Faculty Bibliography

RATIONALE & OBJECTIVE/OBJECTIVE:Frailty is common in individuals with chronic kidney disease (CKD) and increases the risk of adverse outcomes in adults with kidney failure requiring dialysis. However, this relationship has not been thoroughly evaluated among those with non-dialysis-dependent CKD. STUDY DESIGN/METHODS:Prospective cohort study. SETTING & PARTICIPANTS/METHODS:2,539 adults in the Chronic Renal Insufficiency Cohort Study. EXPOSURE/METHODS:Frailty status assessed using 5 criteria: slow gait speed, muscle weakness, low physical activity, exhaustion, and unintentional weight loss. OUTCOME/RESULTS:Atherosclerotic events, incident heart failure, all-cause death, and cardiovascular death. ANALYTICAL APPROACH/METHODS:Cause-specific hazards models. RESULTS:, and the median urine protein was 0.2mg/day. Frailty status was as follows: 12% frail, 51% prefrail, and 37% nonfrail. Over a median follow-up of 11.4 years, there were 393 atherosclerotic events, 413 heart failure events, 497 deaths, and 132 cardiovascular deaths. In multivariable regression analyses, compared with nonfrailty, both frailty and prefrailty status were each associated with higher risk of an atherosclerotic event (HR, 2.03 [95% CI, 1.41-2.91] and 1.77 [95% CI, 1.35-2.31], respectively) and incident heart failure (HR, 2.22 [95% CI, 1.59-3.10] and 1.39 [95% CI, 1.07-1.82], respectively), as well as higher risk of all-cause death (HR, 2.52 [95% CI, 1.84-3.45] and 1.76 [95% CI, 1.37-2.24], respectively) and cardiovascular death (HR, 3.01 [95% CI, 1.62-5.62] and 1.78 [95% 1.06-2.99], respectively). LIMITATIONS/CONCLUSIONS:Self-report of aspects of the frailty assessment and comorbidities, which may have led to bias in some estimates. CONCLUSIONS:In adults with CKD, frailty status was associated with higher risk of cardiovascular events and mortality. Future studies are needed to evaluate the impact of interventions to reduce frailty on cardiovascular outcomes in this population. PLAIN-LANGUAGE SUMMARY/UNASSIGNED:Frailty is common in individuals with chronic kidney disease (CKD) and increases the risk of adverse outcomes. We sought to evaluate the association of frailty status with cardiovascular events and death in adults with CKD. Frailty was assessed according to the 5 phenotypic criteria detailed by Fried and colleagues. Among 2,539 participants in the CRIC Study, we found that 12% were frail, 51% were prefrail, and 37% were nonfrail. Frailty status was associated with an increased risk of atherosclerotic events, incident heart failure, and death.

BACKGROUND:Frailty is associated with poor outcomes in surgical patients including kidney transplant recipients. Transplant centers that measure frailty have better pre- and post-operative outcomes. However, clinical utility of existing tools is low due to time constraints. To address this major barrier to implementation in the pre-operative evaluation of patients, we developed an abridged frailty phenotype. METHODS:The abridged frailty phenotype was developed by simplifying the 5 Physical Frailty Phenotype (PFP) components in a two-center prospective cohort of 3,220 kidney transplant candidates and tested for efficiency (time to completion) in 20 candidates evaluation (1/2009-3/2020). We examined area under curve (AUC) and Cohen's kappa agreement to compare the abridged assessment with the PFP. We compared waitlist mortality risk (competing risks models) by frailty using the PFP and abridged assessment, respectively. Model discrimination was assessed using Harrell's C-statistic. RESULTS:Of 3,220 candidates, the PFP and abridged assessment identified 23.8% and 27.4% candidates as frail, respectively. The abridged frailty phenotype had substantial agreement (kappa=0.69, 95%CI:0.66-0.71) and excellent discrimination (area under the curve=0.861). Among 20 patients at evaluation, abridged assessment took 5-7 minutes to complete. The PFP and abridged assessment had similar associations with waitlist mortality (subdistribution hazard ratio [SHR]=1.62, 95%CI:1.26-2.08 vs. SHR=1.70, 95%CI:1.33-2.16) and comparable mortality discrimination (p=0.51). CONCLUSIONS:The abridged assessment is an efficient and valid way to identify frailty. It predicts waitlist mortality without sacrificing discrimination. Surgical departments should consider utilizing the abridged assessment to evaluate frailty in patients when time is limited.

