Association between dd-cfDNA levels, de novo donor specific antibodies, and eGFR decline: An analysis of the DART cohort.

BACKGROUND: Donor-derived cell-free DNA (dd-cfDNA) is a marker of allograft injury in transplant recipients; however, the relationship between dd-cfDNA and other clinical parameters associated with adverse allograft outcomes is not well-characterized. METHODS: We performed a retrospective analysis of kidney transplant recipients from the DART cohort (ClinicalTrials.gov Identifier: NCT02424227) to evaluate the associations between eGFR decline, de novo donor-specific antibodies (dnDSA), and dd-cfDNA. RESULTS: Both elevated dd-cfDNA (≥1%) and dd-cfDNA variability (≥.34%) in the first post-transplant year were associated with decline in eGFR ≥25% in the second year (21.4% vs. 4.1%, P = .005; 25% vs. 3.6%, P = .002, respectively). Compared to samples from DSA negative patients, samples from patients with concurrent de novo HLA DSAs had higher dd-cfDNA levels (P < .0001). DISCUSSION: Abnormalities in dd-cfDNA levels are associated with clinical parameters commonly used as surrogate endpoints for adverse allograft outcomes, raising the possibility that molecular injury as characterized by dd-cfDNA could help identify patients at risk of these outcomes.

Kidney transplant outcomes from donation after circulatory death donors of advanced age.

BACKGROUND: Continued comparison of kidney transplant outcomes between older DCD and donation after brain death (DBD) donors is needed to safely expand the deceased donor pool. METHODS: We performed a retrospective cohort study using the UNOS/OPTN transplant registry from donors >50 years old between 1994 and 2016. Donor age was stratified into 4 groups: 50-54, 55-59, 60-64, and >65 years old. Rates of delayed graft function (DGF) and primary non-function (PNF) were compared. Multivariable Cox regression models were constructed to identify factors associated with time to graft failure. RESULTS: The DCD donors within each age group had fewer comorbidities than the DBD donors. Graft survival for DCD kidneys was equivalent or superior to DBD kidneys in all donor age groups. DGF rates were significantly greater for DCD kidneys in all age groups. PNF rates across all groups were similar. In multivariable analysis, DCD status was not independently associated with time to all-cause graft failure in the 50-54 donor age group (HR = 1.02, 95% CI = 0.93-1.13), 55-59 donor age group (HR = 1.07, 95% CI = 0.96-1.19), or 60-64 donor age group (HR = 1.135, 95% CI = 0.97-1.32). CONCLUSION: Kidneys from carefully selected older DCD donors, particularly ages 50-64, are a potential means to safely expand the deceased donor pool.

Leveraging marginal structural modeling with Cox regression to assess the survival benefit of accepting vs declining kidney allograft offers.

Existing studies evaluating the survival benefit of kidney transplantation were unable to incorporate time-updated information on decisions related to each organ offer. We used national registry data, including organ turndown data, to evaluate the survival benefit of accepting vs turning down kidney offers in candidates waitlisted from 2007-2013. Among candidates who declined their first offer, only 43% ultimately received organ transplantations. Recipients who later underwent organ transplantation after declining their first offer had markedly longer wait times than recipients who accepted their first offer, and 56% received kidney transplants that were of similar or lower quality compared to their initial offer. In marginal structural modeling analyses accounting for time-updated offer characteristics (including Kidney Donor Profile Index, Public Health System risk status, and pumping), after 3 months posttransplant, there was a significant survival benefit of accepting an offer (adjusted hazard ratio 0.76, 95% confidence interval 0.66-0.89) that was similar among diabetics, candidates aged >65 years, and candidates living in donor service areas with the longest waitlist times. After carefully accounting for the effect of donor quality, we confirm that the survival benefit of accepting an organ offer is clinically meaningful and persistent beyond 3 months post-kidney transplantation, including high-risk subgroups of organ transplantation candidates.

National outcomes of kidney transplantation from deceased diabetic donors.

Use of deceased diabetic donor kidneys has increased over recent decades. However, scarce patient and allograft survival data are available taking into account recipient diabetes status. Here we performed a retrospective cohort study using data from the United Network of Organ Sharing in patients transplanted from 1994 to 2014. Multivariable Cox regression assessed recipient outcomes of 9074 diabetic vs. 152,555 non-diabetic donor kidneys. Recipients of diabetic donor kidneys had elevated rates of all-cause allograft failure (hazard ratio 1.21, 95% confidence interval 1.16-1.26) and death (1.19, 1.13-1.24) compared to recipients of kidneys from non-diabetic donors. Younger recipients of diabetic donor kidneys had worse allograft survival than older recipients of non-diabetic donor kidneys. There was significant interaction between donor and recipient diabetes status. To minimize the effect of unmeasured confounders, we used paired analyses of recipients of mate-kidneys from the same donor, with one diabetic recipient and the other non-diabetic. Among discordant recipient pairs of diabetic donor kidneys, diabetic recipients had significantly higher risk of allograft failure (1.27, 1.05-1.53) and death (1.53, 1.22-1.93) than non-diabetic recipients. After stratifying by Kidney Donor Profile Index risk category, diabetic recipients of diabetic donor kidneys continued to have worse allograft survival compared to all other patients. Thus, risks are associated with the use of diabetic donor kidneys. Understanding these risks will enable clinicians to better educate potential recipients.Kidney International advance online publication, 21 October 2015; doi:10.1038/ki.2015.325.

