Faculty Bibliography

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.

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.

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: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.

BACKGROUND AND OBJECTIVE/OBJECTIVE:Older adults initiating dialysis have a high risk of mortality and that risk may be related to potentially inappropriate medications (PIMs). Our objective was to identify and validate mortality risk associated with American Geriatrics Society Beers Criteria PIM classes and concomitant PIM use. METHODS:We used US Renal Data System data to establish a cohort of adults aged ≥ 65 years initiating dialysis (2013-2014) and had no PIM prescriptions in the 6 months prior to dialysis initiation. In a development cohort (40% sample), adjusted Cox proportional hazards models were performed to determine which of 30 PIM classes were associated with mortality (or "high-risk" PIMs). Adjusted Cox models were performed to assess the association of the number of "high-risk" PIM fills/month with mortality. All models were repeated in the validation cohort (60% sample). RESULTS:In the development cohort (n = 15,570), only 13 of 30 PIM classes were associated with a higher mortality risk. Compared with those with no "high-risk" PIM fills/month, patients having one "high-risk" PIM fill/month had a 1.29-fold (95% confidence interval 1.21-1.38) increased risk of death; those with two or more "high-risk" PIM fills/month had a 1.40-fold (95% confidence interval 1.24-1.58) increased risk. These findings were similar in the validation cohort (n = 23,569). CONCLUSIONS:Only a minority of Beers Criteria PIM classes may be associated with mortality in the older dialysis population; however, mortality risk increases with concomitant use of "high-risk" PIMs. Additional studies are needed to confirm these associations and their underlying mechanisms.

BACKGROUND:Short and long sleep durations are associated with cognitive dysfunction. Given the increased prevalence of sleep abnormalities in the CKD population, we tested whether the association between sleep duration and cognitive function differed between older adults with and without CKD. METHODS:This was a study of 3215 older adults (aged ≥ 60years) enrolled in the National Health and Nutrition Examination Survey (2011-2014) evaluating sleep duration, cognitive function (immediate recall, delayed recall, verbal fluency, executive function and processing speed, and global cognition), and kidney function. We quantified the association between sleep duration and cognitive function using linear regression and tested whether the associations differed among those with CKD and without using a Wald test for interaction. RESULTS:Among 3215 participants, 13.3% reported 2-5 hours of sleep per day, 75.2% reported 6-8 hours, and 11.5% reported ≥ 9 hours. Persons with CKD were more likely to sleep ≥ 9 hours (OR = 1.73, 95% CI: 1.22-2.46). Among participants with CKD, those with sleep duration ≥ 9 hours demonstrated worse global cognitive function (p for interaction = 0.01), immediate recall (p for interaction = 0.01), and verbal fluency (p for interaction = 0.004) than those with 6-8 hours sleep duration; no differences were observed for participants with CKD who slept 2-5 hours. Among participants without CKD, sleep was not associated with any measures of cognitive function. CONCLUSIONS:Longer sleep duration is associated with worse cognitive function only among persons with CKD and global cognition, delayed recall, and verbal fluency are particularly affected. Studies should identify interventions to improve sleep patterns and quality in this population.

SIGNIFICANCE STATEMENT:Cardiovascular diseases account for 32% of deaths among kidney transplant recipients. Statin therapy is common in this population. However, its effect on mortality prevention remains unclear among kidney transplant recipients, whose clinical risk profile might be unique because of concomitant immunosuppressive therapy. In this national study of 58,264 single-kidney transplant recipients, statin use was associated with a 5% decrease in mortality. More importantly, this protective association was stronger among those who used a mammalian target of rapamycin (mTOR) inhibitor for immunosuppression (27% decrease in mTOR inhibitor users versus 5% in nonusers). Our results suggest that statin therapy may reduce mortality in kidney transplant recipients and that the strength of this protective association may vary by immunosuppression regimen. BACKGROUND:Cardiovascular diseases are the leading cause of mortality in kidney transplant (KT) recipients, accounting for 32% of deaths. Statins are widely used in KT recipients, but effectiveness for preventing mortality remains unclear in this population, especially because of interaction between statins and immunosuppressive agents. We analyzed a national cohort to assess the real-world effectiveness of statins for reducing all-cause mortality in KT recipients. METHODS:We studied statin use and mortality among 58,264 adults (18 years or older) who received single kidneys between 2006 and 2016 and had Medicare part A/B/D. Statin use was ascertained from Medicare prescription drug claims and deaths from Center for Medicare and Medicaid Services records. We estimated the association of statin use with mortality using multivariable Cox models, with statin use as a time-varying exposure and immunosuppression regimen as effect modifiers. RESULTS:Statin use increased from 45.5% at KT to 58.2% at 1-year post-KT to 70.9% at 5-year post-KT. We observed 9785 deaths over 236,944 person-years. Overall, statin use was significantly associated with lower mortality (adjusted hazard ratio [aHR], 0.95; 95% confidence interval [CI], 0.90 to 0.99). The strength of this protective association varied by calcineurin inhibitor use (among tacrolimus users, aHR, 0.97; 95% CI, 0.92 to 1.03 versus among calcineurin nonusers, aHR, 0.72; 95% CI, 0.60 to 0.87; interaction P =0.002), mammalian target of rapamycin (mTOR) inhibitor use (among mTOR inhibitor users, aHR, 0.73; 95% CI, 0.57 to 0.92 versus among nonusers, aHR, 0.95; 95% CI, 0.91 to 1.00; interaction P =0.03), and mycophenolate use (among mycophenolate users, aHR, 0.96; 95% CI, 0.91 to 1.02 versus among nonusers, aHR, 0.76; 95% CI, 0.64 to 0.89; interaction P =0.002). CONCLUSION:Real-world evidence supports statin therapy for reducing all-cause mortality in KT recipients. Effectiveness might be greater when combined with mTOR inhibitor-based immunosuppression.