Faculty Bibliography

BACKGROUND AND OBJECTIVES:Older patients with ESKD experience rapid declines in executive function after initiating hemodialysis; these impairments might lead to high rates of dementia and Alzheimer's disease in this population. We estimated incidence, risk factors, and sequelae of diagnosis with dementia and Alzheimer's disease among older patients with ESKD initiating hemodialysis. DESIGN, SETTING, PARTICIPANTS, & MEASUREMENTS:We studied 356,668 older (age ≥66 years old) patients on hemodialysis (January 1, 2001 to December 31, 2013) from national registry data (US Renal Data System) linked to Medicare. We estimated the risk (cumulative incidence) of diagnosis of dementia and Alzheimer's disease and studied factors associated with these disorders using competing risks models to account for death, change in dialysis modality, and kidney transplant. We estimated the risk of subsequent mortality using Cox proportional hazards models. RESULTS:The 1- and 5-year risks of diagnosed dementia accounting for competing risks were 4.6% and 16% for women, respectively, and 3.7% and 13% for men, respectively. The corresponding Alzheimer's disease diagnosis risks were 0.6% and 2.6% for women, respectively, and 0.4% and 2.0% for men, respectively. The strongest independent risk factors for diagnosis of dementia and Alzheimer's disease were age ≥86 years old (dementia: hazard ratio, 2.11; 95% confidence interval, 2.04 to 2.18; Alzheimer's disease: hazard ratio, 2.11; 95% confidence interval, 1.97 to 2.25), black race (dementia: hazard ratio, 1.70; 95% confidence interval, 1.67 to 1.73; Alzheimer's disease: hazard ratio, 1.78; 95% confidence interval, 1.71 to 1.85), women (dementia: hazard ratio, 1.10; 95% confidence interval, 1.08 to 1.12; Alzheimer's disease: hazard ratio, 1.12; 95% confidence interval, 1.08 to 1.16), and institutionalization (dementia: hazard ratio, 1.36; 95% confidence interval, 1.33 to 1.39; Alzheimer's disease: hazard ratio, 1.10; 95% confidence interval, 1.05 to 1.15). Older patients on hemodialysis with a diagnosis of dementia were at 2.14-fold (95% confidence interval, 2.07 to 2.22) higher risk of subsequent mortality; those with a diagnosis of Alzheimer's disease were at 2.01-fold (95% confidence interval, 1.89 to 2.15) higher mortality risk. CONCLUSIONS:Older patients on hemodialysis are at substantial risk of diagnosis with dementia and Alzheimer's disease, and carrying these diagnoses is associated with a twofold higher mortality.

BACKGROUND:Previous studies have reported a wide range of prevalence of post-donation anxiety, depression, and regret in living kidney donors (LKDs). It is also unclear what risk factors are associated with these outcomes. METHODS:We screened 825 LKDs for anxiety and depression using 2-item GAD-2 and PHQ-2 scales and asked about regret. RESULTS:Overall, 5.5% screened positive for anxiety, 4.2% for depression, and 2.1% reported regretting their donation. While there was moderate correlation between positive anxiety and depression screens (r = 0.52), there was no correlation between regret and positive screens (r < 0.1 for both). A positive anxiety screen was more likely in LKDs with a positive depression screen (adjusted relative risk [aRR] 13.72, 95% confidence interval [CI] 6.78-27.74, p < 0.001). Similarly, a positive depression screen was more likely in LKDs with a positive anxiety screen (aRR 19.50, 95% CI 6.94-54.81, p < 0.001), as well as in those whose recipients experienced graft loss (aRR 5.38, 95% CI 1.29-22.32, p = 0.02). Regret was more likely in LKDs with a positive anxiety screen (aRR 5.68, 95% CI 1.20-26.90, p = 0.03). This was a single center cross-sectional study which may limit generalizability and examination of causal effects. Also, due to the low prevalence of adverse psychosocial outcomes, we may lack power to detect some associations between donor characteristics and anxiety, depression, or regret. CONCLUSIONS:Although there is a low prevalence of anxiety, depression, and regret of donation among LKDs, these are interrelated conditions and a positive screen for one condition should prompt evaluation for other conditions.