RATIONALE & OBJECTIVE/UNASSIGNED:Coronavirus disease (COVID)-19 has likely impacted accessibility to transplantation services among older adults (age ≥65 years). We quantified the impact of COVID-19 on kidney transplantation access for older kidney-only candidates registered on the United States (US) kidney waitlist. STUDY DESIGN/UNASSIGNED:Retrospective analysis of registry data. SETTING & PARTICIPANTS/UNASSIGNED:57,222 older adults who were part of or added to the US kidney waitlist between January 1, 2016 and February 28, 2022, identified using the Scientific Registry of Transplant Recipients (SRTR). EXPOSURES/UNASSIGNED:Four COVID-19 waves and one nonwave period based on the national incidence of COVID-19 in the US (initial: March 15-May 30, 2020; winter 2020-2021: December 1, 2020-January 31, 2021; delta: August 1, 2021-September 30, 2021; omicron: December 1, 2021-February 28, 2022; nonwave: inter-wave periods). OUTCOMES/UNASSIGNED:Waitlist registrations, deceased-donor kidney transplants, living-donor kidney transplants, waitlist mortality, and waitlist removals due to deteriorating condition (hereafter referred to as removals). ANALYTICAL APPROACH/UNASSIGNED:Poisson regression for the adjusted incidence rate ratio (aIRR) of each outcome during the COVID-19 waves and the nonwave period relative to reference (January 1, 2016-December 31, 2019), adjusted for seasonality and secular trends. RESULTS/UNASSIGNED:) and has declined since; mortality rates were 139%, 107%, and 251% above expected for Black candidates, men, and candidates aged ≥75 years, respectively, during the winter 2020-2021 wave. Removals increased from 22% below expected levels (initial wave) to 26% above expected levels (omicron wave); removals were nonsignificantly higher than expected during the omicron wave for older Black and Hispanic candidates. LIMITATIONS/UNASSIGNED:The findings are not generalizable to those listed at earlier ages with prolonged waitlist times. Additionally, using national COVID-19 incidence does not consider local policy and health care variations. Lastly, aIRRs must be interpreted cautiously due to smaller daily event counts. CONCLUSIONS/UNASSIGNED:COVID-19 was associated with fewer transplants and increased mortality and removals in older kidney transplant candidates. Transplant providers should consider this impact and implement policies and practices to ensure the continuity of care. PLAIN-LANGUAGE SUMMARY/UNASSIGNED:The proportion of older adults on the kidney transplant waitlist is increasing, but the impact of COVID-19 on this population is not well characterized. In this study, we looked at incident waitlist registrations, deceased- and living-donor kidney transplants, and waitlist mortality and removals due to deteriorating condition over 4 waves of COVID-19. We found that transplantation services did not fully recover to prepandemic levels as of March 2022. Notably, racial/ethnic minorities and older men experienced lower rates of kidney transplants and higher rates of waitlist mortality, respectively, relative to White candidates and older women. Identifying vulnerable subpopulations affected by COVID-19 and its long-term impact is crucial for creating strategies to ensure the continuity of care in this population during public health emergencies.

IntroductionOlder adults with IBD are at higher risk for postoperative complications as compared to their younger counterparts, however factors contributing to this are unknown. We assessed risk factors associated with adverse IBD-related surgical outcomes, evaluated trends in emergency surgery, and explored differential risks by age.MethodsUsing the American College of Surgeons National Surgical Quality Improvement Program (ACS-NSQIP) database, we identified adults ≥18 years of age who underwent an IBD-related intestinal resection from 2005-2019. Our primary outcome included a 30-day composite of mortality, readmission, reoperation, and/or major postoperative complication.ResultsOverall, 49,746 intestinal resections were performed with 9,390 (18.8%) occurring among older adults with IBD. Nearly 37% of older adults experienced an adverse outcome as compared to 28.1% among younger adults with IBD (p<0.01). Among all adults with IBD, the presence of preoperative sepsis (aOR, 2.08; 95%CI 1.94-2.24), malnutrition (aOR, 1.22; 95%CI 1.14-1.31), dependent functional status (aOR, 6.92; 95%CI 4.36-11.57), and requiring emergency surgery (aOR, 1.50; 95%CI 1.38-1.64) increased the odds of an adverse postoperative outcome, with similar results observed when stratifying by age. Further, 8.8% of surgeries among older adults were emergent, with no change observed over time (p=0.16).DiscussionPreoperative factors contributing to the risk of an adverse surgical outcome are similar between younger and older individuals with IBD, and include elements such as malnutrition and functional status. Incorporating these measures into surgical decision-making can reduce surgical delays in older individuals at low-risk and help target interventions in those at high risk, transforming care for thousands of older adults with IBD.

