Incidence of Major Adverse Cardiovascular Events and Cardiac Mortality in High-Risk Kidney-Only and Simultaneous Pancreas-Kidney Transplant Recipients.
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ABSTRACT:
SUBMITTER: Lim WH
PROVIDER: S-EPMC8116724 | biostudies-literature |
REPOSITORIES: biostudies-literature
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Project description:BACKGROUND:The incidence and impact of adverse drug events (ADEs) leading to hospitalization and as a predominant risk factor for late graft loss has not been studied in transplantation. METHODS:This was a longitudinal cohort study of adult kidney recipients transplanted between 2005 and 2010 and followed through 2013. There were 3 cohorts: no readmissions, readmissions not due to an adverse drug event, and adverse drug events contributing to readmissions. The rationale of the adverse drug events contribution to the readmission was categorized in terms of probability, preventability, and severity. RESULTS:A total of 837 patients with 963 hospital readmissions were included; 47.9% had at least one hospital readmission and 65.0% of readmissions were deemed as having an ADE contribute. The predominant causes of readmissions related to ADEs included non-opportunistic infections (39.6%), opportunistic infections (10.5%), rejection (18.1%), and acute kidney injury (11.8%). Over time, readmissions due to under-immunosuppression (rejection) significantly decreased (-1.6% per year), while those due to over-immunosuppression (infection, cancer, or cytopenias) significantly increased (2.1% increase per year [difference 3.7%, P = .026]). Delayed graft function, rejection, creatinine, graft loss, and death were all significantly greater in those with an ADE that contributed to a readmission compared the other two cohorts (P < .05). CONCLUSION:These results demonstrate that ADEs may be associated with a significant increase in the risk of hospital readmission after kidney transplant and subsequent graft loss.
| S-EPMC5780193 | biostudies-literature
Project description:BackgroundThe optimal immunosuppressive regimen in simultaneous pancreas-kidney transplant (SPKT) recipients that prevents acute rejection episodes (AREs) and allows optimal outcome remains elusive.MethodsThis cohort study assessed incidence and time to AREs in 73 consecutive SPKT recipients receiving alemtuzumab induction and steroid-free maintenance with tacrolimus and mycophenolate mofetil. A cohort with single high-dose antithymocyte globulin (ATG; n = 85) and triple therapy served as controls. In addition, we provided mechanistic insights in AREs after alemtuzumab depletion, including composition and alloreactivity of lymphocytes (flow cytometry and mixed lymphocyte reaction) plasma alemtuzumab levels (enzyme-linked immunosorbent assay), and maintenance drug exposure.ResultsOverall number of AREs at 3 years was significantly lower with alemtuzumab versus ATG induction (26.0% vs 43.5%; adjusted hazard ratio, 0.38; P = 0.029). Most AREs (94.6%) with ATG occurred within the first month, whereas 84.2% of AREs with alemtuzumab occurred beyond 3 months. Patients with and without an ARE in the steroid-free alemtuzumab group showed no differences in composition of lymphocytes, or in alemtuzumab levels. Of note, more than two thirds of these AREs were preceded by empiric tacrolimus and/or mycophenolate mofetil dose adjustments due to viral infections, leukopenia, or gastrointestinal symptoms.ConclusionsAlemtuzumab induction resulted in a significant lower incidence of AREs. Empiric dose adjustments beyond 3 months in the absence of steroids carry a significant risk for subsequent rejection in SPKT recipients.
