Transplant nephrectomy improves survival following a failed renal allograft.
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ABSTRACT:
SUBMITTER: Ayus JC
PROVIDER: S-EPMC2834539 | biostudies-literature |
REPOSITORIES: biostudies-literature
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Project description:BackgroundTransplant glomerulopathy, a common glomerular lesion observed after kidney transplant that is associated with poor prognosis, is not a specific entity but rather the end stage of overlapping disease pathways. Its heterogeneity has not been precisely characterized to date.MethodsOur study included consecutive kidney transplant recipients from three centers in France and one in Canada who presented with a diagnosis of transplant glomerulopathy (Banff cg score ≥1 by light microscopy), on the basis of biopsies performed from January of 2004 through December of 2014. We used an unsupervised archetype analysis of comprehensive pathology findings and clinical, immunologic, and outcome data to identify distinct groups of patients.ResultsAmong the 8207 post-transplant allograft biopsies performed during the inclusion period, we identified 552 biopsy samples (from 385 patients) with transplant glomerulopathy (incidence of 6.7%). The median time from transplant to transplant glomerulopathy diagnosis was 33.18 months. Kidney allograft survival rates at 3, 5, 7, and 10 years after diagnosis were 69.4%, 57.1%, 43.3%, and 25.5%, respectively. An unsupervised learning method integrating clinical, functional, immunologic, and histologic parameters revealed five transplant glomerulopathy archetypes characterized by distinct functional, immunologic, and histologic features and associated causes and distinct allograft survival profiles. These archetypes showed significant differences in allograft outcomes, with allograft survival rates 5 years after diagnosis ranging from 88% to 22%. Based on those results, we built an online application, which can be used in clinical practice on the basis of real patients.ConclusionsA probabilistic data-driven archetype analysis approach applied in a large, well defined multicenter cohort refines the diagnostic and prognostic features associated with cases of transplant glomerulopathy. Reducing heterogeneity among such cases can improve disease characterization, enable patient-specific risk stratification, and open new avenues for archetype-based treatment strategies and clinical trials optimization.
| S-EPMC6442337 | biostudies-literature
Project description:BackgroundBlood transfusions have the potential to improve graft survival, induce sensitization, and transmit infections. Current clinical practice is to minimize transfusions in renal transplantation candidates, but it is unclear if the evidence continues to support pre-transplant transfusion avoidance. Changes in the Medicare prospective payment system may increase transfusion rates. Thus there is a need to re-evaluate the literature to improve the management options for renal transplant candidates.MethodsA review applying a systematic approach and conducted using MEDLINE(®), Embase(®), and the Cochrane Library for English-language publications (timeframe: 01/1984-03/2011) captured 180 studies and data from publically available registries and assessed the impact of transfusions on allosensitization and graft survival, and the impact of allosensitization on graft survival and wait time.ResultsBlood transfusions continued to be a major cause of allosensitization, with allosensitization associated with increased rejection and graft loss, and longer wait times to transplantation. Although older studies showed a beneficial effect of transfusion on graft survival, this benefit has largely disappeared in the post-cyclosporine era due to improved graft outcomes with current practice. Recent data suggested that it may be the donor-specific antibody component of allosensitization that carried the risk to graft outcomes.ConclusionsResults of this review indicated that avoiding transfusions whenever possible is a sound management option that could prevent detrimental effects in patients awaiting kidney transplantation.
| S-EPMC4125965 | biostudies-literature
Project description:Laparoscopic Partial Nephrectomy (LPN) after intra-arterial Embolization of renal tumors (LPNE) in a hybrid operating room allows renal tumor enucleation without dissection and clamping of the renal pedicle. The purpose was to assess the potential negative impact of embolization on the renal function. This prospective monocentric study included all patients treated with LPNE between May 2015 and June 2019. Clinical data was collected and incorporated into the UroCCR database (NCT03293563). Glomerular Filtration Rate (GFR) and Computed Tomography Renal Volume (CTRV) were compared before and after 6 months following LPNE. The mean post-operative GFR was 86.6 mL/min (SD 22.9). The mean GFR loss was 9.4% (SD 15.1) and the median renal parenchyma loss was 21 mL (SD 20.6). Using a threshold of 25% GFR loss, age was the only significant predictive factor of renal function impairment according to bivariate (59.5 vs 69.3 years, p = 0.017) and multivariable analysis (OR 1.075, CI 1-1.2], p = 0.05). Significant renal function impairment was not correlated with the renal parenchymal volume loss (OR 0.987, CI [0.95-1.02], p = 0.435). Renal function impairment after LPNE seems to be comparable to other techniques of partial nephrectomy.
