Decreased incidence of acute rejection without increased incidence of cytomegalovirus (CMV) infection in kidney transplant recipients receiving rabbit anti-thymocyte globulin without CMV prophylaxis - a cohort single-center study.

Induction therapy with rabbit anti-thymocyte globulin (rATG) in low-risk kidney transplant recipients (KTR) remains controversial, given the associated increased risk of cytomegalovirus (CMV) infection. This natural experiment compared 12-month clinical outcomes in low-risk KTR without CMV prophylaxis (January/3/13-September/16/15) receiving no induction or a single 3 mg/kg dose of rATG. We used logistic regression to characterize delayed graft function (DGF), negative binomial to characterize length of hospital stay (LOS), and Cox regression to characterize acute rejection (AR), CMV infection, graft loss, death, and hospital readmissions. Recipients receiving 3 mg/kg rATG had an 81% lower risk of AR (aHR 0.14 0.190.25 , P < 0.001) but no increased rate of hospital readmissions because of infections (0.68 0.911.21 , P = 0.5). There was no association between 3 mg/kg rATG and CMV infection/disease (aHR 0.86 1.101.40 , P = 0.5), even when the analysis was stratified according to recipient CMV serostatus positive (aHR 0.94 1.251.65 , P = 0.1) and negative (aHR 0.28 0.571.16 , P = 0.1). There was no association between 3 mg/kg rATG and mortality (aHR 0.51 1.253.08 , P = 0.6), and graft loss (aHR 0.34 0.731.55 , P = 0.4). Among low-risk KTR receiving no CMV pharmacological prophylaxis, 3 mg/kg rATG induction was associated with a significant reduction in the incidence of AR without an increased risk of CMV infection, regardless of recipient pretransplant CMV serostatus.

Prevalence of frailty among kidney transplant candidates and recipients in the United States: Estimates from a National Registry and Multicenter Cohort Study.

Frailty, a measure of physiologic reserve, is associated with poor outcomes and mortality among kidney transplant (KT) candidates and recipients. There are no national estimates of frailty in this population, which may help patient counseling and resource allocation at transplant centers. We studied 4616 KT candidates and 1763 recipients in our multicenter prospective cohort of frailty from 2008-2018 with Fried frailty measurements. Using Scientific Registry of Transplant Recipients (SRTR) data (KT candidates = 560 143 and recipients = 243 508), we projected the national prevalence of frailty (for KT candidates and recipients separately) using standardization through inverse probability weighting, accounting for candidate/recipient, donor, and transplant factors. In our multicenter cohort, 13.3% of KT candidates were frail at evaluation; 8.2% of LDKT recipients and 17.8% of DDKT recipients were frail at transplantation. Projected nationally, our modeling strategy estimated 91 738 KT candidates or 16.4% (95% confidence interval [CI] 14.4%-18.4%) of all KT candidates during the study period were frail, and that 34 822 KT recipients or 14.3% (95% CI 12.3%-16.3%) of all KT recipients were frail (LDKT = 8.2%; DDKT = 17.8%). Given the estimated national prevalence of frailty, transplant programs should consider assessing the condition during KT evaluation to improve patient counseling and resource allocation along with identification of recipients at risk for poor outcomes.

Kidney transplant outcomes in recipients with visual, hearing, physical and walking impairments: a prospective cohort study.

