Dataset Information

A comprehensive characterization of aggravated aging-related changes in T lymphocytes and monocytes in end-stage renal disease: the iESRD study.

ABSTRACT:

Background

Patients with end-stage renal disease (ESRD) exhibit a premature aging phenotype of the immune system. Nevertheless, the etiology and impact of these changes in ESRD patients remain unknown.

Results

Compared to healthy individuals, ESRD patients exhibit accelerated immunosenescence in both T cell and monocyte compartments, characterized by a dramatic reduction in naïve CD4+ and CD8+ T cell numbers but increase in CD8+ T_EMRA cell and proinflammatory monocyte numbers. Notably, within ESRD patients, aging-related immune changes positively correlated not only with increasing age but also with longer dialysis vintage. In multivariable-adjusted logistic regression models, the combination of high terminally differentiated CD8+ T cell level and high intermediate monocyte level, as a composite predictive immunophenotype, was independently associated with prevalent coronary artery disease as well as cardiovascular disease, after adjustment for age, sex, systemic inflammation and presence of diabetes. Levels of terminally differentiated CD8+ T cells also positively correlated with the level of uremic toxin p-cresyl sulfate.

Conclusions

Aging-associated adaptive and innate immune changes are aggravated in ESRD and are associated with cardiovascular diseases. For the first time, our study demonstrates the potential link between immunosenescence in ESRD and duration of exposure to the uremic milieu.

SUBMITTER: Chiu YL

PROVIDER: S-EPMC6223078 | biostudies-literature | 2018

REPOSITORIES: biostudies-literature

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Publications

A comprehensive characterization of aggravated aging-related changes in T lymphocytes and monocytes in end-stage renal disease: the iESRD study.

Chiu Yen-Ling YL Shu Kai-Hsiang KH Yang Feng-Jung FJ Chou Tzu-Ying TY Chen Ping-Min PM Lay Fang-Yun FY Pan Szu-Yu SY Lin Cheng-Jui CJ Litjens Nicolle H R NHR Betjes Michiel G H MGH Bermudez Selma S Kao Kung-Chi KC Chia Jean-San JS Wang George G Peng Yu-Sen YS Chuang Yi-Fang YF

Immunity & ageing : I & A 20181108

<h4>Background</h4>Patients with end-stage renal disease (ESRD) exhibit a premature aging phenotype of the immune system. Nevertheless, the etiology and impact of these changes in ESRD patients remain unknown.<h4>Results</h4>Compared to healthy individuals, ESRD patients exhibit accelerated immunosenescence in both T cell and monocyte compartments, characterized by a dramatic reduction in naïve CD4+ and CD8+ T cell numbers but increase in CD8+ T<sub>EMRA</sub> cell and proinflammatory monocyte n ...[more]

