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1
Kubal, Chandrashekhar. "Comparative models of transplant and non-transplant human kidney disease." Thesis, University of Birmingham, 2012. http://etheses.bham.ac.uk//id/eprint/3827/.
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Late kidney transplant losses along with chronic kidney disease in non-renal solid organ transplantation pose major problem in this field. To address this I compared ischaemia, interstitial scarring and inflammation on the renal biopsies from failing renal transplants and chronic kidney disease outside renal transplantation using native CKD as a control group. For matched renal function, a similar degree of interstitial scarring was observed across the three study groups. Ischaemia was predominant in failing renal transplants; conversely inflammation was predominant in native CKD. The relationship between macrophages and endothelial cells indicated that, despite a lower macrophage load, there may be an allogeneic impact of macrophages on endothelial cells. In the biopsies from CKD, mRNA levels for iNOS, arginase, CX3CL1, BCL-2, MCP-1/CCL2 and FSP-1 were increased in association with an increasing macrophage load. Macrophage load correlated positively with arginase/iNOS mRNA ratio, suggesting M2 phenotypic transformation of the macrophages. Co-localization studies, demonstrated an increased number of macrophages within 5 microns from endothelial cells in failing renal transplants when compared to chronic kidney disease. Further studies directed towards manipulating macrophage-endothelial cell interaction may be potentially beneficial in improving the longevity of renal transplants.
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Wicht, Jonathan H. "Renal Transplant Survey: how standardised is a standard kidney transplant?" Master's thesis, University of Cape Town, 2017. http://hdl.handle.net/11427/24507.
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Aim: The primary intention of the current study was to discover if there are international standards in renal transplantation. Method: A questionnaire was created using an online survey tool (Qualtrics ®), and distributed to a list of email addresses supplied by the unit's senior transplant surgeon. A literature review was performed on the questions and on the history of transplantation. Ethics was approved by FHS HREC number 193/2015. Results: A total of 30 surveys were completed from a total of 147 emails sent (20.4%). Two thirds of respondents work exclusively in the public sector and almost two-thirds (63.3%) of the respondents had been involved in transplantation for over 10 years. Two thirds of the surgeons estimate that their units perform more than 60 transplants per annum. Only 30% (9/30) use living donors in more than 50% of their surgeries. Most (53.3%) perfuse the kidneys both in the donor (in situ) and outside (ex situ or ex vivo). If no anatomic abnormalities were noted in open living donor nephrectomy, 63.3% would prefer to use the left kidney, and the recipient transplantation would be performed on the right side (76.7%). The majority (90%) of surgeons would preserve the vas deferens, but sacrifice the round ligament and inferior epigastric vessels (76.7% and 80% respectively). There is no marked difference for use of either the internal or external iliac artery for the arterial anastomosis, but most use the external iliac vein for venous anastomosis (86.7%). 80% use a ureteroneocystostomy with a tunnel, and 60% use a DJ stent or ureteric catheter and closed suction drain routinely. Two thirds would remove the transurethral catheter on day 4-7 post operatively. 80% routinely biopsy the kidney, and 63.3% would biopsy prior to treating for possible acute renal rejection. Discussion: These results compare with some of the studies found in the literature and operative textbooks. There do appear to be standards noted between most of the respondent's answers. Conclusion: There do appear to be standards for renal transplantation and these are appreciated globally.
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O'Dair, Jonathan David. "Kidney transplant : graft and recipient profiling." Thesis, University of Nottingham, 2009. http://eprints.nottingham.ac.uk/10877/.
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Despite the recent introduction of a number of new and more potent anti-rejection drugs, the incidence of rejection and long-term graft survival remain unchanged. There remains a significant difference in long-term graft survival depending on the source of the donor. The purpose of this study was to examine gene expression in the transplanted kidney using microarray technology to identify potential biomarkers that could be used to predict and monitor graft function so that appropriate interventions could be made in the event of graft dysfunction. Over a 5 year period RNA was extracted from 144 donor kidneys that were transplanted. The initial attempts at probe preparation and hybridization were unsuccessful. This led to the development of a new strategy which involved the use of state-of-the-art microarray technology which embraced the advances realised with the completion of the human genome project. Microarray data was analysed using J-Express and Pathway studio. Significance analysis of microarray, hierachical clustering, gene ontology mapping and pathway analysis was performed. The identification of potential biomarkers that had previously been described by other authors validated this approach. In addition novel genes were identified that may have a role as biomarkers of graft function. Other potential biomarkers were identified that represented cellular processes that could be modified by therapeutic intervention thus possibly changing the clinical outcome or allowing monitoring of the success of therapy. Confirmation of previously described biomarkers and the identification of novel potential biomarkers has confirmed that gene expression profiling has a valuable role in identifying processes that are indicative of disease processes including those involved in kidney transplantation. Furthermore with the development of minimally invasive tests to measure these biomarkers, we can potentially change the natural history of the disease process, and hence, preserve graft function and possibly prolong life.
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Tabata, Masami. "Becoming a kidney transplant citizen: kidney transplantation, race and biological citizenship." Thesis, Boston University, 2013. https://hdl.handle.net/2144/21260.
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Thesis (M.A.) PLEASE NOTE: Boston University Libraries did not receive an Authorization To Manage form for this thesis or dissertation. It is therefore not openly accessible, though it may be available by request. If you are the author or principal advisor of this work and would like to request open access for it, please contact us at open-help@bu.edu. Thank you.I conducted a four-month ethnographic fieldwork study to document the stories of thirteen post-kidney-transplant minority patients and three nephrologists at Boston Medical Center. My research explores how patients’ interactions with health professionals, medical regimens, dialysis treatments, and adaptation to living with transplanted kidneys constantly shape their identities and perceptual worlds. Patients’ narratives highlighted the emotional struggles they encountered along the path of End-Stage Renal Disease, which unfolded as distinct experiences influenced by their varied backgrounds. The majority of my patient-participants lived on the verge of poverty, and in some cases, their insurance status caused delays in their being registered on the transplant waiting list, making them endure a long wait. Some patients were afraid of wearing short sleeves because they thought the scars on their arms from dialysis treatment would lead others to think they were gangsters. Instantiations of various theories emerged from the saturated data and narrative analysis, from Bourdieu’s concept of habitus with regard to the process of how patients alter their consciousness through interactions with medicine to Foucault’s ideas of power relations and technologies of the self that address the issues of agency and power that influence the formation of patients’ identities. The intersection of these theoretical frameworks led me to develop the critical medical anthropological-oriented concept of biological citizenship. This paper examines 1) the ways in which “race” interacts with the theoretical concept of biological citizenship and 2) the ways in which socioeconomic status and race tailor a kidney transplant patient’s illness experience, and related discourse.
2031-01-01
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Solomon, Daniel Aran. "Decision Making by Patients Awaiting Kidney Transplant." Yale University, 2010. http://ymtdl.med.yale.edu/theses/available/etd-03052010-141133/.
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Involving patients in medical decisions by acknowledging patients personal values and individual preferences has become an important goal of providing ethical medical care. Despite a general movement towards a model of shared decision-making, many patients do not fully meet their preferred role in practice. The decision whether or not to accept a kidney once it is offered to a patient awaiting transplant has historically been made predominantly by the transplant surgeon with little involvement from the patient. Because dialysis can provide long-term renal replacement, declining a kidney is a viable option. Patient changes over time and inherent heterogeneity of donor kidneys make this an authentic decision requiring careful analysis of costs and benefits from the patient perspective. The purpose of this study is to improve our understanding of how patients and transplant surgeons prioritize different factors when deciding whether or not to accept a kidney that has become available, in order to empower patients to become more involved in the decision-making process. Phase I: We developed a comprehensive list of factors that patients might consider important through qualitative interviews with patients, and deliberation with a transplant surgeon (SK) and a transplant nephrologists (RF). Phase II: We quantified the relative importance of each factor for patients on the transplant list and for transplant surgeons with a computerized survey using Maximum Differences Scaling. We developed relative importance scores using Heirarchical Bayes analysis, and tested for associations between patient characteristics and relative importance scores using Spearmans correlation coefficient and the Mann Whitney U test for continuous and categorical variables respectively. Of the factors evaluated, patients placed the greatest value on Kidney quality, How closely matched you are to the kidney, and How strongly your surgeon feels you should accept the kidney. Relative importance of different factors did not change based on patient demographic characteristics. Patients who are on the waiting list longer give less importance to kidney quality (standard beta estimate -0.23, p value 0.03) and more importance to How difficult it is for you to be matched to a donor (ie whether or not you are sensitized) (standard beta estimate 0.28, p value 0.01). Surgeons placed the greatest value on Kidney quality, How difficult it is for the patient to be matched to a kidney (ie whether or not the patient is sensitized), and The age of the donor. This pilot study suggests a role for standardized education tools to help empower patients to be involved in this difficult decision. Development of decision aids can be guided by the results of this project.
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Sankaran, David. "Cytokine gene polymorphism and kidney transplant outcome." Thesis, University of Manchester, 1999. http://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.488310.
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The pro-inflammatory cytokine TNF -a. and the immunoregulatory cytokine IL-IO have been implicated in acute rejection of kidney allografts. Similarly, the pro-fibrotic cytokine TGF-IJ 1 has been reported to be involved in the development of chronic rejection. It has also been shown that polymorphisms in the TNFA gene promoter (position -308) and in the TGF-IJI gene (at codon 25) correlate with differential production of these cytokines in vitro. Gene polymorphisms in the IL-IO promoter were also identified previously. However, their function had not been determined. Therefore, the initial part of this study was to investigate the effect of the three single base substitutions (G/A, CIT and CIA) in the IL-IO gene promoter on IL-IO gene expression. The results show that the G/A polymorphism at position -1117 of the a- 10 promoter was associated with differential production of IL-IO in vitro. Homozygous inheritance of a 'G' at this position correlated with a significant increase in the production of IL-IO by Con-A stimulated PBMCs. In addition, a-to gene reporter assays performed in the U937 monocytic cell line demonstrated that the activity of IL-l 0 promoter constructs containing the '0' was significantly higher than constructs containing the 'A' at position -1117 when co-transfected with an Ets-l transcription factor expression vector. Results from gel shift assays suggest that this difference in gene expression may be due to altered binding affinities of transcription factors to the IL-IO promoter. The second part of this study was to determine whether the IL-IO gene polymorphism, together with the TNF-a and TGF-pl gene polymorphisms, could influence the incidence and severity of acute rejection in the first 6 months following renal transplantation. Their effect on chronic transplant dysfunction was also assessed. The cytokine genotypes of 115 consecutive first cadaveric kidney allograft recipients and their corresponding donors were screened. Acute rejection episodes (RE) and the incidence of chronic transplant nephropathy (CTN) were defined clinically and confirmed histologically where possible. RE were further classified according to severity (RS), namely steroid resistant or responsive RE. The patients were categorised as high or low producers of the respective cytokines according to their genotypes and these were then correlated with the RE, RS and CTN. The recipient TNF-a high and IL-IO high producer genotype was significantly associated with multiple RE (~) in HLA-DR mismatched transplants (p=O.0047 and p=O.04S respectively) while only the TNF-a high producer genotype was associated with steroid resistant RE (p=O.02S). Donor cytokine genotypes did not correlate with RE or RS. When cytokine genotype combinations were analysed in context ofHLA-DR mismatching, the recipient T'NF-ahigh/donor TGF-Pl high producer genotype was associated with an increase in the incidence of RE. The recipiem TNF-a higML-lO high producer genotype was associated with an increase in the incidence of multiple RE in HLA-DR mismatched transplants and was also associated with steroid resistant RE. There was no significant association between cytokine genotypes and CTN. In conclusion, cytokine gene polymorphisms are determinants of RE and RS following kidney transplantation. Routine screening of these gene polymorphisms may have a clinical role in identifying patients at risk of multiple RE and severe rejections.
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Singer, Julian John. "The Gut-Kidney Axis in Kidney Transplantation." Thesis, The University of Sydney, 2022. https://hdl.handle.net/2123/29702.
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For the majority of patients with end-stage kidney disease, kidney transplantation remains the optimal treatment modality, offering superior survival and quality of life at a fraction of the cost of dialysis. However, the requirement for long-term immunosuppression increases the susceptibility of transplant recipients to metabolic complications, infection, cancer, and cardiovascular disease, meaning that a “normal” lifespan is rarely, if ever achieved. Innovative strategies are needed to reduce the burden of current immunosuppressive regimens and to maintain the balance between immunosuppression and the maintenance of protective immunity.
The gut microbiome is a critical determinant of human health and modulates host immunity and metabolism through a number of recognised mechanisms, and likely others as yet unrecognised. In transplantation, the gut microbiome offers a novel target to alleviate the deleterious immune and metabolic responses that result from exposure to alloantigen and long-term immunosuppression. Herein, we show for the first time, that dietary modification of the gut microbiome can prevent allograft rejection in a murine model of kidney transplantation through signalling via GPR43 and mediated by the action of T regulatory cells.
