Faculty Bibliography

BACKGROUND:Donor livers with ≥30% macrosteatosis (steatotic livers) represent a possible expansion to the donor pool, but are frequently discarded as they are associated with an increased risk of mortality and graft loss. We hypothesized that there are certain recipient phenotypes that would tolerate donor steatosis well, and are therefore best suited to receive these grafts. METHODS:Using national registry data from the Scientific Registry of Transplant Recipients between 2006 and 2017, we compared 2048 liver transplant recipients of steatotic livers with 69 394 recipients of nonsteatotic (<30%) livers. We identified recipient factors that amplified the impact of donor steatosis on mortality and graft loss using interaction analysis, classifying recipients without these factors as preferred recipients. We compared mortality and graft loss with steatotic versus nonsteatotic livers in preferred and nonpreferred recipients using Cox regression. RESULTS:Preferred recipients of steatotic livers were determined to be first-time recipients with a model for end-stage liver disease 15-34, without primary biliary cirrhosis, and not on life support before transplant. Preferred recipients had no increased mortality risk (hazard ratio [HR]: 0.921.041.16; P = 0.5) or graft loss (HR: 0.931.031.15; P = 0.5) with steatotic versus nonsteatotic livers. Conversely, nonpreferred recipients had a 41% increased mortality risk (HR: 1.171.411.70; P < 0.001) and 39% increased risk of graft loss (HR: 1.161.391.66; P < 0.001) with steatotic versus nonsteatotic livers. CONCLUSIONS:The risks of liver transplantation with steatotic donor livers could be minimized by appropriate recipient matching.

Prioritization of highly sensitized (HS) candidates under the kidney allocation system (KAS) and growth of large, multicenter kidney-paired donation (KPD) clearinghouses have broadened the transplant modalities available to HS candidates. To quantify temporal trends in utilization of these modalities, we used SRTR data from 2009 to 2017 to study 39 907 adult HS (cPRA ≥ 80%) waitlisted candidates and 19 003 recipients. We used competing risks regression to quantify temporal trends in likelihood of DDKT, KPD, and non-KPD LDKT for HS candidates (Era 1: January 1, 2009-December 31, 2011; Era 2: January 1, 2012-December 3, 2014; Era 3: December 4, 2014-December 31, 2017). Although the likelihood of DDKT and KPD increased over time for all HS candidates (adjusted subhazard ratio [aSHR] Era 3 vs 1 for DDKT: _1.74 1.85_1.97 , P < .001 and for KPD: _1.70 2.20_2.84 , P < .001), the likelihood of non-KPD LDKT decreased (aSHR: _0.69 0.82_0.97 , P = .02). However, these changes affected HS recipients differently based on cPRA. Among recipients, more cPRA 98%-99.9% and 99.9%+ recipients underwent DDKT (96.2% in Era 3% vs 59.1% in Era 1 for cPRA 99.9%+), whereas fewer underwent non-KPD LDKT (1.9% vs 30.9%) or KPD (2.0% vs 10.0%). Although KAS increased DDKT likelihood for the most HS candidates, it also decreased the use of non-KPD LDKT to transplant cPRA 98%+ candidates.

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]: _0.18 0.21_0.25 , P < .001), and more likely to receive offers for donors 18-34 years old and KDPI < 35% (aIRR: _1.12 1.20_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: _0.61 0.77_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.

BACKGROUND:Falls occur in 28% of hemodialysis patients and increase the risk of physical impairment, morbidity, and mortality. Therefore, it is likely that kidney transplantation (KT) candidates with recurrent falls are less likely to access KT and more likely to experience adverse post-KT outcomes. METHODS:We used a 2-center cohort study of KT candidates (n = 3666) and recipients (n = 770) (January 2009 to January 2018). Among candidates, we estimated time to listing, waitlist mortality, and transplant rate by recurrent falls (≥2 falls) before evaluation using adjusted regression. Among KT recipients, we estimated risk of mortality, graft loss, and length of stay by recurrent falls before KT using adjusted regression. RESULTS:Candidates with recurrent falls (6.5%) had a lower chance of listing (adjusted hazard ratio [aHR] = 0.68, 95% confidence interval [CI], 0.56-0.83) but not transplant rate; waitlist mortality was 31-fold (95% CI, 11.33-85.93) higher in the first year and gradually decreased over time. Recipients with recurrent falls (5.1%) were at increased risk of mortality (aHR = 51.43, 95% CI, 16.00-165.43) and graft loss (aHR = 33.57, 95% CI, 11.25-100.21) in the first year, which declined over time, and a longer length of stay (adjusted relative ratio [aRR] = 1.13, 95% CI, 1.03-1.25). In summary, 6.5% of KT candidates and 5.1% of recipients experienced recurrent falls which were associated with adverse pre- and post-KT outcomes. CONCLUSIONS:While recurrent falls were relatively rare in KT candidates and recipients, they were associated with adverse outcomes. Transplant centers should consider employing fall prevention strategies for high-risk candidates as part of comprehensive prehabilitation.

