Associations of Apixaban Dose With Safety and Effectiveness Outcomes in Patients With Atrial Fibrillation and Severe Chronic Kidney Disease.

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: Among 4313 apixaban new users, 1705 (40%) received 5 mg and 2608 (60%) received 2.5 mg. Patients treated with 5 mg apixaban were younger (mean age, 72 versus 80 years), with greater weight (95 versus 80 kg) and higher serum creatinine (2.7 versus 2.5 mg/dL). Mean estimated glomerular filtration rate was not different between the groups (24 versus 24 mL·min-1·1.73 m-2). 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.

Abdominal computed tomography measurements of body composition and waitlist mortality in kidney transplant candidates.

Body mass index is often used to determine kidney transplant (KT) candidacy. However, this measure of body composition (BC) has several limitations, including the inability to accurately capture dry weight. Objective computed tomography (CT)-based measures may improve pre-KT risk stratification and capture physiological aging more accurately. We quantified the association between CT-based BC measurements and waitlist mortality in a retrospective study of 828 KT candidates (2010-2022) with clinically obtained CT scans using adjusted competing risk regression. In total, 42.5% of candidates had myopenia, 11.4% had myopenic obesity (MO), 68.8% had myosteatosis, 24.8% had sarcopenia (probable = 11.2%, confirmed = 10.5%, and severe = 3.1%), and 8.6% had sarcopenic obesity. Myopenia, MO, and sarcopenic obesity were not associated with mortality. Patients with myosteatosis (adjusted subhazard ratio [aSHR] = 1.62, 95% confidence interval [CI]: 1.07-2.45; after confounder adjustment) or sarcopenia (probable: aSHR = 1.78, 95% CI: 1.10-2.88; confirmed: aSHR = 1.68, 95% CI: 1.01-2.82; and severe: aSHR = 2.51, 95% CI: 1.12-5.66; after full adjustment) were at increased risk of mortality. When stratified by age, MO (aSHR = 2.21, 95% CI: 1.28-3.83; P interaction = .005) and myosteatosis (aSHR = 1.95, 95% CI: 1.18-3.21; P interaction = .038) were associated with elevated risk only among candidates <65 years. MO was only associated with waitlist mortality among frail candidates (adjusted hazard ratio = 2.54, 95% CI: 1.28-5.05; P interaction = .021). Transplant centers should consider using BC metrics in addition to body mass index when a CT scan is available to improve pre-KT risk stratification at KT evaluation.

Frailty in Kidney Disease: A Comprehensive Review to Advance Its Clinical and Research Applications.

Frailty is a multi-system syndrome of decreased physiologic reserve that has been shown to strongly and independently predict morbidity and mortality. Frailty is prevalent in patients living with kidney disease and occurs earlier in individuals with kidney disease as compared to the general population. In this comprehensive review, we aim to advance the clinical and research applications of frailty in kidney disease populations. Specifically, we clarify the definition of frailty and address its common misconceptions; review the mechanisms and epidemiology of frailty in kidney disease; discuss challenges and limitations in frailty measurement; and provide updated evidence related to risk factors for frailty, its associated adverse outcomes, and interventions. We further add to the literature in this topic by highlighting potential applications of frailty measurement in care of patients with kidney disease and conclude with our recommendations for future research related to this important syndrome.

Advance Care Planning and Palliative Care Consultation in Kidney Transplantation.