The aims of this thesis were to investigate the role of the gut microbiome in mediating immune responses in kidney transplantation, and to assess strategies to measure glycaemic risk (pre-transplant) and status (post-transplant). This thesis comprises a pre-clinical model of kidney transplantation and translational studies in the clinic, and is presented as a collection of published and submitted works.
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Huml, Anne M. "Outcomes of Deceased Donor Kidney Offers to Patients at the Top of the Waiting List." Case Western Reserve University School of Graduate Studies / OhioLINK, 2018. http://rave.ohiolink.edu/etdc/view?acc_num=case1512678441955104.
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Jha, Prakash Teknarayan. "Optimizing Paired Kidney Transplant by Applying Machine Learning." University of Toledo / OhioLINK, 2011. http://rave.ohiolink.edu/etdc/view?acc_num=toledo1301028157.
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Keung, Karen Lok Yee. "The Application of Transcriptomics in Kidney Transplant Injury." Thesis, The University of Sydney, 2019. http://hdl.handle.net/2123/21050.
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This research aimed to address two unmet clinical needs in renal transplantation. Firstly, novel therapeutics to improve allograft outcomes are required. Secondly, non-invasive prognostic biomarkers to predict adverse allograft outcomes are needed to provide an early treatment opportunity. The use of large-scale molecular profiling data coupled with advanced computational strategies to address these needs was the foundation for this research. In chapters 3 and 4, the aim was to describe for the first time the derivation of master regulatory genes, or key drivers, amongst the pathologic molecular pathways in acute rejection (AR) of the renal allograft, and demonstrate that these may serve as novel targets for therapeutic intervention. Using microarray gene expression datasets from human renal allograft biopsy tissue, an integrative network-based computational approach was employed to predict the key driver genes in AR, identifying 14 key drivers. Interrogation of a computational drug-repositioning resource identified drugs in current clinical use as candidates for repositioning in AR prevention. Minocycline was selected for validation in a murine cardiac allograft model of AR. Used alone, it attenuated the inflammatory profile of AR compared with controls, and prolonged graft survival when co-administered with immunosuppression. The aim of the work in chapter 5 was to facilitate the discovery of a whole blood, thus non-invasive, prognostic biomarker signature obtained early in the post-transplant course that could predict patients who will develop allograft fibrosis. Early identification of these patients could provide an opportunity to alter immunosuppression before fibrosis is established. Here, validation of an unpublished prognostic microRNA signature derived from whole blood obtained 3 months post-transplant, to predict those with allograft fibrosis 12 months post-transplant, was sought. This signature was derived from collaborators in the Genomics of Chronic Allograft Dysfunction (GoCAR) study, and validation sought using samples from the Australian Chronic Allograft Dysfunction (AUSCAD) study, a single-centre cohort of transplant patients with prospective collection of renal biopsy and biofluid samples with linked clinical data. The 4-miRNA signature was unable to accurately prognosticate patients that progressed to fibrosis at 12 months in the AUSCAD cohort. How future work could be modified to facilitate the identification and validation of a robust prognostic biomarker signature are addressed.
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Rigatto, Claudio. "Cardiac disease in renal transplant recipients /." St. John's, NF : [s.n.], 2001.
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Molnar, Amber. "Predicting Graft Loss Following Acute Kidney Injury in Patients With a Kidney Transplant." Thesis, Université d'Ottawa / University of Ottawa, 2016. http://hdl.handle.net/10393/34236.
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Acute kidney injury (AKI), characterized by an abrupt loss of kidney function with retention of nitrogenous waste products, is common in the months to years following kidney transplantation and is associated with an increased risk of transplant failure (graft loss). Kidney transplant patients who experience graft loss and return to dialysis have an increased mortality risk and a lower quality of life. Research involving kidney transplant patients can prove challenging, as they are relatively small in number. To increase statistical power, researchers may utilize administrative databases. However, these databases are not designed primarily for research, and knowledge of their limitations is needed, as significant bias can occur. When using administrative databases to study AKI in kidney transplantation, the method used to define AKI should be carefully considered. The power of a study may be greatly increased if AKI can be accurately defined using administrative diagnostic codes because data on AKI will be universally available for all patients in the database. However, the methods by which diagnostic codes are assigned to a patient allow for error to be introduced. We confirmed that, when compared to the gold standard definition for AKI of a rise in serum creatinine, the diagnostic code for AKI has low sensitivity but high specificity in the kidney transplant population (the best performing coding algorithm had a sensitivity of 42.9% (95% CI 29.7, 56.8) and specificity of 89.3% (95% CI 86.2, 91.8) (Chapter 3). We therefore determined that for the study outlined in Chapter 4, defining AKI using diagnostic codes would significantly under-capture AKI and misclassify patients. We decided to define AKI using only serum creatinine criteria even though this would limit our sample size (creatinine data was only available for a subset of patients in the administrative databases). In Chapter 4, we derived an index score to predict the risk of graft loss in kidney transplant patients following an admission to hospital with AKI. The index includes six readily available, objective clinical variables that increased the risk of graft loss: increasing age, increased severity of AKI (as defined by the AKIN staging system), failure to recover from AKI, lower baseline estimated glomerular filtration rate, increased time from kidney transplant to AKI admission, and deceased donor. The derived index requires validation in order to assess its utility in the clinical realm.
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Richards, Roselee Jayne. ""You look very well for a transplant" : autoethnographic narrative and identity in chronic kidney disease, kidney failure and the life post-transplant." Thesis, Stellenbosch : Stellenbosch University, 2012. http://hdl.handle.net/10019.1/19909.
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Thesis (PhD)--Stellenbosch University, 2012.ENGLISH ABSTRACT: Despite the high prevalence of chronic kidney disease, renal narratives are under-reported. Much of what is written on kidney failure is written by health care professionals for health care professionals and about patients. While medical experts and health care practitioners have one type of knowledge, their patients have another type of knowledge acquired through their experience of their own condition. From within the disability and patients’ rights movements urgent calls have been made for the authentic voices of disabled people and patients to be heard without the mediation of professional lenses. In response to this my dissertation combines personal and academic writing to explore my own experience of end-stage renal disease, dialysis, transplantation and the life after transplant. I have used autoethnography as a methodology. Autoethnography is a relatively new, somewhat postmodern form of inquiry that developed from the reflexive turn in anthropology and narrative studies in the latter part of the twentieth century. It is very useful in writing about the experience of illness and reflecting on illness narratives because, in autoethnographic writing, the observer and observed, the narrator and narrated, insider and outsider are the same person. This allows scope for exploring the problematics of representation and for finding alternatives to already existing ways of telling certain stories. Engaging with autoethnography’s postmodern aspects has allowed me to conceptualize experiences that, until I undertook this research, I have never been able to articulate, because the traditional (static) illness narrative forms did not speak to my experience or my understanding of my condition. The central issue in my dissertation lies in the question: How do I tell the story of chronic illness once I have had an organ transplant? Flowing from this are a number of sub-issues: Can my story change? How do I describe myself: The well, the ill, the impaired, the disabled, the afflicted? Do I describe myself living in no man’s land? In my narrative, do I oscillate between being well and ill, or do I occupy another territory entirely? And if I do, what is it? My study shows that writing the story (or stories) of chronic kidney disease is complex, nuanced and dynamic and that, far from being an extended liminal experience, kidney disease is littoral. This distinction is important in coming to narrative terms with an identity that is not damaged so much as different. Through this I hope to demonstrate to both outsiders and insiders, who often submit to narratives that are forced on them, that more satisfying alternatives can be found.
AFRIKAANSE OPSOMMING: Ondanks die hoë voorkomssyfer van chroniese nierkwale word nierverhale nie genoeg aangemeld nie. Die meerderheid van dit wat oor nierversaking geskryf word, word deur gesondheidsorgdeskundiges vir gesondheidsorgdeskundiges en oor pasiënte geskryf. Terwyl mediese deskundiges en gesondheidsorgpraktisyns een soort kennis het, het hulle pasiënte ’n ander soort kennis op grond van hulle ervaring van hulle eie toestande. Van binne die gestremdheid en pasiënteregte-bewegings het ’n dringende oproep weerklink vir die outentieke stemme van mense met gestremdhede en pasiënte om gehoor te word sonder die tussenkoms van professionele perspektiewe. In reaksie hierop kombineer my verhandeling persoonlike en akademiese beskrywings om my eie ervaring van eindstadium- nierkwale, dialise, oorplanting en die lewe na oorplanting te verken. Ek het outo-etnografie as metodologie gebruik. Outo-etnografie is ’n relatief nuwe, ietwat postmoderne vorm van ondersoek wat in die tweede deel van die twintigste eeu uit die refleksiewe wending in antropologie en narratiewe studies ontwikkel het. Dit is baie bruikbaar wanneer oor die belewenis van siekte en besinning oor siekte-narratiewe geskryf word aangesien die waarnemer en die waargeneemde, die verteller en dit wat vertel word, die ingewyde en die buitestander in outo-etnografiese skryfwerk dieselfde persoon is. Dit laat meer ruimte vir verkenning van die problematiek van voorstelling en vir die opspoor van alternatiewe vir reeds bestaande wyses om sekere stories te vertel. My bemoeienis met postmoderne aspekte van outo-etnografie het dit vir my moontlik gemaak om ervaringe wat ek tot en met hierdie navorsing nooit kon artikuleer nie, te konseptualiseer, aangesien die tradisionele (statiese) vorme van siekte-narratiewe nie tot my ervaring of my begrip van my toestand gespreek het nie. ‘Hoe vertel ek die storie van chroniese siekte nadat ek ’n orgaanoorplanting gehad het?’ is ’n sentrale vraagstuk in my verhandeling. Hieruit spruit ’n aantal newevraagstukke voort: Kan my storie verander? Hoe beskryf ek myself: Die gesonde persoon, die sieke, die verswakte, die gestremde, die aangetaste? Hoe beskryf ek myself wat in ’n niemandsland woon? Fluktueer ek in my narratief tussen gesond wees en siek wees of betrek ek ’n geheel ander gebied? En indien wel, wat is dit? My studie toon dat, om die storie (of stories) van chroniese niersiekte te skryf, kompleks, genuanseerd en dinamies is en dat niersiekte glad nie ’n uitgebreide liminale ervaring is nie, maar eerder littoraal is. Dit is belangrik wanneer daar tot ’n narratiewe verstandhouding gekom moet word met ’n identiteit wat nie soseer beskadig is nie, maar eerder anders. Hierdeur hoop ek om aan beide buitestanders en ingewydes, wat dikwels voor narratiewe wat op hulle afgedwing word, moet buig, te wys dat daar meer bevredigende alternatiewe gekry kan word.
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Fergusson, Nicholas Anthony. "Alternative Endpoints and Analysis Techniques in Kidney Transplant Trials." Thesis, Université d'Ottawa / University of Ottawa, 2017. http://hdl.handle.net/10393/36230.
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Clinical trials in kidney transplantation suffer from several major issues including:
1) Unfeasibility due to low short-term event rates of hard outcomes and 2) Reliance on a composite outcome that consists of unequal endpoints that may generate misleading results. This thesis attempts to explore and apply methods to solve these issues and ultimately, improve kidney transplantation trials.
We present a secondary analysis of the ACE trial in kidney transplant using composites with alternative graft function surrogate endpoints. Typically, kidney transplant trials—including the ACE trial— use a time-to-event composite of death, end-stage renal disease (ESRD), and doubling of serum creatinine. Instead of doubling of serum creatinine, we investigated the use of percentage declines of estimate glomerular filtration rate (eGFR) within a time-to-event composite of death and ESRD. Additionally, we present an application of an innovative analysis method, the win ratio approach, to the ACE trial as a way of lessening concerns associated with unequal composite endpoints.
Composites of death, ESRD, and either a 40%, 30% or 20% decline in eGFR did not alter original ACE trial results, interpretations, or conclusions. The win ratio approach, and the presentation of a win ratio, generated very comparable results to a standard time-to-event analysis while lessening the impact of unequal composite endpoints and making fewer statistical assumptions. This research provides a novel, trial-level application of alternative endpoints and analysis techniques within a kidney transplant trial setting.
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Zhang, Haonan. "Machine Learning Approaches for Prediction of Kidney Transplant Survival." University of Toledo / OhioLINK, 2019. http://rave.ohiolink.edu/etdc/view?acc_num=toledo1555953011881185.
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Sharma, Ankit. "The impact of eplet mismatches and de novo donor specific antibodies in kidney and simultaneous pancreas-kidney transplantation." Thesis, University of Sydney, 2020. https://hdl.handle.net/2123/24228.