PMID: 30455721

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Project description:ImportanceMedicare beneficiaries with end-stage renal disease (ESRD) are a medically complex group accounting for less than 1% of the Medicare population but more than 7% of Medicare fee-for-service payments.ObjectiveTo evaluate the association of the Comprehensive End-Stage Renal Disease Care (CEC) model with Medicare payments, health care use, and quality of care.Design, setting, and participantsIn this economic evaluation, a difference-in-differences design estimated the change in outcomes for 73 094 Medicare fee-for-service beneficiaries aligned to CEC dialysis facilities between the baseline (from January 2014 to March 2015) and intervention periods (from October 2015 to December 2017) relative to 60 464 beneficiaries at matched dialysis facilities. In the CEC model, dialysis facilities, nephrologists, and other providers partner to form ESRD Seamless Care Organizations (ESCOs), specialty-oriented accountable care organizations that coordinate care for beneficiaries with ESRD. ESCOs with expenditures below a benchmark set by the Centers for Medicare & Medicaid Services are eligible to share in savings if they meet quality thresholds. A total of 685 dialysis facilities affiliated with 37 ESCOs participated in the CEC model as of January 2017. Thirteen ESCOs joined the CEC model on October 1, 2015 (wave 1), and 24 ESCOs joined on January 1, 2017 (wave 2). Patients with ESRD who were aligned with CEC dialysis facilities were compared with patients at matched dialysis facilities.Main outcomes and measuresMedicare total and service-specific payments per beneficiary per month; hospitalizations, readmissions, and emergency department visits; and select quality measures.ResultsRelative to the comparison group (n = 60 464; 55% men; mean [SD] age, 63.5 [14.4] years), total Medicare payments for CEC beneficiaries (n = 73 094; 56% men; mean [SD] age, 63.0 [14.4] years) decreased by $114 in payments per beneficiary per month (95% CI, -$202 to -$26; P = .01), associated primarily with decreases in payments for hospitalizations and readmissions. Payment reductions were offset by shared savings payments to ESCOs, resulting in net losses of $78 in payments per beneficiary per month (95% CI, -$8 to $164; P = .07). Relative to the comparison group, CEC beneficiaries had 5.01 fewer hospitalizations per 1000 beneficiaries per month (95% CI, -8.45 to -1.56; P = .004), as well as fewer catheter placements (CEC beneficiaries with catheter as vascular access for periods longer than 90 days decreased by 0.78 percentage points [95% CI, -1.36 to -0.19; P = .01]) and fewer hospitalizations for ESRD complications (CEC beneficiaries were 0.11 percentage points less likely [95% CI, -0.20 to -0.02; P = .01] to be hospitalized in a given month). Total dialysis sessions and payments increased, suggesting improved adherence to dialysis treatments.Conclusions and relevanceEarly findings from the CEC model demonstrate that a specialty accountable care organization model focused on a particular population was associated with reduced payments and improved quality of care. Future research can assess the longer-term outcomes of the CEC model and its applicability to populations with other complex chronic conditions.

Project description:Background and objectivesMedicare plans to extend financial structures tested through the Comprehensive End-Stage Renal Disease Care (CEC) Initiative-an alternative payment model for maintenance dialysis providers-to promote high-value care for beneficiaries with kidney failure. The End-Stage Renal Disease Seamless Care Organizations (ESCOs) that formed under the CEC Initiative varied greatly in their ability to generate cost savings and improve patient health outcomes. This study examined whether organizational or community characteristics were associated with ESCOs' performance.Design, setting, participants, & measurementsWe used a retrospective pooled cross-sectional analysis of all 37 ESCOs participating in the CEC Initiative during 2015-2018 (n=87 ESCO-years). Key exposures included ESCO characteristics: number of dialysis facilities, number and types of physicians, and years of CEC Initiative experience. Outcomes of interest included were above versus below median gross financial savings (2.4%) and standardized mortality ratio (0.93). We analyzed unadjusted differences between high- and low-performing ESCOs and then used multivariable logistic regression to construct average marginal effect estimates for parameters of interest.ResultsAbove-median gross savings were obtained by 23 (52%) ESCOs with no program experience, 14 (32%) organizations with 1 year of experience, and seven (16%) organizations with 2 years of experience. The adjusted likelihoods of achieving above-median gross savings were 23 (95% confidence interval, 8 to 37) and 48 (95% confidence interval, 24 to 68) percentage points higher for ESCOs with 1 or 2 years of program experience, respectively (versus none). The adjusted likelihood of achieving above-median gross savings was 1.7 (95% confidence interval, -3 to -1) percentage points lower with each additional affiliated dialysis facility. Adjusted mortality rates were lower for ESCOs located in areas with higher socioeconomic status.ConclusionsSmaller ESCOs, organizations with more experience in the CEC Initiative, and those located in more affluent areas performed better under the CEC Initiative.

