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Since dialysis withdrawal in maintenance dialysis patients with limited life expectancy results always in short-term death, nephrologists need a referenced process to make their decision. This study reviews 8 years of operation of an Ethics Committee in Nephrology (ECN). The ECN, within a multidisciplinary team, once a month explores cases reported by caregivers when maintaining dialysis seems not to be in the patient's best interest. Discussion is required when the vital prognosis is engaged by the evolution of the chronic kidney disease (CKD) or the occurrence of an acute medical event. Data are analyzed using a discussion guide. The informed decision is completed with an appropriated palliative care project involving the patient, and recorded in their file. Since 2006, the ECN has deliberated yearly for 10 sessions on 6-18 cases, concerning 380 identified maintenance dialysis patients. Characteristics of the population, cases, sessions and proposals are recorded and analyzed. The only variable associated with dialysis withdrawal was having at least one new comorbid condition. End of life is supported with the help of the palliative care team in the hospital or exceptionally at home. The ECN, through a multidisciplinary deliberation and resolution process, proposes an ethical shared-decision-making model ensuring that dialysis withdrawal follows professional guidelines, and is registered as a method for evaluating professional practice (EPP). Annual activity reports are submitted to the Hospital's Medical Evaluation and Quality Unit. Benefits are individual and collective for patients, relatives and caregivers. Prospects for reducing non-implemented decisions and identifying cases earlier would improve the Committee effectiveness., (© 2015 The Authors. Therapeutic Apheresis and Dialysis © 2015 International Society for Apheresis.)

Background: Corticosteroid-free maintenance immunosuppression after organ transplantation eliminates the well-known corticosteroid-related side effects and may help to improve long-term outcome. We investigated whether a corticosteroid-free tacrolimus (Tac)/mycophenolate mofetil (MMF) regimen, in combination with daclizumab (Dac) induction therapy, provides adequate immunosuppression after renal transplantation., Methods: This 6-month, open-label, multicenter, parallel-group study involved 538 renal patients randomized (1:1) to a Dac/Tac/MMF regimen (n = 260) or a Tac/MMF/corticosteroids regimen (n = 278) as a control group., Results: Of the patients who completed the study, 88.8% in the Dac/Tac/MMF group were free from corticosteroid therapy at month 6. The incidence of biopsy-proven acute rejection was 16.5% in both treatment groups; the incidence of biopsy-proven corticosteroid-resistant acute rejection was 4.3% and 5.0% with Tac/MMF/corticosteroids and Dac/Tac/MMF, respectively (P = NS for both comparisons). Renal function was also similar in both groups: median serum creatinine at month 6 was 125.0 micromol/L (Tac/MMF/corticosteroids) and 131.0 microml/L (Dac/Tac/MMF), P = 0.277. The overall safety profile was similar with both regimens. However, compared with the Tac/MMF/steroid regimen, a significantly reduced incidence of new-onset insulin-dependent diabetes mellitus (5.4% vs. 0.4%, P = 0.003) was found with steroid-free immunosuppression. Moreover, mean total cholesterol concentrations increased from baseline in the Tac/MMF/corticosteroids group by 0.19 mmol/L, whereas in the Dac/Tac/MMF group, levels decreased by 0.19 mmol/L, P = 0.005., Conclusions: Corticosteroid-free immunosuppression with a Dac/Tac/MMF regimen is as effective at preventing acute rejection after renal transplantation as a standard triple regimen of Tac/MMF/corticosteroids. Furthermore, the safety benefits reported with Dac/Tac/MMF treatment may help improve the long-term outcome for renal-transplant patients.

