Faculty Bibliography

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, 1.05-1.22). The association persisted when adjusting for seasonality. CONCLUSIONS:Patients requiring maintenance dialysis have a higher mortality risk in the 30 days after a hurricane.

OBJECTIVE:Impairment in physical function and physical performance leads to decreased independence and health-related quality of life in people living with chronic kidney disease and end-stage kidney disease. Physical activity and exercise in kidney care are not priorities in policy development. We aimed to identify global policy-related enablers, barriers, and strategies to increase exercise participation and physical activity behavior for people living with kidney disease. DESIGN AND METHODS/METHODS:Guided by the Behavior Change Wheel theoretical framework, 50 global renal exercise experts developed policy barriers and enablers to exercise program implementation and physical activity promotion in kidney care. The consensus process consisted of developing themes from renal experts from North America, South America, Continental Europe, United Kingdom, Asia, and Oceania. Strategies to address enablers and barriers were identified by the group, and consensus was achieved. RESULTS:We found that policies addressing funding, service provision, legislation, regulations, guidelines, the environment, communication, and marketing are required to support people with kidney disease to be physically active, participate in exercise, and improve health-related quality of life. We provide a global perspective and highlight Japanese, Canadian, and other regional examples where policies have been developed to increase renal physical activity and rehabilitation. We present recommendations targeting multiple stakeholders including nephrologists, nurses, allied health clinicians, organizations providing renal care and education, and renal program funders. CONCLUSIONS:We strongly recommend the nephrology community and people living with kidney disease take action to change policy now, rather than idly waiting for indisputable clinical trial evidence that increasing physical activity, strength, fitness, and function improves the lives of people living with kidney disease.

BACKGROUND:Secondary hyperparathyroidism affects nearly all patients with renal failure on dialysis. Medical treatment of secondary hyperparathyroidism has considerably evolved over the past 2 decades, with parathyroidectomy reserved for severe cases. The primary objective of our study was to understand how trends in medical treatments affected parathyroidectomy rates in patients with secondary hyperparathyroidism on dialysis. METHODS:We used the United States Renal Data System to identify 379,835 adult patients (age ≥18) who were on maintenance dialysis in the United States between 2006 and 2016 with Medicare as the primary payor and ascertained treatment for secondary hyperparathyroidism. Adjusted rate ratios for rates of parathyroidectomy were calculated using multivariable-adjusted Poisson regression. RESULTS:Of 379,835 secondary hyperparathyroidism patients, 4,118 (1.1%) underwent parathyroidectomy, 39,835 (10.5%) received cinacalcet, 243,522 (64.1%) received phosphate binders, 17,571 (4.6%) received vitamin D analogs, and 86,899 (22.9%) received no treatment during the 10 years of follow-up. Over the entire study period, there was a 3.5-fold increase in the use of calcimimetics and a 3.4-fold increase in rates of parathyroidectomy. Compared to 2006 through 2009, utilization of parathyroidectomy increased 52% (adjusted rate ratio = 1.52, 95% confidence interval: 1.39-1.65) between 2010 and 2013 and by 106% (adjusted rate ratio = 2.06, 95% confidence interval: 1.90-2.24) between 2014 and 2016. The greatest increase in parathyroidectomy utilization occurred in younger patients (age 18-64 years), Black patients, female patients, those living in higher poverty neighborhoods, those listed for kidney transplant, and those who live in the Southern region of the United States. CONCLUSION:Despite the evolution of medical treatments and an increase in the use of calcimimetics to treat secondary hyperparathyroidism, parathyroidectomy rates have been steadily increasing among dialysis patients with Medicare coverage.

