Better graft outcomes from offspring donor kidneys among living donor kidney transplant recipients in the United States

A recent study reported that kidney transplant recipients of offspring living donors had higher graft loss and mortality. This seemed counterintuitive, given the excellent HLA matching and younger age of offspring donors; we were concerned about residual confounding and other study design issues. We used Scientific Registry of Transplant Recipients data 2001‐2016 to evaluate death‐censored graft failure (DCGF) and mortality for recipients of offspring versus nonoffspring living donor kidneys, using Cox regression models with interaction terms. Recipients of offspring kidneys had lower DCGF than recipients of nonoffspring kidneys (15‐year cumulative incidence 21.2% vs 26.1%, P < .001). This association remained after adjustment for recipient and transplant factors (adjusted hazard ratio [aHR] = _0.730.77_0.82, P < .001), and was attenuated among African American donors (aHR _0.770.85_0.95; interaction: P = .01) and female recipients (aHR _0.770.84_0.91, P < .001). Although offspring kidney recipients had higher mortality (15‐year mortality 56.4% vs 37.2%, P < .001), this largely disappeared with adjustment for recipient age alone (aHR = _1.021.06_1.10, P = .002) and was nonsignificant after further adjustment for other recipient characteristics (aHR = _0.930.97_1.01, P = .1). Kidneys from offspring donors provided lower graft failure and comparable mortality. An otherwise eligible donor should not be dismissed because they are the offspring of the recipient, and we encourage continued individualized counseling for potential donors.     

Your Path to Transplant: A randomized controlled trial of a tailored expert system intervention to increase knowledge,attitudes, and pursuit of kidney transplant

Individually tailoring education over time may help more patients, especially racial/ethnic minorities, get waitlisted and pursue deceased and living donor kidney transplant (DDKT and LDKT, respectively). We enrolled 802 patients pursuing transplant evaluation at the University of California, Los Angeles Transplant Program into a randomized education trial. We compared the effectiveness of Your Path to Transplant (YPT), an individually tailored coaching and education program delivered at 4 time points, with standard of care (SOC) education on improving readiness to pursue DDKT and LDKT, transplant knowledge, taking 15 small transplant-related actions, and pursuing transplant (waitlisting or LDKT rates) over 8 months. Survey outcomes were collected prior to evaluation and at 4 and 8 months. Time to waitlisting or LDKT was assessed with at least 18 months of follow-up. At 8 months, compared to SOC, the YPT group demonstrated increased LDKT readiness (47% vs 33%, P = .003) and transplant knowledge (effect size [ES] = 0.41, P < .001). Transplant pursuit was higher in the YPT group (hazard ratio: 1.44, 95% confidence interval: 1.15-1.79, P = .002). A focused, coordinated education effort can improve transplant-seeking behaviors and waitlisting rates. ClinicalTrials.gov registration: NCT02181114.     

Decreasing deceased donor transplant rates among children (≤6 years) under the new kidney allocation system

The Kidney Allocation System (KAS) was implemented in December 2014 with unknown impact on the pediatric waitlist. To understand the effect of KAS on pediatric registrants, deceased donor kidney transplant (DDKT) rate was assessed using interrupted time series analysis and time‐to‐event analysis. Two allocation eras were defined with an intermediary washout period: Era 1 (01/01/2013‐09/01/2014), Era 2 (09/01/2014‐03/01/2015), and Era 3(03/01/2015‐03/01/2017). When using Cox proportional hazards, there was no significant association between allocation era and DDKT likelihood as compared to Era 1 (Era 3: aHR: 1.07, 95% CI: 0.97‐1.18, P = .17). However, this was not consistent across all subgroups. Specifically, while highly sensitized pediatric registrants were consistently less likely to be transplanted than their less sensitized counterparts, this disparity was attenuated in Era 3 (Era 1 aHR: 0.04, 95%CI: 0.01‐0.14, P < .001; Era 3 aHR: 0.33, 95% CI: 0.21‐0.53, P < .001) whereas the youngest registrants aged 0‐6 experienced a 21% decrease in DDKT likelihood in Era 3 as compared to Era 1 (aHR: 0.79, 95% CI: 0.64‐0.98, P = .03). Thus, while overall DDKT likelihood remained stable with the introduction of KAS, registrants ≤ 6 years of age were disadvantaged, warranting further study to ensure equitable access to transplantation.     

