Kidney regeneration and repair after transplantation

PURPOSE OF REVIEW: To briefly show which are the mechanisms and cell types involved in kidney regeneration and describe some of the therapies currently under study in regenerative medicine for kidney transplantation. RECENT FINDINGS: The kidney contains cell progenitors that under specific circumstances have the ability to regenerate specific structures. Apart from the knowledge gained in the self-regenerative properties of the kidney, new concepts in regenerative medicine such as organ engineering and the use of mesenchymal stem cell-based therapies are currently the focus of attention in the field. SUMMARY: Overall, kidney regeneration is a reality and the knowledge on how to control it will be one of the main scopes in the present and future

Safety and efficacy of eculizumab for the prevention of antibody-mediated rejection after deceased-donor kidney transplantation in patients with preformed donor-specific antibodies

Abstract View references (47) The presence of preformed donor-specific antibodies in transplant recipients increases the risk of acute antibody-mediated rejection (AMR). Results of an open-label single-arm trial to evaluate the safety and efficacy of eculizumab in preventing acute AMR in recipients of deceased-donor kidney transplants with preformed donor-specific antibodies are reported. Participants received eculizumab as follows: 1200 mg immediately before reperfusion; 900 mg on posttransplant days 1, 7, 14, 21, and 28; and 1200 mg at weeks 5, 7, and 9. All patients received thymoglobulin induction therapy and standard maintenance immunosuppression including steroids. The primary end point was treatment failure rate, a composite of biopsy-proved grade II/III AMR (Banff 2007 criteria), graft loss, death, or loss to follow-up, within 9 weeks posttransplant. Eighty patients received transplants (48 women); the median age was 52 years (range 24-70 years). Observed treatment failure rate (8.8%) was significantly lower than expected for standard care (40%; P <.001). By 9 weeks, 3 of 80 patients had experienced AMR, and 4 of 80 had experienced graft loss. At 36 months, graft and patient survival rates were 83.4% and 91.5%, respectively. Eculizumab was well tolerated and no new safety concerns were identified. Eculizumab has the potential to provide prophylaxis against injury caused by acute AMR in such patients (EudraCT 2010-019631-35). \ua9 2019 The Authors. American Journal of Transplantation published by Wiley Periodicals, Inc. on behalf of The American Society of Transplantation and the American Society of Transplant Surgeon

Current preventive strategies and management of Epstein-Barr virus-related post-transplant lymphoproliferative disease in solid organ transplantation in Europe. Results of the ESGICH Questionnaire-based Cross-sectional Survey

There is limited clinical evidence on the utility of the monitoring of Epstein-Barr virus (EBV) DNAemia in the pre-emptive management of post-transplant lymphoproliferative disease (PTLD) in solid organ transplant (SOT) recipients. We investigated current preventive measures against EBV-related PTLD through a web-based questionnaire sent to 669 SOT programmes in 35 European countries. This study was performed on behalf of the ESGICH study group from the European Society of Clinical Microbiology and Infectious Diseases. A total of 71 SOT programmes from 15 European countries participated in the study. EBV serostatus of the recipient is routinely obtained in 69/71 centres (97%) and 64 (90%) have access to EBV DNAemia assays. EBV monitoring is routinely used in 85.9% of the programmes and 77.4% reported performing pre-emptive treatment for patients with significant EBV DNAemia levels. Pre-emptive treatment for EBV DNAemia included reduction of immunosuppression in 50.9%, switch to mammalian target of rapamycin inhibitors in 30.9%, and use of rituximab in 14.5% of programmes. Imaging by whole-body 18-fluoro-deoxyglucose positron emission tomography (FDG-PET) is used in 60.9% of centres to rule out PTLD and complemented computer tomography is used in 50%. In 10.9% of centres, FDG-PET is included in the first-line diagnostic workup in patients with high-risk EBV DNAemia. Despite the lack of definitive evidence, EBV load measurements are frequently used in Europe to guide diagnostic workup and pre-emptive reduction of immunosuppression. We need prospective and controlled studies to define the impact of EBV monitoring in reducing the risk of PTLD in SOT recipients

Cardiovascular risk following conversion to belatacept from a calcineurin inhibitor in kidney transplant recipients: a randomized clinical trial