RATIONALE & OBJECTIVE/UNASSIGNED:Disorders of bone and mineral metabolism frequently develop with advanced kidney disease, may be exacerbated by immunosuppression after kidney transplantation, and increase the risk of fractures. STUDY DESIGN/UNASSIGNED:Retrospective database study. SETTING & PARTICIPANTS/UNASSIGNED:Kidney-only transplant recipients aged ≥18 years from 2005 to 2016 in the United States captured in US Renal Data System records, which integrate Organ Procurement and Transplantation Network/United Network for Organ Sharing records with Medicare billing claims. EXPOSURES/UNASSIGNED:Various immunosuppression regimens in the first 3 months after kidney transplantation. OUTCOMES/UNASSIGNED:The development of fractures, as ascertained using diagnostic codes on Medicare billing claims. ANALYTICAL APPROACH/UNASSIGNED:We used multivariable Cox regression with inverse propensity weighting to compare the incidence of fractures >3 months-to-3 years after kidney transplantation associated with various immunosuppression regimens compared to a reference regimen of antithymocyte globulin (TMG) or alemtuzumab (ALEM) with tacrolimus + mycophenolic acid + prednisone using inverse probability treatment weighting. RESULTS/UNASSIGNED: < 0.001]). Induction with TMG or ALEM and the avoidance or early withdrawal of steroids significantly reduced the risk of fractures in younger (aHR, 0.63; 95% CI, 0.54-0.73) and older (aHR, 0.83; 95% CI, 0.74-0.94) patients. The avoidance or early withdrawal of steroids with any induction was associated with a reduced risk of fractures in women. LIMITATIONS/UNASSIGNED:This was a retrospective study which lacked data on immunosuppression levels. CONCLUSIONS/UNASSIGNED:Fractures after kidney transplantation are associated with significantly increased mortality risk and costs. The early avoidance or early withdrawal of steroids after induction with TMG or ALEM reduces the risk of fractures after kidney transplantation and should be considered for patients at high-risk of this complication, including older adults and women.

Introduction/UNASSIGNED:Depressive symptoms, even without a clinical diagnosis of depression, are common in kidney failure patients and may be a barrier to completing the complex process of kidney transplant (KT) evaluation. We assessed depressive symptom burden and association between depressive symptoms and access to KT waitlist by age. Methods/UNASSIGNED:In a prospective cohort of 3728 KT patients (aged 18-88 years), the Center for Epidemiologic Studies-Depression (CES-D) scale was used to measure depressive symptoms at evaluation. Depressive symptom severity was defined as follows: none: 0; minimal: 1 to 15; mild: 16 to 20; moderate: 21 to 25; severe: 26 to 60. Hazard ratios (HRs) of active listing within 1 year after evaluation were estimated using Cox proportional hazards models, adjusted for clinical and social factors. Results/UNASSIGNED: < 0.001). After adjustment, every 5-point higher CES-D score (more depressive symptoms) was associated with a 13% lower chance of listing (HR = 0.87, 95% CI: 0.85-0.90); the strongest association was found among patients aged ≥70 years (adjusted HR [aHR] = 0.73, 95% CI: 0.62-0.86). Furthermore, minimal (HR = 0.69, 95% CI: 0.60-0.79), mild (HR = 0.57, 95% CI: 0.44-0.72), moderate (HR = 0.53, 95% CI: 0.39-0.71), and severe (HR = 0.44, 95% CI: 0.34-0.57) depressive symptoms were all associated with a lower chance of listing. Conclusion/UNASSIGNED:Older candidates were less likely to report depressive symptoms at KT evaluation. Regardless of age, candidates who did report depressive symptoms, and even minimal symptoms, had a lower chance of listing. Transplant centers should routinely screen patients for depressive symptoms and refer the affected patients to mental health services to improve access to KT.

BACKGROUND AND AIMS/OBJECTIVE: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/UNASSIGNED: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.

BACKGROUND:Air pollution is associated with cardiopulmonary disease and death in the general population. Fine particulate matter (PM2.5) is particularly harmful due to its ability to penetrate into areas of gas exchange within the lungs. Persons with advanced lung disease are believed to be particularly susceptible to PM2.5 exposure but few studies have examined the effect of exposure on this population. Here we investigate the association between PM2.5 exposure and adverse waitlist events among lung transplant (LT) candidates. METHODS:US registry data were used to identify LT candidates listed between 1/1/2010-12/31/2016. Annual PM2.5 concentration at year of listing was estimated for each candidate's ZIP Code using NASA's SEDAC Global Annual PM2.5 Grids. We estimated crude and adjusted hazard ratios for adverse waitlist events, defined as death or removal, using Cox proportional hazards regression. RESULTS:Of the 15,075 included candidates, median age at listing was 60, 43.8% were female and 81.7% were non-Hispanic white. Median ZIP Code PM2.5 concentration was 9.06µg/m3. When compared to those living in ZIP Codes with lower PM2.5 exposure (PM2.5 <10.53µg/m3), candidates in ZIP Codes in the highest quartile of PM2.5 exposure (≥10.53µg/m3) had 1.14-fold (95%CI 1.04-1.25) risk of adverse waitlist events. The result remained significant after adjusting for demographics, education, insurance, smoking, lung allocation score, BMI, and blood type (HR=1.17; 95%CI 1.07-1.29). CONCLUSIONS:Elevated ambient PM2.5 concentration was associated with adverse waitlist events among LT candidates. These findings highlight the impact of air pollution on clinical outcomes in this critically ill population.