| S-EPMC5361562 | biostudies-literature
Project description:Prediction of the risk of cardiovascular events (CVE's) is important to optimize outcomes after kidney transplantation. Aortoiliac stenosis is frequently observed during pre-transplant screening. We hypothesized that these patients are at higher risk of post-transplant CVE's due to the joint underlying atherosclerotic disease. Therefore, we aimed to assess whether aortoiliac stenosis was associated with post-transplant CVE's. This retrospective, single-center cohort study included adult kidney transplant recipients, transplanted between 2000 and 2016, with contrast-enhanced imaging available. Aortoiliac stenosis was classified according to the Trans-Atlantic Inter-Society Consensus (TASC) II classification and was defined as significant in case of ≥50% lumen narrowing. The primary outcome was CVE-free survival. Eighty-nine of 367 patients had significant aortoiliac stenosis and were found to have worse CVE-free survival (median CVE-free survival: stenosis 4.5 years (95% confidence interval (CI) 2.8-6.2), controls 8.9 years (95% CI 6.8-11.0); log-rank test P < .001). TASC II C and D lesions were independent risk factors for a post-transplant CVE with a hazard ratio of 2.15 (95% CI 1.05-4.38) and 6.56 (95% CI 2.74-15.70), respectively. Thus, kidney transplant recipients with TASC II C and D aortoiliac stenosis require extensive cardiovascular risk management pre-, peri,- and post-transplantation.
| S-EPMC9285727 | biostudies-literature
Project description:Background and objectivesBilling claims are increasingly examined beyond administrative functions as outcomes measures in observational research. Few studies have described the performance of billing claims as surrogate measures of clinical events among kidney transplant recipients.Design, setting, participants, & measurementsWe investigated the sensitivity of Medicare billing claims for clinically verified cardiovascular diagnoses (five categories) and procedures (four categories) in a novel database linking Medicare claims to electronic medical records of one transplant program. Cardiovascular events identified in medical records for 571 Medicare-insured transplant recipients in 1991 through 2002 served as reference measures.ResultsWithin a claims-ascertainment period spanning +/-30 d of clinically recorded dates, aggregate sensitivity of single claims was higher for case definitions incorporating Medicare Parts A and B for diagnoses and procedures (90.9%) compared with either Part A (82.3%) or Part B (84.6%) alone. Perfect capture of the four procedures was possible within +/-30 d or with short claims window expansion, but sensitivity for the diagnoses trended lower with all study algorithms (91.2% with window up to +/-90 d). Requirement for additional confirmatory diagnosis claims did not appreciably reduce sensitivity. Sensitivity patterns were similar in the early compared with late periods of the study.ConclusionsCombined use of Medicare Parts A and B billing claims composes a sensitive measure of cardiovascular events after kidney transplant. Further research is needed to define algorithms that maximize specificity as well as sensitivity of claims from Medicare and other insurers as research measures in this population.
| S-EPMC2709516 | biostudies-literature
Project description:T-lymphocyte activation may contribute to atherosclerosis, the prevalence of which is increased in transplant patients. However, the cardiovascular consequences of polyclonal antithymocyte globulin (ATG)-induced immune modifications, which include alterations in T-cell subsets, are unknown. We conducted a retrospective single-center study to assess whether ATG associates with an increased incidence of atherosclerotic events (CVEs) in kidney transplant patients. Propensity score analysis was performed to address potential confounding by indication. We also tested whether ATG use induces a proatherogenic immune status. Sixty-nine (12.2%) CVEs occurred during follow-up (87±31 months). The cumulative incidence of CVEs was higher in ATG-treated patients (14.7% versus 8.2%; P=0.03). Cox regression analysis revealed that ATG use was an independent risk factor for CVEs (hazard ratio [HR], 2.36; 95% confidence interval [95% CI], 1.35 to 4.13; P=0.003). Results obtained in the propensity score match analysis recapitulated those obtained from the overall cohort (HR, 2.09; 95% CI, 1.11 to 3.98; P=0.02). Late-stage differentiated CD8(+) T cells increased 1 year after transplantation only in ATG-treated patients. More generally, ATG associated with features of immune activation. These modifications increased markedly in patients exposed to cytomegalovirus (CMV). Subanalyses suggest that the effect of ATG on CVEs is restricted to CMV-exposed patients. However, CMV infection associated significantly with CVEs only in ATG-treated patients (HR, 2.07; 95% CI, 1.16 to 3.70; P=0.01). In conclusion, ATG associated with both immune activation and post-transplant CVEs in this cohort. Further studies should precisely determine whether ATG-induced immune activation is the causal link between ATG and CVEs.
