Faculty Bibliography

BACKGROUND AND OBJECTIVES/OBJECTIVE:Patients of all ages undergoing hemodialysis (HD) have a high prevalence of cognitive impairment and worse cognitive function than healthy controls, and those with dementia are at high risk of death. Frailty has been associated with poor cognitive function in older adults without kidney disease. We hypothesized that frailty might also be associated with poor cognitive function in adults of all ages undergoing HD. DESIGN, SETTING, PARTICIPANTS, & MEASUREMENTS/METHODS:At HD initiation, 324 adults enrolled (November 2008 to July 2012) in a longitudinal cohort study (Predictors of Arrhythmic and Cardiovascular Risk in ESRD) were classified into three groups (frail, intermediately frail, and nonfrail) based on the Fried frailty phenotype. Global cognitive function (3MS) and speed/attention (Trail Making Tests A and B [TMTA and TMTB, respectively]) were assessed at cohort entry and 1-year follow-up. Associations between frailty and cognitive function (at cohort entry and 1-year follow-up) were evaluated in adjusted (for sex, age, race, body mass index, education, depression and comorbidity at baseline) linear (3MS, TMTA) and Tobit (TMTB) regression models. RESULTS:At cohort entry, the mean age was 54.8 years (SD 13.3), 56.5% were men, and 72.8% were black. The prevalence of frailty and intermediate frailty were 34.0% and 37.7%, respectively. The mean 3MS was 89.8 (SD 7.6), TMTA was 55.4 (SD 29), and TMTB was 161 (SD 83). Frailty was independently associated with lower cognitive function at cohort entry for all three measures (3MS: -2.4 points; 95% confidence interval [95% CI], -4.2 to -0.5; P=0.01; TMTA: 12.1 seconds; 95% CI, 4.7 to 19.4; P<0.001; and TMTB: 33.2 seconds; 95% CI, 9.9 to 56.4; P=0.01; all tests for trend, P<0.001) and with worse 3MS at 1-year follow-up (-2.8 points; 95% CI, -5.4 to -0.2; P=0.03). CONCLUSIONS:In adult incident HD patients, frailty is associated with worse cognitive function, particularly global cognitive function (3MS).

BACKGROUND:In the context of orthotopic liver transplantation (OLT), renal dysfunction is used as a criterion for simultaneous liver-kidney transplantation. Changes in glomerular filtration rate (GFR) the year before and after OLT have not been well defined. METHODS:In a cohort of 416 OLT patients from 1996 to 2009, estimated GFR (eGFR) was assessed during the 12 months before OLT (period A), at time of OLT (period B), and the 12 months after OLT (period C). Outcomes included progression to end stage renal disease (ESRD), length of stay, and mortality. RESULTS:The overall rate of progression to ESRD over 15 years of follow-up was 0.155/person-year and was strongly associated with eGFR <60 (hazard ratio [HR] = 2.7; P < 0.001), diabetes (HR = 2.6; P < 0.001), and with a combination of the 2 (HR = 5.5; P < 0.0001). Mean eGFR decreased from period A (86 mL/min per 1.73 m) to period B (77; P < 0.001) to period C (71; P < 0.001), with similar decreases in eGFR across subgroups of clinical variables. Patients with eGFR less than 60 mL/min per 1.73 m at OLT had acute and large decreases in eGFR from periods A to B, then increases to period C. Length of stay was associated with eGFR at OLT, hepatorenal syndrome, dialysis requirement, model for end-stage liver disease score, and alcoholic liver disease. Twelve-month mortality was strongly associated with time-dependent change in eGFR, hepatorenal syndrome, dialysis requirement, hepatitis C, and model for end-stage liver disease era transplantation but was not associated with eGFR at OLT. CONCLUSIONS:Among OLT patients, renal function worsened in all subgroups from before to after OLT, but the association of progression to ESRD was particularly high among patients with both diabetes and eGFR less than 60 at the time of OLT. This suggests that diabetes could be considered as a criterion when making decisions regarding simultaneous liver-kidney transplantation.

