Faculty Bibliography

BACKGROUND:Although the population of older transplant recipients has increased dramatically, there are limited data describing the impact of immunosuppression regimen choice on outcomes in this recipient group. METHODS:National data for US Medicare-insured adult kidney recipients (N = 67 362; 2005-2016) were examined to determine early immunosuppression regimen and associations with acute rejection, death-censored graft failure, and mortality using multivariable regression analysis in younger (18-64 y) and older (>65 y) adults. RESULTS:The use of antithymocyte globulin (TMG) or alemtuzumab (ALEM) induction with triple maintenance immunosuppression (reference) was less common in older compared with younger (36.9% versus 47.0%) recipients, as was TMG/ALEM + steroid avoidance (19.2% versus 20.1%) and mammalian target of rapamycin inhibitor (mTORi)-based (6.7% versus 7.7%) treatments. Conversely, older patients were more likely to receive interleukin (IL)-2-receptor antibody (IL2rAb) + triple maintenance (21.1% versus 14.7%), IL2rAb + steroid avoidance (4.1% versus 1.8%), and cyclosporine-based (8.3% versus 6.6%) immunosuppression. Compared with older recipients treated with TMG/ALEM + triple maintenance (reference regimen), those managed with TMG/ALEM + steroid avoidance (adjusted odds ratio [aOR], 0.440.520.61) and IL2rAb + steroid avoidance (aOR, 0.390.550.79) had lower risk of acute rejection. Older patients experienced more death-censored graft failure when managed with Tac + antimetabolite avoidance (adjusted hazard [aHR], 1.411.782.25), mTORi-based (aHR, 1.702.142.71), and cyclosporine-based (aHR, 1.411.782.25) regimens, versus the reference regimen. mTORi-based and cyclosporine-based regimens were associated with increased mortality in both older and younger patients. CONCLUSIONS:Lower-intensity immunosuppression regimens (eg, steroid-sparing) appear beneficial for older kidney transplant recipients, while mTORi and cyclosporine-based maintenance immunosuppression are associated with higher risk of adverse outcomes.

Rationale & Objective/UNASSIGNED:Social support in older adults with chronic kidney disease (CKD) is a potentially modifiable factor that may affect important clinical outcomes such as health-related quality of life, cognitive function, and frailty. However, limited data about the effects of social support in older patients with non-dialysis-dependent CKD exist. Our objective was to evaluate the association of social support with health-related quality of life, cognitive function, and frailty in older adults with CKD. Study Design/UNASSIGNED:Cross-sectional analysis of a prospective cohort study. Setting & Population/UNASSIGNED:1,851 participants older than 65 years with CKD enrolled in the Chronic Renal Insufficiency Cohort (CRIC) Study. Exposure/UNASSIGNED:Social support (Lubben Social Network Scale [LSNS]). Outcomess/UNASSIGNED:Health-related quality of life (Kidney Disease Quality of Life-36), cognitive function (Modified Mini-Mental State Examination, Trail Making Test A & B, and Buschke Selective Reminder Tests), and frailty (modified Fried frailty criteria). Analytic Approach/UNASSIGNED:Multivariable, linear, and logistic regression to determine the association between social support and health-related quality of life, cognitive function, and frailty. Results/UNASSIGNED:Low social support, defined as LSNS score < 12, was present in 22% of participants. On multivariable analysis, higher social support was associated with higher health-related quality of life (β coefficient per 1-SD increase in LSNS score; burden subscale, 2.57 (95% CI, 1.57-3.56); effects subscale, 2.21 (95% CI, 1.52-2.9); symptoms subscale, 1.64 (95% CI, 0.88-2.41); mental health composite subscale, 1.91 (95% CI, 1.40-2.43); and physical health composite score, 0.64 (95% CI, 0.03-1.24)). Higher social support was associated with better cognitive function (β coefficient per 1-SD increase in LSNS score; Modified Mini-Mental State Examination, 0.81 (95% CI, 0.44 to 1.19); Trail Making Test A & B, -2.53 (95% CI, -4.29 to -0.76) and -6.53 (95% CI, -10.07 to -2.99), respectively; Buschke Selective Reminder Test 1, 2, and 3, 0.19 (95% CI, 0.07 to 0.30); 1.59 (95% CI, 0.96 to 2.22); and 0.40 (95% CI, 0.23 to 0.56), respectively. Higher social support was associated with higher likelihood of being nonfrail (OR, 1.77; 95% CI per 1-SD higher LSNS score, 1.24-2.53). Limitations/UNASSIGNED:Conclusions about causality cannot be drawn from an observational cross-sectional study. Conclusions/UNASSIGNED:In older patients with CKD, higher social support was associated with higher health-related quality of life and cognitive function and less frailty.

