Dialysis Withdrawal: Impact and Evaluation of a Multidisciplinary Deliberation Within an Ethics Committee as a Shared-Decision-Making Model.

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.

Corticosteroid-free immunosuppression with tacrolimus, mycophenolate mofetil, and daclizumab induction in renal transplantation.

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.

A multicentre study of registration on renal transplantation waiting list of the elderly and patients with type 2 diabetes.

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.

A three-arm study comparing immediate tacrolimus therapy with antithymocyte globulin induction therapy followed by tacrolimus or cyclosporine A in adult renal transplant recipients.

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.