Tumor Recurrence and Graft Survival in Renal Transplant Recipients with a History of Pretransplant Malignancy: A Matched Pair Analysis.
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SUBMITTER: Becker F
PROVIDER: S-EPMC8199231 | biostudies-literature |
REPOSITORIES: biostudies-literature
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Project description:High-density lipoprotein (HDL) particles are involved in the protection against cardiovascular disease by promoting cholesterol efflux, in which accumulated cholesterol is removed from macrophage foam cells. We investigated whether HDL cholesterol efflux capacity is associated with cardiovascular mortality, all-cause mortality, and graft failure in a cohort of renal transplant recipients (n=495, median follow-up 7.0 years). Cholesterol efflux capacity at baseline was quantified using incubation of human macrophage foam cells with apolipoprotein B-depleted plasma. Baseline efflux capacity was not different in deceased patients and survivors (P=0.60 or P=0.50 for cardiovascular or all-cause mortality, respectively), whereas recipients developing graft failure had lower efflux capacity than those with functioning grafts (P<0.001). Kaplan-Meier analysis demonstrated a lower risk for graft failure (P=0.004) but not cardiovascular (P=0.30) or all-cause mortality (P=0.31) with increasing gender-stratified tertiles of efflux capacity. Cox regression analyses adjusted for age and gender showed that efflux capacity was not associated with cardiovascular mortality (hazard ratio [HR], 0.89; 95% confidence interval [95% CI], 0.67 to 1.19; P=0.43). Furthermore, the association between efflux capacity and all-cause mortality (HR, .79; 95% CI, 0.63 to 0.98; P=0.031) disappeared after further adjustment for potential confounders. However, efflux capacity at baseline significantly predicted graft failure (HR, 0.43; 95% CI, 0.29 to 0.64; P<0.001) independent of apolipoprotein A-I, HDL cholesterol, or creatinine clearance. In conclusion, this prospective study shows that cholesterol efflux capacity from macrophage foam cells is not associated with cardiovascular or all-cause mortality but is a strong predictor of graft failure independent of plasma HDL cholesterol levels in renal transplant recipients.
| S-EPMC4731105 | biostudies-literature
Project description:BackgroundThe prevalence and contemporary trends of pre-heart transplantation (HT) coagulopathy and associated clinical outcomes have not been studied from a national database.HypothesisPre-HT coagulopathy is associated with increased in-hospital mortality.MethodsAmong 2454 adult HT recipients from the 2003 to 2010 Nationwide Inpatient Sample databases, 707 (29%) had pre-HT coagulopathy (defined as a comorbidity variable, based on International Classification of Diseases, Ninthe Revision, Clinical Modification and Diagnosis Related Group codes). We used propensity scores for coagulopathy to assemble a matched cohort of 664 pairs of patients with and without coagulopathy balanced in 54 baseline characteristics.ResultsThe prevalence of pre-HT coagulopathy increased from 17% in 2003 to 44% in 2010 (P for trend <0.001). In-hospital mortality occurred in 8.6% and 4.7% of matched HT recipients with and without coagulopathy, respectively (hazard ratio: 1.81; 95% confidence interval [CI]: 1.17-2.80; P = 0.008). Coagulopathy was not significantly associated with post-HT graft complications (odds ratio [OR]: 1.20; 95% CI: 0.95-1.52; P = 0.131) but was associated with increased blood transfusions (OR: 1.92; 95% CI, 1.54-2.41; P < 0.001). Coagulopathy and no-coagulopathy groups had no difference in median length of stay (22 days in each group, P = 0.746), but median total hospital charges were higher among patients with coagulopathy compared to those without (US$425 643 vs US$389 656; P = 0.008).ConclusionsIn this national study of HT recipients, pretransplant coagulopathy was common, increased over time, and was not significantly associated with post-HT graft complications or increased hospital stay. However, it was associated with increased bleeding risk, in-hospital mortality, and total hospital charges. These findings may have implications for the selection of patients for HT.