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Improving kidney transplant graft survival is of critical importance to patients, caregivers and health professionals. Advances in immunosuppression regimens have mitigated the risk and injurious effects of T-cell mediated rejection resulting in increased graft survival rates, particularly in the first year after transplantation. The leading cause of graft attrition is now antibody mediated rejection (AMR), implicated in up to two thirds of graft loss after one year. Donor specific antibodies (DSA) are central to the pathogenesis of AMR, with the presence of pre-transplant DSA (or sensitisation) reducing access to transplantation due to the risk of hyper-acute or acute AMR. Children with end-stage kidney disease (ESKD) are particularly disadvantaged by sensitisation due to their expected need for re-transplantation, yet strategies to avoid sensitisation and overcome this antibody barrier are poorly defined. Chapter 2 of this thesis provides an overview of sensitisation and desensitisation therapies in children with ESKD.
Similar to pre-transplant DSA, de novo DSA (dnDSA) may form after transplantation and are implicated in AMR. The incidence and magnitude of effects of dnDSA on graft and patient outcomes is however variably reported in the literature. Chapter 3 of this thesis provides a systematic review and meta-analysis of the association between dnDSA and graft and patient outcomes.
Greater understanding of the harmful effects of dnDSA has increased interest in developing strategies to avoid their development. Current assessment of histocompatibility considers whole HLA antigen mismatches, the precision of which may be improved by accounting for differences in the surface antibody accessible amino acid sequences (eplets) on donor and recipient HLA. Previous studies have demonstrated that increasing number of eplet mismatches are associated with dnDSA development, acute rejection and transplant glomerulopathy. This relationship is particularly evident for HLA class II eplet mismatches and is modified by immunosuppression. The longitudinal relationship between eplet mismatches, dnDSA and acute rejection outcomes has however been poorly defined in children and is addressed by Chapter 4 of this thesis.
Apart from requiring a greater understanding of the causal pathways between eplet mismatches and graft outcomes, a further challenge to utilising eplet mismatch information in organ allocation is the large number and complexity of mismatches which require consideration. Eplet mismatches are recognised to have innate properties such as electrostatic potential which confer their ability to induce an immune response (immunogenicity) or produce subsequent alloantibody recognition (antigenicity). Differentiating between the specific eplet mismatches which are predictive of adverse graft outcomes and those which are less likely to produce an immune response may allow assignment of unacceptable mismatches and permissible mismatches, thus simplifying implementation into organ allocation. Chapters 5 and 6 of this thesis identify specific eplet mismatches which predict dnDSA and acute rejection outcomes.
The studies within this thesis collectively detail the relationship between eplet mismatches, dnDSA and acute rejection in kidney transplantation and identify specific eplet mismatches which are predictive of adverse graft outcomes.
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Possemato, A. Kyle Geller Pamela A. "An internet-based expressive writing intervention for kidney transplant recipients /." Philadelphia, Pa. : Drexel University, 2007. http://hdl.handle.net/1860/1799.
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Moreno, Maria Fernanda Costa Henriques. "Adesão terapêutica em doentes submetidos a transplante hepático e renal." Master's thesis, Universidade Nova de Lisboa. Escola Nacional de Saúde Pública, 2012. http://hdl.handle.net/10362/9707.
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RESUMO - Introdução - A não adesão à terapêutica nos doentes transplantados foi identificada em diversos estudos e constitui um fator preditivo de morbilidade e mortalidade. Como em Portugal não existe um conhecimento aprofundado sobre os comportamentos de não adesão nos doentes transplantados, este estudo tem como objetivo a avaliação da adesão terapêutica nos doentes submetidos a transplante hepático e renal e a identificação de fatores associados à não adesão.
Metodologia - Foi elaborado e aplicado um questionário a uma amostra de doentes com mais de 18 anos submetidos a transplante renal ou hepático há mais de seis meses. Foi analisada a associação entre o comportamento de não adesão e fatores relacionados com o doente, condição, terapêutica e acesso aos serviços de saúde.
Resultados - Dos 75 inquiridos, 60% eram doentes transplantados de fígado e 40% transplantados renais, com uma média de 48 anos e maioritariamente do sexo masculino (65,3%). Entre os inquiridos, verificou-se que 44% admitiu ter tido um comportamento de não adesão aos medicamentos prescritos. Os doentes que reportaram comportamento de não adesão tinham uma média de idades de 44 anos, possuíam como escolaridade o ensino secundário ou curso profissional, trabalhavam ou estudavam, tomavam menos de oito comprimidos por dia e tinham sido transplantados há mais de 5 anos.
Adicionalmente, verificou-se que a dieta (28,8%), o exercício físico (33,3%) e o deixar de fumar (10,7%) são as indicações dadas pelos profissionais de saúde que os doentes referiram ter mais dificuldade em cumprir.
Conclusão - Com este estudo esperamos ter contribuído para aumentar o conhecimento sobre a adesão à terapêutica nos doentes transplantados, o qual deve ser aprofundado para permitir o desenvolvimento de estratégias efetivas de melhoria da adesão aos planos terapêuticos.ABSTRACT - Introduction - Treatment non adherence in transplant patients has been identified in numerous studies and is a predictive factor of morbidity and mortality in these patients. As the knowledge about the behaviors of non-adherence in transplant patients in Portugal is not very extensive this study aims to assess the treatment adherence in patients undergone liver and kidney transplantation as well as the identification of factors associated with non adherence. Methodology - A questionnaire was developed and applied to a sample of patients with more than 18 years who undergone kidney or liver transplantation, more than six months ago. It was also analyzed the association between non adherent behavior and patient-related factors, condition, treatment and access to healthcare services. Results - Out of 75 respondents, 60% were liver transplant patients and 40% were kidney transplant recipients, with an average age of 48 years and mostly male (65,3%). Amongst the respondents, 44% admitted having had already a non adherent behaviour to prescribed medications. Patients, who reported non adherent behaviour, had an average age of 44 years, secondary education or professional course, worked or studied, took less than eight pills a day and had been transplanted more than 5 years ago. Additionally it was found that the diet (28.8%), exercise (33.3%) and smoking cessation (10.7%) stand as the indications given by healthcare professionals that patients reported having more difficulty to adhere. Conclusion - With this study we hope to have contributed to increase knowledge about treatment adherence in transplant patients in Portugal, which must be deepened in order to allow the development of effective strategies to improve adherence to treatment plans in these patients.
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Daniel, H. Clare. "Illness perceptions and their association with coping responses, perceived health status, beliefs about, and adherence to medicines following a renal transplant." Thesis, Open University, 1997. http://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.387780.
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Ataya, Fernández Michelle 1993. "Adaptive NKG2C+ NK cells and cytomegalovirus infection in kidney transplant recipients." Doctoral thesis, TDX (Tesis Doctorals en Xarxa), 2021. http://hdl.handle.net/10803/671368.
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Cytomegalovirus (CMV) infection in kidney transplant recipients (KTR) is frequent and may reduce graft and patient survival. T lymphocytes are essential to control the virus, which promotes the adaptive differentiation of NK cells characterized by CD94/NKG2C receptor expression. NKG2C+ NK cells and T lymphocytes were analyzed in a cohort of CMV seropositive KTR. Pretransplant NKG2C+ NK cells were associated with reduced incidence of symptomatic infection, and appeared unrelated with CMV-specific T cells in a parallel study, indicating that they may contribute to contain infection progression. Moreover, NKG2C+ NK cell expansions of variable magnitude developed following posttransplant infection. The data suggested that they participate in restoring the long-term CMV control, though their relative role could not be appreciated due to the overlapping effects of the infection on the T cell compartment. Combined assessment of T and NKG2C+ NK cells might allow a more precise assessment of CMV infection in KTR.La infección por citomegalovirus (CMV) en el trasplante renal (TR) es frecuente, reduciendo la supervivencia de injerto y paciente. Los linfocitos T son esenciales para controlar el virus, que además promueve la diferenciación adaptativa de células NK que expresan el receptor CD94/NKG2C. Se analizaron las células NKG2C+ y los linfocitos T en una cohorte de receptores de TR CMV+. Las células NKG2C+ pre-trasplante se asociaron a una menor incidencia de infección sintomática, sin relación con los linfocitos T específicos para CMV, indicando que pueden contribuir a contener la infección. La detección en grado variable de expansiones de células NKG2C+ tras la infección post-trasplante apunta también a su participación el control del CMV, pero su papel relativo no se apreció al solaparse con cambios en los linfocitos T. El estudio conjunto de las células T y NK NKG2C+ puede contribuir a una valoración más precisa de la infección por CMV.
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Patel, Chirag G. "The pharmacokinetics and pharmacodynamics of mycophenolic acid in kidney transplant recipients /." View online ; access limited to URI, 2006. http://0-wwwlib.umi.com.helin.uri.edu/dissertations/fullcit/3239911.
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Leino, Abbie D. "Tacrolimus Intra-Subject Variability in Adherent Kidney and Liver Transplant Recipients." University of Cincinnati / OhioLINK, 2018. http://rave.ohiolink.edu/etdc/view?acc_num=ucin1530265041482671.
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Bezerra, Ana Paula da Silva Azevedo Nora. "INCIDÊNCIA DE COMPLICAÇÕES VASCULARES EM TRANSPLANTE RENAL ENTRE 2013 E 2014 NA SANTA CASA DE MISERICÓRDIA DE GOIÂNIA." Pontifícia Universidade Católica de Goiás, 2016. http://tede2.pucgoias.edu.br:8080/handle/tede/3893.
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Introduction: Even though kidney transplant represents a new perspective to individuals with chronical kidney disease due to its correlation with a better quality of life results and morbimortality indexes, the procedure itself is not free of risks. Vascular complications rates around the world varies from 1 – 23% and it is are also associated with a high risk of kidney graft losses. Objective: To evaluate the incidence of vascular complications among patients submitted to kidney transplant at Santa Casa de Misericórdia de Goiânia on a period of time between January 2013 to December 2014. Material and Methods: It was analyzed 35 files from patients submitted to kidney transplant at Santa Casa de Misericórdia de Goiânia on a period of time between January 2013 and December 2014. It was analyzed the following variables: renal artery stenosis, renal artery thrombosis, renal vein stenosis, renal vein thrombosis, renal artery pseudoaneurysm, arteriovenous fistula, renal artery kinking, kidney graft torsion and kidney infarction. It was also collected data for: kidney graft side, donator´s aspects (alive or deceased), receptor´s age, receptor´s gender, necessity for reintervention and cold ischemia time. Results: It was included 32 patients, 34,38% females and 65,62% males, with median age of 46 years old. Among all surgical complications it was found 3 events of urinary leakage (9,3%), 2 events of retroperitoneal abscess (6,25%), 1 event of kidney graft torsion (3,12%) and 1 event of arterial stenosis (3,12%). All kidney grafts came from deceased donators (100%) and there were no graft losses. Conclusion: Even though the following study had shown a low incidence of vascular complications related with kidney transplant, the TIF more than 24 hours was the only independent risk factor associated with this event.
Introdução: Embora o transplante renal represente uma perspectiva ao indivíduo portador de doença renal crônica terminal por se correlacionar a melhores índices de qualidade de vida e de morbimortalidade, este procedimento não é isento de riscos. As taxas de complicações vasculares variam em todo mundo de 1 – 23% e guardam importância por estar associadas a elevado risco de perda do enxerto. Objetivo: Avaliar a incidência de complicação vascular em pacientes submetidos a transplante renal na Santa Casa de Misericórdia de Goiânia no período entre janeiro de 2013 a dezembro de 2014. Material e Métodos: Foram analisados 35 prontuários de pacientes submetidos a transplante renal na Santa Casa de Misericórdia de Goiânia no período de Janeiro de 2013 a Dezembro de 2014. Foram analisadas as seguintes variáveis: estenose de artéria renal, trombose de artéria renal, estenose de veia renal, trombose de veia renal, pseudoaneurisma de artéria renal, fístula arteriovenosa, kinking de artéria renal, torção de enxerto e infarto. Foi coletado em prontuário: rim transplantado, tipo de doador, idade do receptor, gênero do receptor, reinternação, tempo de isquemia fria. Resultados: A população estudada incluiu 32 pacientes, sendo 34,38% do sexo feminino e 65,62% do sexo masculino, com média de idade de 46 anos. Entre as complicações cirúrgicas, ocorreram 3 casos de fistula urinária (9,3%), 2 casos de coleção (6,25%), 1 caso de torção de enxerto (3,12%) e 1 caso de estenose arterial (3,12%). Todos os enxertos (100%) foram de doador falecido e não houve perda de enxerto em nenhum caso (0%). Conclusões: Embora o presente estudo tenha observado uma baixa incidência de complicação vascular relacionada a transplante renal, o TIF superior a 24hs foi o único fator de risco independente associado a tal evento (p=0,034).
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Salazar, Antony Brayan Campos. "Polimorfismos em genes envolvidos na farmacodinâmica de tacrolimo e everolimo e sua relação com a resposta ao tratamento imunossupressor, em receptores de transplante renal." Universidade de São Paulo, 2017. http://www.teses.usp.br/teses/disponiveis/9/9136/tde-23012018-170420/.