Older compatible living donor kidney transplant (CLDKT) recipients have higher mortality and death-censored graft failure (DCGF) compared to younger recipients. These risks may be amplified in older incompatible living donor kidney transplant (ILDKT) recipients who undergo desensitization and intense immunosuppression. In a 25-center cohort of ILDKT recipients transplanted between September 24, 1997, and December 15, 2016, we compared mortality, DCGF, delayed graft function (DGF), acute rejection (AR), and length of stay (LOS) between 234 older (age ≥60 years) and 1172 younger (age 18-59 years) recipients. To investigate whether the impact of age was different for ILDKT recipients compared to 17 542 CLDKT recipients, we used an interaction term to determine whether the relationship between posttransplant outcomes and transplant type (ILDKT vs CLDKT) was modified by age. Overall, older recipients had higher mortality (hazard ratio: _1.632.07_2.65, P < .001), lower DCGF (hazard ratio: _0.360.53_0.77, P = .001), and AR (odds ratio: _0.390.54_0.74, P < .001), and similar DGF (odds ratio: _0.461.03_2.33, P = .9) and LOS (incidence rate ratio: _0.880.98_1.10, P = 0.8) compared to younger recipients. The impact of age on mortality (interaction P = .052), DCGF (interaction P = .7), AR interaction P = .2), DGF (interaction P = .9), and LOS (interaction P = .5) were similar in ILDKT and CLDKT recipients. Age alone should not preclude eligibility for ILDKT.

BACKGROUND/UNASSIGNED:Advancements in medical technology, healthcare delivery, and organ allocation resulted in improved patient/graft survival for older (age ≥65) kidney transplant (KT) recipients. However, the recent trends in these post-KT outcomes are uncertain in light of the mounting burden of cardiovascular disease, changing kidney allocation policies, heterogeneity in candidates' risk profile, and the coronavirus disease 2019 pandemic. Thus, we examined secular trends in post-KT outcomes among older and younger KT recipients over the last 3 decades. METHODS/UNASSIGNED:We identified 73 078 older and 378 800 younger adult (aged 18-64) recipients using Scientific Registry of Transplant Recipients (1990-2022). KTs were grouped into 6 prepandemic eras and 1 postpandemic-onset era. Kaplan-Meier and Cox proportional hazards models were used to examine temporal trends in post-KT mortality and death-censored graft failure. RESULTS/UNASSIGNED:From 1990 to 2022, a 19-fold increase in the proportion of older KT recipients was observed compared to a 2-fold increase in younger adults despite a slight decline in the absolute number of older recipients in 2020. The mortality risk for older recipients between 2015 and March 14, 2020, was 39% (adjusted hazard ratio [aHR] = 0.61, 95% confidence interval [CI], 0.50-0.75) lower compared to 1990-1994, whereas that for younger adults was 47% lower (aHR = 0.53, 95% CI, 0.48-0.59). However, mortality risk during the pandemic was 25% lower (aHR = 0.75, 95% CI, 0.61-0.93) in older adults and 37% lower in younger adults (aHR = 0.63, 95% CI, 0.56-0.70) relative to 1990-1994. For both populations, the risk of graft failure declined over time and was unaffected during the pandemic relative to the preceding period. CONCLUSIONS/UNASSIGNED:The steady improvements in 5-y mortality and graft survival were disrupted during the pandemic, particularly among older adults. Specifically, mortality among older adults reflected rates seen 20 y prior.