| S-EPMC4033372 | biostudies-other
Project description:Background and objectivesMajor adverse kidney events, a composite of death, new kidney replacement therapy, or persistent kidney dysfunction, is a potential patient-centered outcome for clinical trials in sepsis-associated kidney injury. We sought to determine the incidence of major adverse kidney events within 30 days and validate this end point in pediatric sepsis.Design, setting, participants, & measurementsWe conducted a retrospective observational study using the Pediatric Health Information Systems Plus database of patients >6 months to <18 years old with a diagnosis of severe sepsis/septic shock; orders for bacterial blood culture, antibiotics, and at least one fluid bolus on hospital day 0/1; and known hospital disposition between January 2007 and December 2011. The primary outcome was incidence of major adverse kidney events within 30 days. Major adverse kidney events within 30 days were validated against all-cause mortality at hospital discharge, hospital length of stay, total hospital costs, hospital readmission within 30 days and 1 year, and lowest eGFR between 3 months and 1 year after discharge. We reported incidence of major adverse kidney events within 30 days with 95% confidence intervals using robust SEM and used multivariable logistic regression to test the association of major adverse kidney events within 30 days with hospital costs and mortality.ResultsOf 1685 admissions, incidence of major adverse kidney events within 30 days was 9.6% (95% confidence interval, 8.1% to 11.0%), including 4.5% (95% confidence interval, 3.5% to 5.4%) death, 1.7% (95% confidence interval, 1.1% to 2.3%) kidney replacement therapy, and 5.8% (95% confidence interval, 4.7% to 6.9%) persistent kidney dysfunction. Patients with versus without major adverse kidney events within 30 days had higher all-cause mortality at hospital discharge (28% versus 1%; P<0.001), higher total hospital costs ($61,188; interquartile range, $21,272-140,356 versus $28,107; interquartile range, $13,056-72,697; P<0.001), and higher proportion with eGFR<60 ml/min per 1.73 m2 between 3 months and 1 year after discharge (19% versus 4%; P=0.001). Major adverse kidney events within 30 days was not associated with length of stay or readmissions.ConclusionsIn children with sepsis, major adverse kidney events within 30 days are common, feasible to measure, and a promising end point for future clinical trials.
| S-EPMC6500940 | biostudies-literature
Project description:Depressive symptoms and frailty are each independently associated with morbidity and mortality in kidney transplant (KT) recipients. We hypothesized that having both depressive symptoms and frailty would be synergistic and worse than the independent effect of each. In a multicenter cohort study of 773 KT recipients, we measured the Fried frailty phenotype and the modified 18-question Center for Epidemiologic Studies-Depression Scale (CES-D). Using adjusted Poisson regression and survival analysis, we tested whether depressive symptoms (CES-D score > 14) and frailty were associated with KT length of stay (LOS), death-censored graft failure (DCGF), and mortality. At KT admission, 10.0% of patients exhibited depressive symptoms, 16.3% were frail, and 3.6% had both. Recipients with depressive symptoms were more likely to be frail (aOR = 3.97, 95% CI: 2.28-6.91, P < 0.001). Recipients with both depressive symptoms and frailty had a 1.88 times (95% CI: 1.70-2.08, P < 0.001) longer LOS, 6.20-fold (95% CI:1.67-22.95, P < 0.01) increased risk of DCGF, and 2.62-fold (95% CI:1.03-6.70, P = 0.04) increased risk of mortality, compared to those who were nonfrail and without depressive symptoms. There was only evidence of synergistic effect of frailty and depressive symptoms on length of stay (P for interaction < 0.001). Interventions aimed at reducing pre-KT depressive symptoms and frailty should be explored for their impact on post-KT outcomes.
