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:BACKGROUND:The prevalence and contemporary trends of pre-heart transplantation (HT) coagulopathy and associated clinical outcomes have not been studied from a national database. HYPOTHESIS:Pre-HT coagulopathy is associated with increased in-hospital mortality. METHODS:Among 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. RESULTS:The 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). CONCLUSIONS:In 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:While most human T cells express the CD28 costimulatory molecule constitutively, it is well known that age, inflammation, and viral infection can drive the generation of CD28null T cells. In vitro studies have demonstrated that CD28null cell effector function is not impacted by the presence of the CD28 costimulation blocker belatacept. As such, a prevailing hypothesis suggests that CD28null cells may precipitate costimulation blockade-resistant rejection. However, CD28+ cells possess more proliferative and multifunctional capacity, factors that may increase their ability to successfully mediate rejection. Here, we performed a retrospective immunophenotypic analysis of adult renal transplant recipients who experienced acute rejection on belatacept treatment as compared to those who did not. Intriguingly, our findings suggest that patients possessing higher frequency of CD28+ CD4+ TEM prior to transplant were more likely to experience acute rejection following treatment with a belatacept-based immunosuppressive regimen. Mechanistically, CD28+ CD4+ TEM contained significantly more IL-2 producers. In contrast, CD28null CD4+ TEM isolated from stable belatacept-treated patients exhibited higher expression of the 2B4 coinhibitory molecule as compared to those isolated from patients who rejected. These data raise the possibility that pretransplant frequencies of CD28+ CD4+ TEM could be used as a biomarker to predict risk of rejection following treatment with belatacept.
| S-EPMC5599135 | 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: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 (? = 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:Predicting chronic graft failure in renal transplant recipients (RTR) is an unmet clinical need. Chronic graft failure is often accompanied by transplant vasculopathy, the formation of de novo atherosclerosis in the transplanted kidney. Therefore, we determined whether the 10-year Framingham risk score (FRS), an established atherosclerotic cardiovascular disease prediction module, is associated with chronic graft failure in RTR. In this prospective longitudinal study, 600 well-characterised RTR were followed for 10 years. The association with death-censored chronic graft failure (n = 81, 13.5%) was computed. An extended Cox model showed that each one percent increase of the FRS significantly increased the risk of chronic graft failure by 4% (HR: 1.04, p < 0.001). This association remained significant after adjustment for potential confounders, including eGFR (HR: 1.03, p = 0.014). Adding the FRS to eGFR resulted in a higher AUC in a receiver operating curve (AUC = 0.79, p < 0.001) than eGFR alone (AUC = 0.75, p < 0.001), and an improvement in the model likelihood ratio statistic (67.60 to 88.39, p < 0.001). These results suggest that a combination of the FRS and eGFR improves risk prediction. The easy to determine and widely available FRS has clinical potential to predict chronic graft failure in RTR.
| S-EPMC8348129 | biostudies-literature
Project description:Observational studies have yielded inconsistent findings regarding the association of hemoglobin A(1c) (HbA(1c)) with survival in diabetic patients on dialysis. The association between pretransplant glycemic control and short- and long-term posttransplant outcomes in kidney transplant recipients is not clear.Linking the 5-year patient data of a large dialysis organization (DaVita) to the Scientific Registry of Transplant Recipients, we identified 2,872 diabetic dialysis patients who underwent first kidney transplantation. Mortality or graft failure and delayed graft function (DGF) risks were estimated by Cox regression (hazard ratio [HR]) and logistic regression (odds ratio), respectively.Patients were 53 ± 11 years old and included 36% women and 24% African Americans. In our fully adjusted model, allograft failure-censored, all-cause death HR and 95% CI for time-averaged pretransplant HbA(1c) categories of 7 to <8%, 8 to <9%, 9 to 10%, and ?10%, compared with 6 to <7% (reference), were 0.89 (0.59-1.36), 2.06 (1.31-3.24), 1.41 (0.73-2.74), and 3.43 (1.56-7.56), respectively; and graft failure-censored cardiovascular death HR was 0.38 (0.13-1.05), 1.78 (0.69-4.55), 1.59 (0.44-5.76), and 4.28 (0.85-21.64), respectively. We did not find any difference in risk of death-censored graft failure or DGF with different pretransplant HbA(1c) levels.Poor pretransplant glycemic control appears associated with decreased posttransplant survival in kidney transplant recipients, whereas allograft outcomes may not be affected.
| S-EPMC3220839 | biostudies-other