| S-EPMC7721888 | biostudies-literature
Project description:Renal transplantation is the preferred treatment of end stage renal disease, but allograft survival is limited by development of interstitial fibrosis and tubular atrophy in response to various stimuli. Much effort has been put into identifying new protein markers of fibrosis to support the diagnosis. In present work, we performed an in-depth quantitative proteomics analysis of allograft biopsies from 31 prevalent renal transplant patients and identified correlated the quantified proteins with the volume fraction of fibrosis as determined by a morphometric method. Linear regression analysis identified four proteins that were highly associated with the degree of interstitial fibrosis, namely Coagulation Factor XIII A chain (estimate 18.7, adjusted p<0.03), Uridine Phosphorylase 1 (estimate 19.4, adjusted p<0.001), Actin-related protein 2/3 subunit 2 (estimate 34.2, adjusted p<0.05) and Cytochrome C Oxidase Assembly Factor 6 homolog (estimate -44.9, adjusted p<0.002) even after multiple testing. Proteins that were negatively associated with fibrosis (p < 0.005) were primarily related to normal metabolic processes and respiration, whereas proteins that were positively associated with fibrosis (p < 0.005) were involved in catabolic processes, cytoskeleton organization and immune response. The identified proteins may be candidates for further validation with regards to renal fibrosis. The results support the notion that cytoskeleton organization and immune responses are prevalent processes in renal allograft fibrosis.
2020-05-26 | PXD017867 | Pride
Project description:Interaction between C5a, a product of complement activation, and its receptor (C5aR) upregulates antigen-specific T cell responses by modulating the activation of antigen-presenting cells and T cells. Whether this C5a-C5aR interaction contributes to the immune responses that promote renal allograft rejection is unknown. Here, we found that deficiency of C5aR in both graft and recipient reduced allospecific T cell responses and prolonged renal allograft survival. In addition, lack of C5aR impaired the function of donor and recipient antigen-presenting cells and inhibited the response of recipient T cells to allostimulation. Furthermore, deficiency of C5aR in both graft and recipient reduced early inflammation in the grafts, with less cellular infiltration around the vessels and fewer F4/80 positive cells in the peritubular interstitium. These data demonstrate that C5aR is critical for a full adaptive immune response and mediates renal allograft rejection. Engagement of C5aR on dendritic cells and T cells modulates their function, enhancing allospecific T cell responses that lead to allograft rejection. Targeting C5a signaling may have therapeutic potential for T cell-mediated graft rejection.
| S-EPMC2938594 | biostudies-literature
Project description:Biopsy findings at the time of procurement of deceased donor kidneys remain the most common reason cited for kidney discard. To determine the value of renal allograft histology in predicting outcomes, we evaluated the significance of histologic findings, read by experienced renal pathologists, in 975 postreperfusion biopsy specimens collected from 2005 to 2009 after living donor (n=427) or deceased donor (n=548) renal transplant. We evaluated specimens for the degree of glomerulosclerosis, interstitial fibrosis and tubular atrophy, and vascular disease; specimens with a score of 0 or 1 (scale, 0-3) for each parameter were considered optimal. Overall, 66.3% of living donor kidneys and 50.7% of deceased donor kidneys received an optimal histology score (P<0.001). Irrespective of donor status, suboptimal kidneys came from older donors with a higher incidence of diabetes mellitus, hypertension, and obesity and a higher mean kidney donor risk index (all P<0.001). Death-censored outcomes after transplant differed significantly between optimal and suboptimal kidneys only in the deceased donor transplants (P=0.02). Regardless of histologic classification, outcomes with deceased donor kidneys were inferior to outcomes with living donor kidneys. However, 73.2% of deceased donor kidneys with suboptimal histology remained functional at 5 years. Our findings suggest that histologic findings on postreperfusion biopsy associate with outcomes after deceased donor but not living donor renal transplants, thus donor death and organ preservation-related factors may be of greater prognostic importance. Discarding donated kidneys on the basis of histologic factors may be inappropriate and merits further study.
| S-EPMC5619964 | biostudies-literature
Project description:BackgroundNative nephrectomy (NNx) is often done in patients with autosomal dominant polycystic kidney disease (ADPKD). Controversy exists concerning the need and timing of nephrectomy in transplant candidates. We hypothesize that post-transplant NNx does not negatively impact patient and graft survival.MethodsAmong 470 ADPKD transplant recipients included in the study, 114 (24.3%) underwent pre- (30.7%) or post-transplant (69.3%) NNx. Clinical data was retrieved from electronic records. Follow up was until death, graft loss or June 2014. Perioperative complications were compared between the surgical techniques (open or laparoscopic) and between the pre- and post-transplant nephrectomy groups. The effect of nephrectomy on graft survival was analyzed as a time-dependent covariate when performed post-transplant.ResultsMean age at transplant was 52.4 years, 53.8% were male, 93% white, 70% were from living donors and 56.8% were pre-emptive. Nephrectomy was done laparoscopically in 31% and 86% in the pre- and post- transplant nephrectomy groups, respectively. Complications were less common in those who underwent nephrectomy post-transplant (26.6% vs. 48%, p=0.03) but were similar regardless of surgical technique (open, 33.3% vs. laparoscopic 33%, p=0.66). Patient and graft survival were similar between those who underwent pre-transplant nephrectomy and the rest of the recipients. In the post-transplant nephrectomy group, nephrectomy did not affect patient (HR 0.77, CI 0.38-1.54, p=0.45) or graft survival (HR 1.0, CI 0.57-1.76, p=0.1).ConclusionsNephrectomy does not adversely affect patient or graft survival. Post-transplant nephrectomy is feasible when indicated without compromising long term graft outcome and has fewer complications than pre-transplant nephrectomy.