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O monitoramento de imunossupressores, como os inibidores de calcineurina ou de mTOR, é essencial para evitar desfechos clínicos desfavoráveis, em receptores de transplante renal. Polimorfismos em genes envolvidos na farmacocinética têm sido associados com variabilidade na resposta a imunossupressores, porém o papel de polimorfismos em genes envolvidos na farmacodinâmica é pouco conhecido. O objetivo deste estudo foi investigar a influência de polimorfismos de MTOR, PPP3CA, FKBP1A, FKBP2 e FOXP3, genes envolvidos na farmacodinâmica de imunossupressores, sobre a resposta clínica a tacrolimo e everolimo, em receptores de transplante renal. Foram incluídos 269 pacientes do ensaio clínico original (NCT01354301), realizado no Hospital do Rim e Hipertensão da UNIFESP, e randomizados em três esquemas imunossupressores: tacrolimo 0,05 mg/kg/dia com everolimo 1,5 mg/dia (TAC5/EVR); tacrolimo 0,1 mg/kg/dia com everolimo 1,5 mg/dia (TAC10/EVR); e tacrolimo 0,1 mg/kg/dia com micofenolato de sódio (TAC10/MFS). Foram coletados dados clínicos e laboratoriais, tais como o monitoramento de imunossupressores e desfechos de eficácia de segurança. Os polimorfismos nos genes MTOR (c.4731G>A, c.1437T>C, c.2997C>T); PPP3CA (c.249G>A); FKBP1A (n.259+243936T>C); FBKP2 (c.-2110G>T) e FOXP3 (c.-23+2882A>C, c.-22-902A>G) foram analisados por PCR em tempo real. As frequências alélicas dos polimorfismos estudados foram similares às da população global do projeto 1000genomes. O tratamento com everolimo e tacrolimo em maior dose (TAC10/EVR) foi associado com menor taxa de filtração glomerular estimada (TFGe) e maior creatinina sérica. Enquanto que o tratamento com tacrolimo e micofenolato de sódio (TAC10/MFS) foi associado com maior número de episódios de infecção por citomegalovirus, no 1° ano pós-transplante. Com relação aos desfechos de eficácia, os portadores do genótipo CC de MTOR c.1437T>C e FOXP3 c-23+2882A>C apresentaram maiores concentrações de creatinina sérica, no 12° mês (p<0,05). O polimorfismo FOXP3 c.-23+2882A>C foi associado com maior probabilidade de creatinina sérica aumentada (OR=1,75; IC95%=1,07-2,86; p=0,025). Os resultados da análise de regressão logística mostraram que o alelo MTOR c.4731G (genótipos AG+GG) foi associado com maior risco de rejeição aguda (OR=3,37; IC95%=1,10-10,30; p=0,033). Os portadores do alelo c.4731G apresentaram maior incidência cumulativa de episódios de rejeição, no 1° ano pós-transplante. Com relação aos desfechos de segurança, a variante FKBP2 c.-2110G>T (genótipo GG) foi associada com maior risco de leucopenia (OR=7,10; IC95%=1,81-27,87; p=0,025). O polimorfismo FKBP1A n.259+24936T>C (alelo C) foi associado com maior risco de constipação (OR=2,52; IC95%=1,13 - 5,61; p=0,024), enquanto que os polimorfismos FOXP3 c.-22-902A>G (alelo A) e c.-23+2882A>C (alelo A) foram associados, respectivamente, com maior risco de epigastralgia (OR=2,15; IC95%=1,01-4,56; p=0,047) e náuseas e/ou vômitos (OR=2,38; IC95%=1,05-5,38; p=0,038). O risco de apresentar dislipidemia foi maior nos portadores dos genótipos FKBP2 c.-21110GG (OR=1,92; IC95%=1,01-3,69; p=0,049) e FOXP3 c.-22-902GG (OR=2,06; IC95%=1,08-3,92; p=0,028). Em conclusão, os polimorfismos de genes MTOR, FKBP1A, FKBP2 e FOXP3 influenciam na função renal do enxerto e estão associados com risco de rejeição aguda e de eventos adversos, em receptores de transplante renal.The monitoring of immunosuppressive drugs, such as calcineurin and mTOR inhibitors, is essential to avoid undesirable kidney transplant outcomes. Polymorphisms in pharmacokinetics-related genes have been associated with variability in the response to immunosuppressive drugs, but the role of polymorphisms in pharmacodynamics-related genes is little known. The aim of this work was to investigate the influence of polymorphisms in MTOR, PPP3CA, FKBP1A, FKBP2 and FOXP3, genes involved in the pharmacodynamics of immunosuppressive drugs, on the clinical response to tacrolimus and everolimus in kidney transplant recipients. Two-hundred seventy-five kidney transplant recipients were included in this study, among the enrolled in the original clinical trial (NCT01354301) carried out at the Hospital do Rim e Hipertensão/UNIFESP, and randomized in three immunosuppressive treatments: tacrolimus 0.05 mg/kg/day with everolimus 1.5 mg/day (TAC5/EVR); tacrolimus 0.1 mg/kg/day with everolimus 1.5 mg/day (TAC10/EVR); and tacrolimus 0.1 mg/kg/day with sodium mycophenolate (TAC10/MFS). Clinical and laboratory data, including immunosuppressive drug monitoring, efficacy and safety outcomes, were recorded. Polymorphisms on the MTOR (c.4731G>A, c.1437T>C, c.2997C>T); PPP3CA (c.249G>A); FKBP1A (n.259+243936T>C); FBKP2 (c.-2110G>T) and FOXP3 (c.-23+2882A>C, c.-22-902A>G) genes were analyzed by real-time PCR. Allelic frequencies of the studied polymorphisms were similar to those of the global population reported by the 1000genomes project. Treatment with everolimus and high-dose tacrolimus (TAC10/EVR) was associated with lower estimated glomerular filtration rate (eGFR) and higher serum creatinine. Meanwhile treatment with tacrolimus and sodium mycophenolate (TAC10/MFS) was associated with higher number of cytomegalovirus infections, at 1-year post-transplantation. With regard to the kidney efficacy outcomes, the carriers of the CC genotype of MTOR c.1437T>C and FOXP3 c.-23+2882A>C had higher serum creatinine, at month 12 (p<0.05). The FOXP3 c.-23+2882A>C polymorphism was associated with high likelihood of increased serum creatinine (OR=1.75, 95%IC=1.07-2.86, p=0.025). The results of the logistic regression analysis showed that the allele MTOR c.4731G (AG+GG genotypes) was associated with higher risk of acute rejection (OR=3.37, 95%IC=1.10-10.30, p=0.033). The carriers of the c.4731G allele showed higher cumulative incidence of acute rejection episodes at 1-year post-transplantation. With regard to kidney safety outcomes, the FKBP2 c.-2110G>T variant (GG genotype) was associated with higher risk of leucopenia (OR=7.10, 95%IC=1.81-27.87, p=0.025). The FKBP1A n.259+24936T>C (C allele) polymorphism was associated with higher risk of constipation (OR=2.52, 95%IC=1.13-5.61, p=0.024), whilst FOXP3 c.-22 902A>G (A allele) and c.-23+2882A>C (A allele) were associated, respectively, with higher risk of epigastric pain (OR=2.15, 95%IC=1.01-4.56, p=0.047) and nausea and/or vomiting (OR=2.38, 95%IC=1.05-5.38, p=0.038). The risk of developing dyslipidemia was higher in carriers of the genotypes FKBP2 c.-21110GG (OR=1.92, 95%CI=1.01-3.69, p=0.049) and FOXP3 c.-22-902GG (OR=2.06, 95%CI=1.08-3.92, p=0.028). In conclusion, the polymorphisms in the MTOR, FKBP1A, FKBP2 and FOXP3 genes influence renal graft function and are associated with risk of acute rejection and adverse events in renal transplant recipients.
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Quigley, R. L. "Investigation of the mechanism of induction of immunologic unresponsiveness to renal allografts by blood transfusion." Thesis, University of Oxford, 1988. http://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.233514.
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Pigott, Clive J. "The role of peptide in direct allorecognition in human transplantation." Thesis, Oxford Brookes University, 2002. http://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.250510.
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O'Neill, Stephen. "Role of heat shock protein 90 in modulating ischemia-reperfusion injury in the kidney." Thesis, University of Edinburgh, 2015. http://hdl.handle.net/1842/20410.
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Kidney transplantation is the gold standard treatment for end-stage renal disease. Renal ischemia-reperfusion injury is an unavoidable consequence of the transplantation procedure and is responsible for delayed graft function and poorer long-term outcomes. Pharmacological inhibition of heat shock protein 90 is a preconditioning strategy that has previously been shown to reduce renal ischemia-reperfusion injury. However, the clinical application of heat shock protein 90 inhibitors is limited by their toxicity profile and the exact mechanisms of protection conferred are unknown. The aims of this thesis were to establish mechanisms of protection offered by these drugs and investigate a less toxic analogue that has the potential to be safely translated into human studies. AT13387 is a novel small molecule heat shock protein 90 inhibitor with a low toxicity profile, which is being evaluated in phase II studies in oncology and therefore has excellent translational potential in the context of transplantation. Heat shock protein 90 inhibition up-regulates protective heat shock proteins (especially heat shock protein 70) and potentially down-regulates NF-ҡB activity by disruption of the IҡB kinase complex. Toll-like receptor 4 is a further regulator of NF-ҡB activity and studies have suggested that Toll-like receptor 4 plays a dominant role in mediating kidney damage following ischemia-reperfusion injury. To explore potential molecular mechanisms of protection, human embryonic kidney cells were pre-treated with AT13387 and exposed to endotoxin-free hyaluronan to stimulate sterile Toll-like receptor 4-specific NF-ҡB activation. AT13387-treatment resulted in breakdown of IҡB kinase, which abolished Toll-like receptor 4-mediated NF-ҡB activation by hyaluronan. Inhibition of autophagy prevented IҡB kinase-α degradation by heat shock protein 90 inhibition and resulted in regain of NF-ҡB activity by hyaluronan. In subsequent investigations, AT13387 decreased pro-inflammatory cytokine release following hyaluronan stimulation and increased cell viability in an in vitro model of oxidative stress. In mice, AT13387 induced heat shock protein 70 expression in the kidney. AT13387 pre-treatment then significantly reduced kidney injury following renal ischemia-reperfusion injury. In contrast, in severe combined immunodeficient mice, AT13387 no longer reduced kidney injury from renal ischemia-reperfusion injury. This emphasises the potential importance of the adaptive immune system in the protective effect of this agent. This resonates with reports of heat shock protein 70 up-regulation in the context of heat preconditioning, which leads to renal protection from renal ischemia-reperfusion injury that is lymphocyte-dependent. Secondary lung injury is an additional consequence of renal ischemia-reperfusion injury. In further experiments, pre-treatment with AT13387 again did not reduce kidney injury following renal ischemia-reperfusion injury in severe combined immunodeficient mice. However, AT13387 did reduce secondary lung injury. This lung protective effect may have been related to heat shock protein 70 up-regulation in the lungs by AT13387. A rationale for enhancing recovery, following renal ischemia-reperfusion injury, by inhibiting heat shock protein 90 was then sought. This investigation was undertaken in order to broaden the range of the available therapies to a wider group of patients including renal transplant recipients. AT13387 pre-treatment of the recipient mice preceded an isograft renal transplantation with a kidney harvested from a treatment naive mouse and cold stored for 4 hours. Although a significant reduction in tubular necrosis was not demonstrated following AT13387 treatment, the feasibility of the treatment strategy was demonstrated and interestingly lung injury secondary to transplantation was reduced. This thesis therefore highlights AT13387 as a new agent with the potential of reducing kidney injury and secondary lung injury following renal ischemia-reperfusion injury. The findings also demonstrate that the mechanisms of protection offered by this drug may involve the adaptive immune system. In addition to the induction of heat shock protein 70 expression in the kidney and repression of Toll-like receptor 4-mediated NF-ҡB signalling through breakdown of IҡB kinase.
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Coletta, Dawn K., Latoya E. Campbell, Jennifer Weil, Bruce Kaplan, Marie Clarkson, Jean Finlayson, Lawrence J. Mandarino, and Harini A. Chakkera. "Changes in Pre- and Post-Exercise Gene Expression among Patients with Chronic Kidney Disease and Kidney Transplant Recipients." PUBLIC LIBRARY SCIENCE, 2016. http://hdl.handle.net/10150/621483.