| S-EPMC6711011 | biostudies-literature
Project description:BackgroundBK virus (BKV) is a significant cause of nephropathy in kidney transplantation. The goal of this study was to characterize the course and source of BKV in kidney transplant recipients.MethodsWe prospectively collected pretransplant plasma and urine samples from living and deceased kidney donors and performed BKV polymerase chain reaction (PCR) and immunoglobulin G (IgG) testing on pretransplant and serially collected posttransplant samples in kidney transplant recipients.ResultsAmong deceased donors, 8.1% (17/208) had detectable BKV DNA in urine prior to organ procurement. BK viruria was observed in 15.4% (6/39) of living donors and 8.5% (4/47) of deceased donors of recipients at our institution (P = .50). BKV VP1 sequencing revealed identical virus between donor-recipient pairs to suggest donor transmission of virus. Recipients of BK viruric donors were more likely to develop BK viruria (66.6% vs 7.8%; P < .001) and viremia (66.6% vs 8.9%; P < .001) with a shorter time to onset (log-rank test, P < .001). Though donor BKV IgG titers were higher in recipients who developed BK viremia, pretransplant donor, recipient, and combined donor/recipient serology status was not associated with BK viremia (P = .31, P = .75, and P = .51, respectively).ConclusionsDonor BK viruria is associated with early BK viruria and viremia in kidney transplant recipients. BKV PCR testing of donor urine may be useful in identifying recipients at risk for BKV complications.
| S-EPMC6603974 | biostudies-literature
Project description:Allogeneic stem cell transplantation is used in the treatment of high-risk hematological malignancies. However, this treatment is associated with severe treatment-related morbidity and mortality. The metabolic status of the recipient may be associated with the risk of development of transplant-associated complications such as graft-versus-host disease (GVHD). To better understand the impact of the lipidomic profile of transplant recipients on posttransplant complications, we evaluated the lipid signatures of patients with hematological disease using non-targeted lipidomics. In the present study, we studied pretransplant serum samples derived from 92 consecutive patients with acute myeloid leukemia (AML) or high-risk myelodysplastic syndrome (MDS). A total of 960 lipid biochemicals were identified, and the pretransplant lipidomic profiles differed significantly when comparing patients with and without the risk factors: (i) pretransplant inflammation, (ii) early fluid overload, and (iii) patients with and without later steroid-requiring acute GVHD. All three factors, but especially patients with pretransplant inflammation, were associated with decreased levels of several lipid metabolites. Based on the overall concentrations of various lipid subclasses, we identified a patient subset characterized by low lipid levels, increased frequency of MDS patients, signs of inflammation, decreased body mass index, and an increased risk of early non-relapse mortality. Metabolic targeting has been proposed as a possible therapeutic strategy in allotransplant recipients, and our present results suggest that the clinical consequences of therapeutic intervention (e.g., nutritional support) will also differ between patients and depend on the metabolic context.
| S-EPMC9220974 | biostudies-literature
Project description:BackgroundDue to their history of renal disease and exposure to immunosuppression, kidney transplant recipients with a failing graft may be at higher risk of adverse outcomes compared to nontransplant controls. Understanding the burden of disease in transplant recipients may inform treatment decisions of people whose native kidneys are failing and may be eligible for a transplant.ObjectiveTo compare mortality and morbidity in kidney transplant recipients with a failing graft to matched nontransplant controls.DesignRetrospective cohort study.SettingAlberta, Canada.PatientsKidney transplant recipients with a failing graft were identified as having at least 2 estimated glomerular filtration rate (eGFR) measurements between 15-30 mL/min/1.73 m2 (90-365 days apart). We also identified nontransplant controls with a similar degree of kidney dysfunction.MeasurementsMortality and hospitalization.MethodsWe propensity-score matched 520 kidney transplant recipients with a failing graft to 520 nontransplant controls.ResultsThe median age of the matched cohort was 57 years and 40% were women. Compared to matched nontransplant controls, recipients with a failing graft had a higher hazard of death (hazard ratio, 1.54; 95% confidence interval [CI], 1.28-1.85; p < .001) and a higher rate of all-cause hospitalization (rate ratio, 1.67; 95% CI, 1.42-1.97; p < .001). Kidney transplant recipients also had a higher rate of several cause-specific hospitalizations including genitourinary, cardiovascular, and infectious causes.LimitationsObservational design with the risk of residual confounding.ConclusionsA failing kidney transplant is associated with an increased burden of mortality and morbidity beyond chronic kidney disease. This information may assist the discussion of prognosis in kidney transplant recipients with a failing graft and the design of strategies to minimize risks.