The Incremental Cost of Incompatible Living Donor Kidney Transplantation: A National Cohort Analysis

Incompatible living donor kidney transplantation (ILDKT) has been established as an effective option for end‐stage renal disease patients with willing but HLA‐incompatible living donors, reducing mortality and improving quality of life. Depending on antibody titer, ILDKT can require highly resource‐intensive procedures, including intravenous immunoglobulin, plasma exchange, and/or cell‐depleting antibody treatment, as well as protocol biopsies and donor‐specific antibody testing. This study sought to compare the cost and Medicare reimbursement, exclusive of organ acquisition payment, for ILDKT (n = 926) with varying antibody titers to matched compatible transplants (n = 2762) performed between 2002 and 2011. Data were assembled from a national cohort study of ILDKT and a unique data set linking hospital cost accounting data and Medicare claims. ILDKT was more expensive than matched compatible transplantation, ranging from 20% higher adjusted costs for positive on Luminex assay but negative flow cytometric crossmatch, 26% higher for positive flow cytometric crossmatch but negative cytotoxic crossmatch, and 39% higher for positive cytotoxic crossmatch (p < 0.0001 for all). ILDKT was associated with longer median length of stay (12.9 vs. 7.8 days), higher Medicare payments ($91 330 vs. $63 782 p < 0.0001), and greater outlier payments. In conclusion, ILDKT increases the cost of and payments for kidney transplantation.     

The Changing Financial Landscape of Renal Transplant Practice: A National Cohort Analysis

Kidney transplantation has become more resource intensive as recipient complexity has increased and average donor quality has diminished over time. A national retrospective cohort study was performed to assess the impact of kidney donor and recipient characteristics on transplant center cost (exclusive of organ acquisition) and Medicare reimbursement. Data from the national transplant registry, University HealthSystem Consortium hospital costs, and Medicare payments for deceased donor (N = 53 862) and living donor (N = 36 715) transplants from 2002 to 2013 were linked and analyzed using multivariate linear regression modeling. Deceased donor kidney transplant costs were correlated with recipient (Expected Post Transplant Survival Score, degree of allosensitization, obesity, cause of renal failure), donor (age, cause of death, donation after cardiac death, terminal creatinine), and transplant (histocompatibility matching) characteristics. Living donor costs rose sharply with higher degrees of allosensitization, and were also associated with obesity, cause of renal failure, recipient work status, and 0‐ABDR mismatching. Analysis of Medicare payments for a subsample of 24 809 transplants demonstrated minimal correlation with patient and donor characteristics. In conclusion, the complexity in the landscape of kidney transplantation increases center costs, posing financial disincentives that may reduce organ utilization and limit access for higher‐risk populations.     

Integrating kidney transplantation into value‐based care for people with renal failure

Healthcare reimbursement is increasingly tied to value instead of volume, with special attention paid to resource‐intensive populations such as patients with renal disease. To this end, Medicare has sponsored pilot projects to encourage providers to develop care coordination and population health management strategies to provide quality care while reducing resource utilization. In this Personal Viewpoint essay, we argue in favor of expanding one such pilot project—the Comprehensive ESRD Care (CEC) initiative—to include patients with advanced chronic kidney disease and kidney transplant recipients. The implementation of the Medicare Access and CHIP Reauthorization Act (MACRA) offers a time‐sensitive incentive for transplant centers in particular to align with extant CECs. An “expanded” CEC model proffers opportunity for robust cooperation between general nephrology practices, dialysis providers, and transplant centers to develop care coordination strategies for all patients with renal disease, realign incentives for all clinical stakeholders to increase kidney transplantation rates, and reduce total costs of care.     

