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This study evaluated 7-year efficacy and safety outcomes in transplant recipients assigned to a more-intensive or less-intensive belatacept regimen or cyclosporine for immunosuppression. Both belatacept regimens were associated with significantly superior patient and graft survival. The use of prolonged maintenance immunosuppressive therapy after kidney transplantation has improved the short-term outcomes, 1 but the effect on long-term allograft survival is not known. 2 Prospective, phase 3, randomized studies examining the outcomes of immunosuppressive regimens beyond 5 years or showing a survival advantage of newer immunosuppressive regimens over that afforded by regimens containing the calcineurin inhibitor cyclosporine are lacking. 3 – 5 Belatacept is a selective costimulation blocker that has been developed to improve long-term outcomes in kidney-transplant recipients by providing effective immunosuppression without the toxic effects of calcineurin inhibitors. Current standard-of-care immunosuppressive regimens combine calcineurin inhibitors with antiproliferative drugs, with . . .

Non-nephrotoxic immunosuppressive strategies that allow reduction of calcineurin-inhibitor exposure without compromising safety or efficacy remain a goal in kidney transplantation. Immunosuppression based on the mammalian-target-of-rapamycin inhibitor everolimus was assessed as a strategy for elimination of calcineurin-inhibitor exposure and optimisation of renal-graft function while maintaining efficacy. In the ZEUS multicentre, open-label study, 503 patients (aged 18–65 years) who had received de-novo kidney transplants were enrolled. After initial treatment with ciclosporin, based on trough concentrations, and enteric-coated mycophenolate sodium (1440 mg/day, orally), corticosteroids (≥5 mg/day prednisolone or equivalent, orally), and basiliximab induction (20 mg, intravenously, on day 0 [2 h before transplantation], and on day 4), 300 (60%) patients were randomly assigned at 4·5 months in a 1:1 ratio to undergo calcineurin-inhibitor elimination (everolimus-based regimen that was based on trough concentrations [6–10 ng/mL] and enteric-coated mycophenolate sodium [1440 mg/day] with corticosteroids), or continue standard ciclosporin-based treatment. Randomisation was done by use of a central, validated system that automated the random assignment of treatment groups to randomisation numbers. The primary objective was to show better renal function (glomerular filtration rate [GFR]; Nankivell formula) with the calcineurin-inhibitor-free everolimus regimen at 12 months after transplantation. Analysis was by intention to treat. This study is registered with ClinicalTrials.gov, number NCT00154310. 118 (76%) of 155 everolimus-treated patients and 117 (81%) of 145 ciclosporin-treated patients completed treatment with study drug up to 12 months after transplantation. At this timepoint, the everolimus regimen was associated with a significant improvement in GFR versus the ciclosporin regimen (71·8 mL/min per 1·73 m2vs 61·9 mL/min per 1·73 m2, respectively; mean difference 9·8 mL/min per 1·73 m2, 95% CI −12·2 to −7·5). Rates of biopsy-proven acute rejection were higher in the everolimus group than in the ciclosporin group after randomisation (15 [10%] of 154 vs five [3%] of 146; p=0·036), but similar for the full study period (23 [15%] vs 22 [15%]). Compared with the ciclosporin regimen, higher mean lipid concentrations, slightly increased urinary protein excretion, and lower haemoglobin concentrations were noted with the everolimus regimen; thrombocytopenia, aphthous stomatitis, and diarrhoea also occurred more often in the everolimus group. A higher incidence of hyperuricaemia was noted with ciclosporin. Early elimination of calcineurin inhibitor by use of everolimus-based immunosuppression improved renal function at 12 months while maintaining efficacy and safety, indicating that this strategy may facilitate improved long-term outcomes in selected patients. Novartis Pharma.