| S-EPMC7158256 | biostudies-literature
Project description:Taurine is a sulfur containing nutrient that has been shown to protect against oxidative stress, which has been implicated in the pathophysiology leading to late graft failure after renal transplantation. We prospectively investigated whether high urinary taurine excretion, reflecting high taurine intake, is associated with low risk for development of late graft failure in renal transplant recipients (RTR). Urinary taurine excretion was measured in a longitudinal cohort of 678 stable RTR. Prospective associations were assessed using Cox regression analyses. Graft failure was defined as the start of dialysis or re-transplantation. In RTR (58% male, 53 ± 13 years old, estimated glomerular filtration rate (eGFR) 45 ± 19 mL/min/1.73 m2), urinary taurine excretion (533 (210-946) µmol/24 h) was significantly associated with serum free sulfhydryl groups (β = 0.126; P = 0.001). During median follow-up for 5.3 (4.5-6.0) years, 83 (12%) patients developed graft failure. In Cox regression analyses, urinary taurine excretion was inversely associated with graft failure (hazard ratio: 0.74 (0.67-0.82); P < 0.001). This association remained significant independent of potential confounders. High urinary taurine excretion is associated with low risk of late graft failure in RTR. Therefore, increasing taurine intake may potentially support graft survival in RTR. Further studies are warranted to determine the underlying mechanisms and the potential of taurine supplementation.
| S-EPMC6770760 | biostudies-literature
Project description:BackgroundDirect-acting antivirals (DAAs) have revolutionized the treatment of hepatitis C virus (HCV). The impact of DAAs on recurrence of hepatocellular carcinoma (HCC) after liver transplantation (LT) remains uncertain.ObjectiveWe aimed to evaluate the risk of HCC recurrence in LT recipients cleared of HCV with DAAs at the time of LT compared to a control group of LT recipients who were viremic at the time of LT.MethodsThe study was a single-center, retrospective cohort study of patients undergoing LT for HCV-related HCC from 2002 to 2017. We compared time to post-LT HCC recurrence in patients with a sustained virological response (SVR) from DAAs prior to LT (DAA group) to patients who were viremic at LT (HCV+ group) using Kaplan-Meier analysis. We performed a secondary analysis comparing post-LT HCC recurrence in the DAA group to LT recipients with SVR from interferon-based treatment prior to LT (IFN group).ResultsOne hundred fifty-one patients underwent LT for HCC related to HCV: 34 patients in DAA group, 95 patients in HCV+ group, and 22 in IFN group. Kaplan-Meier estimates of being HCC free were 96.2, 96.2, and 78.8% at 6, 12, and 24 months in DAA group, respectively, and 100, 98.6, and 95.8% at 6, 12, and 24 months in the HCV+ group, respectively; p = 0.08. There was no difference observed for HCC recurrence between the DAA and IFN groups. In a multivariate Cox proportional hazards model, DAA use increased the risk of post-LT HCC recurrence (HR 5.2, 95% CI 0.9-29.81, p = 0.07).ConclusionsA strong trend was observed on both Kaplan-Meier and multivariate analyses toward increased post-LT HCC recurrence in patients who achieved SVR prior to LT with DAAs compared to patients who were viremic at LT. Caution is required when considering pre-LT treatment of HCV with DAAs in patients with HCC.