UNLABELLED:The unplanned use of dual induction therapy with interleukin-2 receptor-blocking antibodies (IL2rAb) and antithymocyte globulin (ATG) may portend adverse outcomes. METHODS/UNASSIGNED:]). RESULTS/UNASSIGNED: < 0.0001). CONCLUSIONS/UNASSIGNED:Further research is needed to develop risk-prediction tools to further inform optimal, individualized induction protocols for kidney transplant recipients.

BACKGROUND AND OBJECTIVES:Patients with kidney failure report a high symptom burden, which likely increases while on dialysis due to physical and mental stressors and decreases after kidney transplantation due to restoration of kidney function. DESIGN, SETTING, PARTICIPANTS, & MEASUREMENTS:=190), and post-transplantation symptom score trajectories (mixed effects models). RESULTS:At evaluation, candidates reported being moderately to extremely bothered by fatigue (32%), xeroderma (27%), muscle soreness (26%), and pruritus (25%); 16% reported high and 21% reported very high symptom burden. Candidates with very high symptom burden were at greater waitlist mortality risk (adjusted subdistribution hazard ratio, 1.67; 95% confidence interval, 1.06 to 2.62). By transplantation, 34% experienced an increased symptom burden, whereas 42% remained unchanged. The estimated overall symptom score was 82.3 points at transplantation and 90.6 points at 3 months (10% improvement); the score increased 2.75 points per month (95% confidence interval, 2.38 to 3.13) from 0 to 3 months, and plateaued (-0.06 points per month; 95% confidence interval, -0.30 to 0.18) from 3 to 12 months post-transplantation. There were early (first 3 months) improvements in nine of 11 symptoms; pruritus (23% improvement) and fatigue (21% improvement) had the greatest improvements. CONCLUSIONS:Among candidates, very high symptom burden was associated with waitlist mortality, but for those surviving and undergoing kidney transplantation, symptoms improved.

Background/UNASSIGNED:Among adult kidney transplant (KT) recipients, the risk of post-KT adverse outcomes differs by type of induction immunosuppression. Immune response to induction differs as recipients age; yet, choice of induction is barely tailored by age likely due to a lack of evidence of the risks and benefits. Methods/UNASSIGNED:Using Scientific Registry of Transplant Recipients data, we identified 39336 first-time KT recipients (2010-2016). We estimated the length of stay (LOS), acute rejection (AR), graft failure, and death by induction type using logistic and Cox regression weighted by propensity score to adjust for confounders. We tested whether these estimates differed by age (65+ versus 18-64 y) using a Wald test. Results/UNASSIGNED: = 0.03 and 0.003) differed by recipient age. Discharge was on average 11% shorter in rATG among younger recipients (relative time = 0.89; 95% confidence interval [CI], 0.81-0.99) but not among older recipients (relative time = 1.01; 95% CI, 0.95-1.08). rATG was not associated with mortality among older (hazard ratio = 1.05; 95% CI, 0.96-1.15), but among younger recipients (hazard ratio = 0.87; 95% CI, 0.80-0.95), it was associated with reduced mortality risk. Conclusions/UNASSIGNED:rATG should be considered to prevent AR, especially among recipients with high-immunologic risk regardless of age; however, choice of induction should be tailored to reduce LOS and risk of mortality, particularly among younger recipients.

