Faculty Bibliography

BACKGROUND:End-stage kidney disease (ESKD) patients are living longer, often into older age, and commonly pursue kidney transplantation. Successful aging, a multidimensional construct of physical and social wellbeing, has been expanded and adapted for patients with chronic disease. However, perceptions of, barriers to, and experiences with successful aging among adults with ESKD are unclear and likely differ based on whether they have received a kidney transplant. METHODS:Ten focus groups were held with 39 total ESKD patients aged ≥50 years (19 transplant candidates, 20 transplant recipients). Transcriptions were analyzed thematically by 2 independent coders using an inductive, constant comparative approach. RESULTS:The mean age was 64.8 (SD = 7.5); 51% were African American and 64% were males. Six themes were identified: familiarity with successful aging, perceptions of successful aging after ESKD diagnosis, barriers to successful aging, experiences with successful aging among transplant candidates, experiences with successful aging among transplant recipients, and suggested interventions. While all participants sought to achieve successful aging while living with ESKD, experiences with successful aging differed between candidates and recipients. Candidates struggled with the limitations of dialysis; some viewed transplantation as an opportunity to age successfully, while others were resigned to the drawbacks of dialysis. In contrast, transplant recipients were optimistic about their ability to age successfully, believing their transplant facilitated successful aging. Participants believed support groups for adults with ESKD and more thoughtful health care for aging adults would promote successful aging. CONCLUSIONS:Adults with ESKD may benefit from discussions with their clinicians and caregivers about goals, barriers, and strategies regarding successful aging.

BACKGROUND:Placing an arteriovenous fistula (AVF) in older hemodialysis patients at great risk of primary failure leads to prolonged dependency on central venous catheter (CVC). A model which accurately predicts AVF maturation can facilitate better clinical determination for AVF placement. METHODS:We assembled a retrospective cohort of 14 892 patients aged 67 years and older who started hemodialysis with a CVC between 7/1/2010 and 6/30/2012 and had a subsequent, incident AVF placement from the United States Renal Data System (USRDS). We used random survival forests (RSF) with competing risks to identify important predictors for AVF maturation. RESULTS:Approximately 49.7% patients achieved AVF maturation and 13.6% had a competing event. The median time to maturation was 4 (IQR: 3-5) months. Patient's gender had the highest variable importance (VIMP, 0.0027), followed by race, being institutionalized, days on hemodialysis without an AVF, estimated glomerular filtration rate, and body mass index with borderline importance (VIMP ≥0.0005). The out-of-bag (OOB) error rate of the RSF was 45.3% and 45.8% for AVF maturation in the training and validation data sets, respectively. CONCLUSIONS:Predictors in USRDS data have limited ability to predict AVF maturation. Patient's gender might be considered as the most important predictor for AVF maturation.

BACKGROUND:The short physical performance battery (SPPB) test is an objective measurement of lower extremity function (walk speed, balance, chair stands). SPPB impairment is associated with longer length of stay and increased mortality in kidney transplant (KT) recipients. Furthermore, the SPPB test may represent an objective quantification of the "foot of the bed test" utilized by clinicians; therefore, impairment may translate with decreased access to KT. METHODS:We studied 3255 participants (2009-2018) at 2 KT centers. SPPB impairment was defined as a score of ≤10. We estimated time to listing, waitlist mortality, and transplant rate by SPPB impairment status using Cox proportional hazards, competing risks, and Poisson regression. RESULTS:The mean age was 54 years (SD = 14; range 18-89) and 54% had SPPB impairment. Impaired participants were less likely to be listed for KT (adjusted hazard ratio: 0.70, 95% CI: 0.64-0.77, P < 0.001). Also, once listed, impaired candidates had a 1.6-fold increased risk of waitlist mortality (adjusted subhazard ratio: 1.56, 95% CI: 1.18-2.06, P = 0.002). Furthermore, impaired candidates were transplanted 16% less frequently (adjusted incidence rate ratio: 0.84, 95% CI: 0.73-0.98, P = 0.02). CONCLUSIONS:SPPB impairment was highly prevalent in KT candidates. Impaired candidates had decreased chance of listing, increased risk of waitlist mortality, and decreased rate of KT. Identification of robust KT candidates and improvement in lower extremity function are potential ways to improve survival on the waitlist and access to KT.