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Introduction Decreased insulin sensitivity blunts the normal increase in gene expression from skeletal muscle after exercise. In addition, chronic inflammation decreases insulin sensitivity. Chronic kidney disease (CKD) is an inflammatory state. How CKD and, subsequently, kidney transplantation affects skeletal muscle gene expression after exercise are unknown. Methods Study cohort: non-diabetic male/female 4/1, age 52 +/- 2 years, with end-stage CKD who underwent successful kidney transplantation. The following were measured both pre-transplant and post-transplant and compared to normals: Inflammatory markers, euglycemic insulin clamp studies determine insulin sensitivity, and skeletal muscle biopsies performed before and within 30 minutes after an acute exercise protocol. Microarray analyses were performed on the skeletal muscle using the 4x44K Whole Human Genome Microarrays. Since nuclear factor of activated T cells (NFAT) plays an important role in T cell activation and calcineurin inhibitors are mainstay immunosuppression, calcineurin/NFAT pathway gene expression was compared at rest and after exercise. Log transformation was performed to prevent skewing of data and regression analyses comparing measures pre- and post-transplant performed. Result Markers of inflammation significantly improved post-transplantation. Insulin infusion raised glucose disposal slightly lower post-transplant compared to pre-transplant, but not significantly, thus concluding differences in insulin sensitivity were similar. The overall pattern of gene expression in response to exercise was reduced both pre- and post- transplant compared to healthy volunteers. Although significant changes were observed among NFAT/Calcineurin gene at rest and after exercise in normal cohort, there were no significant differences comparing NFAT/calcineurin pathway gene expression pre- and post-transplant. Conclusions Despite an improvement in serum inflammatory markers, no significant differences in glucose disposal were observed post- transplant. The reduced skeletal muscle gene expression, including NFAT/calcineurin gene expression, in response to a single bout of exercise was not improved post- transplant. This study suggests that the improvements in inflammatory mediators post- transplant are unrelated to changes of NFAT/calcineurin gene expression.
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Peters, Björn. "Clinical and quality aspects of native and transplant kidney biopsies in Sweden." Doctoral thesis, Umeå universitet, Medicin, 2016. http://urn.kb.se/resolve?urn=urn:nbn:se:umu:diva-124615.
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Percutaneous kidney biopsies have been performed since 1944 to establish diagnoses and treatment. Risk factors based on a limited amount of data have shown age, blood pressure, kidney function and needle size as some risk factors for biopsy complications. Although the techniques of biopsy have improved over the years, it is still an invasive procedure and serious complications can occur. The overall aim of this thesis was to obtain a large series of data from biopsy procedures and to use these to bring further light on risk factors to help minimize the risk for patients and to optimize diagnostics. Specific aims were to clarify if different factors, such as gender, diagnoses, localization of biopsies, needle types and sizes, could be useful to help minimize complication risks in native kidney biopsies (Nkb) and transplant kidney biopsies (Txb). Another point to investigate was the value of the Resistive Index (RI) obtained at ultrasound before performing Txb. Materials and methods: A protocol for prospective multicentre registration of various factors and complications associated with Nkb and Txb was designed. Consecutive data were obtained from seven hospitals. All biopsies, except one computer tomography-guided Nkb, were performed using real-time ultrasound guidance and an automated spring-loaded biopsy device. For the biopsies 14- to 20- Gauge (G) needles were used. The kidney function level, i.e. estimated glomerular filtration rate (eGFR), was calculated using the Modification of Diet in Renal Disease (MDRD) formula (GFR in mL/min per 1.73m2). For statistical analyses the IBM SPSS Statistic 22 (Armonk, NY, USA) and OpenEpi (Open Source Epidemiologic Statistics for Public Health, www.OpenEpi.com) were used. Data were presented as Odds Ratio (OR), Risk Ratio (RR) and Confidence Intervals (CI). A two sided p-value of <0.05 was considered significant. In total 1299 consecutive biopsies (1039 native and 260 transplant kidneys) in 1178 patients (456 women and 722 men) were used for investigation. The median age of patients was 55 years (range 16 to 90 years). Major (require an intervention) and minor biopsy complications (no need of intervention) were registered. Results: The overall frequency of biopsy complications for Nkb was 8.8% (major 6.7%, minor 2.1%) and for Txb was 6.5% (major 3.8%, minor 2.7%); no death. Women had a higher risk for development of major (10.7% versus 4.7%, OR 2.4, CI 1.4-4.2) and overall biopsy complications (13.2% versus 6.5%, OR 2.2, CI 1.4-3.5) compared to men in Nkb. In Nkb, major complications were more common after biopsies from the right kidney in women versus men (10.8% vs 3.1%, OR 3.7, CI 1.5–9.5), in patients with lower versus higher BMI (25.5 vs 27.3, p=0.016) and for younger versus older age (44.8 vs 52.3 years, p=0.002). Lower (90 mmHg) compared to higher (98 mmHg) mean arterial pressure in Txb indicated a risk of major complications (p=0.039). Factors such as number of passes and kidney function did not influence complication rates. Biopsy needles of 16 G compared to 18 G showed more glomeruli per pass in Nkb (11 vs 8, p<0.001) and in Txb (12 vs 8, p<0.001). Sub-analysis revealed that 18 G 19 mm side-notch needles in Nkb resulted in more major (11.3% vs 3%, OR 4.1, CI 1.4-12.3) and overall complications (12.4% vs 4.8%, OR 2.8, CI 1.1-7.1) in women than in men. If the physician had performed less compared to more than four Nkb per year, minor (3.5% vs 1.4%, OR 2.6, CI 1.1-6.2) and overall complications (11.5% vs 7.4%, OR 1.6, CI 1.1-2.5) were more common. The localization of biopsy within the kidney (Nkb and Txb) was not a risk factor for complications. Patients with IgA-nephritis compared to patients with other diseases had a higher risk of major complications (11.7% vs 6.4 %, OR 1.8, CI 1.1–3.2). More major complications were found in Nkb if they had higher versus lower degree of glomerulosclerosis (31% vs 20 %, p=0.008) and in Txb if there was a higher versus lower degree of interstitial fibrosis (82% vs 33%, p<0.001). Re-biopsies (Nkb) were more common in patients with IgA-nephritis than those with other diseases (4.7% vs 1.3 %, OR 4, CI 1.5–11), in younger versus older age (42.6 vs 52.3 years, p=0.031), and in those with a higher versus lower degree of interstitial fibrosis (63% vs 34 %, p=0.046). In Txb, a RI≥0.8 compared to RI<0.8 predicted major (13.3% vs 3.2%, RR 4.2, CI 1.3-14.1) and overall biopsy complications (16.7% vs 5.3%, RR 3.2, CI 1.2-8.6). In the group <0.8, RI correlated with age (rs=0.28, p<0.001) and systolic blood pressure (rs=0.18, p=0.02). In the group ≥0.8, RI correlated with degree of interstitial fibrosis (rs=0.65, p=0.006) and systolic blood pressure (rs=0.40, p=0.03). The multiple regression analysis showed that the <0.8 RI group correlated only with age (p<0.001), whereas the ≥0.8 RI group correlated only with the degree of interstitial fibrosis (p=0.003). Conclusions: The present results motivate greater attention to be paid to the possibility of major side-effects after Nkb in women and biopsies from their right side, but as well in younger patients, and in those with lower BMI. This also applies for patients with presumptive IgA-nephritis and higher degree of glomerulosclerosis. In Txb, patients with higher degree of interstitial fibrosis had a greater risk of major complications. Moreover, the present data indicate that Nkb and Txb should be preferably taken with 16 G needles with 20 mm sample size. This results in better histological quality and there is a lower risk for major complications as compared to 18 G needles. The localization of biopsy within the kidney (Nkb and Txb) does not alter complication rates. For Nkb there were fewer complications if the physician had performed at least four biopsies per year. A RI≥0.8 in Txb indicates a greater risk for major and overall complications.
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Mollon, Jennifer. "Statistical analysis of genome-genome interaction with reference to kidney transplant outcome." Thesis, King's College London (University of London), 2014. https://kclpure.kcl.ac.uk/portal/en/theses/statistical-analysis-of-genomegenome-interaction-with-reference-to-kidney-transplant-outcome(581ae9b3-83b5-4d13-985f-2c57a248bc07).html.
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Though widely believed to exist, few convincing examples of genetic interactions have been detected through statistical approaches in genome-wide association studies. The first piece of work in this thesis attempts to determine if there is evidence for the existence of such interactions within genes identified through protein-protein interactions. A software package is developed and applied to data from a recent publically available genetic study. No evidence was found for an enrichment of such interactions in the available data. The second study applies three current methods for interaction detection to a real data set with compelling evidence of an interaction. Sparse Partitioning, SNPHarvester and Random Jungle were selected, with the later two being followed by the HyperLasso as a post-processing step. Only one method, SNPHarvester, was able to detect the interaction. The third study outlines a local pilot project in renal transplant dysfunction. Genetic variants from donors and recipients are examined using survival analysis. Interactions between the two genomes are tested for an effect on the survival time of the kidney. Secondary renal phenotypes of acute rejection and progression to end-stage renal failure are also considered. There were no strongly significant associations discovered in this data. The final study is a multi-centre renal transplant study analysing over 2000 donor recipient pairs throughout the UK and Ireland. Although much larger than the pilot, this study also failed to detect any associations with graft survival time or the secondary phenotypes. SNPHarvester was applied to the data and there are some indications of potential interactions, but replication is essential before the results can be trusted. An outline of an extension to SNPHarvester to better handle survival data is presented. Results from all of these studies were largely negative. Detecting interactions in genome-wide data remains a difficult task. Narrowing the search space by filtering may be a better approach than attempting a genome-wide search, though SNPHarvester has proven to be useful and is a good choice if a true genome-wide search is required.
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Akhtar, Mohammed Zeeshan. "Improving the outcomes of kidney transplantation from deceased organ donors." Thesis, University of Oxford, 2016. https://ora.ox.ac.uk/objects/uuid:cd7c49f5-e5ce-415b-bdcb-7b59197bc1d0.
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This thesis sought to improve our understanding of how kidneys become injured as a consequence of organ donation, with the aim of improving the outcomes of transplantation. Every year, hundreds of patients on the waiting list die whilst awaiting a kidney transplant. With an ever-increasing demand for suitable organs, supply cannot keep up with the pressures on the transplant waiting list. As a consequence the transplant community are forced to use organs that previously would not have been considered suitable for transplant, including from older donors with additional comorbidities. This thesis aimed to develop an understanding as to how the kidney becomes injured during the donation process, identifying which key cellular homeostatic processes are disturbed as a consequence of donation. The thesis outlines the experimental development of rodent models of organ donation replicating the donation process for donation after brain death (DBD) and donation after circulatory death (DCD) donors and also the development of a kidney ischaemia reperfusion injury (IRI) model. Proteomics was subsequently used to identifying global protein alterations in the kidney as a consequence of brain death and ischemia reperfusion injury using bioinformatics tools to identify involvement of cellular pathways. The results indicated alterations in mitochondrial function and metabolic homeostasis occurring following brain death. Alterations in cellular metabolism and mitochondrial function were then confirmed using metabolomics and mitochondrial functional assays. I subsequently evaluated how alterations in cellular hypoxia and the hypoxia inducible factor system is altered in the brain dead organ donor kidney and aimed to target this system as a means of conditioning the brain dead organ donor to prevent mitochondrial and metabolic mediated injury to kidney cells following brain death. This involved exploring the role of prolyl hydroxylase inhibitors, including dimethyloxalylglycine, on mitochondrial function and whether this could be a therapeutic target in organ donation. This thesis provides important insights into the mechanism of injury of kidneys following brain death, providing evidence that even before procurement and preservation in the DBD donor alterations in mitochondrial function and metabolic homeostasis occur. I provide preliminary data on the use of prolyl hydroxylase inhibitors in altering mitochondrial function. I also outline my involvement in other ongoing projects in organ donation and machine perfusion that also aim to improve the outcomes of deceased donor kidney and liver transplantation.
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Rosales, Brenda Maria. "Cancer and Kidney Failure; Screening, Mortality, and Transmission." Thesis, The University of Sydney, 2021. https://hdl.handle.net/2123/27196.
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Cancer impacts people with kidney failure in multiple ways, however, we still do not fully understand the epidemiology of cancer mortality, feasibility of cancer screening and probability of cancer transmission in organ donation and transplant. This thesis aims to understand the impact of cancer on outcomes for people with kidney failure, utilising existing clinical and health administrative datasets in novel ways. Where existing data is unavailable, it generates new information. Methods: Chapters 2 and 3 estimate cancer mortality in people on dialysis and kidney transplant recipients, compared to the general population, in a bi-national data-linkage study, 1980-2013. Chapters 4 and 5, estimate the prevalence of anal cytological abnormalities and HPV DNA in kidney transplant recipients and, evaluates the acceptability of anal cancer screening intervention, in a cross-sectional study. Chapter 6 and 7 describe a population-based data-linkage study that aims to improve estimates of disease transmission risk in solid organ donation. They explore how real-time data access could support decision making at referral by comparing agreement between suspected and verified risk of melanoma in solid organ donor referrals and tabulated them against donation outcomes, to identify potential missed opportunities for donation. Results: People with on dialysis for kidney failure and kidney transplant recipients experience two- and three-times excess deaths from all-site cancer, respectively, compared to the general population. The relative risk of cancer death was highest for urinary related cancers in people on dialysis and immune related cancers in kidney transplant recipients. Although relative mortality has decreased over time for people on dialysis, this has not reached general population levels. Relative mortality in kidney transplant recipients, remains unchanged. Prevalence of anal cancer precursors in kidney transplant recipients was higher than other immune-compromised populations. An anal cancer screening intervention may be well received in this population. Less than 1% of solid organ donor were suspected of melanoma at referral, however over two-thirds were not verified. Acceptance of these donors would have increased the donor pool by 2%. Conclusion: The impact of cancer in people with kidney failure is reflected in their increased risk of cancer mortality compared to the general population and the limitation of deceased donor kidneys available due to misclassified cancer transmission risk. Concerted efforts at an individual, risk-based approach to cancer prevention, including targeted screening programs, and guideline-based assessment of deceased donor cancers may improve cancer outcomes in this population.