Hospital readmissions following HLA‐incompatible live donor kidney transplantation: A multi‐center study

Thirty percent of kidney transplant recipients are readmitted in the first month posttransplantation. 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% confidence interval [CI] 1.13‐1.46; P < .001). Risk peaked at 6‐12 months (relative risk [RR] 1.67, 95% CI 1.49‐1.87; P < .001), attenuating by 24‐36 months (RR 1.24, 95% CI 1.10‐1.40; P < .001). ILDKTs had a 5.86‐fold higher readmission risk (95% CI 4.96‐6.92; P < .001) in the first month compared to waitlist‐only controls. At 12‐24 (RR 0.85, 95% CI 0.77‐0.95; P = .002) and 24‐36 months (RR 0.74, 95% CI 0.66‐0.84; P < .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.     

Immune responses following tocilizumab therapy to desensitize HLA-sensitized kidney transplant candidates

Kidney transplant candidates (KTCs) who are HLA highly sensitized (calculated panel-reactive alloantibodies >95%) have poor access to deceased kidney transplantation. In this single-center prospective study, 13 highly sensitized desensitization-naïve KTCs received IV tocilizumab (8 mg/kg) every 4 weeks. We evaluated tolerability as well as immune responses, that is, T cell, B cell, T follicular helper (Tfh) subsets, blood cytokines (IL-6, soluble IL-6 receptor-sIL-6R-, IL-21), blood chemokines (CXCL10, CXCL13), and anti-HLA alloantibodies. Tocilizumab treatment was well-tolerated except in one patient who presented spondylodiscitis, raising a note of caution. Regarding immune parameters, there were no significant changes of percentages of lymphocyte subsets, that is, CD3⁺, CD3⁺/CD4⁺, CD3⁺/CD8⁺ T cells, and NK cells. This was also the case for Tfh cell subsets, B cells, mature B cells, plasma cells, pre-germinal center (GC) B cells, and post-GC B cells, whereas we observed a significant increase in naïve B cells (p = .02) and a significant decrease in plasmablasts (p = .046) over the tocilizumab treatment course. CXCL10, CXCL13, IL-21, total IgG, IgA, and IgM levels did not significantly change during tocilizumab therapy; conversely, there was a significant increase in IL-6 levels (p = .03) and a huge increase in sIL-6R (p = .00004). There was a marginal effect on anti-HLA alloantibodies (class I and class II). To conclude in highly sensitized KTCs, tocilizumab as a monotherapy limited B cell maturation; however, it had almost no effect on anti-HLA alloantibodies.     

Can donor narratives yield insights? A natural language processing proof of concept to facilitate kidney allocation

Although expedited placement could ameliorate stagnant kidney utilization, precisely identifying difficult‐to‐place organs is crucial to mitigate potential harms associated with this policy. Existing algorithms have only leveraged structured data from the Organ Procurement and Transplantation Network (OPTN); however, detailed, free text case information about a donor exists. No known research exists about the utility of these data. We developed a model to predict the probability of delay or discard for adult deceased kidney donors between 2010 and 2018, leveraging donor free text data. The resultant model had a c‐statistic of 0.75 compared to 0.80 (

1. Reduced Probability of Delay or Discard [model],

r‐PODD) and 0.77 (

1. Kidney Donor Profile Index,

KDPI) on the test dataset. Analysis of the top predictive words suggest both known and potentially novel clinical factors (ie, a known factor such as hypertension vs a novel factor such as stents), and nuanced social factors (intravenous drug use) could negatively affect kidney utilization. These findings suggest that donor narratives have utility; the natural language processing (NLP) model is only moderately correlated with existing indices and provides directional evidence about additional cardiovascular risk factors that may affect kidney utilization. More research is needed to understand the potential to enhance existing indices of kidney utilization to better enable and mitigate the effects of policy interventions such as expedited placement.     