RATIONALE & OBJECTIVE: Because of the high risk of waitlist mortality and posttransplant complications, kidney transplant (KT) patients may benefit from advance care planning (ACP) and palliative care consultation (PCC). We quantified the prevalence and racial disparities in ACP and PCC among KT candidates and recipients. STUDY DESIGN: Prospective cohort study. SETTING & PARTICIPANTS: 2,575 adult KT candidates and 1,233 adult recipients (2008-2020). EXPOSURE: Race and ethnicity. OUTCOMES: All reports of ACP and PCC were abstracted from chart review. ACP was defined as patient self-report of an advance directive, presence of an advance directive in the medical record, or a documented goals-of-care conversation with a provider. PCC was defined as an ordered referral or a documented palliative care note in the medical record. ANALYTICAL APPROACH: Racial/ethnic disparities in ACP/PCC were estimated using adjusted logistic regression. RESULTS: 21.4% of KT candidates and 34.9% of recipients engaged in ACP. There were racial/ethnic disparities in ACP among KT candidates (White, 24.4%; Black, 19.1%; Hispanic, 15%; other race and ethnicity, 21.1%; P=0.008) and recipients (White, 39.5%; Black, 31.2%; Hispanic, 26.3%; other race and ethnicity, 26.6%; P=0.007). After adjustment, Black KT recipients had a 29% lower likelihood of engaging in ACP (OR, 0.71; 95% CI, 0.55-0.91) than White KT recipients. Among older (aged≥65 years) recipients, those who were Black had a lower likelihood of engaging in ACP, but there was no racial disparity among younger recipients (P=0.020 for interaction). 4.2% of KT candidates and 5.1% of KT recipients engaged in PCC; there were no racial disparities in PCC among KT candidates (White, 5.3%; Black, 3.6%; Hispanic, 2.5%; other race and ethnicity, 2.1%; P=0.13) or recipients (White, 5.5%; Black, 5.6%; Hispanic, 0.0%; other race and ethnicity, 1.3%; P = 0.21). LIMITATIONS: Generalizability may be limited to academic transplant centers. CONCLUSIONS: ACP is not common among KT patients, and minoritized transplant patients are least likely to engage in ACP; PCC is less common. Future efforts should aim to integrate ACP and PCC into the KT process. PLAIN-LANGUAGE SUMMARY: Kidney transplant (KT) candidates and recipients are at elevated risk of morbidity and mortality. They may benefit from completing a document or conversation with their palliative care provider that outlines their future health care wishes, known as advance care planning (ACP), which is a component of palliative care consultation (PCC). We wanted to determine how many KT candidates and recipients have engaged in ACP or PCC and identify potential racial disparities. We found that 21.4% of candidates and 34.9% of recipients engaged in ACP. After adjustment, Black recipients had a 29% lower likelihood of engaging in ACP. We found that 4.2% of KT candidates and 5.1% of KT recipients engaged in PCC, with no racial disparities found in PCC.

Frailty and Cardiovascular Outcomes in Adults With CKD: Findings From the Chronic Renal Insufficiency Cohort (CRIC) Study.

RATIONALE & 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: Prospective cohort study. SETTING & PARTICIPANTS: 2,539 adults in the Chronic Renal Insufficiency Cohort Study. EXPOSURE: Frailty status assessed using 5 criteria: slow gait speed, muscle weakness, low physical activity, exhaustion, and unintentional weight loss. OUTCOME: Atherosclerotic events, incident heart failure, all-cause death, and cardiovascular death. ANALYTICAL APPROACH: Cause-specific hazards models. RESULTS: At study entry, the participants' mean age was 62 years, 46% were female, the mean estimated glomerular filtration rate was 45.4mL/min/1.73m2, 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: 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: 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.

Extreme Humid-Heat Exposure and Mortality Among Patients Receiving Dialysis.

RATIONALE & OBJECTIVE: Exposure to extreme heat events has been linked to increased morbidity and mortality in the general population. Patients receiving maintenance dialysis may be vulnerable to greater risks from these events, but this is not well understood. We sought to characterize the association of extreme heat events and the risk of death among patients receiving dialysis in the United States. STUDY DESIGN: Retrospective cohort study. SETTING & PARTICIPANTS: Data from the United States Renal Data System were used to identify adults living in US urban settlements prone to extreme heat who initiated maintenance dialysis between 1997 and 2016. EXPOSURE: An extreme heat event was defined as a time-updated heat index (a humid-heat metric) exceeding 40.6°C for ≥2 days or 46.1°C for ≥1 day. OUTCOME: Death. ANALYTICAL APPROACH: Cox proportional hazards regression to estimate the elevation in risk of death during a humid-heat event adjusted for age, sex, year of dialysis initiation, dialysis modality, poverty level, and climate region. Interactions between humid-heat and these same factors were explored. RESULTS: Among 945,251 adults in 245 urban settlements, the mean age was 63 years and 44% were female. During a median follow-up of 3.6 years, 498,049 adults were exposed to at least one of 7,154 extreme humid-heat events, and 500,025 deaths occurred. In adjusted models, there was an increased risk of death (hazard ratio 1.18; 95% confidence interval 1.15-1.20) during extreme humid-heat exposure. Relative mortality risk was higher among patients living in the Southeast (P<0.001) compared with the Southwest. LIMITATIONS: Possibility of exposure misclassification, did not account for land use and air pollution co-exposures. CONCLUSIONS: This study suggests that patients receiving dialysis face an increased risk of death during extreme humid-heat exposure.