OBJECTIVE:Gout prevalence is high in older adults and those affected are at risk of physical disability, yet it is unclear whether they have worse physical function. METHODS:We studied gout, hyperuricemia, and physical function in 5,819 older adults (age ≥65 years) attending the 2011-2013 Atherosclerosis Risk in Communities Study visit, a prospective US population-based cohort. Differences in lower extremity function (Short Physical Performance Battery [SPPB] and 4-meter walking speed) and upper extremity function (grip strength) by gout status and by hyperuricemia prevalence were estimated in adjusted ordinal logistic regression (SPPB) and linear regression (walking speed and grip strength) models. Lower scores or times signify worse function. The prevalence of poor physical performance (first quartile) by gout and hyperuricemia was estimated using adjusted modified Poisson regression. RESULTS:Ten percent of participants reported a history of gout and 21% had hyperuricemia. There was no difference in grip strength by history of gout (P = 0.77). Participants with gout performed worse on the SPPB test; they had 0.77 times (95% confidence interval [95% CI] 0.65, 0.90, P = 0.001) the prevalence odds of a 1-unit increase in SPPB score and were 1.18 times (95% CI 1.07, 1.32, P = 0.002) more likely to have poor SPPB performance. Participants with a history of gout had slower walking speed (mean difference -0.03; 95% CI -0.05, -0.01, P < 0.001) and were 1.19 times (95% CI 1.06, 1.34, P = 0.003) more likely to have poor walking speed. Similarly, SPPB score and walking speed, but not grip strength, were worse in participants with hyperuricemia. CONCLUSION/CONCLUSIONS:Older adults with gout and hyperuricemia are more likely to have worse lower extremity, but not upper extremity, function.

The emerging epidemic of older patients with cirrhosis has led to a sharp increase in the number of ≥65 year olds considering liver transplantation (LT). However, clinicians lack objective measures to risk stratify older patients. We aimed to determine whether the short physical performance battery (SPPB), a well-validated geriatric measure of physical function, has greater prognostic value in older versus younger LT candidates. Adult outpatients listed for LT with laboratory Model for End-Stage Liver Disease score ≥ 12 underwent physical function testing using the SPPB, consisting of gait speed, chair stands, and balance. Patients were categorized by age ("younger," < 65 years; "older," ≥ 65 years) and SPPB ("impaired," ≤ 9; "robust," > 9). Competing risks models associated age and SPPB with wait-list death/delisting. Of 463 LT candidates, 21% were ≥ 65 years and 18% died or were delisted. Older patients had slower gait (1.1 versus 1.3 m/seconds; P < 0.001), a trend of slower chair stands (12.8 versus 11.8 seconds; P = 0.06), and a smaller proportion able to complete all balance tests (65% versus 78%; P = 0.01); SPPB was lower in older versus younger patients (10 versus 11; P = 0.01). When compared to younger robust patients as a reference group, younger impaired patients (hazard ratio [HR], 1.77; P = 0.03) and older impaired patients (HR, 2.70; P = 0.003) had significantly higher risk of wait-list mortality, but there was no difference in risk for older robust patients (HR 1.38; P = 0.35) [test of equality, P = 0.01]. After adjustment for Model for End-Stage Liver Disease-sodium (MELD-Na) score, only older impaired patients had an increased risk of wait-list mortality compared to younger robust patients (HR, 2.36; P = 0.01; test of equality P = 0.05). In conclusion, functional impairment, as assessed by the SPPB, predicts death/delisting for LT candidates ≥65 years independent of MELD-Na. Further research into activity-based interventions to reduce adverse transplant outcomes in this population is warranted.

Deceased donors are labeled increased risk for disease transmission (IRD) if they meet certain criteria. New PHS guidelines were recently implemented; the impact of these changes remains unknown. We aimed to quantify the impact of the new guidelines on the proportion of deceased donors labeled IRD, as well as demographic and clinical characteristics. We used Poisson regression with an interaction term for era (new vs. old guidelines) to quantify changes. Under the new guidelines, 19.5% donors were labeled IRD, compared to 10.4%, 12.2%, and 12.3% in the 3 most recent years under the old guidelines (IRR = 1.45, p < 0.001). Increases were consistent across OPOs: 44/59 had an increase in the percent of donors labeled IRD, and 14 OPOs labeled 25% of their donors IRD under the new guidelines (vs. 5 OPOs under the old). African-Americans were 52% more likely to be labeled IRD under the new guidelines (RR = 1.52, p = 0.01). There has been a substantial increase in donors labeled IRD under the new PHS guidelines; it is important to understand the mechanism and consequences to ensure an optimal balance of patient safety and organ utilization is achieved.