BACKGROUND:Given the potential utility of frailty, a clinical phenotype of decreased physiologic reserve and resistance to stressors, to predict postkidney transplant (KT) outcomes, we sought to understand the perceptions and practices regarding frailty measurement in US KT programs. METHODS:Surveys were emailed to American Society of Transplantation Kidney/Pancreas Community of Practice members and 202 US transplant programs (November 2017 to April 2018). Program characteristics were gleaned from Scientific Registry of Transplant Recipients. RESULTS:The 133 responding programs (response rate = 66%) represented 77% of adult KTs and 79% of adult KT candidates in the United States. Respondents considered frailty to be a useful concept in evaluating candidacy (99%) and endorsed a need to develop a frailty measurement specific to KT (92%). Frailty measurement was more common during candidacy evaluation (69%) than during KT admission (28%). Of the 202 programs, 38% performed frailty assessments in all candidates while 23% performed assessments only for older candidates. There was heterogeneity in the frailty assessment method; 18 different tools were utilized to measure frailty. The most common tool was a timed walk test (19%); 67% reported performing >1 tool. Among programs that measure frailty, 53% reported being less likely to list frail patients for KT. CONCLUSIONS:Among US KT programs, frailty is recognized as a clinically relevant construct and is commonly measured at evaluation. However, there is considerable heterogeneity in the tools used to measure frailty. Efforts to identify optimal measurement of frailty using either an existing or a novel tool and subsequent standardization of its measurement and application across KT programs should be considered.

BACKGROUND:Early steroid withdrawal (ESW) is associated with acceptable outcomes in kidney transplant (KT) recipients. Recipients with delayed graft function (DGF), however, often have a suboptimal allograft milieu, which may alter the risk/benefit equation for ESW. This may contribute to varying practices across transplant centers. METHODS:Using the Scientific Registry of Transplant Recipients, we studied 110,019 adult deceased-donor KT recipients between 2005 and 2017. We characterized the association of DGF with the use of ESW versus continued steroid maintenance across KT centers, and quantified the association of ESW with acute rejection, graft failure, and mortality using multivariable logistic and Cox regression with DGF-ESW interaction terms. RESULTS:=0.6). CONCLUSIONS:KT centers in the United States use ESW inconsistently in recipients with DGF. Our findings suggest ESW may lead to worse KT outcomes in recipients with DGF.

BACKGROUND:Frailty, originally characterized in community-dwelling older adults, is increasingly being studied and implemented for adult patients with end-stage kidney disease (ESKD) of all ages (>18 years). Frailty prevalence and manifestation are unclear in younger adults (18-64 years) with ESKD; differences likely exist based on whether the patients are treated with hemodialysis (HD) or kidney transplantation (KT). METHODS:We leveraged 3 cohorts: 378 adults initiating HD (2008-2012), 4,304 adult KT candidates (2009-2019), and 1,396 KT recipients (2008-2019). The frailty phenotype was measured within 6 months of dialysis initiation, at KT evaluation, and KT admission. Prevalence of frailty and its components was estimated by age (≥65 vs. <65 years). A Wald test for interactions was used to test whether risk factors for frailty differed by age. RESULTS:In all 3 cohorts, frailty prevalence was higher among older than younger adults (HD: 71.4 vs. 47.3%; candidates: 25.4 vs. 18.8%; recipients: 20.8 vs. 14.3%). In all cohorts, older patients were more likely to have slowness and weakness but less likely to report exhaustion. Among candidates, older age (odds ratio [OR] = 1.79, 95% CI: 1.47-2.17), non-Hispanic black race (OR = 1.30, 95% CI: 1.08-1.57), and dialysis type (HD vs. no dialysis: OR = 2.06, 95% CI: 1.61-2.64; peritoneal dialysis vs. no dialysis: OR = 1.78, 95% CI: 1.28-2.48) were associated with frailty prevalence, but sex and Hispanic ethnicity were not. These associations did not differ by age (pinteractions > 0.1). Similar results were observed for recipients and HD patients. CONCLUSIONS:Although frailty prevalence increases with age, younger patients have a high burden. Clinicians caring for this vulnerable population should recognize that younger patients may experience frailty and screen all age groups.