Sociodemographic disparities in sodium-glucose cotransporter-2 inhibitor use among US kidney transplant recipients: An observational study of real-world pharmacy records.

BACKGROUND: Recent clinical trials demonstrate benefits of sodium-glucose cotransporter-2 inhibitors (SGLT2i) in patients with chronic kidney disease, but data on use in kidney transplant (KTx) recipients are limited. METHODS: We examined a novel database linking SRTR registry data for KTx recipients (2000-2021) with outpatient fill records from a large pharmaceutical claims warehouse (2015-2021). Adult (≥18 years) KTx recipients treated with SGLT2i were compared to those who received other noninsulin diabetes medications without SGLT2i. Characteristics associated with SGLT2i use were quantified by multivariable logistic regression (adjusted odds ratio, 95%LCLaOR95%UCL). RESULTS: Among 18 988 KTx recipients treated with noninsulin diabetes agents in the study period, 2224 filled an SGLT2i. Mean time from KTx to prescription was 6.7 years for SGLT2i versus 4.7 years for non-SGLT2i medications. SGLT2i use was more common in Asian adults (aOR, 1.091.311.58) and those aged > 30-59 years (compared with 18-30 years) or with BMI > 35 kg/m2 (aOR, 1.191.411.67), and trended higher with self-pay status. SGLT2i use was lower among KTx recipients who were women (aOR, .79.87.96), Black (aOR, .77.881.00) and other (aOR, .52.751.07) race, publicly insured (aOR, .82.921.03), or with less than college education (aOR, .78.87.96), and trended lower in those age 75 years and older. SGLT2i use in KTx patients increased dramatically in 2019-2021 (aOR, 5.015.636.33 vs. prior years). CONCLUSION: SGLT2i use is increasing in KTx recipients but varies with factors including race, education, and insurance. While ongoing study is needed to define risks and benefits of SGLT2i use in KTx patients, attention should also focus on reducing treatment disparities related to sociodemographic traits.

Frailty, but not cognitive impairment, improves mortality risk prediction among those with chronic kidney disease-a nationally representative study.

BACKGROUND: Though older adults with chronic kidney disease (CKD) have a greater mortality risk than those without CKD, traditional risk factors poorly predict mortality in this population. Therefore, we tested our hypothesis that two common geriatric risk factors, frailty and cognitive impairment, and their co-occurrence, might improve mortality risk prediction in CKD. METHODS: Among participants aged ≥ 60 years from National Health and Nutrition Examination Survey (2011-2014), we quantified associations between frailty (physical frailty phenotype) and global/domain-specific cognitive function (immediate-recall [CERAD-WL], delayed-recall [CERAD-DL], verbal fluency [AF], executive function/processing speed [DSST], and global [standardized-average of 4 domain-specific tests]) using linear regression, and tested whether associations differed by CKD using a Wald test. We then tested whether frailty, global cognitive impairment (1.5SD below the mean), or their combination improved prediction of mortality (Cox models, c-statistics) compared to base models (likelihood-ratios) among those with and without CKD. RESULTS: Among 3,211 participants, 1.4% were cognitively impaired, and 10.0% were frail; frailty and cognitive impairment co-occurrence was greater among those with CKD versus those without (1.2%vs.0.1%). Frailty was associated with worse global cognitive function (Cohen's d = -0.26SD,95%CI -0.36,-0.17), and worse cognitive function across all domains; these associations did not differ by CKD (pinteractions > 0.05). Mortality risk prediction improved only among those with CKD when accounting for frailty (p[likelihood ratio test] < 0.001) but not cognitive impairment. CONCLUSIONS: Frailty is associated with worse cognitive function regardless of CKD status. While CKD and frailty improved mortality prediction, cognitive impairment did not. Risk prediction tools should incorporate frailty to improve mortality prediction among those with CKD.

Statins in Kidney Transplant Recipients: Usage, All-Cause Mortality, and Interactions with Maintenance Immunosuppressive Agents.

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.

Trends in the survival benefit of repeat kidney transplantation over the past 3 decades.