BACKGROUND:Live donor kidney transplantation (LDKT), an optimal therapy for many patients with end-stage kidney disease, is underutilized, particularly by African Americans. Potential recipient difficulties initiating and sustaining conversations about LDKT, identifying willing and medically eligible donors, and potential donors' logistical and financial hurdles have been cited as potential contributors to race disparities in LDKT. Few interventions specifically targeting these factors have been tested. METHODS/DESIGN/METHODS:We report the protocol of the Talking about Living Kidney Donation Support (TALKS) study, a study designed to evaluate the effectiveness of behavioral, educational and financial assistance interventions to improve access to LDKT among African Americans on the deceased donor kidney transplant recipient waiting list. We adapted a previously tested educational and social worker intervention shown to improve consideration and pursuit of LDKT among patients and their family members for its use among patients on the kidney transplant waiting list. We also developed a financial assistance intervention to help potential donors overcome logistical and financial challenges they might face during the pursuit of live kidney donation. We will evaluate the effectiveness of these interventions by conducting a randomized controlled trial in which patients on the deceased donor waiting list receive 1) usual care while on the transplant waiting list, 2) the educational and social worker intervention, or 3) the educational and social worker intervention plus the option of participating in the financial assistance program. The primary outcome of the randomized controlled trial will measure potential recipients' live kidney donor activation (a composite rate of live donor inquiries, completed new live donor evaluations, or live kidney donation) at 1 year. DISCUSSION/CONCLUSIONS:The TALKS study will rigorously assess the effectiveness of promising interventions to reduce race disparities in LDKT. TRIAL REGISTRATION/BACKGROUND:NCT02369354.

Prescription narcotic use among living kidney donors is not well described. Using a unique database that integrates national registry identifiers for living kidney donors (1987-2007) in the United States with billing claims from a private health insurer (2000-2007), we identified pharmacy fills for prescription narcotic medications in periods 1-4 and >4 yr post-donation and estimated relative likelihoods of post-donation narcotic use by Cox regression. We also compared narcotic fill rates and medication possession ratios (MPRs, defined as (days of medication supplied)/(days observed)), between donors and age- and sex-matched non-donors. Overall, rates of narcotic medication fills were 32.3 and 32.4 per 100 person-years in periods 1-4 and >4 yr post-donation. After age and race adjustment, women were approximately twice as likely as men to fill a narcotic prescription in years 1-4 (adjusted hazard ratio, aHR, 2.28; 95% confidence interval, CI, 1.86-2.79) and >4 yr (aHR 1.70; 95% CI 1.50-1.93). MPRs in donors were low (<2.5% days exposed), and lower than among age- and sex-matched non-donors. Prescription narcotic medication use is more common among women than men in the intermediate term after live kidney donation. Overall, total narcotic exposure is low, and lower than among non-donors from the general population.

OBJECTIVES/OBJECTIVE:To understand the natural history of frailty after an aggressive surgical intervention, kidney transplantation (KT). DESIGN/METHODS:Prospective cohort study (December 2008-March 2014). SETTING/METHODS:Baltimore, Maryland. PARTICIPANTS/METHODS:Kidney transplantation recipients (N = 349). MEASUREMENTS/METHODS:The Fried frailty score was measured at the time of KT and during routine clinical follow-up. Using a Cox proportional hazards model, factors associated with improvements in frailty score after KT were identified. Using a longitudinal analysis, predictors of frailty score changes after KT were identified using a multilevel mixed-effects Poisson model. RESULTS:At KT, 19.8% of recipients were frail; 1 month after KT, 33.3% were frail; at 2 months, 27.7% were frail; and at 3 months, 17.2% were frail. On average, frailty scores had worsened by 1 month (mean change 0.4, P < .001), returned to baseline by 2 months (mean change 0.2, P = .07), and improved by 3 months (mean change -0.3, P = .04) after KT. The only recipient or transplant factor associated with improvement in frailty score after KT was pre-KT frailty (hazard ratio = 2.55, 95% confidence interval (CI) = 1.71-3.82, P < .001). Pre-KT frailty status (relative risk (RR) = 1.49, 95% CI = 1.29-1.72, P < .001), recipient diabetes mellitus (RR = 1.26, 95% CI = 1.08-1.46, P = .003), and delayed graft function (RR = 1.22, 95% CI = 1.04-1.43, P = .02) were independently associated with long-term changes in frailty score. CONCLUSION/CONCLUSIONS:After KT, in adult recipients of all ages, frailty initially worsens but then improves by 3 months. Although KT recipients who were frail at KT had higher frailty scores over the long term, they were most likely to show improvements in their physiological reserve after KT, supporting the transplantation in these individuals and suggesting that pretransplant frailty is not an irreversible state of low physiological reserve.