BACKGROUND: Disability in general has been associated with poor outcomes in kidney transplant (KT) recipients. However, disability can be derived from various components, specifically visual, hearing, physical and walking impairments. Different impairments may compromise the patient through different mechanisms and might impact different aspects of KT outcomes. METHODS: In our prospective cohort study (June 2013-June 2017), 465 recipients reported hearing, visual, physical and walking impairments before KT. We used hybrid registry-augmented Cox regression, adjusting for confounders using the US KT population (Scientific Registry of Transplant Recipients, N = 66 891), to assess the independent association between impairments and post-KT outcomes [death-censored graft failure (DCGF) and mortality]. RESULTS: In our cohort of 465 recipients, 31.6% reported one or more impairments (hearing 9.3%, visual 16.6%, physical 9.1%, walking 12.1%). Visual impairment was associated with a 3.36-fold [95% confidence interval (CI) 1.17-9.65] higher DCGF risk, however, hearing [2.77 (95% CI 0.78-9.82)], physical [0.67 (95% CI 0.08-3.35)] and walking [0.50 (95% CI 0.06-3.89)] impairments were not. Walking impairment was associated with a 3.13-fold (95% CI 1.32-7.48) higher mortality risk, however, visual [1.20 (95% CI 0.48-2.98)], hearing [1.01 (95% CI 0.29-3.47)] and physical [1.16 (95% CI 0.34-3.94)] impairments were not. CONCLUSIONS: Impairments are common among KT recipients, yet only visual impairment and walking impairment are associated with adverse post-KT outcomes. Referring nephrologists and KT centers should identify recipients with visual and walking impairments who might benefit from targeted interventions pre-KT, additional supportive care and close post-KT monitoring.

Frailty and Changes in Cognitive Function after Kidney Transplantation.

BACKGROUND: Restoration of kidney function after kidney transplant generally improves cognitive function. It is unclear whether frail recipients, with higher susceptibility to surgical stressors, achieve such post-transplant cognitive improvements or whether they experience subsequent cognitive decline as they age with a functioning graft. METHODS: In this two-center cohort study, we assessed pretransplant frailty (Fried physical frailty phenotype) and cognitive function (Modified Mini-Mental State Examination) in adult kidney transplant recipients. To investigate potential short- and medium-term effects of frailty on post-transplant cognitive trajectories, we measured cognitive function up to 4 years post-transplant. Using an adjusted mixed effects model with a random slope (time) and intercept (person), we characterized post-transplant cognitive trajectories by pretransplant frailty, accounting for nonlinear trajectories. RESULTS: Of 665 recipients (mean age 52.0 years) followed for a median of 1.5 years, 15.0% were frail. After adjustment, pretransplant cognitive scores were significantly lower among frail patients compared with nonfrail patients (89.0 versus 90.8 points). By 3 months post-transplant, cognitive performance improved for both frail (slope =0.22 points per week) and nonfrail (slope =0.14 points per week) recipients. Between 1 and 4 years post-transplant, improvements plateaued among nonfrail recipients (slope =0.005 points per week), whereas cognitive function declined among frail recipients (slope =-0.04 points per week). At 4 years post-transplant, cognitive scores were 5.8 points lower for frail recipients compared with nonfrail recipients. CONCLUSIONS: On average, both frail and nonfrail recipients experience short-term cognitive improvement post-transplant. However, frailty is associated with medium-term cognitive decline post-transplant. Interventions to prevent cognitive decline among frail recipients should be identified.

Center-level trends in utilization of HCV-exposed donors for HCV-uninfected kidney and liver transplant recipients in the United States.

Several single-center reports of using HCV-viremic organs for HCV-uninfected (HCV-) recipients were recently published. We sought to characterize national utilization of HCV-exposed donors for HCV- recipients (HCV D+/R-) in kidney transplantation (KT) and liver transplantation (LT). Using SRTR data (April 1, 2015-December 2, 2018) and Gini coefficients, we studied center-level clustering of 1193 HCV D+/R- KTs and LTs. HCV-viremic (NAT+) D+/R- KTs increased from 1/month in 2015 to 22/month in 2018 (LTs: 0/month to 12/month). HCV-aviremic (Ab+/NAT-) D+/R- KTs increased from < 1/month in 2015 to 26/month in 2018 (LTs: <1/month to 8/month). HCV- recipients of viremic and aviremic kidneys spent a median (interquartile range [IQR]) of 0.7 (0.2-1.6) and 1.6 (0.4-3.5) years on the waitlist versus 1.8 (0.5-4.0) among HCV D-/R-. HCV- recipients of viremic and aviremic livers had median (IQR) MELD scores of 24 (21-30) and 25 (21-32) at transplantation versus 29 (23-36) among HCV D-/R-. 12 KT and 14 LT centers performed 81% and 76% of all viremic HCV D+/R- transplants; 11 KT and 13 LT centers performed 76% and 69% of all aviremic HCV D+/R- transplants. There have been marked increases in HCV D+/R- transplantation, although few centers are driving this practice; centers should continue to weigh the risks and benefits of HCV D+/R- transplantation.