BACKGROUND:Prescription opioid and benzodiazepine use have been associated with morbidity and mortality among some groups of solid organ transplant recipients, but implications for outcomes among lung transplant patients are not well described. METHODS:). RESULTS:). These effects were independent, and interactions were not detected. CONCLUSIONS:Benzodiazepine prescription fills before and after lung transplant, and opioid fills after transplant, are independently associated with posttransplant mortality. Review of benzodiazepine and opioid use history is relevant to risk-stratifying patients before and after lung transplant.

Purpose of Review/UNASSIGNED:To summarize the research on post-operative delirium among patients undergoing solid organ transplantation in efforts to improve recognition, evaluation, and management, as well as highlight areas for future research. Recent Findings/UNASSIGNED:Delirium is a common complication in patients with organ failure before and after undergoing solid organ transplant (range: 4.7-47%). However, it is frequently unrecognized and underdiagnosed-even among those closely monitored after major surgery-given that its manifestation is often variable and inconsistent. Delirium has multifactorial etiologies comprising of a complex mix of predisposing recipient, donor, and transplant factors, as well as intraoperative and perioperative factors. Evidence suggests that delirium risk increases with presence of a greater number of such risk factors, and can lead to adverse outcomes such as increased hospital length of stay, time in the ICU, time on mechanical ventilators, graft dysfunction, graft loss, and mortality. Though no trials have been conducted among transplant populations specifically, delirium has been shown to be preventable among hospitalized older adults generally. Multicomponent, primary prevention strategies designed to target multiple risk factors of delirium, such as cognitive impairment, sleep deprivation, immobility, visual impairment, hearing impairment, and dehydration, have been identified as most effective. Whether these approaches translate to improvements in quality of life and long-term health outcomes among patients with organ failure before and after transplantation is yet to be determined. Summary/UNASSIGNED:Delirium is an important, common, yet potentially preventable complication among patients with organ failure. Future studies are needed to test the efficacy of multicomponent, primary prevention strategies on long-term health outcomes among these vulnerable populations.

Frailty is a multidimensional condition and is the result of the body's age-associated decline in physical, cognitive, physiological, and immune reserves. The aim of this systematic review is to assess the quality of evidence of the included studies, determine the prevalence of frailty among kidney transplant candidates, and evaluate the relationship between frailty and associated patient characteristics and outcomes after kidney transplantation.

INTRODUCTION:We developed the strength training intervention (STRIVE), a home-based exercise program targeting physical function in patients with cirrhosis. In this pilot study, we aimed to evaluate the safety and efficacy of STRIVE. METHODS:Eligible were adult patients with cirrhosis at 3 sites. Patients were randomized 2:1-12 weeks of STRIVE, a 30-minute strength training video plus a health coach or standard of care (SOC). Physical function and quality of life were assessed using the Liver Frailty Index (LFI) and Chronic Liver Disease Questionnaire (CLDQ), respectively. RESULTS:Fifty-eight and 25 were randomized to STRIVE and SOC arms, respectively: 43% women, median age was 61 years, MELDNa, Model for End-Stage Liver Disease Sodium was 14, and 54% were Child-Pugh B/C. Baseline characteristics were similar in the STRIVE vs SOC arms except for rates of hepatic encephalopathy (19 vs 36%). LFI @ 12 weeks was available in 43 STRIVE and 20 SOC participants. After 12 weeks, the median LFI improved from 3.8 to 3.6 (ΔLFI -0.1) in the STRIVE arm and 3.7 to 3.6 (ΔLFI -0.1) in the SOC arm (P = 0.65 for ΔLFI difference). CLDQ scores improved from 4.6 to 5.2 in STRIVE participants (ΔCLDQ 0.38) and did not change in SOC participants (4.2-4.2; ΔCLDQ -0.03) (P = 0.09 for ΔCLDQ difference). One patient died (SOC arm) of bleeding. Only 14% of STRIVE participants adhered to the strength training video for 10-12 weeks. No adverse events were reported by STRIVE participants. DISCUSSION:STRIVE, a home-based structured exercise program for patients with cirrhosis, was safely administered at 3 sites, but adherence was low. Although all participants showed minimal improvement in the LFI, STRIVE was associated with a substantial improvement in quality of life.