Campath, calcineurin inhibitor reduction and chronic allograft nephropathy (3C) study: background, rationale, and study protocol.

BACKGROUND: Kidney transplantation is the best treatment for patients with end-stage renal failure, but uncertainty remains about the best immunosuppression strategy. Long-term graft survival has not improved substantially, and one possible explanation is calcineurin inhibitor (CNI) nephrotoxicity. CNI exposure could be minimized by using more potent induction therapy or alternative maintenance therapy to remove CNIs completely. However, the safety and efficacy of such strategies are unknown. METHODS/DESIGN: The Campath, Calcineurin inhibitor reduction and Chronic allograft nephropathy (3C) Study is a multicentre, open-label, randomized controlled trial with 852 participants which is addressing two important questions in kidney transplantation. The first question is whether a Campath (alemtuzumab)-based induction therapy strategy is superior to basiliximab-based therapy, and the second is whether, from 6 months after transplantation, a sirolimus-based maintenance therapy strategy is superior to tacrolimus-based therapy. Recruitment is complete, and follow-up will continue for around 5 years post-transplant. The primary endpoint for the induction therapy comparison is biopsy-proven acute rejection by 6 months, and the primary endpoint for the maintenance therapy comparison is change in estimated glomerular filtration rate from baseline to 2 years after transplantation. The study is sponsored by the University of Oxford and endorsed by the British Transplantation Society, and 18 centers for adult kidney transplant are participating. DISCUSSION: Late graft failure is a major issue for kidney-transplant recipients. If our hypothesis that minimizing CNI exposure with Campath-based induction therapy and/or an elective conversion to sirolimus-based maintenance therapy can improve long-term graft function and survival is correct, then patients should experience better graft function for longer. A positive outcome could change clinical practice in kidney transplantation. TRIAL REGISTRATION: ClinicalTrials.gov, NCT01120028 and ISRCTN88894088.RIGHTS : This article is licensed under the BioMed Central licence at http://www.biomedcentral.com/about/license which is similar to the 'Creative Commons Attribution Licence'. In brief you may : copy, distribute, and display the work; make derivative works; or make commercial use of the work - under the following conditions: the original author must be given credit; for any reuse or distribution, it must be made clear to others what the license terms of this work are

Alemtuzumab-based induction treatment versus basiliximab-based induction treatment in kidney transplantation (the 3C Study): a randomised trial.

Background: Calcineurin inhibitors (CNIs) reduce short-term kidney transplant failure, but might contribute to transplant failure in the long-term. The role of alemtuzumab (a potent lymphocyte-depleting antibody) as an induction treatment followed by an early reduction in CNI and mycophenolate exposure and steroid avoidance, after kidney transplantation is uncertain. We aimed to assess the efficacy and safety of alemtuzumab-based induction treatment compared with basiliximab-based induction treatment in patients receiving kidney transplants. Methods: For this randomised trial, we enrolled patients aged 18 years and older who were scheduled to receive a kidney transplant in the next 24 h from 18 transplant centres in the UK. Using minimised randomisation, we randomly assigned patients (1:1; minimised for age, sex, and immunological risk) to either alemtuzumab-based induction treatment (ie, alemtuzumab followed by low-dose tacrolimus and mycophenolate without steroids) or basiliximab-based induction treatment (basiliximab followed by standard-dose tacrolimus, mycophenolate, and prednisolone). Participants were reviewed at discharge from hospital and at 1, 3, 6, 9, and 12 months after transplantation. The primary outcome was biopsy-proven acute rejection at 6 months, analysed by intention to treat. The study is registered at ClinicalTrials.gov, number NCT01120028, and isrctn.org, number ISRCTN88894088. Findings: Between Oct 4, 2010, and Jan 21, 2013, we randomly assigned 852 participants to treatment: 426 to alemtuzumab-based treatment and 426 to basiliximab-based treatment. Overall, individuals allocated to alemtuzumab-based treatment had a 58% proportional reduction in biopsy-proven acute rejection compared with those allocated to basiliximab-based treatment (31 [7%] patients in the alemtuzumab group vs 68 [16%] patients in the basiliximab group; hazard ratio (HR) 0·42, 95% CI 0·28-0·64; log-rank p<0·0001). We detected no between-group difference in treatment effect on transplant failure during the first 6 months (16 [4%] patients vs 13 [3%] patients; HR 1·23, 0·59-2·55; p=0·58) or serious infection (135 [32%] patients vs 136 [32%] patients; HR 1·02, 0·80-1·29; p=0·88). During the first 6 months after transplantation, 11 (3%) patients given alemtuzumab-based treatment and six (1%) patients given basiliximab-based treatment died (HR 1·79, 95% CI 0·66-4·83; p=0·25). Interpretation: Compared with standard basiliximab-based treatment, alemtuzumab-based induction therapy followed by reduced CNI and mycophenolate exposure and steroid avoidance reduced the risk of biopsy-proven acute rejection in a broad range of patients receiving a kidney transplant. Long-term follow-up of this trial will assess whether these effects translate into differences in long-term transplant function and survival