The landscape of international living kidney donation in the United States.

In the United States, kidney donation from international (noncitizen/nonresident) living kidney donors (LKDs) is permitted; however, given the heterogeneity of healthcare systems, concerns remain regarding the international LKD practice and recipient outcomes. We studied a US cohort of 102 315 LKD transplants from 2000-2016, including 2088 international LKDs, as reported to the Organ Procurement and Transplantation Network. International LKDs were more tightly clustered among a small number of centers than domestic LKDs (Gini coefficient 0.76 vs 0.58, P < .001). Compared with domestic LKDs, international LKDs were more often young, male, Hispanic or Asian, and biologically related to their recipient (P < .001). Policy-compliant donor follow-up was substantially lower for international LKDs at 6, 12, and 24 months postnephrectomy (2015 cohort: 45%, 33%, 36% vs 76%, 71%, 70% for domestic LKDs, P < .001). Among international LKDs, Hispanic (aOR = 0.23 0.360.56 , P < .001) and biologically related (aOR = 0.39 0.590.89 , P < .01) donors were more compliant in donor follow-up than white and unrelated donors. Recipients of international living donor kidney transplant (LDKT) had similar graft failure (aHR = 0.78 0.891.02 , P = .1) but lower mortality (aHR = 0.53 0.620.72 , P < .001) compared with the recipients of domestic LDKT after adjusting for recipient, transplant, and donor factors. International LKDs may provide an alternative opportunity for living donation. However, efforts to improve international LKD follow-up and engagement are warranted.

Racial differences in inflammation and outcomes of aging among kidney transplant candidates.

BACKGROUND: Inflammation is more common among African Americans (AAs), and it is associated with frailty, poor physical performance, and mortality in community-dwelling older adults. Given the elevated inflammation levels among end-stage renal disease (ESRD) patients, inflammation may be associated with adverse health outcomes such as frailty, physical impairment, and poor health-related quality of life (HRQOL), and these associations may differ between AA and non-AA ESRD patients. METHODS: One thousand three ESRD participants were recruited at kidney transplant evaluation (4/2014-5/2017), and inflammatory markers (interleukin-6 [IL-6], tumor necrosis factor-a receptor-1 [TNFR1], C-reactive protein [CRP]) were measured. We quantified the association with frailty (Fried phenotype), physical impairment (Short Physical Performance Battery [SPPB]), and fair/poor HRQOL at evaluation using adjusted modified Poisson regression and tested whether these associations differed by race (AA vs. non-AA). RESULTS: Non-AAs had lower levels of TNFR1 (9.7 ng/ml vs 14.0 ng/ml, p < 0.001) and inflammatory index (6.7 vs 6.8, p < 0.001) compared to AAs, but similar levels of IL-6 (4.5 pg/ml vs 4.3 pg/ml, p > 0.9) and CRP (4.7 µg/ml vs 4.9 µg/ml, p = 0.4). Non-AAs had an increased risk of frailty with elevated IL-6 (RR = 1.58, 95% CI:1.27-1.96, p < 0.001), TNFR1 (RR = 1.60, 95% CI:1.25-2.05, p < 0.001), CRP (RR = 1.41, 95% CI:1.10-1.82, p < 0.01), and inflammatory index (RR = 1.82, 95% CI:1.44-2.31, p < 0.001). The associations between elevated inflammatory markers and frailty were not present among AAs. Similar results were seen with SPPB impairment and poor/fair HRQOL. CONCLUSIONS: Non-AAs with elevated inflammatory markers may need closer follow-up and may benefit from prehabilitation to improve physical function, reduce frailty burden, and improve quality of life prior to transplant.

The future of HIV Organ Policy Equity Act is now: the state of HIV+ to HIV+ kidney transplantation in the United States.