Repeat kidney transplantation (re-KT) is the preferred treatment for patients with graft failure. Changing allocation policies, widening the risk profile of recipients, and improving dialysis care may have altered the survival benefit of a re-KT. We characterized trends in re-KT survival benefit over 3 decades and tested whether it differed by age, race/ethnicity, sex, and panel reactive assay (PRA). By using the Scientific Registry of Transplant Recipient data, we identified 25 419 patients who underwent a re-KT from 1990 to 2019 and 25 419 waitlisted counterfactuals from the same year with the same waitlisted time following graft failure. In the adjusted analysis, a re-KT was associated with a lower risk of death (adjusted hazard ratio [aHR] = 0.63; 95% confidence interval [CI], 0.61-0.65). By using the 1990-1994 era as a reference (aHR = 0.77; 95% CI, 0.69-0.85), incremental improvements in the survival benefit were noted (1995-1999: aHR = 0.72; 95% CI, 0.67-0.78: 2000-2004: aHR = 0.59; 95% CI, 0.55-0.63: 2005-2009: aHR = 0.59; 95% CI, 0.56-0.63: 2010-2014: aHR = 0.57; 95% CI, 0.53-0.62: 2015-2019: aHR = 0.64; 95% CI, 0.57-0.73). The survival benefit of a re-KT was noted in both younger (age = 18-64 years: aHR = 0.63; 95% CI, 0.61-0.65) and older patients (age ≥65 years: aHR = 0.66; 95% CI, 0.58-0.74; Pinteraction = .45). Patients of all races/ethnicities demonstrated similar benefits with a re-KT. However, it varied by the sex of the recipient (female patients: aHR = 0.60; 95% CI, 0.56-0.63: male patients: aHR = 0.66; 95% CI, 0.63-0.68; Pinteraction = .004) and PRA (0-20: aHR = 0.69; 95% CI, 0.65-0.74: 21-80: aHR = 0.61; 95% CI, 0.57-0.66; Pinteraction = .02; >80: aHR = 0.57; 95% CI, 0.53-0.61; Pinteraction< .001). Our findings support the continued practice of a re-KT and efforts to overcome the medical, immunologic, and surgical challenges of a re-KT.

Characterizing the risk of human leukocyte antigen-incompatible living donor kidney transplantation in older recipients.

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: 1.632.072.65, P < .001), lower DCGF (hazard ratio: 0.360.530.77, P = .001), and AR (odds ratio: 0.390.540.74, P < .001), and similar DGF (odds ratio: 0.461.032.33, P = .9) and LOS (incidence rate ratio: 0.880.981.10, 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.

Preoperative Risk Factors for Adverse Events in Adults Undergoing Bowel Resection for Inflammatory Bowel Disease: 15-Year Assessment of the American College of Surgeons National Surgical Quality Improvement Program.

INTRODUCTION: Older adults with inflammatory bowel disease (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. METHODS: Using the American College of Surgeons National Surgical Quality Improvement Program database, we identified adults ≥18 years of age who underwent an IBD-related intestinal resection from 2005 to 2019. Our primary outcome included a 30-day composite of mortality, readmission, reoperation, and/or major postoperative complication. RESULTS: Overall, 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 (adjusted odds ratio [aOR], 2.08; 95% confidence interval [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. Furthermore, 8.8% of surgeries among older adults were emergent, with no change observed over time ( P = 0.16). DISCUSSION: Preoperative 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.

Association between Abdominal CT Measurements of Body Composition before Deceased Donor Liver Transplant with Posttransplant Outcomes.