Updated Pathway to Micro-elimination of Hepatitis C Virus in the Hemodialysis Population.

Chronic hepatitis C virus (HCV) infection continues to be transmitted to hemodialysis (HD) patients within HD facilities globally. The goal of the World Health Organization to micro-eliminate HCV infection from the HD population by the year 2030 is not on target to be achieved. Obstacles to eliminate HCV in HD settings remain daunting due to a complex system created by a confluence of guidelines, legislation, regulation, and economics. HCV prevalence remains high and seroconversion continues among the HD patient population globally as a result of the HD procedure. Preventive strategies that effectively prevent HCV transmission, treatment-as-prevention, and rapid referral to treatment balanced with kidney transplant candidacy should be added to the current universal precautions approach. A safer system must be designed before HCV transmission can be halted and eliminated from the HD population.

Association of Racial/Ethnic and Gender Concordance Between Patients and Physicians With Patient Experience Ratings.

Importance: The Press Ganey Outpatient Medical Practice Survey is used to measure the patient experience. An understanding of the patient- and physician-related determinants of the patient experience may help identify opportunities to improve health care delivery and physician ratings. Objective: To evaluate the associations between the patient experience as measured by scores on the Press Ganey survey and patient-physician racial/ethnic and gender concordance. Design, Setting, and Participants: A cross-sectional analysis of Press Ganey surveys returned for outpatient visits within the University of Pennsylvania Health System between 2014 and 2017 was performed. Participants included adult patient and physician dyads for whom surveys were returned. Data analysis was performed from January to June 2019. Exposures: Patient-physician racial/ethnic and gender concordance. Main Outcomes and Measures: The primary outcome was receipt of the maximum score for the "likelihood of your recommending this care provider to others" question in the Care Provider domain of the Press Ganey survey. Secondary outcomes included each of the remaining 9 questions in the Care Provider domain. Generalized estimating equations clustering on physicians with exchangeable intracluster correlations and cluster-robust standard errors were used to investigate associations between the outcomes and patient-physician racial/ethnic and gender concordance. Results: In total, 117 589 surveys were evaluated, corresponding to 92 238 unique patients (mean [SD] age, 57.7 [15.6] years; 37 002 men [40.1%]; 75 307 White patients [81.6%]) and 747 unique physicians (mean [SD] age 45.5 [10.6] years; 472 men [63.2%]; 533 White physicians [71.4%]). Compared with racially/ethnically concordant patient-physician dyads, discordance was associated with a lower likelihood of physicians receiving the maximum score (adjusted odds ratio [OR], 0.88; 95% CI, 0.82-0.94; P < .001). Black (adjusted OR, 0.73; 95% CI, 0.68-0.78; P < .001) and Asian (adjusted OR, 0.55; 95% CI, 0.50-0.60; P < .001) patient race were both associated with lower patient experience ratings. Patient-physician gender concordance was not associated with Press Ganey scores (adjusted OR, 1.00; 95% CI, 0.96-1.04; P = .90). Conclusions and Relevance: In this study, higher Press Ganey survey scores were associated with racial/ethnic concordance between patients and their physicians. Efforts to improve physician workforce diversity are imperative. Delivery of health care in a culturally mindful manner between racially/ethnically discordant patient-physician dyads is also essential. Furthermore, Press Ganey scores may differ by a physician's patient demographic mix; thus, care must be taken when publicly reporting or using Press Ganey scores to evaluate physicians on an individual level.

Living Kidney Donor Phenotype and Likelihood of Postdonation Follow-up.