BACKGROUND:The prevalence of sarcopenia is markedly higher in kidney transplant candidates than in the general population. It is a syndrome characterized by progressive and generalized loss of skeletal muscle mass and strength, which increases the risk of adverse postoperative outcomes. METHODS:We studied the impact of computed tomography defined preoperative sarcopenia, defined as a skeletal muscle index below age and gender specific cut-off values, on postoperative physical functional outcomes (grip strength, 4-m walking test, timed up and go, and sit to stand) at 6 months follow up. RESULTS: = 0.154). CONCLUSIONS:We identified a significant association between sarcopenia existing pre-transplantation and poorer 6 months post-transplantation physical functioning with respect to hand grip strength and timed up and go tests in kidney transplant recipients. These results could be used to preoperatively identify patients with an increased risk of poor postoperative physical functional outcome, allowing for preoperative interventions to mitigate these risks.

BACKGROUND:Recommendations for apixaban dosing on the basis of kidney function are inconsistent between the US Food and Drug Administration and European Medicines Agency for patients with atrial fibrillation. Optimal apixaban dosing in chronic kidney disease remains unknown. METHODS:With the use of deidentified electronic health record data from the Optum Labs Data Warehouse, patients with atrial fibrillation and chronic kidney disease stage 4/5 initiating apixaban between 2013 and 2021 were identified. Risks of bleeding and stroke/systemic embolism were compared by apixaban dose (5 versus 2.5 mg), adjusted for baseline characteristics by the inverse probability of treatment weighting. The Fine-Gray subdistribution hazard model was used to account for the competing risk of death. Cox regression was used to examine risk of death by apixaban dose. RESULTS:). In inverse probability of treatment weighting analysis, apixaban 5 mg was associated with a higher risk of bleeding (incidence rate 4.9 versus 2.9 events per 100 person-years; incidence rate difference, 2.0 [95% CI, 0.6-3.4] events per 100 person-years; subdistribution hazard ratio, 1.63 [95% CI, 1.04-2.54]). There was no difference between apixaban 5 mg and 2.5 mg groups in the risk of stroke/systemic embolism (3.3 versus 3.0 events per 100 person-years; incidence rate difference, 0.2 [95% CI, -1.0 to 1.4] events per 100 person-years; subdistribution hazard ratio, 1.01 [95% CI, 0.59-1.73]), or death (9.9 versus 9.4 events per 100 person-years; incidence rate difference, 0.5 [95% CI, -1.6 to 2.6] events per 100 person-years; hazard ratio, 1.03 [95% CI, 0.77-1.38]). CONCLUSIONS:Compared with 2.5 mg, use of 5 mg apixaban was associated with a higher risk of bleeding in patients with atrial fibrillation and severe chronic kidney disease, with no difference in the risk of stroke/systemic embolism or death, supporting the apixaban dosing recommendations on the basis of kidney function by the European Medicines Agency, which differ from those issued by the US Food and Drug Administration.

Understanding the physiological basis of physical resilience to clinical stressors is crucial for the well-being of older adults. This article presents a novel framework to discover the biological underpinnings of physical resilience in older adults as part of the "Characterizing Resiliencies to Physical Stressors in Older Adults: A Dynamical Physiological Systems Approach" study, also known as The Study of Physical Resilience and Aging (SPRING). Physical resilience, defined as the capacity of a person to withstand clinical stressors and quickly recover or improve upon a baseline functional level, is examined in adults aged 55 years and older by studying the dynamics of stress response systems. The hypothesis is that well-regulated stress response systems promote physical resilience. The study employs dynamic stimulation tests to assess energy metabolism, the hypothalamic-pituitary-adrenal axis, the autonomic nervous system, and the innate immune system. Baseline characteristics influencing resilience outcomes are identified through deep phenotyping of physical and cognitive function, as well as of biological, environmental, and psychosocial characteristics. SPRING aims to study participants undergoing knee replacement surgery (n = 100), bone and marrow transplantation (n = 100), or anticipating dialysis initiation (n = 60). Phenotypic and functional measures are collected pre-stressor and at multiple times after stressor for up to 12 months to examine resilience trajectories. By improving our understanding of physical resilience in older adults, SPRING has the potential to enhance resilient outcomes to major clinical stressors. The article provides an overview of the study's background, rationale, design, pilot phase, implementation, and implications for improving the health and well-being of older adults.