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:This SuperSeries is composed of the SubSeries listed below.
2024-10-15 | GSE250536 | GEO
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:ImportanceThere are limited data for the utility of statins for primary prevention of atherosclerotic cardiovascular disease (ASCVD) and death in adults with chronic kidney disease (CKD).ObjectiveTo evaluate the association of statin use with all-cause mortality and major adverse cardiovascular events (MACE) among US veterans older than 65 years with CKD stages 3 to 4.Design, setting, and participantsThis cohort study used a target trial emulation design for statin initiation among veterans with moderate CKD (stages 3 or 4) using nested trials with a propensity weighting approach. Linked Veterans Affairs (VA) Healthcare System, Medicare, and Medicaid data were used. This study considered veterans newly diagnosed with moderate CKD between 2005 and 2015 in the VA, with follow-up through December 31, 2017. Veterans were older than 65 years, within 5 years of CKD diagnosis, had no prior ASCVD or statin use, and had at least 1 clinical visit in the year prior to trial baseline. Eligibility criteria were assessed for each nested trial, and Cox proportional hazards models with bootstrapping were run. Analysis was conducted from July 2021 to October 2023.ExposureStatin initiation vs none.Main outcomes and measuresPrimary outcome was all-cause mortality; secondary outcome was time to first MACE (myocardial infarction, transient ischemic attack, stroke, revascularization, or mortality).ResultsIncluded in the analysis were 14 828 veterans. Mean (SD) age at CKD diagnosis was 76.9 (8.2) years, 14 616 (99%) were men, 10 539 (72%) White, and 2568 (17%) Black. After expanding to person-trials and assessing eligibility at each baseline, there were 151 243 person-trials (14 685 individuals) of nonstatin initiators and 2924 person-trials (2924 individuals) of statin initiators included. Propensity score adjustment via overlap weighting with nonparametric bootstrapping resulted in covariate balance, with mean (SD) follow-up of 3.6 (2.7) years. The hazard ratio for all-cause mortality was 0.91 (95% CI, 0.85-0.97) comparing statin initiators to noninitiators. The hazard ratio for MACE was 0.96 (95% CI, 0.91-1.02). Results remained consistent in prespecified subgroup analyses.Conclusions and relevanceIn this target trial emulation of statin initiation in US veterans older than 65 years with CKD stages 3 to 4 and no prior ASCVD, statin initiation was significantly associated with a lower risk of all-cause mortality but not MACE. Results should be confirmed in a randomized clinical trial.
| S-EPMC10701610 | biostudies-literature
Project description:BackgroundWhether time-in-target range (TTR) for systolic blood pressure (SBP) associates with adverse kidney and cardiovascular events remains incompletely understood.MethodsThis study included participants in 2 clinical trials that compared intensive (<120 mm Hg) and standard (<140 mm Hg) SBP lowering. SBP-TTR for months 0 to 3 was calculated using therapeutic ranges of 110 to 130 mm Hg and 120 to 140 mm Hg for the intensive and standard arms, respectively. Adverse kidney events included the composite of dialysis, kidney transplant, serum creatinine >3.3 mg/dL, sustained eGFR <15 mL/(min·1.73 m2), or sustained eGFR decline >40%. Adverse cardiovascular events included myocardial infarction, stroke, heart failure, and cardiovascular death. Adjusted Cox proportional hazards regression models were used to estimate the association between SBP-TTR and kidney and cardiovascular events.ResultsParticipants with higher TTR were younger and less likely to have preexisting cardiovascular disease. Compared with participants with TTR of 0%, the risk of adverse kidney events was lower for participants with TTR of >0% to 43% (hazard ratio [95% CI], 0.57 [0.42-0.76]; P<0.001), 43% to <70% (0.57 [0.42-0.78]; P=0.001), 70% to <100% (0.53 [0.38-0.74]; P<0.001), and 100% (0.33 [0.20-0.57]; P<0.001) in fully adjusted models. The risk of major adverse cardiovascular events was lower for participants with TTR of >0% to 43% (0.66 [0.52-0.83]; P=0.001), 43% to <70% (0.70 [0.55-0.90]; P=0.005), 70% to <100% (0.65 [0.50-0.84]; P=0.001), or 100% (0.56 [0.39-0.80]; P=0.001) compared with those with TTR of 0%.ConclusionsHigher SBP-TTR associates with lower risks of adverse kidney and cardiovascular events in adults with hypertension. SBP-TTR may be a potential therapeutic target and quality metric.
| S-EPMC9851984 | 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