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Francis, Anna. "Long-Term Outcomes of Children and Adolescents with Chronic Kidney Disease." Thesis, The University of Sydney, 2019. http://hdl.handle.net/2123/20404.
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Chronic kidney disease (CKD) or end stage kidney disease (ESKD) in children is devastating. The overall annual mortality rate for children with ESKD is around 30 times higher than the age matched general population. Cancer after kidney transplantation in adults contributes to mortality risk, but the impact on childhood transplant recipients is unclear. Cancer is not the only complication of transplantation, with disease recurrence a possibility for some children, particularly those with focal segmental glomerulosclerosis (FSGS). In addition, the detrimental effect of kidney disease on the quality of life (QoL) of adults is well known, but poorly described in children across all stages of kidney disease. Finally, adolescents with kidney disease need to transition to adult care. This is well known to be a high-risk period for graft loss and other complications, but the optimal method for transitioning care is unknown. The aim of this program of research was to define long-term medical and psychosocial outcomes for children with CKD and the risk factors for these outcomes. The first chapter summarizes research around selected psychosocial (QoL) and medical (cancer and disease recurrence) complications of CKD. Chapter 2 investigates the QoL of children with kidney disease. Chapter 3 describes the incidence and predictors of skin and non-skin cancers after childhood kidney transplantation. Chapter 4 compares the incidence of post-transplant lymphoproliferative disease (PTLD) between adult and paediatric kidney transplant recipients and chapter 5 investigates the patient and graft survival after a diagnosis of PTLD. Chapter 6 examines the incidence and risk factors of FSGS recurrence. Chapter 7 details treatments of recurrent FSGS in children and adolescents. Finally, chapter 8 explores complications surrounding transition to adult care and details different models of care.
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Au, Eric Hoi Kit. "Improving the health outcomes of people after kidney transplantation." Thesis, The University of Sydney, 2022. https://hdl.handle.net/2123/29752.
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For patients with end-stage kidney disease, kidney transplantation generally offers the best survival and quality of life. Complications such as cancer and cardiovascular disease are now the most important causes of morbidity and mortality in kidney transplant recipients past the initial post-transplant period. The overarching aim of this thesis was to improve our understanding of cancer in people after kidney transplantation. Chapter 2 provides a comprehensive literature review of the topic of cancer and kidney transplantation. Chapter 3 provides a review of the process of creating a risk prediction model, including an illustrative example. Prediction models may be applied to transplant recipients to predict the risk of experiencing an outcome, such as cancer. Chapters 4 and 5 were population-based registry studies using data from the Australia and New Zealand Dialysis and Transplant Registry. Chapter 4 demonstrated the greatly increased risk of cancer mortality in kidney transplant recipients, particularly in de novo cancers that arise after kidney transplantation. Chapter 5 explored the changes in cancer risk as patients progress through different treatment modalities for end-stage kidney disease, from dialysis to kidney transplantation to graft loss to subsequent kidney transplantation, and demonstrated increased risk of cancer after kidney transplantation, and reduction in cancer risk after loss of the first kidney transplant. In Chapter 6, data from the DETECT study was analysed and novel risk factors for advanced colorectal neoplasia in patients with chronic kidney disease, including patients on dialysis and kidney transplant recipients, were identified. Chapter 7 was a systematic review of trial registrations which demonstrated that cancer is an infrequently reported outcome and is inconsistently defined in trials of kidney transplant recipients, despite the importance of cancer as an outcome to kidney transplant recipients and other stakeholders.
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Malatesta, Muncher Rossana. "Early cardiac dysfunction in pediatric patients on maintenance dialysis and post kidney transplant." University of Cincinnati / OhioLINK, 2012. http://rave.ohiolink.edu/etdc/view?acc_num=ucin1342730689.
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Nguyen, Ngoc khanh. "Characterization of BKPyV-specific monoclonal antibodies in kidney transplant recipients after BKPyV reactivation." Thesis, Nantes, 2021. http://www.theses.fr/2021NANT1004.
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Le polyomavirus BK (BKPyV) est ubiquitaire et persiste asymptomatiquement dans le rein. La réactivation virale peut être observée chez les greffés du rein qui reçoivent des traitements d'immunosuppression. La réplication active peut causer une morbidité significative. Puisqu'aucune thérapie antivirale à action directe n'est disponible, les anticorps neutralisants représentent des thérapies possibles. L'objectif principal de ma thèse a été de générer des monoclonaux neutralisants à potentiel thérapeutique ainsi que de caractériser le répertoire des récepteurs de cellules B spécifiques de BKPyV (BCR) chez les receveurs de rein avec une réactivation virale. Pour cela, nous avons utilisé des particules virales de BKPyV couplées aux fluorochromes pour isoler une population de cellules B spécifiques de BKPyV. Nous avons obtenu 2158 séquences d'anticorps spécifiques, via single-cell RNA seq. Après analyse bioinformatique, nos résultats montrent que le répertoire BCR est très diversifié en termes de clonotypes et d'utilisation du gène V. La réponse anticorps spécifique au BKPyV est dominée par l'IgM, puis l'IgG. Bien que les cellules B mémoires de types IgG et IgM soient hypermutées somatiquement et expriment des répertoires BCR distincts, le profil d'expression génique de ces deux sous-populations est très similaire. En outre, le regroupement basé sur la séquence nous a permis d'identifier un groupe d'anticorps neutralisants 41F17-like. Après expression in vitro et caractérisation de plus de 20 candidats, nous avons trouvé l'anticorps 120 représentant un anticorps puissant à des fins thérapeutiques en raison de son activité antivirale neutralisante plus forte que le 41F17The BK polyomavirus (BKPyV) is ubiquitous and persists asymptomatically in the kidney. BKPyV reactivation can be seen in kidney transplant (KTx) recipients who receive immunosuppression treatments. The active replication can cause significant morbidity. Since no directly acting antiviral therapies are available, neutralizing antibodies represent possible therapeutics. The main objective of my PhD was, therefore, to generate neutralizing monoclonals with therapeutic potential. We also wanted to characterize the BKPyV-specific Bcell receptor (BCR) repertoire in KTx recipients with BKPyV reactivation. For that, we used fluorescence-labeled BKPyV virus-like particles (VLPs) to isolate a population of BKPyV-specific B cells. Using single-cell RNA seq technique, we obtained 2158 BKPyV-specific antibody sequences which were subsequently submitted to bioinformatic analysis. Our results show that the BCR repertoire was highly diverse in terms of both V-gene usage and clonotype diversity. The BKPyV-specific antibody response was dominated by IgM, then IgG. Although memory IgG and memory IgM B-cells were somatically hypermutated and expressed distinct BCR repertoires, the gene expression profile of these two B-cell subsets was highly similar. Furthermore, sequence-based clustering allowed us to identify a group of 41F17-like broadly neutralizing antibodies. After in vitro expression and characterization of more than 20 candidates, we found the antibody 120 representing a potent antibody for therapeutic purposes due to its stronger neutralizing antiviral activity compared to 41F17
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Rebafka, Anne Katharina. "Medication adherence following kidney transplantation : a grounded theory study of transplant recipients' perspectives." Thesis, Cardiff University, 2016. http://orca.cf.ac.uk/87329/.
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Background: Medication adherence has shown to be problematic for many renal transplant recipients. While factors promoting or inhibiting medication adherence have been extensively researched, little is known about the processes leading to this behaviour as perceived by kidney transplant recipients. Also, no research on the perspectives of German kidney transplant recipients has yet been carried out. Research Question: The question underpinning this research was: “How do German renal transplant recipients perceive the processes leading to medication adherence or non-adherence?” Methods: Following informed consent, telephone interviews with 17 German renal transplant recipients were conducted, transcribed verbatim, and analysed according to the tenets of constructive Grounded Theory, until theoretical saturation was reached. The research has been approved by the research ethics committees of the School of Healthcare Sciences and the German Society of Nursing Science. Results: This research established the theory of medication-taking as a symbol of living with a chronic condition. This theory is underpinned by two categories: in the category reflecting on one’s own position, the participants discussed their role regarding the intake of medication, which was perceived very ambivalently and as just one component of self-management following transplantation. In the category experiencing facilitators and challenges, participants reported factors supporting or impeding medication-taking. Crucially, these are perceived very individually: what one finds helpful or challenging may be perceived in a fundamentally different way by someone else. Conclusions: This research has similar findings to other research in this field, such as the fact that renal transplantation is not a cure for a chronic condition. However, in contrast to other research, it has found a strong connection between medication-taking and participants’ self-reflection of being chronically ill. In this regard, it has emphasised the need for individualised care, preferably in the form of a team approach that includes patients and families as well as the different healthcare professions.
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Kellerman, Quinn Dione. "Looking beyond social support: examining dimensions of relationship quality in kidney transplant recipients." Diss., University of Iowa, 2012. https://ir.uiowa.edu/etd/3481.
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Perceived availability or receipt of tangible or instrumental social support has generally been associated with favorable outcomes in kidney transplant recipients, yet there has been insufficient attention in the literature to other social relationship processes beyond support that may contribute to mental and physical health. The overall objective of the current study was to examine whether specific dimensions of relationship quality, such as emotional closeness, sexual relations, support transactions, respect/acceptance, and conflict/negative communication, within the context of a close interpersonal relationship, were associated with psychosocial and medical outcomes in kidney transplant recipients when accounting for the effects of global social support. Participants had received a living or deceased donor kidney transplant and were 6 months - 5 years post-surgery at the time of enrollment in the study. A total of 93 participants completed self-report measures and a semi-structured clinical interview via telephone that assessed each of the aforementioned dimensions with regard to a specified relationship. A subsample of 67 participants were married or involved in a committed dating relationship and responded to interview questions with their partner in mind; the remaining participants selected the person to whom they felt closest over the preceding 6 months (e.g., friend, sibling, parent).
Structural equation modeling and linear regression were used to analyze the data. Results suggested that the distinct yet highly correlated dimensions reflected an underlying 'relationship quality' construct. Poorer relationship quality was associated with increased symptoms of depression, decreased feelings of well-being, and worse mental health-related quality of life for both the full sample and the subsample of participants in a romantic relationship. The path between relationship quality and depression remained significant for romantic relationship participants when global social support was included in the model, but global social support was more strongly associated with depression, well-being, and health-related quality of life for all participants. Relationship quality was not associated with adherence or graft function in this sample. However, interesting interaction effects were found, such that high conflict and lack of emotional intimacy were more strongly associated with poorer self-reported adherence in women. In addition, women who reported higher conflict in their relationship also endorsed increased depression, decreased well-being, and worse mental health-related functioning compared to men. These findings are consistent with previous research that has cited the importance of global social support for patients who have received a kidney transplant. The present study also provides novel evidence that other dimensions of relationship quality contribute to outcomes in this population. A comprehensive assessment of recipients' close relationships throughout the transplant process, particularly of conflict and emotional intimacy in women, would allow clinicians to recommend psychosocial interventions that could improve patient outcomes.
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Cena, Tiziana. "Post-kidney transplant malignancies affect graft survival: results from a time-dependent analysis." Doctoral thesis, Università del Piemonte Orientale, 2018. http://hdl.handle.net/11579/105206.
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Aim of this study was to evaluate the association between cancer occurrence and risk of graft failure in kidney transplant recipients. From 1998 to 2013, 672 adults receiving their first kidney transplant from a deceased donor, with at least six months of follow-up, were included in the study. To illustrate the effect of tumors incidence on graft failure risk, a modified Kaplan-Meier method was used. To quantify the tumor effect as hazard ratio, multivariable adjusted Cox models were fitted considering the diagnosis of non-cutaneous malignancies (NCM) and non-melanoma skin cancer (NMSC) as a time-dependent covariates.