Background Pre-liver transplant (LT) sarcopenia is associated with poor survival. Methods exist for measuring body composition with use of CT scans; however, it is unclear which components best predict post-LT outcomes. Purpose To quantify the association between abdominal CT-based body composition measurements and post-LT mortality in a large North American cohort. Materials and Methods This was a retrospective cohort of adult first-time deceased-donor LT recipients from 2009 to 2018 who underwent pre-LT abdominal CT scans, including at the L3 vertebral level, at Johns Hopkins Hospital. Measurements included sarcopenia (skeletal muscle index [SMI] <50 in men and <39 in women), sarcopenic obesity, myosteatosis (skeletal muscle CT attenuation <41 mean HU for body mass index [BMI] <25 and <33 mean HU for BMI ≥25), visceral adipose tissue (VAT), subcutaneous adipose tissue (SAT), and VAT/SAT ratio. Covariates in the adjusted models were selected with use of least absolute shrinkage and selection operator regression with lambda chosen by means of 10-fold cross-validation. Cox proportional hazards models were used to quantify associations with post-LT mortality. Model discrimination was quantified using the Harrell C-statistic. Results A total of 454 recipients (median age, 57 years [IQR, 50-62 years]; 294 men) were evaluated. In the adjusted model, pre-LT sarcopenia was associated with a higher hazard ratio (HR) of post-LT mortality (HR, 1.6 [95% CI: 1.1, 2.4]; C-statistic, 0.64; P = .02). SMI was significantly negatively associated with survival after adjustment for covariates. There was no evidence that myosteatosis was associated with mortality (HR, 1.3 [95% CI: 0.86, 2.1]; C-statistic, 0.64; P = .21). There was no evidence that BMI (HR, 1.2 [95% CI: 0.95, 1.4]), VAT (HR, 1.0 [95% CI: 0.98, 1.1]), SAT (HR, 1.0 [95% CI: 0.97, 1.0]), and VAT/SAT ratio (HR, 1.1 [95% CI: 0.90, 1.4]) were associated with mortality (P = .15-.77). Conclusions Sarcopenia, as assessed on routine pre-liver transplant (LT) abdominal CT scans, was the only factor significantly associated with post-LT mortality. © RSNA, 2022 See also the editorial by Ruehm in this issue.

Frailty, mortality, and health care utilization after liver transplantation: From the Multicenter Functional Assessment in Liver Transplantation (FrAILT) Study.

BACKGROUND AND AIMS: Frailty is a well-established risk factor for poor outcomes in patients with cirrhosis awaiting liver transplantation (LT), but whether it predicts outcomes among those who have undergone LT is unknown. APPROACH AND RESULTS: Adult LT recipients from 8 US centers (2012-2019) were included. Pre-LT frailty was assessed in the ambulatory setting using the Liver Frailty Index (LFI). "Frail" was defined by an optimal cut point of LFI ≥ 4.5. We used the 75th percentile to define "prolonged" post-LT length of stay (LOS; ≥12 days), intensive care unit (ICU) days (≥4 days), and inpatient days within 90 post-LT days (≥17 days). Of 1166 LT recipients, 21% were frail pre-LT. Cumulative incidence of death at 1 and 5 years was 6% and 16% for frail and 4% and 10% for nonfrail patients (overall log-rank p = 0.02). Pre-LT frailty was associated with an unadjusted 62% increased risk of post-LT mortality (95% CI, 1.08-2.44); after adjustment for body mass index, HCC, donor age, and donation after cardiac death status, the HR was 2.13 (95% CI, 1.39-3.26). Patients who were frail versus nonfrail experienced a higher adjusted odds of prolonged LT LOS (OR, 2.00; 95% CI, 1.47-2.73), ICU stay (OR, 1.56; 95% CI, 1.12-2.14), inpatient days within 90 post-LT days (OR, 1.72; 95% CI, 1.25-2.37), and nonhome discharge (OR, 2.50; 95% CI, 1.58-3.97). CONCLUSIONS: Compared with nonfrail patients, frail LT recipients had a higher risk of post-LT death and greater post-LT health care utilization, although overall post-LT survival was acceptable. These data lay the foundation to investigate whether targeting pre-LT frailty will improve post-LT outcomes and reduce resource utilization.

Sleep duration and cognitive function among older adults with chronic kidney disease: results from the National Health and Nutrition Examination Survey (2011-2014).

BACKGROUND: Short and long sleep durations are associated with cognitive dysfunction. Given the increased prevalence of sleep abnormalities in the chronic kidney disease (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 (age ≥60 years) enrolled in the National Health and Nutrition Examination Survey (2011-14) 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/day, 75.2% reported 6-8 hours, and 11.5% reported ≥9 hours. Persons with CKD were more likely to sleep ≥9 hours [odds ratio 1.73 (95% confidence interval 1.22-2.46)]. Among participants with CKD, those with a sleep duration ≥9 hours demonstrated worse global cognitive function (P for interaction = .01), immediate recall (P for interaction = .01) and verbal fluency (P for interaction = .004) than those with a sleep duration of 6-8 h; 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.

