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Left atrial diameter and survival among renal allograft recipients.

ABSTRACT: BACKGROUND AND OBJECTIVES: Sequential echocardiography is routinely performed in patients with ESRD listed for transplantation. The benefit of this labor- and time-intensive measure, however, remains unclear. Thus, this study elucidated the various obtained routine echocardiography parameters that best predicted mortality and graft survival after renal transplantation. DESIGN, SETTING, PARTICIPANTS, & MEASUREMENTS: This study investigated 553 first renal transplant recipients listed in the Austrian Dialysis and Transplant Registry between 1992 and 2011 who had echocardiographic analysis at transplantation and survived at least 1 year. Cox proportional hazards models with the purposeful selection algorithms for covariables were used to identify predictors of mortality and graft loss. A Fine and Gray model was used to evaluate cause-specific death. RESULTS: During a median follow-up of 7.14 years, 81 patients died, and 59 patients experienced graft loss after the first year. The Kaplan-Meier analysis showed that 85% of patients with a left atrial diameter below the median of 53 mm were alive 10 years after transplantation, whereas only 70% of those patients with a left atrial diameter equal to or above the median had survived (P<0.001). In the multivariable model, left atrial diameter (per millimeter) independently predicted overall mortality (hazard ratio, 1.06; 95% confidence interval, 1.03 to 1.08; P<0.001) and cause-specific cardiac death (hazard ratio, 1.04; 95% confidence interval, 1.00 to 1.08; P=0.04). Functional graft loss was predicted by the right atrial diameter (hazard ratio, 1.04; 95% confidence interval, 1.02 to 1.07; P=0.001). CONCLUSION: The left atrial diameter determined at transplantation predicted overall and cardiac mortality. Patients with widely enlarged left atria exhibit a considerably reduced life expectancy. It remains to be determined, however, whether renal transplantation is futile in these patients.

SUBMITTER: Kainz A

PROVIDER: S-EPMC3848405 | biostudies-other | 2013 Dec

REPOSITORIES: biostudies-other

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Left atrial diameter and survival among renal allograft recipients.

Kainz Alexander A Goliasch Georg G Wiesbauer Franz F Binder Thomas T Maurer Gerald G Nesser Hans-Joachim HJ Mascherbauer Regina R Ebner Christian C Kramar Reinhard R Wilflingseder Julia J Oberbauer Rainer R

Clinical journal of the American Society of Nephrology : CJASN 20130905 12

<h4>Background and objectives</h4>Sequential echocardiography is routinely performed in patients with ESRD listed for transplantation. The benefit of this labor- and time-intensive measure, however, remains unclear. Thus, this study elucidated the various obtained routine echocardiography parameters that best predicted mortality and graft survival after renal transplantation.<h4>Design, setting, participants, & measurements</h4>This study investigated 553 first renal transplant recipients listed ...[more]

PMID: 24009216

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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.

Project description:Steroid-refractory acute rejection is a risk factor for inferior renal allograft outcome. We aimed to gain insight into the mechanisms underlying steroid resistance by identifying novel molecular markers of steroid-refractory acute rejection. Eighty-three kidney transplant recipients (1995-2005), who were treated with methylprednisolone during a first acute rejection episode, were included in this study. Gene expression patterns were investigated in a discovery cohort of 36 acute rejection biopsies, and verified in a validation cohort of 47 acute rejection biopsies. In the discovery set, expression of metallothioneins (MT) was significantly (P<0.000001) associated with decreased response to steroid treatment. Multivariate analysis resulted in a predictive model containing MT-1 as an independent covariate (AUC=0.88, P<0.0000001). In the validation set, MT-1 expression was also significantly associated with steroid resistance (P=0.029). Metallothionein expression was detected in macrophages and tubular epithelial cells. Parallel to the findings in patients, in vitro experiments of peripheral blood mononuclear cells from 11 donors showed that non-response to methylprednisolone treatment is related to highly elevated MT levels. High expression of metallothioneins in renal allografts is associated with resistance to steroid treatment. Metallothioneins regulate intracellular concentrations of zinc, through which they may diminish the zinc-requiring anti-inflammatory effect of the glucocorticoid receptor. Transcriptional profiles of 40 renal allograft biopsy samples were analyzed using Illumina HumanRef-8 v3.0 BeadChips (Illumina, San Diego, CA). Expression profiles were investigated in total RNA isolated from biopsy samples of 18 patients with steroid responsive acute rejection and 18 patients with steroid resistant acute rejection. Four biopsies, taken during acute decrease of graft function but with no histomorphologic indication of rejection, were included as controls.

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Left atrial diameter and survival among renal allograft recipients.

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Left atrial diameter and survival among renal allograft recipients.

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