Living donor age and kidney transplant outcomes: an assessment of risk across the age continuum

Detailed data on living donor age, and its interplay with recipient age, in predicting allograft and recipient outcomes are wanting. We used the Scientific Registry of Transplant Recipients (2000–2009, n = 49 589) to assess the effect of living donor age on delayed graft function (DGF), total graft failure, death‐censored graft failure, death with graft function, and graft failure with death as a competing risk using logistic and Cox proportional hazards models. Potential nonlinear associations were modeled using fractional polynomial functions. There was a significant 1.87‐fold increase in the adjusted odds of DGF in the oldest versus youngest age groups. The 10‐year adjusted hazard ratios (HR) for total graft failure, death‐censored graft failure, and death with graft function increased in a nonlinear fashion across the range of living donor age studied. Graft failure was most accentuated in the youngest recipient age groups in competing risk models. Adjustment for renal function at 6‐ and 12‐months post‐transplant markedly attenuated the association between living donor age and graft/patient outcomes. Our findings confirm the important influence of living donor age on transplant outcomes and provide detailed estimates of risk across the living donor age continuum.     

Changes in offer and acceptance patterns for pediatric kidney transplant candidates under the new Kidney Allocation System

Stakeholders have expressed concerns regarding decreased deceased donor kidney transplant (DDKT) rates for pediatric candidates under the Kidney Allocation System (KAS). To better understand what might be driving this, we studied Scientific Registry of Transplant Recipients kidney offer data for 3642 pediatric (age <18 years) kidney‐only transplant candidates between December 31, 2012 to December 3, 2014 (pre‐KAS) and December 4, 2014 to January 6, 2017 (post‐KAS). We used negative binomial regression and multilevel logistic regression to compare offer and acceptance rates pre‐ and post‐KAS. We stratified by donor age (<18, 18‐34, and 35+ years) and KDPI (<35% and ≥35%) to reflect differing allocation prioritization pre‐KAS and post‐KAS. As might be expected from prioritization changes, post‐KAS candidates were less likely to receive offers for donors 18‐34 years old with KDPI ≥ 35% (adjusted incidence rate ratio [aIRR]: _0.180.21_0.25, P < .001), and more likely to receive offers for donors 18‐34 years old and KDPI < 35% (aIRR: _1.121.20_1.29, P < .001). However, offer acceptance practices also changed post‐KAS: kidneys from donors 18‐34 years old and KDPI < 35% were 23% less likely to be accepted post‐KAS (adjusted odds ratio: _0.610.77_0.98, P = .03). Using kidneys from donors 18‐34 years old with KDPI < 35% post‐KAS to the same extent they were used pre‐KAS might be an effective strategy to mitigate any decrease in DDKT rates for pediatric candidates.     

The benefit to waitlist patients in a national paired kidney exchange program: Exploring characteristics of chain end living donor transplants

Nondirected kidney donors can initiate living donor chains that end to patients on the waitlist. We compared 749 National Kidney Registry (NKR) waitlist chain end transplants to other transplants from the NKR and the Scientific Registry of Transplant Recipients between February 2008 and September 2020. Compared to other NKR recipients, chain end recipients were more often older (53 vs. 52 years), black (32% vs. 15%), publicly insured (71% vs. 46%), and spent longer on dialysis (3.0 vs. 1.0 years). Similar differences were noted between chain end recipients and non-NKR living donor recipients. Black patients received chain end kidneys at a rate approaching that of deceased donor kidneys (32% vs. 34%). Chain end donors were older (52 vs. 44 years) with slightly lower glomerular filtration rates (93 vs. 98 ml/min/1.73 m²) than other NKR donors. Chain end recipients had elevated risk of graft failure and mortality compared to control living donor recipients (both p < .01) but lower graft failure (p = .03) and mortality (p < .001) compared to deceased donor recipients. Sharing nondirected donors among a multicenter network may improve the diversity of waitlist patients who benefit from living donation.