Project description:ObjectiveSerum albumin is a marker of malnutrition and inflammation and has been demonstrated as a strong predictor of mortality in chronic kidney disease (CKD) and end-stage renal disease (ESRD) patients. Yet, whether serum albumin levels in late-stage CKD are associated with adverse outcomes after the transition to ESRD is unknown. We hypothesize that lower levels and a decline in serum albumin in late-stage CKD are associated with higher risk of mortality and hospitalization rates 1 year after transition to ESRD.Design and methodsThis retrospective cohort study included 29,124 US veterans with advanced CKD transitioning to ESRD between 2007 and 2015. We evaluated the association of pre-ESRD (91 days before transition) serum albumin with 12-month post-ESRD all-cause, cardiovascular, and infection-related mortalities and hospitalization rates as well as the association of 1-year pre-ESRD albumin slope and 12-month post-ESRD mortality using hierarchical multivariable adjustments.ResultsThere was a negative linear association between serum albumin and all-cause mortality, such that risk doubled (hazard ratio [HR]: 2.07, 95% confidence interval [CI]: 1.87, 2.28) for patients with the lowest serum albumin <2.8 g/dL (ref: ≥4.0 g/dL) after full adjustment. A consistent relationship was observed between serum albumin and cardiovascular and infection-related mortality, and hospitalization outcomes. An increase in serum albumin of >0.25 g/dL/year was associated with reduced mortality risk (HR: 0.76, 95% CI: 0.63, 0.91) compared with a slight decline in albumin (ref: >-0.25 to 0 g/dL/year), whereas a decline more than 0.5 g/dL/year was associated with a 55% higher risk in mortality (HR: 1.55, 95% CI: 1.43, 1.68) in fully adjusted models.ConclusionsLower pre-ESRD serum albumin was associated with higher post-ESRD all-cause, cardiovascular, and infection-related mortalities and hospitalization rates. Declining serum albumin levels in the pre-ESRD period were also associated with worse 12-month post-ESRD mortality.

Project description:BackgroundPrevious studies have demonstrated that early pre-end-stage renal disease (ESRD) nephrology care could improve postdialysis prognosis. However, less is known about the specific types of interventions responsible for the improved outcomes. We hypothesized that more frequent predialysis laboratory testing is associated with better postdialysis outcomes in incident ESRD patients.MethodsIn all, 23 089 patients with available outpatient laboratory tests performed during the 2-year predialysis (i.e. prelude) period were identified from a total of 52 172 American veterans with chronic kidney disease (CKD) transitioning to dialysis between October 2007 and September 2011. The associations between the frequency of combined laboratory tests, including serum creatinine, serum potassium and hemoglobin (test trio), with postdialysis mortality and hospitalization were examined in multivariable adjusted Cox and logistic regression models.ResultsWhen entering the 2-year prelude period, the mean age (Standard Deviation) of the patients was 66.2 (SD 11.3) years and the mean estimated glomerular filtration rate was 46.8 (SD 23.9) mL/min/1.73 m2. In all, 14% of patients had the test trio performed less than twice in 24 months and 8.9% had the trio measured more often than every other month. Over a 2.5-year median postdialysis follow-up period, 15 303 (66.3%) patients died (mortality rate 260/1000 patient-years). The adjusted hazard ratio of all-cause mortality and adjusted odds ratio of the composite of hospitalization or death associated with lab testing done >12/24 months compared with 2-≤4/24 months were 0.68 [95% confidence interval (CI) 0.65-0.73] and 0.70 (95% CI 0.62-0.79), respectively.ConclusionsMore frequent laboratory testing in patients with advanced CKD is associated with better clinical outcomes after dialysis. Further examination in clinical trials is needed before the implementation of more frequent laboratory testing in clinical practice.

Dataset Information

A comprehensive characterization of aggravated aging-related changes in T lymphocytes and monocytes in end-stage renal disease: the iESRD study.

Background

Results

Conclusions

Publications

A comprehensive characterization of aggravated aging-related changes in T lymphocytes and monocytes in end-stage renal disease: the iESRD study.

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