PURPOSE OF REVIEW: We report the current state of HIV+ to HIV+ kidney transplantation in the United States and remaining challenges in implementing this practice nationally. RECENT FINDINGS: The HIV Organ Policy Equity (HOPE) Act, which was the first step in unlocking the potential of HIV+ organ donors, mandates clinical research on HIV+ to HIV+ transplantation. As of March 2019, there have been 57 HOPE donors, including both true and false positive HOPE donors resulting in more than 120 transplants. SUMMARY: The HOPE Act, signed in 2013, reversed the federal ban on the transplantation of organs from HIV+ donors into HIV+ recipients. Ongoing national studies are exploring the safety, feasibility, and efficacy of both kidney and liver transplantation in this population. If successfully and fully implemented, HIV+ to HIV+ transplantation could attenuate the organ shortage for everyone waiting, resulting in a far-reaching public health impact.

The first 9 years of kidney paired donation through the National Kidney Registry: Characteristics of donors and recipients compared with National Live Donor Transplant Registries.

The practice of kidney paired donation (KPD) is expanding annually, offering the opportunity for live donor kidney transplant to more patients. We sought to identify if voluntary KPD networks such as the National Kidney Registry (NKR) were selecting or attracting a narrower group of donors or recipients compared with national registries. For this purpose, we merged data from the NKR database with the Scientific Registry of Transplant Recipients (SRTR) database, from February 14, 2008, to February 14, 2017, encompassing the first 9 years of the NKR. Compared with all United Network for Organ Sharing (UNOS) live donor transplant patients (49 610), all UNOS living unrelated transplant patients (23 319), and all other KPD transplant patients (4236), the demographic and clinical characteristics of NKR transplant patients (2037) appear similar to contemporary national trends. In particular, among the NKR patients, there were a significantly (P < .001) greater number of retransplants (25.6% vs 11.5%), hyperimmunized recipients (22.7% vs 4.3% were cPRA >80%), female recipients (45.9% vs 37.6%), black recipients (18.2% vs 13%), and those on public insurance (49.7% vs 41.8%) compared with controls. These results support the need for greater sharing and larger pool sizes, perhaps enhanced by the entry of compatible pairs and even chains initiated by deceased donors, to unlock more opportunities for those harder-to-match pairs.

Knowledge, attitudes, and planned practice of HIV-positive to HIV-positive transplantation in US transplant centers.

BACKGROUND: HIV+ donor organs can now be transplanted into HIV+ recipients (HIV D+/R+) following the HIV Organ Policy Equity (HOPE) Act. Implementation of the HOPE Act requires transplant center awareness and support of HIV D+/R+ transplants. METHODS: To assess center-level barriers to implementation, we surveyed 209 transplant centers on knowledge, attitudes, and planned HIV D+/R+ protocols. RESULTS: Responding centers (n = 114; 56%) represented all UNOS regions. Fifty centers (93 organ programs) planned HIV D+/R+ protocols (kidney n = 48, liver n = 34, pancreas n = 8, heart n = 2, lung = 1), primarily in the eastern United States (28/50). Most (91.2%) were aware that HIV D+/R+ transplantation is legal; 21.4% were unaware of research restrictions. Respondents generally agreed with HOPE research criteria except the required experience with ≥5 HIV+ transplants by organ type. Centers planning HIV D+/R+ protocols had higher transplant volume, HIV+ recipient volume, increased infectious risk donor utilization, and local HIV prevalence (P < 0.01). Centers not planning HIV D+/R+ protocols were more likely to believe their HIV+ candidates would not accept HIV+ donor organs (P < 0.001). Most centers (83.2%) supported HIV+ living donation. CONCLUSIONS: Although many programs plan HIV D+/R+ transplantation, center-level barriers remain including geographic clustering of kidney/liver programs and concerns about HIV+ candidate willingness to accept HIV+ donor organs.

HIV+ deceased donor referrals: A national survey of organ procurement organizations.