Post-kidney transplant body mass index trajectories are associated with graft loss and mortality.

BACKGROUND: Early post-kidney transplantation (KT) changes in physiology, medications, and health stressors likely impact body mass index (BMI) and likely impact all-cause graft loss and mortality. METHODS: We estimated 5-year post-KT (n = 151 170; SRTR) BMI trajectories using an adjusted mixed effects model. We estimated long-term mortality and graft loss risks by 1-year BMI change quartile (decrease [1st quartile]: change < -.07 kg/m2 /month; stable [2nd quartile]: -.07 ≤ change ≤ .09 kg/m2 /month; increase [3rd, 4th quartile]: change > .09 kg/m2 /month) using adjusted Cox proportional hazards models. RESULTS: BMI increased in the 3 years post-KT (.64 kg/m2 /year, 95% CI: .63, .64) and decreased in years 3-5 (-.24 kg/m2 /year, 95% CI: -.26, -.22). 1-year post-KT BMI decrease was associated with elevated risks of all-cause mortality (aHR = 1.13, 95% CI: 1.10-1.16), all-cause graft loss (aHR = 1.13, 95% CI: 1.10-1.15), death-censored graft loss (aHR = 1.15, 95% CI: 1.11-1.19), and mortality with functioning graft (aHR = 1.11, 95% CI: 1.08-1.14). Among recipients with obesity (pre-KT BMI≥30 kg/m2 ), BMI increase was associated with higher all-cause mortality (aHR = 1.09, 95% CI: 1.05-1.14), all-cause graft loss (aHR = 1.05, 95% CI: 1.01-1.09), and mortality with functioning graft (aHR = 1.10, 95% CI: 1.05-1.15) risks, but not death-censored graft loss risks, relative to stable weight. Among individuals without obesity, BMI increase was associated with lower all-cause graft loss (aHR = .97, 95% CI: .95-.99) and death-censored graft loss (aHR = .93, 95% CI: .90-.96) risks, but not all-cause mortality or mortality with functioning graft risks. CONCLUSIONS: BMI increases in the 3 years post-KT, then decreases in years 3-5. BMI loss in all adult KT recipients and BMI gain in those with obesity should be carefully monitored post-KT.

Hurricanes and Mortality among Patients Receiving Dialysis.

BACKGROUND: Hurricanes are severe weather events that can disrupt power, water, and transportation systems. These disruptions may be deadly for patients requiring maintenance dialysis. We hypothesized that the mortality risk among patients requiring maintenance dialysis would be increased in the 30 days after a hurricane. METHODS: Patients registered as requiring maintenance dialysis in the United States Renal Data System who initiated treatment between January 1, 1997 and December 31, 2017 in one of 108 hurricane-afflicted counties were followed from dialysis initiation until transplantation, dialysis discontinuation, a move to a nonafflicted county, or death. Hurricane exposure was determined as a tropical cyclone event with peak local wind speeds ≥64 knots in the county of a patient's residence. The risk of death after the hurricane was estimated using time-varying Cox proportional hazards models. RESULTS: The median age of the 187,388 patients was 65 years (IQR, 53-75) and 43.7% were female. There were 27 hurricanes and 105,398 deaths in 529,339 person-years of follow-up on dialysis. In total, 29,849 patients were exposed to at least one hurricane. Hurricane exposure was associated with a significantly higher mortality after adjusting for demographic and socioeconomic covariates (hazard ratio, 1.13; 95% confidence interval, 1.05 to 1.22). The association persisted when adjusting for seasonality. CONCLUSIONS: Patients requiring maintenance dialysis have a higher mortality risk in the 30 days after a hurricane.

Revision of frailty assessment in kidney transplant recipients: Replacing unintentional weight loss with CT-assessed sarcopenia in the physical frailty phenotype.