BACKGROUND: The Organ Procurement and Transplantation Network requires that United States transplant centers maintain follow-up with living donors for 2 years postdonation, but lack of donor follow-up is pervasive. Donor characteristics, including younger age, minority race, and lower education, have been associated with incomplete follow-up, but it is unknown whether altruistic donors, having no previous connection to their recipient, differ from traditional donors in their likelihood of follow-up. METHODS: Using the Scientific Registry of Transplant Recipients data, we examined all adult living kidney donors from 2005 to 2015 (n = 63 592) classified as altruistic or traditional, and compared likelihood of 6-month medical follow-up using modified Poisson regression. RESULTS: Altruistic donors did not differ from traditional donors in likelihood of follow-up (adjusted relative risk [aRR], 1.02; 95% confidence interval [CI], 0.99-1.06). Among previously identified at-risk subgroups, however, altruistic donors were more likely to have follow-up than their traditional counterparts, including those who were younger (aRR, 1.04; 95% CI, 1.00-1.09), had less than college education (aRR, 1.05; 95% CI, 1.00-1.11), and were unmarried (aRR, 1.08; 95% CI, 1.04-1.12). Having medical follow-up at 6 months was significantly associated with having follow-up at 1 year (aRR, 1.84; 95% CI, 1.75-1.93) and 2 years (aRR, 1.63; 95% CI, 1.56-1.70) postdonation. CONCLUSIONS: These data provide additional granularity on living donor phenotypes associated with short-term (6 month) postdonation follow-up, which is important given its association with future likelihood of follow-up. These findings offer the opportunity to tailor and direct educational efforts to increase living donor follow-up, particularly among groups at higher risk of loss to follow-up.

Safety and Feasibility of Outpatient Rabbit Antithymocyte Globulin Induction Therapy Administration in Kidney Transplant Recipients.

BACKGROUND: Kidney transplant induction therapy often includes inpatient administration of rabbit antithymocyte globulin (rATG) over multiple days. To reduce hospital length of stay (LOS) and drug expenditures, the rATG induction course was completed in the outpatient setting via peripheral intravenous administration. The present study assesses early readmission trends ascribable to an outpatient rATG administration protocol to ensure initial reduction in hospital LOS is sustained early after discharge. METHODS: This was a retrospective study of kidney recipient outcomes for patients transplanted between January 1, 2008, and February 29, 2016, immediately following implementation of an outpatient rATG protocol. Readmission data within 7 days of outpatient rATG administration were collected. The relatedness of rATG administration to an adverse drug reaction resulting in readmission was determined by the World Health Organization-Uppsala Monitoring Centre Causality Assessment Scale and the Naranjo Adverse Drug Reaction Probability Scale. RESULTS: A total of 1104 patients received outpatient doses of rATG and were included. An upward trend in kidney transplant volume and outpatient rATG administrations per year was found from 2008-2015. Following protocol implementation, the percentage of overall readmissions ranged from 9% to just over 12% from 2008-2014 and remained less than 10% for 2014 through 2016. The percentage of outpatient rATG infusions that potentially led to rATG-related readmissions was less than 4% per year over the study period. A total of 1124 hospital days were saved, 125 days per year on average. CONCLUSIONS: Outpatient administration of rATG is feasible, safe, and did not increase readmissions in the period directly following administration. The findings of this analysis support our continued use of the outpatient rATG protocol at our institution.

Survival Benefit of Transplantation with a Deceased Diabetic Donor Kidney Compared with Remaining on the Waitlist.

BACKGROUND AND OBJECTIVES: Use of diabetic donor kidneys has been a necessary response to the donor organ shortage. Recipients of diabetic donor kidneys have higher mortality risk compared with recipients of nondiabetic donor kidneys. However, the survival benefit of transplantation with diabetic donor kidneys over remaining on the waitlist has not been previously evaluated. DESIGN, SETTING, PARTICIPANTS, & MEASUREMENTS: We performed an observational cohort study of 437,619 kidney transplant candidates from the Organ Procurement and Transplantation Network database, including 8101 recipients of diabetic donor kidneys and 126,560 recipients of nondiabetic donor kidneys. We used time-varying Cox proportional hazards modeling to assess the mortality risk of accepting a diabetic donor kidney compared with remaining on the waitlist or receiving a nondiabetic donor kidney. RESULTS: Among transplant recipients, median follow-up was 8.9 years and mortality rate was 35 deaths per 1000 person-years. Recipients of diabetic donor kidneys had 9% lower mortality compared with remaining on the waitlist or transplantation with a nondiabetic donor kidney (adjusted hazard ratio, 0.91; 95% confidence interval, 0.84 to 0.98). Although recipients of nondiabetic donor kidneys with a Kidney Donor Profile Index score >85% had lower mortality risk (adjusted hazard ratio, 0.86; 95% confidence interval, 0.81 to 0.91), recipients of diabetic donor kidneys with an index score >85% did not show any difference (adjusted hazard ratio, 1.09; 95% confidence interval, 0.97 to 1.22). Patients aged <40 years attained no survival benefit from transplantation with diabetic donor kidneys; diabetic patients at centers with long waitlist times attained the greatest survival benefit. CONCLUSIONS: Diabetic donor kidneys appear associated with higher mortality risk compared with nondiabetic donor kidneys, but offer greater survival benefit compared with remaining on the waitlist for many candidates. Patients with high risk of mortality on the waitlist at centers with long wait times appear to benefit most from transplantation with diabetic donor kidneys.