Background: Studies in the USA have shown that some patients (African-Americans, women, the elderly and diabetics) were less likely to receive renal transplants. In order to identify patient characteristics modifying the likelihood of being wait-listed, we studied registration on renal transplantation waiting list (WLR) focusing on elderly (age > or =60 years) and on patients with type 2 diabetes (D2) in three departments of nephrology in the Rhône-Alpes county in France., Methods: In a cohort of 549 patients who reached end-stage renal disease (ESRD) between 1995 and 1998 in these units, we analysed the rates of pre-transplant evaluation (PTE), the duration of PTE, the rates of exclusion from transplantation by PTE and the rates of WLR. With Cox regression model, we identified the characteristics that have independent and significant effects on the likelihood of being registered after the first renal replacement therapy (RRT)., Results: In this cohort, 185 patients (33.7%) were wait-listed by 31.03.00 and no patient > or =70 years was evaluated or registered. In univariate analysis, PTE and WLR rates were lower in the elderly (21.5 and 20.0%, respectively) than those <60 years (79.1 and 70.2%, P < 0.001) and in D2 (33.0 and 24.2%) than in non-D2 (65.8 and 60.6%, P < 0.001). The duration of PTE was longer in D2 than in non-D2 (12.7 +/- 11.0 vs 7.5 +/- 7.1 months, P < 0.01). Among patients excluded from PTE, more patients without relevant co-morbidities [e.g. rapidly progressive ESRD, cardiovascular disease (CVD), malignancy] were present in the elderly (> or =70 years: 14.8%; 60-69 years: 17.0%; <60 years: 6.4%) and in D2 (18.0%) than in non-D2 (10.9%). The adjusted relative risks (aRR) of being wait-listed after first RRT were significantly lowered by age and D2 (aRR, 95% CI): 60-64 year olds (0.44%: 0.26-0.75), 65-69 year olds (0.07%: 0.03-0.20) and D2 (0.41%: 0.24-0.69). Other conditions associated with a lower aRR were rapidly progressive ESRD (0.21%: 0.08-0.55), CVD (0.59%: 0.36-0.94), malignancy (0.13%: 0.04-0.46) and psychosis (0.05%: 0.01-0.35)., Conclusion: Advanced age and D2 were associated with low PTE and WLR rates even after adjustment for other patient characteristics.

Background: Induction therapy with antithymocyte globulin (ATG) reduces the incidence of acute rejection after transplantation. A study was undertaken to assess the efficacy and safety of ATG induction on tacrolimus-based and cyclosporine A (CsA)-based therapies compared with immediate tacrolimus triple therapy in kidney transplant recipients., Methods: In a 6-month, open-label, randomized, prospective study conducted in 30 European centers, 555 renal transplant patients were randomly assigned to tacrolimus triple therapy (Tac triple, n=185), ATG induction with tacrolimus (ATG-Tac, n=186), or ATG induction with CsA microemulsion (ATG-CsA, n=184); all were combined with azathioprine and corticosteroids. The primary endpoint was incidence and time to first acute rejection episode confirmed by biopsy., Results: Patient demographics and clinical parameters at baseline were similar. Patient and graft survival rates were similar in all groups. The incidence of clinically apparent acute rejection was significantly higher (P=0.003) for Tac triple (33.0%) compared with ATG-Tac (22.6%) and the incidence for ATG-Tac was significantly lower (P=0.004) than for ATG-CsA (37.0%). The incidences of acute rejection confirmed by biopsy (primary endpoint) were 25.4%, 15.1%, and 21.2% for Tac triple, ATG-Tac, and ATG-CsA, respectively (Tac triple vs. ATG-Tac, P=0.004). The incidences of corticosteroid-resistant acute rejection were 7.0% (Tac triple), 4.8% (ATG-Tac), and 10.9% (ATG-CsA) (ATG-Tac vs. ATG-CsA, P=0.038). In the ATG groups, the incidences of leukopenia, thrombocytopenia, serum sickness, fever, and cytomegalovirus infection were significantly higher (P<0.05)., Conclusions: Acute rejection was significantly lower in the ATG-Tac group compared with the ATG-CsA and Tac triple groups. Significantly more hematologic and infectious adverse events were observed in both ATG induction groups.