BACKGROUND: HIV-infected (HIV+) donor organs can be transplanted into HIV+ recipients under the HIV Organ Policy Equity (HOPE) Act. Quantifying HIV+ donor referrals received by organ procurement organizations (OPOs) is critical for HOPE Act implementation. METHODS: We surveyed the 58 USA OPOs regarding HIV+ referral records and newly discovered HIV+ donors. Using data from OPOs that provided exact records and CDC HIV prevalence data, we projected a national estimate of HIV+ referrals. RESULTS: Fifty-five (95%) OPOs reported HIV+ referrals ranging from 0 to 276 and newly discovered HIV+ cases ranging from 0 to 10 annually. Six OPOs in areas of high HIV prevalence reported more than 100 HIV+ donor referrals. Twenty-seven (47%) OPOs provided exact HIV+ referral records and 28 (51%) OPOs provided exact records of discovered HIV+ cases, totaling 1450 HIV+ referrals and 39 discovered HIV+ donors in the prior year. These OPOs represented 67% and 59% of prevalent HIV cases in the USA; thus, we estimated 2164 HIV+ referrals and 66 discovered HIV+ cases nationally per year. CONCLUSIONS: OPOs reported a high volume of HIV+ referrals annually, of which a subset will be medically eligible for donation. Particularly in areas of high HIV prevalence, OPOs require ongoing support to implement the HOPE Act.

Changes in practice and perception of hepatitis C and liver transplantation: Results of a national survey.

With new practice guidelines, it is important to understand how liver transplant (LT) centers have incorporated direct-acting antivirals (DAAs) into the management of hepatitis C virus-infected (HCV+) candidates and recipients. To explore how DAAs have affected LT centers' willingness to treat HCV+ candidates and recipients and to use HCV+ donors, we surveyed high volume US LT centers (11/2014-12/2015) regarding practices for HCV+ candidates, recipients, and donors, before vs after DAAs. We used the Scientific Registry of Transplant Recipients to compare centers' number of LTs, HCV+ recipients, and HCV+ donors in the years before (1/1/2012-12/31/2013) and after (1/1/2016-12/31/2017) survey administration. Of 80 centers contacted, 57 (71.3%) responded, representing 69.0% of the total volume of LTs in 2013. After DAAs, most centers increased treating candidates with low (≤15) model for end-stage liver disease (MELD) (85.2%), intermediate/high (>15) MELD (92.6%), and hepatocellular carcinoma (79.6%). There was consensus to treat low MELD candidates (90.8% "most of the time/always"), but less certainty for intermediate/high MELD candidates (48.2% "sometimes"). Universal post-LT HCV treatment increased (7.4% vs 57.4%). After DAAs, 42.6% were more willing to use HCV+ donors for HCV+ candidates, and 38.9% were willing to consider using HCV+ donors for HCV- candidates. Overall, with DAAs, centers were more willing to treat HCV+ candidates and recipients and to use HCV+ donors; recent recommendations may help to guide treatment decisions for intermediate/high MELD candidates.

Frailty, Length of Stay, and Mortality in Kidney Transplant Recipients: A National Registry and Prospective Cohort Study.

OBJECTIVE: To test whether frailty, a novel measure of physiologic reserve, is associated with longer kidney transplant (KT) length of stay (LOS), and modifies the association between LOS and mortality. BACKGROUND: Better understanding of LOS is necessary for informed consent and discharge planning. Mortality resulting from longer LOS has important regulatory implications for hospital and transplant programs. Which recipients are at risk of prolonged LOS and its effect on mortality are unclear. Frailty is a novel preoperative predictor of poor KT outcomes including delayed graft function, early hospital readmission, immunosuppression intolerance, and mortality. METHODS: We used registry-augmented hybrid methods, a novel approach to risk adjustment, to adjust for LOS risk factors from the Scientific Registry of Transplant Recipients (n = 74,859) and tested whether (1) frailty, measured immediately before KT in a novel cohort (n = 589), was associated with LOS (LOS: negative binomial regression; LOS ≥2 weeks: logistic regression) and (2) whether frailty modified the association between LOS and mortality (interaction term analysis). RESULTS: Frailty was independently associated with longer LOS [relative risk = 1.15, 95% confidence interval (CI): 1.03-1.29; P = 0.01] and LOS ≥2 weeks (odds ratio = 1.57, 95% CI: 1.06-2.33; P = 0.03) after accounting for registry-based risk factors, including delayed graft function. Frailty also attenuated the association between LOS and mortality (nonfrail hazard rate = 1.55 95% CI: 1.30-1.86; P < 0.001; frail hazard rate = 0.97, 95% CI: 0.79-1.19, P = 0.80; P for interaction = 0.001). CONCLUSIONS: Frail KT recipients are more likely to experience a longer LOS. Longer LOS among nonfrail recipients may be a marker of increased mortality risk. Frailty is a measure of physiologic reserve that may be an important clinical marker of longer surgical LOS.