BACKGROUND:Dialysis-dependent patients and kidney transplant recipients may be at increased risk for Achilles tendon rupture (ATR). METHODS:We studied Medicare patients with end-stage renal disease (ESRD) from 1999 through 2013. Patients were categorized as waitlisted for a transplant, not waitlisted, or received a transplant. We performed multivariate negative binomial regression using demographic characteristics, comorbidities, and year of study entry to estimate adjusted incidence rate ratios (aIRRs), identify ATR risk factors, and determine treatment patterns and outcomes. RESULTS:We identified 1091 ATRs (incidence, 3.80/10 000 person-years; 95% confidence interval [CI], 3.58-4.03). Compared with transplant recipients, nonwaitlisted patients had a lower incidence (aIRR, 0.44; 95% CI, 0.37-0.53), and waitlisted patients had a similar incidence (aIRR, 0.94; 95% CI, 0.78-1.12) of ATR. ATR incidence was higher among patients taking fluoroquinolones (aIRR, 1.65; 95% CI, 1.32-1.84) and corticosteroids (aIRR, 1.72; 95% CI, 1.44-2.05) compared with those who did not. Patients with ATR were younger, had higher mean body mass index, and had fewer comorbidities than patients without ATR. Seventeen percent of patients received operative treatment within 14 days of ATR diagnosis. The 30-day cumulative incidence of operative site infections was 6.5%. CONCLUSION:The incidence of ATR was higher among transplant recipients and waitlisted patients compared with nonwaitlisted patients. Younger age, higher body mass index, fewer comorbidities, fluoroquinolone use, and corticosteroid use were risk factors for ATR. Patients were more likely to receive nonoperative than operative treatment for ATR. Those who underwent operative treatment had a low incidence of operative site infection. LEVEL OF EVIDENCE:Prognostic level III, comparative study.

The Kidney Allocation System fundamentally altered kidney allocation, causing a substantial increase in regional and national sharing that we hypothesized might impact geographic disparities. We measured geographic disparity in deceased donor kidney transplant (DDKT) rate under KAS (6/1/2015-12/1/2016), and compared that with pre-KAS (6/1/2013-12/3/2014). We modeled DSA-level DDKT rates with multilevel Poisson regression, adjusting for allocation factors under KAS. Using the model we calculated a novel, improved metric of geographic disparity: the median incidence rate ratio (MIRR) of transplant rate, a measure of DSA-level variation that accounts for patient casemix and is robust to outlier values. Under KAS, MIRR was _1.75 1.81_1.86 for adults, meaning that similar candidates across different DSAs have a median 1.81-fold difference in DDKT rate. The impact of geography was greater than the impact of factors emphasized by KAS: having an EPTS score ≤20% was associated with a 1.40-fold increase (IRR = _1.35 1.40_1.45 , P < .01) and a three-year dialysis vintage was associated with a 1.57-fold increase (IRR = _1.56 1.57_1.59 , P < .001) in transplant rate. For pediatric candidates, MIRR was even more pronounced, at _1.66 1.92_2.27 . There was no change in geographic disparities with KAS (P = .3). Despite extensive changes to kidney allocation under KAS, geography remains a primary determinant of access to DDKT.