| S-EPMC4788702 | biostudies-literature
Project description:Kidney transplants that develop dysfunction or proteinuria after one year post transplant are at considerable risk for progression to renal failure. Identifying the molecules associated with graft failure could potentially lead to interventions that would slow the progression of organ failure. We analyzed the relationship between gene expression in late biopsies for cause in human kidney transplants and subsequent graft loss, and assessed the predictive value of gene expression. We evaluated the performance of these genes in an independent , and in a population of early biopsies that have a very low risk of subsequent graft failure. All consenting renal transplant patients undergoing biopsies for cause as standard of care between 09/2004 and 10/2007 at the university of Alberta or between 11/2006 and 02/2007 at the University of Illinois were included in the analysis. In addition, biopsies obtained from Minnesota between 09/2006 and 09/2007 were used as an independent . In addition to the cores required for standard histopathology, we collected one core for gene expression studies. the relationship between gene expression in the biopsy and subsequent graft loss was analyzed. This dataset is part of the TransQST collection.
2010-05-24 | E-GEOD-21374 | biostudies-arrayexpress
Project description:BackgroundThe effect of donor hypertension on the blood pressure of renal transplant recipients and the allograft outcomes are unclear. The aim of this study was to summarize the evidence about the effects of donor hypertension on renal transplant recipients' blood pressure, renal allograft outcomes and mortality.MethodsStudies published from January 1960 to 31 January 2019 in English were identified through a systematic search of six databases; PubMed, Embase, SCOPUS, Web of Science, Cochrane Database of Systematic Reviews, and CINAHL. Eligible observational studies with at least 1 year of follow-up were selected. Pooled estimates were obtained using random effects model.ResultsWe identified 15 papers from eight countries containing data on donor hypertension and renal transplantation carried out between 1963 and 2014. The median (range) follow-up period of the studies was 3.8 (1-11.9) years. The prevalence of post-transplant hypertension among recipients of a renal allograft from a normotensive donor range from 8 to 17.6%, while the prevalence of post-transplant hypertension among recipients of a renal allograft from a hypertensive donor range from 2.9 to 25%. Overall, pooled risk ratios (RR) indicated that donor hypertension was a risk factor for allograft failure or loss among renal transplant recipients (RR 1.31; 95% CI 1.06-1.63: P = 0.014). However, donor hypertension was not a risk factor for mortality among renal transplant recipients (RR 0.996; 95% CI 0.652-1.519: P = 0.984).ConclusionsDonor hypertension increases the risk of post-transplant hypertension among renal transplant recipients and increases the risk of allograft failure, However, donor hypertension was not a risk factor for mortality among renal transplant recipients, Closer monitoring should be given to renal allograft recipients from hypertensive donors, and further well-designed studies are needed to expand our knowledge of the impact of donor hypertension on the survival of renal allograft recipients.
| S-EPMC6737352 | biostudies-literature
Project description:Renal transplantation is the preferred treatment of end stage renal disease, but allograft survival is limited by the development of interstitial fibrosis and tubular atrophy in response to various stimuli. Much effort has been put into identifying new protein markers of fibrosis to support the diagnosis. In the present work, we performed an in-depth quantitative proteomics analysis of allograft biopsies from 31 prevalent renal transplant patients and correlated the quantified proteins with the volume fraction of fibrosis as determined by a morphometric method. Linear regression analysis identified four proteins that were highly associated with the degree of interstitial fibrosis, namely Coagulation Factor XIII A chain (estimate 18.7, adjusted p < 0.03), Uridine Phosphorylase 1 (estimate 19.4, adjusted p < 0.001), Actin-related protein 2/3 subunit 2 (estimate 34.2, adjusted p < 0.05) and Cytochrome C Oxidase Assembly Factor 6 homolog (estimate -44.9, adjusted p < 0.002), even after multiple testing. Proteins that were negatively associated with fibrosis (p < 0.005) were primarily related to normal metabolic processes and respiration, whereas proteins that were positively associated with fibrosis (p < 0.005) were involved in catabolic processes, cytoskeleton organization and the immune response. The identified proteins may be candidates for further validation with regards to renal fibrosis. The results support the notion that cytoskeleton organization and immune responses are prevalent processes in renal allograft fibrosis.
| S-EPMC7177439 | biostudies-literature