Renal transplantation is the standard of care for patients with end-stage renal disease, but current immunosuppressive regimens, particularly those with calcineurin inhibitors, cause renal injury. In this noninferiority study, belatacept, an investigational selective costimulation blocker, and cyclosporine resulted in similar rates of acute rejection at six months, but belatacept may have better preserved renal function and prevented allograft nephropathy. Current immunosuppressive regimens cause renal injury. In this noninferiority study, belatacept and cyclosporine resulted in similar rates of acute rejection at six months, but belatacept may have better preserved renal function and prevented allograft nephropathy. Renal transplantation, the standard of care for patients with end-stage renal disease, improves survival and the quality of life. 1 – 4 Current regimens of immunosuppression yield excellent one-year rates of patient and graft survival; however, five-year survival rates among recipients of kidneys from cadaveric donors and living related donors are only 66 percent and 79 percent, respectively. 5 Paradoxically, the commonly used calcineurin inhibitors, effective for immunosuppression, contribute to late allograft loss and death. Calcineurin inhibitors are nephrotoxic and have adverse effects on blood pressure, lipid levels, and glucose homeostasis. 6 , 7 Thus, calcineurin inhibitors promote cardiovascular disease, the most common cause of . . .

The rising trend of End-stage Renal Disease (ESRD) patients requiring dialysis or transplantation needs a more therapeutic plan. As the best strategy for ESRD patients, kidney transplantation still needs outcome improvement. Macrolide drugs display antimicrobial and anti-inflammatory properties in chronic disease and intraoperatively and can concentrate in tissues for extended periods. Hence, theoretically, the drug prescription to the donor and accumulation in the kidney can cause graft immunomodulation and improve kidney transplantation outcomes. This double-blinded randomized clinical trial was conducted on 62 eligible kidney donors randomly allocated to the azithromycin or placebo group and treated with a single dose (one gram) one day before surgery. The primary outcome was kidney graft function, and secondary outcomes included rejection rate, urinary tract infections in graft recipients, pain and systemic inflammatory response syndrome in live donors, and complications in donors and recipients. Outcomes were measured at baseline and every day in the first week after transplantation in both live donors and recipients and 30 and 90 days after transplantation. The adverse events were recorded as well. The mean age was 39 (SD, 13) years; 40% were women, and 11.6% were diabetic. Mean creatinine was 6.11 mL/min/1.73m2. Most patients in both arms were male (61.3%) and in early middle age. Hypertension was the most common cause of ESRD. Azithromycin could reduce the rejection rate in the first few days after kidney transplantation. Inflammatory mediators were lower in the azithromycin group, and fewer cases of urinary tract infection were found in the azithromycin group (p < 0.05). Azithromycin reduces adverse outcomes and enhances graft function. It would offer an intervention that is easy to use and economical, lowering post-transplant risks.

Background Because of the deceased donor organ shortage, more kidney patients are considering whether to receive kidneys from family and friends, a process called living donor kidney transplantation (LDKT). Although Blacks and Hispanics are 3.4 and 1.5 times more likely, respectively, to develop end stage renal disease (ESRD) than Whites, they are less likely to receive LDKTs. To address this disparity, a new randomized controlled trial (RCT) will assess whether Black, Hispanic, and White transplant patients’ knowledge, readiness to pursue LDKT, and receipt of LDKTs can be increased when they participate in the Your Path to Transplant (YPT) computer-tailored intervention. Methods/Design Nine hundred Black, Hispanic, and White ESRD patients presenting for transplant evaluation at University of California, Los Angeles Kidney and Pancreas Transplant Program (UCLA-KPTP) will be randomly assigned to one of two education conditions, YPT or Usual Care Control Education (UC). As they undergo transplant evaluation, patients in the YPT condition will receive individually-tailored telephonic coaching sessions, feedback reports, video and print transplant education resources, and assistance with reducing any known socioeconomic barriers to LDKT. Patients receiving UC will only receive transplant education provided by UCLA-KPTP. Changes in transplant knowledge, readiness, pros and cons, and self-efficacy to pursue LDKT will be assessed prior to presenting at the transplant center (baseline), during transplant evaluation, and 4- and 8-months post-baseline, while completion of transplant evaluation and receipt of LDKTs will be assessed at 18-months post-baseline. The RCT will determine, compared to UC, whether Black, Hispanic, and White patients receiving YPT increase in their readiness to pursue LDKT and transplant knowledge, and become more likely to complete transplant medical evaluation and pursue LDKT. It will also examine how known patient, family, and healthcare system barriers to LDKT act alone and in combination with YPT to affect patients’ transplant decision-making and behavior. Statistical analyses will be performed under an intent-to-treat approach. Discussion At the conclusion of the study, we will have assessed the effectiveness of an innovative and cost-effective YPT intervention that could be utilized to tailor LDKT discussion and education based on the needs of individual patients of different races in many healthcare settings. Trial registration ClinicalTrials.gov, number NCT02181114 .