The 5-year cumulative incidence of graft failure was 7.5% (95%CI: 5.3-10.0), with 59 events (39 due to chronic rejection and 20 for other causes). Forty patients developed a NCM (5-yrs cumulative incidence: 5.6%), and 47 developed a NMSC (5-yrs cumulative incidence: 6.5%). From the multivariable Cox model, the adjusted hazard ratio of graft failure associated with NCM was 3.27 (95%CI=1.44-7.44, p=0.005). The occurrence of a NMSC was not associated with graft failure (HR = 0.80; 95% CI = 0.30-2.14, p = 0.66). The model validation procedure (a leave-one out cross validation) showed a C-statistics of 0.80 (95%CI: 0.72-0.88) for the cross-validated cohort, ruling out model overfitting and validating its predictive ability. Investigating the effects of NCM on cause-specific graft failure, an NCM diagnosis seemed to have a different association (P = 0.002) when considering graft failed due to chronic rejection (HR 0.55, 95% CI: 0.07-4.08) or for other causes (HR 15.59, 95% CI 5.43-44.76). The reduction of the immunosuppression after NCM was not associated with a greater risk of graft failure. In conclusion, our data suggest that post-transplant NCM may be a strong risk factor for graft failure, particularly for causes other than chronic rejection, and more efforts should be addressed to improve graft outcomes acting on malignancy-associated nephropathies.
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Cesca, Eleonora. "Pediatric Kidney Transplant. Effect of brain-dead donor resuscitation on delayed graft function." Doctoral thesis, Università degli studi di Padova, 2012. http://hdl.handle.net/11577/3422497.
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ABSTRACT
Introduction and Aim of the Study. Studies devoted to brain dead donor parameters are all based on adult populations. The aim of this study was to analyze the correlation of delayed graft function (DGF) with brain-dead donor variables in a population of 116 consecutive pediatric recipients and to compare the clinical outcomes of non-DGF versus DGF recipients.
Patients and Methods. We classified the recipients into two groups: group 0 (No. 11) with DGF and group 1 (No. 105) without DGF. Endpoints of the study were: DGF, 6 months graft function and short-term patient and graft survival. Multivariate analysis was performed to determine independent risk factors of DGF.
Results. Monovariate analysis of donor parameters showed that donor age above 15 years, gender combination female donor/male recipients, and vascular cause of donor brain death were risk factors for prolonged DGF. The multivariate logistic regression model confirmed as independent risk factors for DGF donor age > 15 years and gender combination female donor to male recipient. After 6 months follow-up, the DGF group showed worse graft function, as well as a smaller incidence of normal histological pattern at graft biopsies.
Conclusions. About parameters associated with brain-death donor resuscitation, except for non-traumatic cause of death, the others did not demonstrate any relationship with DGF. Importantly we show that donor age > 15 years and gender combination female donor to male recipient are clearly major independent risk factors for prolonged DGF in children. Furthermore in our paediatric series DGF revealed an important predictor of poor short-term graft function.RIASSUNTO Introduzione e scopo dello studio. In pazienti adulti, danni legati allo stato di morte cerebrale e alle manovre rianimatorie possono influenzare la ”delayed graft function” (DGF) e l‟outcome dell‟organo trapiantato. Scopo dello studio è stato valutare, in trapiantati di rene in età pediatrica, la correlazione tra parametri rianimatori del donatore cadavere e l‟outcome dell‟organo trapiantato. Materiali e Metodi. Il campione casistico è consistito in 116 pazienti (età ≤ 16 anni), sottoposti a trapianto di rene da cadavere dal 2004 al 2011. I pazienti sono stati divisi in gruppo 0 (No. 11) con DGF e gruppo 1 (No. 105) senza DGF. Gli “endpoints” dello studio sono stati: DGF, funzione dell‟organo trapiantato a 6 mesi dal trapianto e sopravvivenza del paziente e del rene trapiantato a 6 mesi. Risultati. L‟analisi monovariata dei parametri del donatore in morte cerebrale ha dimostrato che l‟età superiore a 15 anni, la combinazione donatore femmina/ricevente maschio e morte da accidente cerebrovascolare rappresentano fattori di rischio per lo sviluppo di DGF. Il modello di regressione logistica multivariata ha confermato come fattori di rischio indipendente per DGF l‟età del donatore e la combinazione donatore femmina/ricevente maschio. A 6 mesi di follow-up, il gruppo con DGF ha dimostrato una funzionalità renale e un quadro istologico bioptico significativamente peggiori rispetto al gruppo senza DGF. Conclusioni. Ad eccezione della causa di morte non traumatica, nessuna variabile ha influenzato la DGF nei bambini trapiantati. L'età del donatore (>15 anni) e la combinazione donatore femmina/ricevente maschio si sono rivelati importanti fattori di rischio indipendente per lo sviluppo di DGF. Inoltre, la DGF è risultato un fattore predittivo di funzionalità a breve termine dell‟organo trapiantato.
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Nguyen, Huong. "Molecular Pathways Involved In Calcineurin Inhibitor Nephrotoxicity In Kidney Allograft Transplants." VCU Scholars Compass, 2011. http://scholarscompass.vcu.edu/etd/2545.
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ABSTRACT MOLECULAR MECHANISMS AND GENE SIGNATURES INVOVLED IN CALCINEURIN INHIBITOR NEPHROTOXICITY IN KIDNEY ALLOGRAFT By Huong Le Diem Nguyen, M.S. A thesis submitted in partial fulfillment of the requirements for the degree of Master of Science in Physiology at Virginia Commonwealth University. Virginia Commonwealth University, 2011. Major Director: Valeria Mas, Ph.D. Associate Professor, Department of Surgery and Pathology Director of Molecular Transplant Research Laboratory, Division of Transplant Calcineurin inhibitors (CNI), cyclosporin A and tacrolimus, are potent immunosuppressive agents but induce toxicities causing damages and graft dysfunction, and have been suggested to contribute to late-term loss of graft in kidney transplant recipients. Even though insights on mechanism of CNI nephrotoxicity have been uncovered, prevention and treatment of these toxicities remain a major challenge in the clinical administration of CNI due to low dose-toxicity correlation, difficulty in establishing a differential patho-histological diagnosis, and varying individual susceptibility. We hypothesize that CNI nephrotoxicity follows distinct disease pathways and is characterized by significant gene signatures that differentiate it from other conditions such as acute rejection and chronic allograft dysfunction. Moreover, we postulate that CNI-induced toxicity profiles contribute to the IF/TA signatures. Microarray analysis and gene annotation were done on the study database included of tissues diagnosed with CNI nephrotoxicity (n = 9), interstitial fibrosis/tubular atrophy (IF/TA, n=10), and normal allografts (NA, n = 8). All samples were histologically classified based on the revised Banff ‘07 criteria for renal allograft pathology. Top-scored biological networks in CNI tissues were related to metabolic disease, cellular development, renal necrosis, apoptosis cell-death, immunological disease, inflammatory disease, and many others. Canonical pathway analysis emphasized oxidative stress response mediated by NRF2 and various cell-death signaling pathways including 14-3-3 signaling pathway, p53 signaling pathway, and TGF-β signaling pathway. Profiling of differentially expressed genes was done based on their statistical significance and biological relevance to the unique pathology of CNI nephrotoxicity. Among these, three genes RGS1, CXCR4, and TGIF1 were further quantitatively evaluated using real time-PCR. Between CNI group and normal allograft, t-test results showed only RGS1 gene expression level was statistically significant. Between IF/TA group in normal allograft, both RGS1 and CXCR4 showed statistical significance. The calculated relative fold changes revealed an up-regulated pattern of RGS1 and CXCR4 expression in association with pathological groups (CNI and IF/TA). We did not, however, find any association between the expression of TGIF1 in either CNI group or IF/TA group.
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Morton, David. "Epstein-Barr virus infection in adult renal transplant recipients." Thesis, University of Manchester, 2013. https://www.research.manchester.ac.uk/portal/en/theses/epsteinbarr-virus-infection-in-adult-renal-transplant-recipients(bc856b34-7164-45e5-8a64-71693a104912).html.
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Aims: To explore the clinical significance of EBV infection in adult renal transplant recipients when detected in the late post-transplant period. Methods: (1) A prospective observational study recruiting 499 stable adult kidney transplant recipients with serial blood sampling for EBV DNAemia and assessment of clinical outcomes and associated factors. (2) A retrospective analysis of PTLD incidence, timing and outcomes in relation to EBV infection. Results: EBV DNAemia in stable kidney transplant recipients is common, found in 46% of recruited individuals screened over 1 year, with persistent DNAemia seen in 10%. DNAemia prevalence increased significantly with time from transplant (p<0.0001) from 16% within 1 year of transplant to 66% in those transplanted for 20-24 years. High baseline DNA levels predicted persistence of DNAemia. Time adjusted analyses showed significant association of DNAemia with EBV seronegative status and previous PTLD and low DNAemia rates with Mycophenolate Mofetil (MMF) use and lymphopenia. The mechanism did not appear to be directly linked to MMF induced B cell depletion. Chronic high viral load detection was significantly associated with time from transplant, EBV seronegative status at transplant, ciclosporin use and plasma detection of DNA. No significant differences in overall patient survival at 3 years, clinical symptoms or clinical findings such as anaemia, thrombocytopenia or rate of decline in renal function were seen between stable transplant recipients with and without EBV DNAemia. PTLD incidence also increases with time from transplant and was greatest during the 10th-14th post-transplant years. Disease was EBV positive in 68% cases. No statistically significant differences in overall patient survival, or overall disease complete response rates were seen in relation to recipient EBV serostatus or EBV status of PTLD histology. Conclusions: EBV DNAemia prevalence increases with time from transplant but was not associated with worse patient or graft survival or specific symptoms. PTLD incidence including EBV negative disease also increases with time from transplant but response rates and survival were not influenced by EBV serostatus or histological status.
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Hanson, Camilla Sara. "Improving Access and Outcomes in Living Kidney Donor Transplantation." Thesis, The University of Sydney, 2017. http://hdl.handle.net/2123/17370.
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Shortages in deceased organ donation have necessitated widespread acceptance of living donor kidney transplantation, which offers better outcomes in terms of graft survival, life expectancy and quality of life for many patients with end-stage kidney disease, compared with deceased donor kidney transplantation and dialysis. However, there are barriers and challenges that exist in the current practice of living kidney donor transplantation. Overall, the rates of living kidney donor transplantation have decreased or plateaued, with ethic and socio-economic disparities in access to living kidney donation reported in many countries that remain largely unexplained. Living donors must accept risks associated with undergoing nephrectomy, yet the evidence on the long-term risks of living kidney donation remains uncertain. In response, there have been efforts to identify and describe the barriers and disparities in living kidney donor transplantation, improve the pathway for living donors and to assess a range of outcomes for living donors. A comprehensive understanding of the values, beliefs, experiences, priorities and preferences of the key stakeholders, including donors and health professionals involved in their care is needed to ensure that research; clinical practice and policy in living kidney donation address their needs and priorities. This is a thesis by publication containing published and submitted work. The aims of the studies included in this thesis are: 1) To identify and describe the beliefs, attitudes and expectations of patients with CKD regarding living kidney donation. 2) To describe kidney donors’ experiences of the evaluation process, and the motivations and challenges to sustaining commitment prior to donation. 3) To describe nephrologists’ perspectives on barriers to living kidney donation and disparities in access to living kidney donor transplantation. 4) To identify living kidney donors’ priorities for outcomes and describe the reasons for their choices. 5) To determine the characteristics and heterogeneity of outcomes reported in randomised trials and observational studies in adult living kidney donors
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Swanson, Dorothy Roberta. "The relationship between uncertainty and coping strategies used by long-term kidney transplant patients." Thesis, University of British Columbia, 1991. http://hdl.handle.net/2429/29743.
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This descriptive correlational study was done to describe the perceptions of uncertainty and coping strategies used by adult kidney transplant patients. In addition, the study was designed to identify relationships between uncertainty and coping strategies used by long-term kidney transplant patients. The stress, appraisal, and coping theory developed by Lazarus and Folkman (1984) served as the theoretical framework.
A convenience sample of 88 subjects who received either a living-related or cadaveric donor kidney transplant and were three and more years post-transplant completed the Uncertainty Stress Scale (USS), the revised Jalowiec Coping Scale (JCS), and a patient information sheet. The subjects were mailed the questionnaire.
For the majority of patients, this was their first kidney transplant. The number of years that patients had lived with their current kidney transplant ranged from 3.1 to 20.9 years with the majority of patients transplanted under 10 years.
Overall, long-term kidney transplant patients perceived moderately low levels of uncertainty. The nature of uncertainty appears to be primarily generated by the indeterminateness of the situation. Numbers of health or medical problems aside from renal disease and educational level appear to be significant factors in the uncertainty of patients with a long-term kidney transplant. More health problems and lower levels of education appear to be associated with higher levels of uncertainty.
Kidney transplant patients use various coping strategies to manage uncertainty and the stress it generates. There was a preference to use optimistic, self-reliant, and confrontive coping. There was also a general tendency to use problem oriented forms of coping. Patients appear to concentrate on the elements of hope, positive thinking, control, and a rational and constructive approach to problem-solving.
Significant positive relationships between uncertainty and coping strategies supported the stress, appraisal, and coping theory. Findings indicate that patients with higher levels of uncertainty generally tend to use emotion-focused strategies such as evasive, fatalistic, and emotive coping. Long-term kidney transplant patients perceived low levels of stress generated by their uncertainty. The direction and the magnitude of the relationship suggests a significant positive association between uncertainty and stress (r =.94, p =.00).
