (88 +/- 2.6%, alpha = 0.005) and CA (66.4 +/- 4.1%, alpha = 0.01) than with PAN (36.2 +/- 6.2%). Hemodialysis on CU, CA, and PAN was associated with a 2- to 3-fold CD11b and CD45 overexpression on peripheral monocytes; these molecules also increased on circulating granulocytes but to a lesser extent on PAN than on CU and CA (alpha < 0.05). There were no hemodialysis-induced changes in CD11a and CD54 expression on circulating monocytes or granulocytes. The upregulation of CD11b may provide a molecular mechanism for the sequestration of monocytes and granulocytes in the circulation during hemodialysis, while upregulation of CD45 might reflect mechanisms regulating the leukocyte activation state.(ABSTRACT TRUNCATED AT 250 WORDS)

Anaphylactoid reactions during hemodialysis on AN69 membranes in patients receiving ACE inhibitors.

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.

Potentiation of the effects of enoximone by a dobutamine infusion.

Enoximone is a new inotropic agent, which acts by the inhibition of the type III phosphodiesterase (PDE) enzyme. The present report describes a 81-year-old female patient with severe heart failure following aortic valve replacement. Her cardiac activity was paced. The addition of enoximone (two doses of 0.5 mg/kg) to an intravenous infusion of dobutamine (8 mcg/kg/min) and sodium nitroprusside significantly increased cardiac output (CO) from 3.2 to 3.9 l/min and decreased pulmonary artery occlusive pressure (PAOP) from 22 to 16 mmHg. Another dose of enoximone 12 h later had similar effects. However, another 12 h later, after dobutamine had been discontinued, two successive injections of 0.5 mg/kg of enoximone were totally ineffective (CO from 2.6 to 2.5 l/min, PAOP 23 mmHg). When the dobutamine infusion was restarted (at 8 mcg/kg/min), the positive effects of 0.5 mg/kg of enoximone were again present (CO from 3.0 to 3.6 l/min, PAOP from 19 to 14 mmHg). This observation underscores the therapeutic value of the combination of PDE inhibitors such as enoximone with adrenergic agents such as dobutamine in the management of severe heart failure.