Faculty Bibliography

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.

The Best Practice in Live Kidney Donation Consensus Conference held in June of 2014 included the Best Practices in Living Donor Education Workgroup, whose charge was to identify best practice strategies in education of living donors, community outreach initiatives, commercial media, solicitation, and state registries. The workgroup's goal was to identify critical content to include in living kidney donor education and best methods to deliver educational content. A detailed summary of considerations regarding educational content issues for potential living kidney donors is presented, including the consensus that was reached. Educational topics that may require updating on the basis of emerging studies on living kidney donor health outcomes are also presented. Enhancing the educational process is important for increasing living donor comprehension to optimize informed decision-making.

Kidney transplantation is a viable treatment for select patients with HIV and ESRD, but data are lacking regarding long-term outcomes and comparisons with appropriately matched HIV-negative patients. We analyzed data from the Scientific Registry of Transplant Recipients (SRTR; 2002-2011): 510 adult kidney transplant recipients with HIV (median follow-up, 3.8 years) matched 1:10 to HIV-negative controls. Compared with HIV-negative controls, HIV-infected recipients had significantly lower 5-year (75.3% versus 69.2%) and 10-year (54.4% versus 49.8%) post-transplant graft survival (GS) (hazard ratio [HR], 1.37; 95% confidence interval [95% CI], 1.15 to 1.64; P<0.001) that persisted when censoring for death (HR, 1.43; 95% CI, 1.12 to 1.84; P=0.005). However, compared with HIV-negative/hepatitis C virus (HCV)-negative controls, HIV monoinfected recipients had similar 5-year and 10-year GS, whereas HIV/HCV coinfected recipients had worse GS (5-year: 64.0% versus 52.0%, P=0.02; 10-year: 36.2% versus 27.0%, P=0.004 [HR, 1.38; 95% CI, 1.08 to 1.77; P=0.01]). Patient survival (PS) among HIV-infected recipients was 83.5% at 5 years and 51.6% at 10 years and was significantly lower than PS among HIV-negative controls (HR, 1.34; 95% CI, 1.08 to 1.68; P<0.01). However, PS was similar for HIV monoinfected recipients and HIV-negative/HCV-negative controls at both times. HIV/HCV coinfected recipients had worse PS compared with HIV-negative/HCV-infected controls (5-year: 67.0% versus 78.6%, P=0.007; 10-year: 29.3% versus 56.23%, P=0.002 [HR, 1.57; 95% CI, 1.11 to 2.22; P=0.01]). In conclusion, HIV-negative and HIV monoinfected kidney transplant recipients had similar GS and PS, whereas HIV/HCV coinfected recipients had worse outcomes. Although encouraging, these results suggest caution in transplanting coinfected patients.