Background: The aim of this study was to compare the efficacy and safety of induction treatment with antithymocyte globulins (ATG) followed by tacrolimus therapy with immediate tacrolimus therapy in renal transplant recipients., Methods: This 12-month, open, prospective study was conducted in 15 centers in France and 1 center in Belgium; 309 patients were randomized to receive either induction therapy with ATG (n=151) followed by initiation of tacrolimus on day 9 or immediate tacrolimus-based triple therapy (n=158). In both study arms, the initial daily tacrolimus dose was 0.2 mg/kg. Steroid boluses were given in the first 2 days and tapered thereafter from 20 mg/day to 5 mg/day. Azathioprine was administered at 1-2 mg/kg per day., Results: At month 12, biopsy-confirmed acute rejections were reported for 15.2% (induction) and 30.4% (noninduction) of patients (P=0.001). The incidence of steroid-sensitive acute rejections was 7.9% (induction) and 22.2% (noninduction)(P=0.001). Steroid-resistant acute rejections were reported for 8.6% (induction) and 8.9% (noninduction) of patients. A total of nine patients died. Patient survival and graft survival at month 12 was similar in both treatment groups (97.4% vs. 96.8% and 92.1% vs. 91.1%, respectively). Statistically significant differences in the incidence of adverse events were found for cytomegalovirus (CMV) infection (induction, 32.5% vs. noninduction, 19.0%, P=0.009), leukopenia (37.3% vs. 9.5%, P<0.001), fever (25.2% vs. 10.1%, P=0.001), herpes simplex (17.9% vs. 5.7%, P=0.001), and thrombocytopenia (11.3% vs. 3.2%, P=0.007). In the induction group, serum sickness was observed in 10.6% of patients. The incidence of new onset diabetes mellitus was 3.4% (induction) and 4.5% (noninduction)., Conclusion: Low incidences of acute rejection were found in both treatment arms. Induction treatment with ATG has the advantage of a lower incidence of acute rejection, but it significantly increases adverse events, particularly CMV infection.

Background: Oxygen free-radical mediated lipid peroxidation has been implicated in many diseases such as chronic renal failure, hemodialysis and chronic kidney transplant rejection. However, insight into the role of free radical generation in kidney transplantation has been constrained by the limitations of current indexes of oxidant stress in vivo. Isoprostaglandin F2alpha type-III (iPF2alpha-III, formerly known as 8-iso-prostaglandin F2alpha) is emerging as a reliable marker of oxidant stress in vivo. The purpose of our study was to investigate iPF2alpha-III formation as an index of lipid peroxidation in the 5 d following kidney transplantation., Methods: Urinary iPF2alpha-III measurements were performed by enzyme immunoassay from day I to 5 in 11 patients undergoing kidney transplantation. Results were compared with 11 healthy volunteers matched in sex, age and cigarette smoking., Results: Urinary excretion of iPF2alpha-III at day 1 did not significantly differ between control and transplant group (111 +/- 17 vs. 92 +/- 10 pM/ mM creatinine, respectively, NS). Urinary iPF2alpha-III levels did not differ between day 1 to 5, and were not correlated to cold ischaemia time., Conclusion: Our study shows no evidence of enhanced lipid peroxidation in the first 5 d following kidney transplantation.