Background The Southeastern United States has the lowest kidney transplant rates in the nation, and racial disparities in kidney transplant access are concentrated in this region. The Southeastern Kidney Transplant Coalition (SEKTC) of Georgia, North Carolina, and South Carolina is an academic and community partnership that was formed with the mission to improve access to kidney transplantation and reduce disparities among African American (AA) end stage renal disease (ESRD) patients in the Southeastern United States. Methods/Design We describe the community-based participatory research (CBPR) process utilized in planning the R educing D isparities I n A ccess to kid N ey T ransplantation (RaDIANT) Community Study, a trial developed by the SEKTC to reduce health disparities in access to kidney transplantation among AA ESRD patients in Georgia, the state with the lowest kidney transplant rates in the nation. The SEKTC Coalition conducted a needs assessment of the ESRD population in the Southeast and used results to develop a multicomponent, dialysis facility-randomized, quality improvement intervention to improve transplant access among dialysis facilities in GA. A total of 134 dialysis facilities are randomized to receive either: (1) standard of care or “usual” transplant education, or (2) the multicomponent intervention consisting of transplant education and engagement activities targeting dialysis facility leadership, staff, and patients within dialysis facilities. The primary outcome is change in facility-level referral for kidney transplantation from baseline to 12 months; the secondary outcome is reduction in racial disparity in transplant referral. Discussion The RaDIANT Community Study aims to improve equity in access to kidney transplantation for ESRD patients in the Southeast. Trial registration Clinicaltrials.gov number NCT02092727 .

BackgroundThe aim of this study was to analyze changes in renal function in HBsAg-positive renal transplant recipients receiving lamivudine who did or did not switch to telbivudine.MethodsIn this prospective randomized clinical trial (RCT), HBsAg-positive renal transplant recipients who had received lamivudine prophylaxis for at least 6 months were 1:2 randomized to receive either lamivudine or telbivudine for another 24 months. Renal function was evaluated by creatinine level and estimated glomerular filtration rate (eGFR) at the time of randomization (baseline), 6, 12, 18, and 24 months respectively.ResultsThis RCT was prematurely terminated after recruiting only 17 patients due to a high incidence (61.5%; 8/13) of clinical myalgia in the telbivudine group. Cox’s proportional hazards model revealed that there was no independent predictor of myalgia. Based on intention-to-treat and per protocol analyses using generalized estimating equations, the patients in the randomized telbivudine group had a significantly increased eGFR and the patients in the lamivudine group had a significantly decreased eGFR at the end of follow-up compared to the values at study enrollment. However, there was no significant difference between the lamivudine and telbivudine groups.ConclusionsThe renal protective effect of telbivudine for HBsAg positive renal transplant recipients was uncertain for high incidence of myalgia and only patients who were on telbivudine for 24 months had renal function maintenance.