Persistently elevated abnormal B-cell subpopulations and anti-core antibodies in patients co-infected with HIV/HCV who relapse.

Hepatitis C (HCV) treatment for patients coinfected with human immunodeficiency virus (HIV) and HCV is associated with modest rates of sustained virologic response (SVR) and an increased rate of relapse when compared to HCV monoinfected patients. As patients who attain SVR and patients who relapse are clinically indistinguishable during treatment, where both groups have fully suppressed HCV viral load, it has not been possible to identify in advance those who will relapse. Biomarkers that may distinguish patients with differential treatment response may be clinically useful and provide insight into mechanisms of relapse. In this retrospective study, serum and PBMCs were obtained from 41 HIV/HCV co-infected patients and 17 healthy volunteers. Changes in antibody titers to various regions of the HCV proteome during treatment for HCV were determined using a novel luciferase immunoprecipitation assay. Changes in B-cell subtypes in patients with differential treatment response as well as healthy volunteers were compared. This study demonstrates that elevated anti-HCV core antibody titers persisted during HCV treatment in patients who relapsed when compared to those who attained SVR. Furthermore, characterization of B cells in patients who relapsed demonstrated an abnormal B-cell phenotype distribution characterized by elevated frequencies of exhausted B cells among relapsers at baseline, which persisted despite suppression of HCV viremia at 24 weeks, along with increased frequencies of plasmablasts. These data suggest that anti-HCV specific B cells may be responding to ongoing subclinical HCV replication in patients who will relapse.

Treatment of hepatitis C: a systematic review.

IMPORTANCE: Hepatitis C virus (HCV) infects more than 185 million individuals worldwide. Twenty percent of patients chronically infected with HCV progress to cirrhosis. New, simpler therapeutics using direct-acting antivirals that target various stages of the HCV life cycle are in development to eradicate HCV without concomitant interferon. OBJECTIVES: To summarize published evidence on safety, efficacy (measured by a sustained virologic response [SVR], which is the treatment goal of undetectable plasma HCV RNA 12 or 24 weeks after therapy completion), and tolerability of current US Food and Drug Administration-approved interferon-based regimens and oral interferon-free regimens used for treating HCV infection and coinfection with human immunodeficiency virus (HIV) and HCV; to provide treatment recommendations for specialists and generalists based on published evidence. EVIDENCE REVIEW: A literature search of Web of Science, Scopus, Embase, Agricola, Cochrane Library, Cinahl Plus, ClinicalTrials.gov, Conference Papers Index, Gideon, PsycINFO, Google Scholar, and Oaister was conducted from January 1, 2009, to May 30, 2014. Publications describing phase 2, 3, and 4 studies evaluating the treatment of HCV were included. Forty-one studies involving 19,063 adult patients were included. Strength of clinical data and subsequent HCV treatment recommendations were graded according to the Oxford Centre for Evidence-Based Medicine. FINDINGS: Patients infected with HCV genotype 1 represent 60% to 75% of HCV infections in the United States. Hepatitis C virus genotype 1 is more difficult to cure than genotype 2 or genotype 3. Patients with HCV genotype 1 should receive treatment with sofosbuvir + pegylated interferon + ribavirin because of the shorter duration of therapy and high rates of SVR (89%-90%). Simeprevir + pegylated interferon + ribavirin is an alternative for patients with HCV genotype 1 (SVR, 79%-86%). Patients with HCV genotypes 2 and 3, representing 20% to 29% of US HCV infections, should receive therapy with sofosbuvir + ribavirin alone (SVR for genotype 2, 12 weeks' duration: 82%-93%; SVR for genotype 3, 24 weeks' duration, 80%-95%). Patients with HIV-HCV coinfection and patients with compensated cirrhosis (ie, cirrhosis but preserved synthetic liver function) should receive the same treatment as HCV-monoinfected patients. CONCLUSIONS AND RELEVANCE: New, short-duration, simpler therapies result in high SVR rates for HCV-infected patients. In conjunction with increased screening for HCV as suggested by recent Centers for Disease Control and Prevention guidelines, availability of new therapies may lead to the treatment of many more people with chronic HCV infection.