BACKGROUND:Cardiovascular safety of dipeptidyl peptidase-IV inhibitors (DPP-4i) in patients without cardiovascular or renal disease, a majority of newly diagnosed patients with type 2 diabetes often excluded from clinical trials on this association, is poorly understood. Thus, we investigate the risk of major adverse cardiovascular events (MACE) associated with DPP-4i in low-risk patients with diabetes. METHODS:Using a new-user retrospective cohort derived from IBM MarketScan Commercial Claims and Encounters (2010-2015), we identified patients aged 35-65 with type 2 diabetes, without cardiovascular or renal disease, initiating DPP-4i, sulfonylureas, or metformin. Primary composite outcome of time to first MACE was defined as the first of any of the following: myocardial infarction, cardiac arrest, coronary artery bypass graft, coronary angioplasty, heart failure, and stroke. Secondary outcomes were time to first heart failure, acute myocardial infarction, and stroke. We compared outcomes for DPP-4i versus sulfonylurea and DPP-4i versus metformin using propensity score weighted Cox proportional hazards, adjusting for demographics, baseline comorbidities, concomitant medications, and cumulative exposure. RESULTS:Of 445,701 individuals, 236,431 (53.0%) were male, median age was 51 (interquartile range: [44, 57]), 30,267 (6.79%) initiated DPP-4i, 52,138 (11.70%) initiated sulfonylureas, and 367,908 (82.55%) initiated metformin. After adjustment, DPP-4i was associated with lower risk of MACE than sulfonylurea (adjusted hazard ratio (aHR) = 0.87; 95% confidence interval (CI): 0.78-0.98), and similar risk to metformin (aHR = 1.07; 95% CI: 0.97-1.18). Risk for acute myocardial infarction (aHR = 0.70; 95% CI: 0.51-0.96), stroke (aHR = 0.57; 95% CI: 0.41-0.79), and heart failure (aHR = 0.57; 95% CI: 0.41-0.79) with DPP-4i was lower compared to sulfonylureas. CONCLUSION:Our findings show that for this cohort of low-risk patients newly treated for type 2 diabetes, DPP-4i exhibited 13% lower risk for MACE compared to sulfonylureas and similar risk for MACE compared to metformin, suggesting DPP-4i is a low cardiovascular risk option for low-risk patients initiating antihyperglycemic treatment.

BACKGROUND:Choice of vascular access for older hemodialysis patients presents a special challenge since the rate of arteriovenous fistula (AVF) primary failure is high. The Lok's risk equation predicting AVF primary failure has achieved good prediction accuracy and holds great potential for clinical use, but it has not been validated in the United States older hemodialysis patients. METHODS:We assembled a validation data set of 14,892 patients aged 67 years and older who initiated hemodialysis with a central venous catheter between July 1, 2010, and June 30, 2012, and had a subsequent, incident AVF placement from the United States Renal Data System. We examined the external validity of Lok's model by applying it to this validation data set. The discriminatory accuracy and calibration were evaluated by the concordance index (C-statistics) and calibration plot, respectively. RESULTS:The observed frequency of AVF primary failure varied from 0.45 to 0.53 in hemodialysis patients in the validation data set. The predicted probabilities of AVF primary failure calculated by using the Lok's risk equation ranged from 0.08 to 0.61, and 77.8, 40.5, and 51.7% of patients were categorized as having high, intermediate, and low risk of AVF primary failure, respectively. The C-statistics of the Lok's risk equation in the validation data set was 0.53 (95% CI 0.52-0.54). The predicted probabilities of AVF primary failure corresponded poorly with the observed proportions in the calibration plot. CONCLUSIONS:When externally applied to a cohort of U.S. older hemodialysis patients, the Lok's risk equation exhibited poor discrimination and calibration accuracy. It is invalid to use it to predict AVF primary failure. A more complex model with strong predictors is expected to better serve clinical determination for AVF placement in this population.