Xenotransplantation: Where Are We with Potential Kidney Recipients? Recent Progress and Potential Future Clinical Trials

AbstractPurposeInterspecies transplantation, xenotransplantation, is becoming a realistic strategy to solve the organ shortage crisis. Here, we focus on seminal publications that have driven research in xenotransplantation, as well as recently published literature and future endeavors.Recent FindingsAdvances in gene editing technology have allowed for the efficient production of multitransgenic porcine donors leading improved xenograft survival in baboons, up to 2  years following heterotopic heart xenotransplantation and from weeks to several months following life-supporting kidney xenotransplanation. As technology evolves, additional challenges have arisen, including the development of proteinuria, early graft loss associated with porcine CMV, disparities in organ growth between donors and recipients, as well as high-dose continuous immunosuppression requirements. To address these issues, our laboratory developed a tolerance-inducing protocol which has allowed for>6-month survival of a life-supporting kidney with further approaches currently underway to address the challenges mentioned above.SummaryOur recent findings, reviewed in this article, led us to develop methods to overcome obstacles, which, in conjunction with the work of others, are promising for future clinical applications of xenotransplantation.
Source: Current Transplantation Reports - Category: Transplant Surgery Source Type: research

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In this study, we therefore examined whether FKN could stimulate the process of EMT, NF-kB, TGFβ, CCL22, F4/80, inflammation, and tubulointerstitial fibrosis in a murine model of LN. We also determined whether FKN was involved in the EMT process of Wnt/β-catenin-expressing HK-2 cells. Mechanistically, we ascertained, for the first time, whether FKN up-regulated EMT-related gene signatures (e.g., vimentin, α-SMA), and hence, renal tubulointerstitial fibrogenesis, and the role of the Wnt/β-catenin signaling pathway in this process. Materials and Methods Cell Culture, Stable Infection, and Grouping HK-...
Source: Frontiers in Immunology - Category: Allergy & Immunology Source Type: research
Giuseppe Ristagno1*, Francesca Fumagalli1, Barbara Bottazzi2, Alberto Mantovani2,3,4, Davide Olivari1, Deborah Novelli1 and Roberto Latini1 1Department of Cardiovascular Research, Mario Negri Institute for Pharmacological Research IRCCS, Milan, Italy 2Humanitas Clinical and Research Center-IRCCS, Milan, Italy 3Humanitas University, Milan, Italy 4The William Harvey Research Institute, Queen Mary University of London, London, United Kingdom The long pentraxin PTX3 is a member of the pentraxin family produced locally by stromal and myeloid cells in response to proinflammatory signals and microbial moieties. The p...
Source: Frontiers in Immunology - Category: Allergy & Immunology Source Type: research
Conclusion As a critical regulator of inflammation and cell survival, the NFκB pathway is a promising target for diagnosing and treating kidney diseases. For modulation of the NFκB pathway in the clinic, a number of molecules can effectively inhibit NFκB signaling by targeting the receptors, associated adaptors, IKKs, IκBs and transcriptional regulators (144). There is further clinical evidence on small-molecule inhibitors of IKKα and NIK from recent trials on anti-cancer therapies (145). These clinical trials showed that the cancer-selective pharmacodynamic response of DTP3, the co-inhibitor...
Source: Frontiers in Immunology - Category: Allergy & Immunology Source Type: research
Discussion: Incomplete septal cirrhosis is an uncommon cause of non-cirrhotic portal hypertension. Its definition is not well known, morphological and pathophysiological. We have not found published cases of post-RT ascites secondary to this pathology, described as possibly associated with drugs, immune alterations, infections, hypercoagulability and genetic predisposition. PMID: 30897191 [PubMed - as supplied by publisher]
Source: Jornal Brasileiro de Nefrologia - Category: Urology & Nephrology Tags: J Bras Nefrol Source Type: research
Abstract Dengue-related renal manifestations such as proteinuria, hematuria in the absence of thrombocytopenia, rhabdomyolysis, and acute kidney injury (AKI) are not uncommon. There is relatively sparse data on the renal manifestations of dengue viral infection (DVI). Hence, a retrospective study was conducted to investigate the incidence, characteristics, and clinical outcome of DVI with renal manifestations. A total of 2416 patients were admitted to our hospital with the diagnosis of dengue fever during the study period from 2012 to 2015. Data were collected from the electronic medical records and were analyzed ...