A Paired Kidney Analysis of Multiorgan Transplantation: Implications for Allograft Survival.

BACKGROUND: United Network for Organ Sharing multiorgan transplantation allocation policy allows sequestration of a kidney by another solid organ regardless of the priority of the candidate for the kidney allograft. The implications of this policy for kidney allograft survival are not well understood. METHODS: We conducted a retrospective cohort analysis of pairs of deceased donor kidney transplants where 1 kidney was allocated to a simultaneous liver-kidney (SLK) or simultaneous heart-kidney (SHK) recipient and the contralateral kidney to a kidney transplant alone (KTA) recipient (cohort from February 2002 to December 2010). Graft and patient survivals were assessed with Cox regression models. RESULTS: There were 1998 SLK and 276 SHK transplants with matching KTA transplants. Five-year kidney graft (64% [SLK] vs 75% [KTA], P < 0.001) and patient survivals (66% [SLK] vs 81% [KTA], P < 0.001) were significantly lower in SLK versus KTA recipients of the contralateral kidney. Among the entire cohort of SLK in this analysis, the cumulative difference in graft survival 1 year after transplant was 115 years, and by 5 years, the difference increased to 1062 years. Among the SHK arm of our study, 5-year graft survival (72% [SHK] vs 73% [KTA], P = 0.71) did not significantly differ, although patient survival (75% [SHK] vs 84% [KTA], P = 0.02) was higher in KTA recipients. CONCLUSIONS: Kidney graft survival is inferior among SLK relative to KTA, but not SHK. Multiorgan transplantation allocation may not be congruent with the intention of new kidney allocation policies that attempt to maximize survival after kidney transplantation.

Blood pressure variability of two ambulatory blood pressure monitors.

OBJECTIVE: There are no data on the evaluation of blood pressure (BP) variability comparing two ambulatory blood pressure monitoring monitors worn at the same time. Hence, this study was carried out to compare variability of BP in healthy untreated adults using two ambulatory BP monitors worn at the same time over an 8-h period. METHODS: An Accutorr device was used to measure office BP in the dominant and nondominant arms of 24 participants.Simultaneous 8-h BP and heart rate data were measured in 24 untreated adult volunteers by Mobil-O-Graph (worn for an additional 16 h after removing the Spacelabs monitor) and Spacelabs with both random (N=12) and nonrandom (N=12) assignment of each device to the dominant arm. Average real variability (ARV), SD, coefficient of variation, and variation independent of mean were calculated for systolic blood pressure, diastolic blood pressure, mean arterial pressure, and pulse pressure (PP). RESULTS: Whether the Mobil-O-Graph was applied to the dominant or the nondominant arm, the ARV of mean systolic (P=0.003 nonrandomized; P=0.010 randomized) and PP (P=0.009 nonrandomized; P=0.005 randomized) remained significantly higher than the Spacelabs device, whereas the ARV of the mean arterial pressure was not significantly different. The average BP readings and ARVs for systolic blood pressure and PP obtained by the Mobil-O-Graph were considerably higher for the daytime than the night-time. CONCLUSION: Given the emerging interest in the effect of BP variability on health outcomes, the accuracy of its measurement is important. Our study raises concerns about the accuracy of pooling international ambulatory blood pressure monitoring variability data using different devices.

A comparison of two ambulatory blood pressure monitors worn at the same time.

There are limited data in the literature comparing two simultaneously worn ambulatory blood pressure (BP) monitoring (ABPM) devices. The authors compared BPs from two monitors (Mobil-O-Graph [I.E.M., Stolberg, Germany] and Spacelabs 90207 [Spacelabs Medical, Issequah, WA]). In the nonrandomized component of the study, simultaneous 8-hour BP and heart rate data were measured by Mobil-O-Graph, consistently applied to the nondominant arm, and Spacelabs to the dominant arm on 12 untreated adults. Simultaneous 8-hour BP and heart data were obtained by the same monitors randomly assigned to a dominant or nondominant arm on 12 other untreated adults. Oscillometric BP profiles were obtained in the dominant and nondominant arms of the above 24 patients using an Accutorr (Datascope, Mahwah, NJ) device. The Spacelabs monitor recorded a 10.2-mm Hg higher systolic pressure in the nonrandomized (P=.0016) and a 7.9-mm Hg higher systolic pressure in the randomized studies (P=.00008) compared with the Mobil-O-Graph. The mean arterial pressures were 1 mm Hg to 2 mm Hg different between monitors in the two studies, and heart rates were nearly identical. Our observations, if confirmed in larger cohorts, support the concern that ABPM device manufacturers consider developing normative databases for their devices.