Introduction: A previous trial in renal transplantation comparing sirolimus (rapamycin) to cyclosporine (CsA) in a triple-drug therapy regimen with azathioprine and corticosteroids found that the incidence of acute rejection was similar (approximately 40%) with a trend for better renal function with sirolimus., Methods: In 14 European centers, first cadaveric renal allograft recipients were randomized to receive sirolimus (n = 40) or CsA (n = 38) in an open-label design. All patients received corticosteroids and mycophenolate mofetil 2 g/day. Sirolimus and CsA were concentration controlled; trough levels of mycophenolic acid and prednisolone were also measured., Results: At 12 months, graft survival (92.5% sirolimus vs. 89.5% CsA), patient survival (97.5% sirolimus vs. 94.7% CsA), and the incidence of biopsy-proven acute rejection (27.5% sirolimus vs. 18.4% CsA) were not statistically different. The use of antibodies to treat suspected rejection episodes was also similar (7.5% sirolimus vs. 5.3% CsA). More sirolimus patients received bolus steroid therapy (20 vs. 11, P = 0.068). From month 2 onward, the calculated glomerular filtration rate was consistently higher in sirolimus-treated patients. The adverse events reported more frequently with sirolimus were thrombocytopenia (45% vs. 8%) and diarrhea (38% vs. 11%). In the CsA group, increased creatinine (18% vs. 39%), hyperuricemia (3% vs. 18%), cytomegalovirus infection (5% vs. 21%), and tremor (5% vs. 21%) were observed significantly more often., Discussion: Patient and graft survival and the incidence of biopsy-proven acute rejection at 12 months were comparable between sirolimus and CsA, whereas safety profiles were different. These data suggest that sirolimus may be used as primary therapy for the prevention of acute rejection.

Acute allograft rejection is the major risk factor of renal function decline and graft loss. Beside histocompatibility matches and pharmacological immunosuppression, blood transfusion is empirically used to detect responder subjects and to induce immune tolerance. Alloimmunization associated with blood transfusions readily detected by anti-HLA antibodies could induce acute vascular rejection episodes during the early period after grafting. Our open prospective study was aimed at analyzing the 1 year follow-up of 105 successive first cadaver renal transplant recipients according to the transfusion protocol as assessed by anti-HLA antibody production, acute rejection episodes, and graft survival. Our conventional transfusion protocol involved 3 nonphenotyped blood transfusions set up at least 20 days before grafting in a control cohort (group A) and was compared with a single pretransplant HLA haplo- or semi-identical blood transfusion in a successive group of patients (group B). Our results suggest that both protocols were associated with similar 1-year graft survivals (> 96% in both groups) and number of patients experiencing rejection episodes (20.7% in group A; 9.6% in group B; P NS). HLA haplo- or semi-identical transfusion was significantly beneficial in naive patients without previous alloantigen contact by pregnancy or blood transfusions during dialysis. Naive patients in group B did not develop post-transfusion anti-HLA antibodies compared to naive patients in group A (16.6%; P < 0.001), and they experienced significantly less acute rejection episodes (2.7%) compared to group A naive patients (20.8%; P = 0.02).

Thirty human cryoglobulin precipitates obtained from 21 patients were fixed and examined by electron microscopy; following biochemical isolation and identification. This study showed that the fine structure of cryoprecipitates depends on the involved immunoglobulins and on their respective quantities. Monoclonal IgG kappa 1 or 3 cryoglobulins with antibody activity form crystalling precipitates of 22-nm diameter rods and annuli. When polyclonal, they form 6-nm-wide filaments. Mixed IgG and IgM cryoprecipitates appear as cylindric and annular bodies with an internal diameter of 12 nm and a total diameter of 62 nm. When IgM predominates over IgG, globular condensations with a diameter of 30 nm are seen. Mixtures in which the IgG is more abundant than the IgM include fingerprint-like periodic condensations.

A prospective randomised trial was carried out in 14 patients with severe 'idiopathic' acute crescentic glomerulonephritis. The mean percentage of crescents was 78 per cent and 11 patients were anuric at presentation. Eight patients received pulses of methylprednisolone, immunosuppressive drugs and anticoagulants and six the same therapeutic regimen plus plasma exchanges for one to two months. Mean follow-up was 22 months. Recovery was statistically better in the PE+ group (p less than 0.02), but for discontinuation of dialysis, the difference is significant only at two months (p less than 0.02), perhaps because of the small number of patients. For this reason and because all pathological subgroups cannot be analysed separately, this study is continuing.