Association of Socioeconomic Status and Comorbidities with Racial Disparities during Kidney Transplant Evaluation.

BACKGROUND AND OBJECTIVES: Black patients referred for kidney transplantation have surpassed many obstacles but likely face continued racial disparities before transplant. The mechanisms that underlie these disparities are unclear. We determined the contributions of socioeconomic status (SES) and comorbidities as mediators to disparities in listing and transplant. DESIGN, SETTING, PARTICIPANTS, & MEASUREMENTS: We studied a cohort (n=1452 black; n=1561 white) of patients with kidney failure who were referred for and started the transplant process (2009-2018). We estimated the direct and indirect effects of SES (self-reported income, education, and employment) and medical comorbidities (self-reported and chart-abstracted) as mediators of racial disparities in listing using Cox proportional hazards analysis with inverse odds ratio weighting. Among the 983 black and 1085 white candidates actively listed, we estimated the direct and indirect effects of SES and comorbidities as mediators of racial disparities on receipt of transplant using Poisson regression with inverse odds ratio weighting. RESULTS: Within the first year, 876 (60%) black and 1028 (66%) white patients were waitlisted. The relative risk of listing for black compared with white patients was 0.76 (95% confidence interval [95% CI], 0.69 to 0.83); after adjustment for SES and comorbidity, the relative risk was 0.90 (95% CI, 0.83 to 0.97). The proportion of the racial disparity in listing was explained by SES by 36% (95% CI, 26% to 57%), comorbidity by 44% (95% CI, 35% to 61%), and SES with comorbidity by 58% (95% CI, 44% to 85%). There were 409 (42%) black and 496 (45%) white listed candidates transplanted, with a median duration of follow-up of 3.9 (interquartile range, 1.2-7.1) and 2.8 (interquartile range, 0.8-6.3) years, respectively. The incidence rate ratio for black versus white candidates was 0.87 (95% CI, 0.79 to 0.96); SES and comorbidity did not explain the racial disparity. CONCLUSIONS: SES and comorbidity partially mediated racial disparities in listing but not for transplant.

Patient and Kidney Allograft Survival with National Kidney Paired Donation.

BACKGROUND AND OBJECTIVES: In the United States, kidney paired donation networks have facilitated an increasing proportion of kidney transplants annually, but transplant outcome differences beyond 5 years between paired donation and other living donor kidney transplant recipients have not been well described. DESIGN, SETTING, PARTICIPANTS, & MEASUREMENTS: Using registry-linked data, we compared National Kidney Registry (n=2363) recipients to control kidney transplant recipients (n=54,497) (February 2008 to December 2017). We estimated the risk of death-censored graft failure and mortality using inverse probability of treatment weighted Cox regression. The parsimonious model adjusted for recipient factors (age, sex, black, race, body mass index ≥30 kg/m2, diabetes, previous transplant, preemptive transplant, public insurance, hepatitis C, eGFR, antibody depleting induction therapy, year of transplant), donor factors (age, sex, Hispanic ethnicity, body mass index ≥30 kg/m2), and transplant factors (zero HLA mismatch). RESULTS: National Kidney Registry recipients were more likely to be women, black, older, on public insurance, have panel reactive antibodies >80%, spend longer on dialysis, and be previous transplant recipients. National Kidney Registry recipients were followed for a median 3.7 years (interquartile range, 2.1-5.6; maximum 10.9 years). National Kidney Registry recipients had similar graft failure (5% versus 6%; log-rank P=0.2) and mortality (9% versus 10%; log-rank P=0.4) incidence compared with controls during follow-up. After adjustment for donor, recipient, and transplant factors, there no detectable difference in graft failure (adjusted hazard ratio, 0.95; 95% confidence interval, 0.77 to 1.18; P=0.6) or mortality (adjusted hazard ratio, 0.86; 95% confidence interval, 0.70 to 1.07; P=0.2) between National Kidney Registry and control recipients. CONCLUSIONS: Even after transplanting patients with greater risk factors for worse post-transplant outcomes, nationalized paired donation results in equivalent outcomes when compared with control living donor kidney transplant recipients.