BACKGROUND:In older adults (≥65) access to and outcomes following kidney transplantation (KT) have improved over the past three decades. It is unknown if there were parallel trends in re-KT. We characterized the trends, changing landscape, and outcomes of re-KT in older adults. METHODS:Among the 44,149 older kidney-only recipients (1995-2016) in the Scientific Registry of Transplant Recipients, we identified 1,743 who underwent re-KT. We analyzed trends and outcomes (mortality, death-censored graft failure [DCGF]) by eras (1995-2002, 2003-2014 and 2015-2016) that were defined by changes to the ECD and KDPI policies. RESULTS:Among all older kidney-only recipients during 1995-2002, 2003-2014, 2015-2016 the proportion that were re-KTs increased from 2.7%-4.2%-5.7% p<0.001, respectively. Median age at re-KT (67-68-68, p=0.04), years on dialysis after graft failure (1.4-1.5-2.2, p=0.003), donor age (40.0-43.0-43.5, p=0.04), proportion with PRA 80-100 (22.0%-32.7%-48.7%, p<0.001) and donations after circulatory death (1.1%-13.4%-19.5%, p<0.001) have increased. Despite this, the 3-year cumulative incidence for mortality (22.3%-19.1%-11.5%, p=0.002) and DCGF (13.3%-10.0%-5.1%, p=0.01) decreased over time. Compared with deceased donor re-transplant recipients during 1995-2002, those during 2003-2014 and 2015-2016 had lower mortality hazard (aHR=0.78, 95%CI:0.63-0.86 and aHR=0.55, 95%CI:0.35-0.86, respectively). These declines were noted but not significant for DCGF and in living donor re-KTs. CONCLUSIONS:In older re-transplant recipients, outcomes have improved significantly over time despite higher risk profiles; yet they represent a fraction of the KTs performed. Our results support increasing access to re-KT in older adults; however, approaches to guide the selection and management in those with graft failure need to be explored.

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.

Acute kidney injury (AKI) and frailty are major drivers of outcomes among patients with cirrhosis. What is unknown is the impact of physical frailty on the development of AKI. We included adults with cirrhosis without hepatocellular carcinoma listed for liver transplantation at nine US centers (n = 1,033). Frailty was assessed using the Liver Frailty Index (LFI); "frail" was defined by LFI ≥ 4.2. Chronic kidney disease as a baseline estimated glomerular filtration rate <60 mL/min/1.73 m² . Our primary outcome, AKI, was defined as an increase in serum creatinine ≥0.3 mg/dL or a serum creatinine ≥1.5-fold increase. Wait-list mortality was defined as either a death on the wait list or removal for being too sick. We performed Cox regression analyses to estimate the hazard ratios (HRs) for AKI and wait-list mortality. Of 1,033 participants, 41% were frail and 23% had CKD. Twenty-one percent had an episode of AKI during follow-up. Frail versus nonfrail patients were more likely to develop AKI (25% vs. 19%) and wait-list mortality (21% vs. 13%) (P < 0.01 for each). In multivariable Cox regression, each of the following groups was associated with a higher risk of AKI as compared with not frail/no CKD: frail/no CKD (adjusted HR [aHR] = 1.87, 95% confidence interval [CI] = 1.29-2.72); not frail/CKD (aHR = 4.30, CI = 2.88-6.42); and frail/CKD (aHR = 4.85, CI = 3.33-7.07). We use a readily available metric, LFI, to identify those patients with cirrhosis most at risk for AKI. We highlight that serum creatinine and creatinine-based estimations of glomerular filtration rate may not fully capture a patient's vulnerability to AKI among the frail phenotype. Conclusion: Our work lays the foundation for implementing physical frailty in clinical practice to identify AKI earlier, implement reno-protective strategies, and expedite liver transplantation.