Source: Saudi Journal of Kidney Diseases and Transplantation - Category: Urology & Nephrology Authors: Tags: Saudi J Kidney Dis Transpl Source Type: research
​BY ANDRZEJ KIELTYKA, PA; PARDEEP THANDI, MD; &ANUMEHA SINGH, MDA 56-year-old man presented to the emergency department with shortness of breath for one month and pleural effusions on an outpatient chest x-ray. He had been taking adalimumab, methotrexate, and steroids for arthritis and Sjogren's syndrome.A right pleural effusion in a patient with nephrotic syndrome.His monoclonal gammopathy of undetermined significance (MGUS) was monitored annually, but no medical intervention beyond surveillance was required. He had excessive thirst but normal urine output. He noted face and hand swelling in the morning that gave wa...
Source: The Case Files - Category: Emergency Medicine Tags: Blog Posts Source Type: research
We report a case of capillary leak that developed during treatment of antibody-mediated rejection in a kidney transplant recipient. A 53-year-old female transplant recipient experienced an increase in serum creatinine from 1.1 to 1.8  mg/dL. Antibody-mediated rejection was diagnosed by graft biopsy. She was treated with five plasmapheresis sessions (on alternate days with albumin replacement), five doses of immunoglobulin (5 g/dose at 100 mg/kg), a single dose of rituximab (500 mg), and four doses of bortezomib on days 1, 4, 7, and 10 (1.72 mg/dose at 1.3 mg/m2 body surface area). During treat...
Source: CEN Case Reports - Category: Urology & Nephrology Source Type: research
Over the last decade, advances in left ventricular assist device (LVAD) therapy have revolutionized care of advanced heart failure (HF) patients with excellent long-term survival and quality of life. Approval of LVAD in transplant ineligible patients as destination therapy (DT) allowed for broader application of this technology in older and sicker patient populations. Chronic kidney disease (CKD) is among the most prevalent comorbidities in advanced HF due to coexisting intrinsic renal disease and/or adverse hemodynamics.
Source: The Journal of Heart and Lung Transplantation - Category: Transplant Surgery Authors: Source Type: research
Abstract ObjectiveTo evaluate the health impact of nephrectomy on living kidney donors (LKDs) by comparing the health‐related quality of life (HrQOL) scores measured by Short Form‐36 (SF36) between those with and without postdonation renal function impairment (PRFI). MethodsEighty‐two LKDs (47 females, mean age=50.2±11.2 years) were prospectively recruited to participate in a SF‐36 HrQOL survey. Chart review, individual baseline, and postoperative renal function (eGFR) was determined using the Modification of Diet in Renal Disease formula. PRFI was defined as eGFR
Source: Clinical Transplantation - Category: Transplant Surgery Authors: Tags: ORIGINAL ARTICLE Source Type: research
Abstract ObjectiveTo evaluate the health impact of nephrectomy on LKDs by comparing the HrQOL scores measured by Short Form‐36 (SF36) between those with and without post‐donation renal function impairment (PRFI). Methods82 LKDs (47 females, mean age = 50.2 ± 11.2 years) were prospectively recruited to participate in a SF‐36 HrQOL survey. Chart review, individual baseline and postoperative renal function (eGFR) was determined using the Modification of Diet in Renal Disease (MDRD) formula. PRFI was defined as eGFR
Source: Clinical Transplantation - Category: Transplant Surgery Authors: Tags: Original Article Source Type: research
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