| S-EPMC6440201 | biostudies-literature
Project description:BackgroundStatins achieve potent LDL lowering in the general population leading to a significant cardiovascular (CV) risk reduction. In renal transplant recipients (RTR) statins are included in treatment guidelines, however, conclusive evidence of improved cardiovascular outcomes has not been uniformly provided and concerns have been raised about simultaneous use of statins and the immunosuppressant cyclosporine. This study aimed to elucidate the effect of statins on a compound CV endpoint, comprised of ischaemic CV events and CV mortality in RTR, with subgroup analysis focussing on cyclosporine users.Method622 included RTR (follow-up 5.4 years) were matched based on propensity scores and dichotomized by statin use. Survival analysis was conducted.ResultsCox regression showed that statin use was not significantly associated with the compound CV endpoint in a fully adjusted model (HR = 0.81, 95% CI = 0.53-1.24, P = .33). Subgroup analyses in RTR using cyclosporine revealed a strong positive association of statin use with the CV compound outcome in a fully adjusted model (HR = 6.60, 95% CI 1.75-24.9, P = .005). Furthermore, statin use was positively correlated with cyclosporine trough levels (correlation coefficient 0.11, P = .04).ConclusionIn conclusion, statin use does not significantly decrease incident CV events in an overall RTR cohort, but is independently associated with CV-specific mortality and events in cyclosporine using RTR, possibly due to a bilateral pharmacological interaction.
| S-EPMC8596424 | biostudies-literature
Project description:Renal transplantation is the treatment of choice in patients with end-stage renal disease. Major adverse cardiac events (MACE) are common after renal transplant, especially in the perioperative period, leading to excess morbidity and mortality. The predictors and long-term prognostic implications of MACE are poorly understood. We analyzed predictors and implications of MACE in a cohort of 321 consecutive adult patients, who received renal allograft transplantation between 1995 and 2003 at our institution. The characteristics of 321 patients were: age at transplant 44 ± 13 years, 60% male, 36% diabetes mellitus (DM), left ventricular ejection fraction (LVEF) 60 ± 16%. MACE occurred in 21 patients with cumulative rate of 6.5% over 3 years after renal transplant, 57% occurring within 30 days, 67% within 90 days, and 86% within 180 days. MACE was not predicted by any clinical or pharmacological variables including age, gender, hypertension, DM, prior myocardial infarction, smoking, duration of dialysis, LVEF, or therapy with β-blockers (BB), angiotensin converting enzyme inhibitors, or calcium channel blockers. However, a clinical decision to perform a stress test or a coronary angiogram was predictive of higher MACE rate. MACE, irrespective of type, was independently associated with higher mortality over a period up to 15 years and this seemed to be blunted by BB therapy. MACE rate after renal transplantation decreases over time, most occurring in the first 90 days and is not predicted by any of the traditional risk factors or drug therapies. It is associated with higher long-term mortality.
| S-EPMC4082448 | biostudies-other
Project description:Concerns about adverse effects of calcineurin inhibitors (CNIs) have prompted development of protocols that minimize their use. Whereas previous CNI withdrawal trials in heterogeneous cohorts showed unacceptable rates of acute rejection (AR), we hypothesized that we could identify individuals capable of tolerating CNI withdrawal by targeting immunologically quiescent kidney transplant recipients. The Clinical Trials in Organ Transplantation-09 Trial was a randomized, prospective study of nonsensitized primary recipients of living donor kidney transplants. Subjects received rabbit antithymocyte globulin, tacrolimus, mycophenolate mofetil, and prednisone. Six months post-transplantation, subjects without de novo donor-specific antibodies (DSAs), AR, or inflammation at protocol biopsy were randomized to wean off or remain on tacrolimus. The intended primary end point was the change in interstitial fibrosis/tubular atrophy score between implantation and 24-month protocol biopsies. Serially collected urine CXCL9 ELISA results were correlated with outcomes. The study was terminated prematurely because of unacceptable rates of AR (4 of 14) and/or de novo DSAs (5 of 14) in the tacrolimus withdrawal arm. Positive urinary CXCL9 predated clinical detection of AR by a median of 15 days. Analyses showed that >16 HLA-DQ epitope mismatches and pretransplant, peripheral blood, donor-reactive IFN-? ELISPOT assay results correlated with development of DSAs and/or AR on tacrolimus withdrawal. Although data indicate that urinary CXCL9 monitoring, epitope mismatches, and ELISPOT assays are potentially informative, complete CNI withdrawal must be strongly discouraged in kidney transplant recipients who are receiving standard-of-care immunosuppression, including those who are deemed to be immunologically quiescent on the basis of current clinical and laboratory criteria.
| S-EPMC4657844 | biostudies-literature