The Influence of Antithymocyte Globulin Dose on the Incidence of CMV Infection in High-risk Kidney Transplant Recipients Without Pharmacological Prophylaxis.

BACKGROUND: Optimizing antithymocyte globulin (ATG) dosage is critical, particularly for high-risk kidney transplant (KT) recipients without cytomegalovirus (CMV) prophylaxis. METHODS: We studied 630 KT recipients with expanded criteria donors or panel reactive antibody ≥50% at Hospital do Rim, Brazil (January 1, 2013 to May 21, 2015) to determine whether a single ATG dose was safe and effective in patients without CMV prophylaxis. Patients received ≥4 doses (1-1.5 mg/kg/per dose) until June 17, 2014, when the induction protocol changed to a single ATG dose (3 mg/kg). We used Cox regression to compare the risk of CMV infection and acute rejection (AR) among KT recipients by ATG dose. RESULTS: Adjusting for clinical and transplant factors, a single ATG dose was associated with a lower risk of CMV infection (adjusted hazard ratio [aHR]: 0.63; 95% confidence interval [CI], 0.42-0.93; P = 0.02) and a similar risk of AR (aHR: 1.16; 95% CI, 0.47-2.83; P = 0.8), compared to multiple doses. We found no differences in death-censored graft loss (5.0% versus 4.8%, aHR: 1.06; 95% CI, 0.51-2.23; P = 0.9) or mortality (4.7% versus 3.4%; aHR: 1.42; 95% CI, 0.62-3.24; P = 0.4) at 1-year post-KT by ATG dose. CONCLUSIONS: In our study of high-risk KT recipients without CMV prophylaxis, a single ATG dose decreased the risk of CMV infection without increasing the risk of AR or compromising graft or patient survival.

Kidney Transplant Outcomes in Recipients With Cognitive Impairment: A National Registry and Prospective Cohort Study.

BACKGROUND: Cognitive impairment is common in patients with end-stage renal disease and is associated with poor outcomes on dialysis. We hypothesized that cognitive impairment might be associated with an increased risk of all-cause graft loss (ACGL) in kidney transplant (KT) recipients. METHODS: Using the Modified Mini-Mental State (3MS) examination, we measured global cognitive function at KT hospital admission in a prospective, 2-center cohort of 864 KT candidates (August 2009 to July 2016). We estimated the association between pre-KT cognitive impairment and ACGL using Cox regression, adjusting for recipient, donor, and transplant factors. RESULTS: In living donor KT (LDKT) recipients, the prevalence was 3.3% for mild impairment (60 ≤ 3MS < 80) and 3.3% for severe impairment (3MS < 60). In deceased donor KT (DDKT) recipients, the prevalence was 9.8% for mild impairment and 2.6% for severe impairment. The LDKT recipients with cognitive impairment had substantially higher ACGL risk than unimpaired recipients (5-year ACGL: 45.5% vs 10.6%; P < 0.01; adjusted hazard ratio [aHR] any impairment, 5.40 (95% confidence interval [CI], 1.78-16.34; P < 0.01); aHR severe impairment, 5.57 (95% CI, 1.29-24.00; P = 0.02). Similarly, DDKT recipients with severe impairment had higher ACGL risk than recipients without severe impairment (5-year ACGL, 53.0% vs 24.2%; P = 0.04); aHR severe impairment, 2.92 (95% CI, 1.13-7.50; P = 0.03). CONCLUSIONS: Given the elevated risk of ACGL among KT recipients with cognitive impairment observed in this 2-center cohort, research efforts should explore the mechanisms of graft loss and mortality associated with cognitive impairment and identify potential interventions to improve posttransplant survival.