30% of kidney transplant recipients are readmitted in the first month post-transplant. Those with donor-specific antibody requiring desensitization and incompatible live donor kidney transplantation (ILDKT) constitute a unique subpopulation that might be at higher readmission risk. Drawing on a 22-center cohort, 379 ILDKTs with Medicare primary insurance were matched to compatible transplant matched controls and to waitlist-only matched controls on panel reactive antibody, age, blood group, renal replacement time, prior kidney transplantation, race, gender, diabetes, and transplant date/waitlisting date. Readmission risk was determined using multilevel, mixed-effects Poisson regression. In the first month, ILDKTs had a 1.28-fold higher readmission risk than compatible controls (95%CI: 1.13-1.46; P<0.001). Risk peaked at 6-12 months (RR 1.67; 95%CI: 1.49-1.87; P<0.001), attenuating by 24-36 months (RR 1.24; 95%CI: 1.10-1.40; P<0.001). ILDKTs had a 5.86-fold higher readmission risk (95%CI: 4.96-6.92; P<0.001) in the first month compared to waitlist-only controls. At 12-24 (RR 0.85; 95%CI: 0.77-0.95; P=0.002) and 24-36 months (RR 0.74; 95% CI: 0.66-0.84; P<0.001), ILDKTs had a lower risk than waitlist-only controls. These findings of ILDKTs having a higher readmission risk than compatible controls, but a lower readmission risk after the first year than waitlist-only controls should be considered in regulatory/payment schemas and planning clinical care.

To assess factors that influence the choice of induction regimen in contemporary kidney transplantation, we examined center-identified, national transplant registry data for 166 776 US recipients (2005-2014). Bilevel hierarchical models were constructed, wherein use of each regimen was compared pairwise with use of interleukin-2 receptor blocking antibodies (IL2rAb). Overall, 82% of patients received induction, including thymoglobulin (TMG, 46%), IL2rAb (22%), alemtuzumab (ALEM, 13%), and other agents (1%). However, proportions of patients receiving induction varied widely across centers (0-100%). Recipients of living donor transplants and self-pay patients were less likely to receive induction treatment. Clinical factors associated with use of TMG or ALEM (vs. IL2rAb) included age, black race, sensitization, retransplant status, nonstandard deceased donor, and delayed graft function. However, these characteristics explained only 10-33% of observed variation. Based on intraclass correlation analysis, "center effect" explained most of the variation in TMG (58%), ALEM (66%), other (51%), and no induction (58%) use. Median odds ratios generated from case-factor adjusted models (7.66-11.19) also supported large differences in the likelihood of induction choices between centers. The wide variation in induction therapy choice across US transplant centers is not dominantly explained by differences in patient or donor characteristics; rather, it reflects center choice and practice.

BACKGROUND:Up to 31% of kidney transplant (KT) recipients experience early hospital readmission (EHR). We hypothesized that EHR among older KT recipients is higher than younger recipients due to increased comorbidities and higher prevalence of frailty. METHODS:We identified 22,458 older (age ≥65) and 86,372 younger (18 to < 65) first-time KT recipients (December 1, 1999 - December 31, 2014) using United States Renal Data System data. We estimated the association between patient-level characteristics and EHR (30 days post-KT discharge) with modified Poisson regression among older and younger KT recipients, separately. We estimated the association between graft loss and mortality and EHR using Cox proportional hazards. RESULTS:EHR was more common in older KT recipients (30.1 vs. 27.6%; p < 0.001). Risk factors for EHR that differed by recipient age included female sex, African American race, diabetes, smoking, dialysis vintage, donor age, and length of stay. Risk of graft loss associated with EHR was greater among older KT recipients (adjusted hazard ratio [aHR] 1.64, 95% CI 1.51-1.77, p < 0.001) than younger KT recipients (aHR 1.43, 95% CI 1.38-1.48, p < 0.001; interaction p < 0.01). However, the risk of mortality associated with EHR was greater among younger recipients (aHR 1.52, 95% CI 1.47-1.57, p < 0.001) than that in older -recipients (aHR 1.40, 95% CI 1.34-1.47, p < 0.001; interaction p < 0.01). CONCLUSIONS:Older KT recipients are more likely to experience EHR and are at a higher risk of graft loss after EHR than younger recipients. Targeted interventions to prevent EHR and subsequent graft loss in this population should be identified.