Based upon the findings of this study, implications were suggested for new directions for the provision of effective health care for kidney transplant patients. It is recommended that further research is needed to identify and explore relationships among appraisal, coping strategies, and outcomes of patients with kidney transplants over time.Applied Science, Faculty of
Nursing, School of
Graduate
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Asderakis, Argiris. "Influence of cytokine gene polymorphisms on kidney transplant outcome : the case of IFN-γ." Thesis, University of Manchester, 2008. http://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.493685.
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Samples from 93 of 115 consecutive cadaveric renal transplants were selected to define polymorphisms in both IFN-γ and IL-10. A 12 CA repeat IFN-γ polymorphic allele was found in 73 patients (70 in patients analysed further). This polymorphism was associated with high IFN-γ production in vitro. According to the presence or not of the 12 CA repeat allele patients were separated in high and low producer genotype groups. The incidence of acute rejection was 54.3% in this high IFN-γ genotype group, contrasting with 44.4% in the low IFN-γ. Requirement for ATG therapy was greater in the high IFN-γ group (odds ratio [OR]=2.5). Among HLA-DR-mismatched patients, IFN-γ high producer genotype was more strongly associated with rejection (OR=1.6). In the cyclosporine monotherapy subgroup, 11 out of 14 patients with IFN-γ high genotype (78%) had acute rejection (OR=2.88, p=0.09). Graft survival was similar between the two IFN-γ groups. When the analysis was controlled for the presence of delayed graft function, 40.5% of the high IFN-γ genotype patients had serum creatinine levels above 200 micromoles/L contrasting with only 14.3% of the low IFN-γ genotype recipients at 5 years after transplantation (p=0.05). In a regression model of creatinine at 1 year the significant variables were the presence of DGF, donor age greater than 50, greater than two rejection episodes, DR mismatch, donor female to male recipient sex, IL-10 high genotype, and IFN-γ high genotype. Conclusion: The 12 CA repeat IFN-γ polymorphic allele is associated with high IFN-γ production. We have shown that this high producer genotype for IFN-γ influences acute rejection in kidney transplantation, particularly in high-risk groups; it is also associated with worse long-term graft function.
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Almehmadi, Mazen. "CD56+ T-cells in relation to cytomegalovirus in healthy subjects and kidney transplant patients." Thesis, University of Liverpool, 2014. http://livrepository.liverpool.ac.uk/2008213/.
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Human T cells expressing CD56 are capable of tumour cell lysis following activation with interleukin-2 but their role in viral immunity has been less well studied. The work described in this thesis aimed to investigate CD56+ T-cells in relation to cytomegalovirus infection in healthy subjects and kidney transplant patients (KTPs). Proportions of CD56+ T cells were found to be highly significantly increased in healthy cytomegalovirus-seropositive (CMV+) compared to cytomegalovirus-seronegative (CMV-) subjects (8.38% ± 0.33 versus 3.29%± 0.33; P < 0.0001). In donor CMV-/recipient CMV- (D-/R-)- KTPs levels of CD56+ T cells were 1.9% ±0.35 versus 5.42% ±1.01 in D+/R- patients and 5.11% ±0.69 in R+ patients (P 0.0247 and < 0.0001 respectively). CD56+ T cells in both healthy CMV+ subjects and KTPs expressed markers of effector memory-RA T-cells (TEMRA) while in healthy CMV- subjects and D-/R- KTPs the phenotype was predominantly that of naïve T-cells. Other surface markers, CD8, CD4, CD58, CD57, CD94 and NKG2C were expressed by a significantly higher proportion of CD56+ T-cells in healthy CMV+ than CMV- subjects. Functional studies showed levels of pro-inflammatory cytokines IFN-γ and TNF-α, as well as granzyme B and CD107a were significantly higher in CD56+ T-cells from CMV+ than CMV- subjects following stimulation with CMV antigens. This also resulted in higher levels of proliferation in CD56+ T-cells from CMV+ than CMV- subjects. Using class I HLA pentamers, it was found that CD56+ T-cells from CMV+ subjects contained similar proportions of antigen-specific CD8+ T cells to CD56- T cells in healthy donors of several different HLA types. A comprehensive gene expression profile by microarrays of CMV-stimulated sorted CD56+ T-cells was conducted which showed that expression of 106 genes involved in innate and adaptive immune responses was significantly changed, almost all being increased. Some of these changes were validated via RT-PCR and flow cytometry, the latter indicating higher ISG-15 protein expression in response to CMV stimulation in CMV+ than CMV- subjects. Overall, these differences may reflect the expansion and enhanced functional activity of CMV-specific CD56+ memory T cells. In view of the link between CD56 expression and T-cell cytotoxic function, this strongly implicates CD56+ T cells as being an important component of the cytotoxic T-cell response to CMV.
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Lima, Gilson José de. "Avaliação do desenvolvimento pondero-estatural em pacientes pediátricos submetidos a transplante renal no Hospital das Clínicas da Faculdade de Medicina de Ribeirão Preto da Universidade de São Paulo." Universidade de São Paulo, 2015. http://www.teses.usp.br/teses/disponiveis/17/17137/tde-07012016-104855/.
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Introdução: A prevalência de doença renal crônica na faixa etária pediátrica ainda é desconhecida. O tratamento de escolha é o transplante renal, independente da idade. Os principais objetivos do tratamento são a manutenção do desenvolvimento físico, neurológico e esquelético, prevenção da doença do metabolismo mineral e ósseo (DMMO), adequada maturação sexual e da função endócrina. O déficit de crescimento está relacionado com a idade de surgimento da insuficiência renal e ocorre devido à má-nutrição energético-calórica, DMMO e uso de corticoide, além dos efeitos deletérios da anemia, uremia e resistência ao hormônio do crescimento. Causas relacionadas ao paciente como retardo de crescimento intra-uterino e malformações congênitas também estão relacionadas. Objetivos: avaliar o desenvolvimento pondero-estatural dos pacientes pediátricos submetidos a transplante renal no Hospital das Clínicas da Faculdade de Medicina de Ribeirão Preto da Universidade de São Paulo (HC FMRP-USP). Casuística: revisão dos prontuários dos pacientes pediátricos submetidos a transplante renal no HC FMRP-USP e análise do desenvolvimento pondero-estatural comparando os score-z altura para idade e índice de massa corporal (IMC) para idade durante o acompanhamento. As variáveis analisadas foram sexo, faixa etária, uso de Basiliximab, realização ou não de diálise, tipo de transplante realizado (doador falecido ou doador vivo relacionado), hipertensão arterial, dose de manutenção de prednisona. Resultados: foi possível avaliar os dados de 31 pacientes, 10 femininos e 21 masculinos. Ao longo do tempo houve ganho significativo em peso (p< 0,0001) e estatura (p< 0,0001) mas nenhuma das variáveis analisadas mostrou diferença estatisticamente significativa. Houve interação significativa do uso de Basiliximab e da faixa etária sobre o IMC e do uso de Basiliximab, faixa etária e dose de prednisona utilizada sobre a evolução da estatura. A estatura manteve abaixo da média padrão durante todo o acompanhamento e nenhum paciente atingiu a altura final esperada. O IMC estava abaixo da média padrão na ocasião do transplante mas a partir do primeiro ano recuperou e manteve estável em torno do percentil 0. Conclusões: a doença renal crônica na infância compromete o desenvolvimento ponderoestatural dos pacientes afetados.Introduction: The prevalence of chronic kidney disease in the pediatric age range is still unknown. The treatment of choice is a renal transplant, regardless of age. The main objectives of treatment are the maintenance of physical, neurological and skeletal development, the prevention of renal osteodystrophy, and appropriate sexual and endocrine function maturation. The growth deficit is related to the age at onset of renal failure and is due to energy-calorie malnutrition, to renal osteodystrophy and to corticoid use, in addition to the deleterious effects of anemia, uremia and of resistance to growth hormone. Additional patient-related causes are intrauterine growth retardation and congenital malformations. Objectives: to assess the weight-height development of pediatric patients submitted to renal transplantation at the University Hospital, Faculty of Medicine of Ribeirão Preto, University of São Paulo (HC FMRP-USP). Patients: The medical records of pediatric patients submitted to renal transplantation at HC FMRP-USP were reviewed and weight-height development was analyzed by comparing the zscores for height for age and body mass index (BMI) for age during follow-up. The variables analyzed were: sex, age range, use of Basiliximab, having undergone dialysis or not, type of transplant performed (cadaver donor or related live donor), arterial hypertension, and maintenance dose of prednisone. Results: it was possible to assess the data of 31 patients, 10 girls and 21 boys. A significant weight gain (p<0.0001) and height (p<0.0001) occurred over time but none of the variables analyzed showed a statistically significant difference. There was a significant interaction between age range and BMI, between the use of Basiliximab and age range and between the prednisone dose used and height evolution. Height was below the standard mean value throughout follow-up and no patient reached the expected final height. BMI was below the standard mean value at the time of transplantation, but recovered after the first year and remained stable at a value of about 0. Conclusions: renal failure during childhood compromises the weight-height development of affected patients.
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Lam, Susanna. "EVALUATING THE CLOSED INCISION NEGATIVE PRESSURE WOUND THERAPY SYSTEM ON WOUND COMPLICATIONS IN KIDNEY TRANSPLANT RECIPIENTS." Thesis, The University of Sydney, 2022. https://hdl.handle.net/2123/29839.
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Objectives: Closed incision negative pressure wound therapy systems have been efficacious in reducing wound complications in many surgical specialties. Kidney transplantation is unique in combining immunosuppression with a large lower abdominal incision in patients with multiple comorbidities. The aim of this study was to evaluate the association of closed incision negative wound therapy, “Prevena” with wound complications in kidney transplant recipients.
Material and Methods: A prospective cohort study was performed in a single centre. Consecutive kidney transplant recipients deemed high risk for wound complications were selected to receive a closed incision negative pressure wound therapy system (ciNPWT). The results were compared with a concurrent cohort of recipients who used conventional dressings. Further analysis for obese recipients and propensity score matching was performed.
Results There were 127 adults (≥18 years) who underwent a kidney transplant. Thirty received a ciNPWT dressing, 97 recipients received a conventional dressing. Wound complications occurred in 21.3% (27/127) of all kidney transplant recipients. The ciNPWT when compared with conventional dressing did not reduce the rate of wound complications (23.3% (7/30) vs 20.6% (20/97), p=.75). In the obese subset there was a no significant reduction in wound complications (31.1% vs 36.8%, p =.73). Propensity score matching yielded 26 matched pairs with equivalent rates of wound complications (23.1% (6/26)).
Conclusion: This study is the first reported cohort study examining the use of the closed incision negative pressure wound therapy, Prevena, in kidney transplant recipients. The ciNPWT was not associated with a significant reduction in wound complications.
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Varnell, Charles D. Jr. "Barriers to Taking Medication Predict Acute Rejection in Children and Adolescents with a Kidney Transplant." University of Cincinnati / OhioLINK, 2018. http://rave.ohiolink.edu/etdc/view?acc_num=ucin1522414353651158.
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Wan, Susan Si-Shun. "Donor Specific Anti-HLA Antibodies in Kidney Transplantation." Thesis, The University of Sydney, 2019. https://hdl.handle.net/2123/22006.
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This thesis synthesises the current literature on ABMR treatment and describes the development of dnDSA in kidney transplant recipients of low, moderate and high immune risk. Risk factors for dnDSA, including eplet mismatch load and early tacrolimus exposure, are explored with the aim of identifying strategies to prevent dnDSA and ABMR. Methods: A systematic review and meta-analysis of controlled trials for the treatment of ABMR is presented in Chapter 2. Chapter 3 estimates the incidence of dnDSA through a longitudinal cohort study with prospective DSA screening. The accuracy of high resolution HLA typing imputation compared to next generation sequencing (NGS) is assessed in Chapter 4. In Chapter 5, early tacrolimus exposure is explored as a risk factor for dnDSA. Results: No evidence for reduction in graft failure was found on pooled analysis of antibody removal, yet plasma exchange and IVIG (PLEX) have become the standard of care for acute ABMR. The incidence of dnDSA in recipients of low immunological risk was 16%, compared to 30% in moderate risk and 29% in high risk recipients. High resolution typing imputation performed poorly compared to NGS. Class II and HLA-DQ eplet mismatch load were associated with an increased risk of dnDSA. Compared to a mean tacrolimus concentration <11 ng/mL, mean concentrations 11-12.9 ng/mL over the first 90 days were associated with a decreased risk of dnDSA. Conclusions: The optimal treatment of ABMR remains unclear. Despite this, PLEX has become the standard of care for active ABMR. dnDSA developed in 16% of low-risk recipients and 30% of moderate and high-risk recipients. Risk factors for dnDSA included higher Class II eplet mismatch load, and lower early tacrolimus exposure. Collaborative studies are required to confirm the increased risk of dnDSA in higher immune-risk recipients, devise strategies for their prevention, and provide a platform for future trials in the prevention and treatment of ABMR.