Kidney transplantation (KT) experts did not support the use of subjective unintentional weight loss to measure shrinking in the physical frailty phenotype (PFP); a clinically feasible and predictive measure of shrinking is needed. To test whether unintentional weight loss could be replaced by an assessment of sarcopenia using existing CT scans, we performed a prospective cohort study of adult KT recipients with original PFP (oPFP) measured at admission (December 2008-February 2020). We ascertained sarcopenia by calculating skeletal muscle index from available, clinically obtained CTs within 1-year pre-KT (male < 50 cm2 /m2 ; female < 39 cm2 /m2 ) and combined it with the original four components to determine new PFP (nPFP) scores. Frailty was classified by frailty score: 0: non-frail; 1-2: pre-frail; ≥3: frail. Mortality and graft loss hazard ratios (HRs) were estimated using adjusted Cox proportional hazard models. Model discrimination was quantified using Harrell's C-statistic. Among 1113 recipients, 18.6% and 17.1% were frail by oPFP and nPFP, respectively. Compared to non-frail recipients, frail patients by either PFP had higher risks of mortality (oPFP HR = 1.67, 95% CI: 1.07-2.62, C = 0.710; nPFP HR = 1.68, 95% CI: 1.06-2.66, C = 0.710) and graft loss (oPFP HR = 1.67, 95% CI: 1.17-2.40, C = 0.631; nPFP HR = 1.66, 95% CI: 1.15-2.40, C = 0.634) with similar discriminations. oPFP and nPFP are equally useful in risk prediction for KT recipients; oPFP may aid in screening patients for pre-KT interventions, while nPFP may assist in nuanced clinical decision-making.

Delirium, changes in cognitive function, and risk of diagnosed dementia after kidney transplantation.

Kidney transplant (KT) recipients with delirium, a preventable surgical complication, are likely to reap cognitive benefits from restored kidney function, but may be more vulnerable to longer-term neurotoxic stressors post-KT (i.e., aging, immunosuppression). In this prospective cohort study, we measured delirium (chart-based), global cognitive function (3MS), and executive function (Trail Making Test Part B minus Part A) in 894 recipients (2009-2021) at KT, 1/3/6-months, 1-year, and annually post-KT. Dementia was ascertained using linked Medicare claims. We described repeated measures of cognitive performance (mixed effects model) and quantified dementia risk (Fine & Gray competing risk) by post-KT delirium. Of 894 recipients, 43(4.8%) had post-KT delirium. Delirium was not associated with global cognitive function at KT (difference = -3.2 points, 95%CI: -6.7, 0.4) or trajectories post-KT (0.03 points/month, 95%CI: -0.27, 0.33). Delirium was associated with worse executive function at KT (55.1 s, 95%CI: 25.6, 84.5), greater improvements in executive function <2 years post-KT (-2.73 s/month, 95%CI: -4.46,-0.99), and greater decline in executive function >2 years post-KT (1.72 s/month, 95%CI: 0.22, 3.21). Post-KT delirium was associated with over 7-fold greater risk of dementia post-KT (adjusted subdistribution hazard ratio = 7.84, 95%CI: 1.22, 50.40). Transplant centers should be aware of cognitive risks associated with post-KT delirium and implement available preventative interventions to reduce delirium risk.

mTOR inhibitors, mycophenolates, and other immunosuppression regimens on antibody response to SARS-CoV-2 mRNA vaccines in solid organ transplant recipients.

A recent study concluded that SARS-CoV-2 mRNA vaccine responses were improved among transplant patients taking mTOR inhibitors (mTORi). This could have profound implications for vaccine strategies in transplant patients; however, limitations in the study design raise concerns about the conclusions. To address this issue more robustly, in a large cohort with appropriate adjustment for confounders, we conducted various regression- and machine learning-based analyses to compare antibody responses by immunosuppressive agents in a national cohort (n = 1037). MMF was associated with significantly lower odds of positive antibody response (aOR = 0.09 0.130.18 ). Consistent with the recent mTORi study, the odds tended to be higher with mTORi (aOR = 1.00 1.452.13 ); however, importantly, this seemingly protective tendency disappeared (aOR = 0.47 0.731.12 ) after adjusting for MMF. We repeated this comparison by combinations of immunosuppression agents. Compared to MMF + tacrolimus, MMF-free regimens were associated with higher odds of positive antibody response (aOR = 2.39 4.267.92 for mTORi+tacrolimus; 2.34 5.5415.32 for mTORi-only; and 6.78 10.2515.93 for tacrolimus-only), whereas MMF-including regimens were not, regardless of mTORi use (aOR = 0.81 1.542.98 for MMF + mTORi; and 0.81 1.512.87 for MMF-only). We repeated these analyses in an independent cohort (n = 512) and found similar results. Our study demonstrates that the recently reported findings were confounded by MMF, and that mTORi is not independently associated with improved vaccine responses.