| S-EPMC7590751 | biostudies-literature
Project description:BackgroundLow physical activity (PA) has been associated with higher rates of cardiovascular disease (CVD) and mortality in the general population. Despite the benefits of kidney transplantation, kidney transplant recipients (KTRs) remain at elevated risk for CVD and mortality compared to individuals without kidney disease.MethodsA prospective cohort of 507 adult KTRs from three academic centers completed the Physical Activity Scale for the Elderly (PASE) at transplantation. PASE scores were divided into tertiles.ResultsPA was lower with older age, history of CVD, smoking, and diabetes. During the median 8-year follow-up period, 128 individuals died, among whom 101 had a functioning allograft. In multivariable Cox regression for all-cause mortality, greater PA was strongly associated with better survival (HR: 0.52 for most active vs. inactive tertiles, 95% CI: 0.31-0.87, p = 0.01). Secondary analyses, in which (1) death with a functioning graft was the primary outcome, and (2) PASE scores were converted to the metabolic equivalent of task, revealed similar results. We did not find an association between change of PA after transplantation and mortality.ConclusionsPA at the time of kidney transplantation is a strong predictor of all-cause mortality and death with graft function. Evaluation of PA level among kidney transplant candidates may be a useful method to risk-stratify patients for survival after kidney transplantation. Kidney transplant candidates and recipients should also be encouraged to be physically active.
| S-EPMC3251242 | biostudies-literature
Project description:Little is known about the outcomes among solid organ transplant recipients with a pretransplant cancer diagnosis. We used linked data from the Scientific Registry of Transplant Recipients with 33 US cancer registries. Cox proportional hazards models assessed associations of pretransplant cancer with overall mortality, cancer-specific mortality, and development of a new posttransplant cancer. Among 311 677 recipients, the presence of a single pretransplant cancer was associated with increased overall mortality (adjusted hazard ratio [aHR], 1.19; 95% CI, 1.15-1.23) and cancer-specific mortality (aHR, 1.93; 95% CI, 1.76-2.12); results for 2+ pretransplant cancers were similar. Cancer-specific mortality was not significantly increased for uterine, prostate, or thyroid cancers (aHRs were 0.83, 1.22, and 1.54, respectively) but strongly elevated for lung cancer and myeloma (aHRs were 3.72 and 4.42, respectively). A pretransplant cancer diagnosis was also associated with increased risk of developing posttransplant cancer (aHR, 1.32; 95% CI, 1.23-1.40). Among 306 recipients whose cancer death was confirmed by cancer registry data, 158 deaths (51.6%) were from a de novo posttransplant cancer and 105 (34.3%) from the pretransplant cancer. Pretransplant cancer diagnoses are associated with increased mortality after transplantation, but some deaths are related to posttransplant cancers and other causes. Improved candidate selection and cancer screening and prevention may reduce mortality in this population.
| S-EPMC9978936 | biostudies-literature
Project description:IntroductionKidney transplantation remains the gold standard of treatment for end-stage renal disease (ESRD), with improved patient outcomes compared with dialysis. Epigenome-Wide Association Analysis (EWAS) of DNA methylation may identify markers that contribute to an individual's risk of adverse transplant outcomes, yet only a limited number of EWAS have been conducted in kidney transplant recipients. This EWAS aimed to interrogate the methylation profile of a kidney transplant recipient cohort with minimal posttransplant complications, exploring differences in samples pretransplant and posttransplant.MethodsWe compared differentially methylated cytosine-phosphate-guanine sites (dmCpGs) in samples derived from peripheral blood mononuclear cells of the same kidney transplant recipients, collected both pretransplant and posttransplant (N = 154), using the Infinium MethylationEPIC microarray (Illumina, San Diego, CA). Recipients received kidneys from deceased donors and had a mean of 17 years of follow-up.ResultsFive top-ranked dmCpGs were significantly different at false discovery rate (FDR) adjusted P ≤ 9 × 10-8; cg23597162 within JAZF1, cg25187293 within BTNL8, cg17944885, located between ZNF788P and ZNF625-ZNF20, cg14655917 located between ASB4 and PDK4 and cg09839120 located between GIMAP6 and EIF2AP3.ConclusionFive dmCpGs were identified at the generally accepted EWAS critical significance level of FDR adjusted P (P FDRadj) ≤ 9 × 10-8, including cg23597162 (within JAZF1) and cg17944885, which have prior associations with chronic kidney disease (CKD). Comparing individuals with no evidence of posttransplant complications (N = 105) demonstrated that 693,555 CpGs (89.57%) did not display any significant difference in methylation (P FDRadj ≥ 0.05), thereby this study establishes an important reference for future epigenetic studies that seek to identify markers of posttransplant complications.
| S-EPMC9939425 | biostudies-literature