Rationale & Objective: In kidney transplant recipients (KTRs), a belatacept-based immunosuppressive regimen is associated with beneficial effects on cardiovascular (CV) risk factors compared with calcineurin inhibitor (CNI)-based regimens. Our objective was to compare the calculated CV risk between belatacept and CNI (predominantly tacrolimus) treatments using a validated model developed for KTRs.Study Design: Prospective, randomized, open-label, parallel-group, investigator-initiated, international multicenter trial.Setting & Participants: KTRs aged 18-80 years with a stable graft function (estimated glomerular filtration rate > 20 mL/min/1.73 m2), 3-60 months after transplantation, treated with tacrolimus or cyclosporine A, were eligible for inclusion.Intervention: Continuation with a CNI-based regimen or switch to belatacept for 12 months.Outcomes: Comparison of the change in the esti-mated 7-year risk of major adverse CV events and all-cause mortality, changes in traditional markers of CV health, as well as measures of arterial stiffness.Results: Among the 105 KTRs randomized, we found no differences between the treatment groups in the predicted risk for major adverse CV events or mortality. Diastolic blood pres-sure, measured both centrally by using a SphygmoCor device and peripherally, was lower after the belatacept treatment than after the CNI treatment. The mean changes in traditional cardiovascular (CV) risk factors, including kidney transplant function, were otherwise similar in both the treatment groups. The belatacept group had 4 acute rejection episodes; 2 were severe rejections, of which 1 led to graft loss.Limitations: The heterogeneous baseline esti-mated glomerular filtration rate and time from transplantation to trial enrollment in the partici-pants. A limited study duration of 1 year.Conclusions: We found no effects on the calculated CV risk by switching to the belata-cept treatment. Participants in the belatacept group had not only lower central and peripheral diastolic blood pressure but also a higher rejection rate.Funding: The trial has received a financial grant from Bristol-Myers Squibb.Trial Registration: EudraCT no. 2013-001178-20.Nephrolog

The role of Mediterranean sponges in benthic-pelagic coupling processes: Aplysina aerophoba and Axinella polypoides case studies

Sponges are important components of marine benthic communities with a worldwide distribution ranging frompolar to tropical regions. They play a key role in benthic-pelagic coupling processes through their active suspension feeding, providing a trophic link between the benthos and the overlying water column. Little is known about their broad-scale distribution and feeding ecology. The general tendency is to quantify their trophic impact through small patch estimations. In this work, two of the most abundant sponges in Mediterranean coastal bottoms (Aplysina aerophoba and Axinella polypoides) were studied combining remotely operated vehicle (ROV) survey with in situ feeding experiments. Spatial, bathymetrical distribution and population size structure of these species were analysed, together with their trophic ecology, in spring and autumn.We found that A. aerophoba is distributed between 5 and 20 m depth, withmaximumdensities of 1.6 sponges m-2. This species ingested 0.12-0.39 mg of carbon (C) g AFDW-1 (ash free dry weight) day-1 in spring and 0.09-0.13 mg C g AFDW-1 day-1 in autumn. Conversely, A. polypoides was found between 10 and 70mdepth, with maximum densities of 7.6 sponges m-2. This species ingested 0.07-0.17 mgC g AFDW-1 day-1 1 in spring, and 0.18-0.60 mg C g AFDW-1 day-1 in autumn. The highest uptake of C concentrated between 5 and 15 m depth for A. aerophoba and between 65 and 70 m depth for A. polypoides. In the 1.14 ha of studied coastal bottom, A. aerophoba ingested 1.87 g C during spring and 0.19 g C during autumn, whereas A. polypoides 13.60 g C and 29.36 g C during spring and autumn, respectively. The present approach allowed a spatially explicit quantification of benthic-pelagic coupling processes produced by two of the most common sponges in a Mediterranean coastal area. This methodology, applied to benthic communities, mirrors similar approaches used in terrestrial forestry studies for C flux estimation

Distribution and diversity of cold-water coral assemblages on the Cabliers Mound (Alboran Sea, western Mediterranean): an ROV and predictive mapping approach

18th International Symposium Marine Geological and Biological Habitat Mapping (GeoHab 2018), 7-11 May 2018, Santa Barbara, CaliforniaPeer Reviewe