Prevalence and Co-Occurrence of Geriatric Syndromes in People Aged 75 Years and Older in France: Results From the Bordeaux Three-city Study

BACKGROUND: Geriatric syndromes (GSs) are often the result of cumulative insults to multiple organ systems and are considered common in older adults. However, their frequency and co-occurrence are not well known in the elderly population. This study aimed to determine the prevalence of several GSs and to analyze the co-occurrence of these syndromes in a general population of elderly individuals. METHODS: A cross-sectional analysis of 630 adults aged 75 years or older participating in the 10-year follow-up of the Bordeaux sample of the French Three-City Study was conducted. The following 10 GSs were assessed: physical frailty, dementia and cognitive impairment, depressive symptoms, polymedication, social isolation, thinness, falls, dependence, sensory deficit, and incontinence. The prevalence of the 10 GSs was estimated, and multiple correspondence analysis (MCA) models were used to explore the mutual associations between these GSs. RESULTS: The mean age of the participants was 83.3 years; 69% were women, and 80.5% [95% confidence interval (CI) = 76.3–82.7] had at least one GS. The most frequent GSs were polymedication (50.6% 95%CI = 46.7–54.5) and falls (43.1% 95%CI = 38.4–46.1). The MCA models identified two major dimensions of the 10 GSs: “Dementia–Dependence–Incontinence” and “Frailty–Depression–Isolation.” CONCLUSION: GSs were very common in this French elderly population and were grouped into two major dimensions: the “Dementia–Dependence–Incontinence” and “Frailty–Depression–Isolation.

Inducción con anticuerpos antilinfocitarios y minimización de esteroides en trasplante renal

Steroid minimization after kidney transplantation has become more widely practiced as transplant clinicians seek the potential benefits such as reduced cardiovascular risk factors, improved growth in pediatric patients, and improved compliance with the immunosuppression regimen. Steroid avoidance (i.e. no steroids after the first week) is generally favored compared to later withdrawal. Induction therapy is routine in this setting, frequently rabbit antithymocyte globulin (rATG, Thymoglobulin®) or off-license use of alemtuzumab. Direct comparisons of steroid minimization regimens versus standard steroid regimens are rare. However, the available data show that the risk of acute rejection is low when rATG or alemtuzumab induction is given to support steroid-avoidance regimens after kidney transplantation. Steroid avoidance may be inadvisable in patients at high immunological risk or at risk of recurrent glomerular disease. Steroid withdrawal after day 8 may be possible without additional risk of rejection in patients iven rATG induction, but while encouraging, the data are too sparse for firm onclusions. In summary, steroid avoidance may be beneficial for patients after renal transplantation, with the potential to avoid or reduce steroid-related comorbidities. Whilst depleting induction therapy could be the treatment of choice, results of prospective randomized, controlled studies are eagerly awaitedJulio Pascual and Marta Crespo are supported by grants FIS PI13/00598 and Redinren RD12/0021/0024

Campath, calcineurin inhibitor reduction and chronic allograft nephropathy (3C) study: background, rationale, and study protocol

Background Kidney transplantation is the best treatment for patients with end-stage renal failure, but uncertainty remains about the best immunosuppression strategy. Long-term graft survival has not improved substantially, and one possible explanation is calcineurin inhibitor (CNI) nephrotoxicity. CNI exposure could be minimized by using more potent induction therapy or alternative maintenance therapy to remove CNIs completely. However, the safety and efficacy of such strategies are unknown. Methods/Design The Campath, Calcineurin inhibitor reduction and Chronic allograft nephropathy (3C) Study is a multicentre, open-label, randomized controlled trial with 852 participants which is addressing two important questions in kidney transplantation. The first question is whether a Campath (alemtuzumab)-based induction therapy strategy is superior to basiliximab-based therapy, and the second is whether, from 6 months after transplantation, a sirolimus-based maintenance therapy strategy is superior to tacrolimus-based therapy. Recruitment is complete, and follow-up will continue for around 5 years post-transplant. The primary endpoint for the induction therapy comparison is biopsy-proven acute rejection by 6 months, and the primary endpoint for the maintenance therapy comparison is change in estimated glomerular filtration rate from baseline to 2 years after transplantation. The study is sponsored by the University of Oxford and endorsed by the British Transplantation Society, and 18 centers for adult kidney transplant are participating. Discussion Late graft failure is a major issue for kidney-transplant recipients. If our hypothesis that minimizing CNI exposure with Campath-based induction therapy and/or an elective conversion to sirolimus-based maintenance therapy can improve long-term graft function and survival is correct, then patients should experience better graft function for longer. A positive outcome could change clinical practice in kidney transplantation