Xenotransplantation offers a potential solution to the organ shortage crisis. A 62-year-old hemodialysis-dependent man with long-standing diabetes, advanced vasculopathy, and marked dialysis-access challenges received a gene-edited porcine kidney with 69 genomic edits, including deletion of three glycan antigens, inactivation of porcine endogenous retroviruses, and insertion of seven human transgenes. The xenograft functioned immediately. The patient’s creatinine levels decreased promptly and progressively, and dialysis was no longer needed. After a T-cell–mediated rejection episode on day 8, intensified immunosuppression reversed rejection. Despite sustained kidney function, the patient died from unexpected, sudden cardiac causes on day 52; autopsy revealed severe coronary artery disease and ventricular scarring without evident xenograft rejection. (Funded by Massachusetts General Hospital and eGenesis.) This report describes the transplantation of a gene-edited porcine kidney in a hemodialysis-dependent man with long-standing diabetes, advanced vasculopathy, and marked dialysis-access challenges.

There is strong evidence of an association between chronic kidney disease (CKD) and cardiovascular disease. To date, however, proof that a reduction in glomerular filtration rate (GFR) is a causative factor in cardiovascular disease is lacking. Kidney donors comprise a highly screened population without risk factors such as diabetes and inflammation, which invariably confound the association between CKD and cardiovascular disease. There is strong evidence that increased arterial stiffness and left ventricular hypertrophy and fibrosis, rather than atherosclerotic disease, mediate the adverse cardiovascular effects of CKD. The expanding practice of live kidney donation provides a unique opportunity to study the cardiovascular effects of an isolated reduction in GFR in a prospective fashion. At the same time, the proposed study will address ongoing safety concerns that persist because most longitudinal outcome studies have been undertaken at single centers and compared donor cohorts with an inappropriately selected control group. The reduction in GFR accompanying uninephrectomy causes (1) a pressure-independent increase in aortic stiffness (aortic pulse wave velocity) and (2) an increase in peripheral and central blood pressure. This is a prospective, multicenter, longitudinal, parallel group study of 440 living kidney donors and 440 healthy controls. All controls will be eligible for living kidney donation using current UK transplant criteria. Investigations will be performed at baseline and repeated at 12 months in the first instance. These include measurement of arterial stiffness using applanation tonometry to determine pulse wave velocity and pulse wave analysis, office blood pressure, 24-hour ambulatory blood pressure monitoring, and a series of biomarkers for cardiovascular and bone mineral disease. These data will prove valuable by characterizing the direction of causality between cardiovascular and renal disease. This should help inform whether targeting reduced GFR alongside more traditional cardiovascular risk factors is warranted. In addition, this study will contribute important safety data on living kidney donors by providing a longitudinal assessment of well-validated surrogate markers of cardiovascular disease, namely, blood pressure and arterial stiffness. If any adverse effects are detected, these may be potentially reversed with the early introduction of targeted therapy. This should ensure that kidney donors do not come to long-term harm and thereby preserve the ongoing expansion of the living donor transplant program (NCT01769924).

Background Kidney transplantation is the best strategy for the management of end-stage renal disease; however, the outcomes need to improve further. Macrolides show antimicrobial and anti-inflammatory properties in chronic diseases and intraoperatively, and can accumulate in tissues for extended periods. Therefore, theoretically, when administered to a donor and because of accumulation in the donor kidney, macrolides can cause graft immunomodulation and improve kidney transplantation outcomes. Methods This study is a single-center, randomized clinical trial. A total of 60 kidney donors will be randomly allocated to the azithromycin or placebo group and treated with a single dose (1 g) of azithromycin or placebo, respectively, 1 day before surgery. Recruitment commenced in September 2016 and is expected to be completed by March 2018. The primary outcome is kidney graft function. The secondary outcomes include rejection rate, urinary tract infections in graft recipients, pain and systemic inflammatory response syndrome in live donors, and complications in both donors and recipients. Outcomes will be evaluated at baseline and every day in the first week after transplantation, as well as at 1 and 3 months post transplantation. Adverse reactions will be documented. If the efficacy of azithromycin in reducing adverse outcomes is confirmed, it would serve as an easy to use, economic intervention able to lower post-transplantation risks. Discussion Short and mid-term analyses of blood and urine samples as well as immunological assays will facilitate a more in-depth analysis of the effects of azithromycin on transplantation outcomes. Trial registration Iranian Clinical Trial Registry, IRCT201606141853N11 , registered on September 5, 2016.