We examined a novel database linking national donor registry identifiers to records from a US pharmaceutical claims warehouse (2007-2015) to describe opioid and NSAID prescription patterns among LKDs during the first year postdonation, divided into three periods: 0-14 days, 15-182 days, and 183-365 days. Associations of opioid and NSAID prescription fills with baseline factors were examined by logistic regression (adjusted odds ratio, _LCL aOR_UCL ). Among 23,565 donors, opioid prescriptions were highest during days 0-14 (36.6%), but 12.6% of donors filled opioids during days 183-365. NSAID prescriptions rose from 0.5% during days 0-14 to 3.3% during days 183-365. Women filled opioids more commonly than men, and black donors filled both opioids and NSAIDs more commonly than white donors. After covariate adjustment, significant correlates of opioid prescription fills during days 183-365 included obesity (aOR,_1.24 1.38_1.53 ), less than college education (aOR,_1.19 1.31_1.43 ), smoking (aOR,_1.33 1.45_1.58 ), and nephrectomy complications (aOR,_1.11 1.29_1.49 ). NSAID prescription fills in year 1 were not associated with differences in estimated glomerular filtration rate, incidence of proteinuria or new-onset hypertension at the first and second year postdonation. Prescription fills for opioids and NSAIDs for LKDs varied with demographic and clinic traits. Future work should examine longer-term outcome implications to help inform safe analgesic regimen choices after donation.

BACKGROUND:Steatotic donor livers (SDLs, ≥30% macrosteatosis on biopsy) are often declined, as they are associated with a higher risk of graft loss, even though candidates may wait an indefinite time for a subsequent organ offer. We sought to quantify outcomes for transplant candidates who declined or accepted an SDL offer. METHODS:We used Scientific Registry of Transplant Recipients offer data from 2009 to 2015 to compare outcomes of 759 candidates who accepted an SDL to 13 362 matched controls who declined and followed candidates from the date of decision (decline or accept) until death or end of study period. We used a competing risk framework to understand the natural history of candidates who declined and Cox regression to compare postdecision survival after declining versus accepting (ie, what could have happened if candidates who declined had instead accepted). RESULTS:Among those who declined an SDL, only 53.1% of candidates were subsequently transplanted, 23.8% died, and 19.4% were removed from the waitlist. Candidates who accepted had a brief perioperative risk period within the first month posttransplant (adjusted hazard ratio [aHR]: 2.493.494.89, P < 0.001), but a 62% lower mortality risk (aHR: 0.310.380.46, P < 0.001) beyond this. Although the long-term survival benefit of acceptance did not vary by candidate model for end-stage liver disease (MELD), the short-term risk period did. MELD 6-21 candidates who accepted an SDL had a 7.88-fold higher mortality risk (aHR: 4.807.8812.93, P < 0.001) in the first month posttransplant, whereas MELD 35-40 candidates had a 68% lower mortality risk (aHR: 0.110.320.90, P = 0.03). CONCLUSIONS:Appropriately selected SDLs can decrease wait time and provide substantial long-term survival benefit for liver transplant candidates.

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.

The construct of frailty was first developed in gerontology to help identify older adults with increased vulnerability when confronted with a health stressor. This article is a review of studies in which frailty has been applied to pre- and post-kidney transplantation (KT) populations. Although KT is the optimal treatment for end-stage kidney disease (ESKD), KT candidates often must overcome numerous health challenges associated with ESKD before receiving KT. After KT, the impacts of surgery and immunosuppression represent additional health stressors that disproportionately impact individuals with frailty. Frailty metrics could improve the ability to identify KT candidates and recipients at risk for adverse health outcomes and those who could potentially benefit from interventions to improve their frail status. The Physical Frailty Phenotype (PFP) is the most commonly used frailty metric in ESKD research, and KT recipients who are frail at KT (~20% of recipients) are twice as likely to die as nonfrail recipients. In addition to the PFP, many other metrics are currently used to assess pre- and post-KT vulnerability in research and clinical practice, underscoring the need for a disease-specific frailty metric that can be used to monitor KT candidates and recipients. Although frailty is an independent risk factor for post-transplant adverse outcomes, it is not factored into the current transplant program risk-adjustment equations. Future studies are needed to explore pre- and post-KT interventions to improve or prevent frailty.

Background/UNASSIGNED:Caring for dialysis patients is difficult, and this burden often falls on a spouse or cohabiting partner (henceforth referred to as caregiver-partners). At the same time, these caregiver-partners often come forward as potential living kidney donors for their loved ones who are on dialysis (henceforth referred to as patient-partners). Caregiver-partners may experience tangible benefits to their well-being when their patient-partner undergoes transplantation, yet this is seldom formally considered when evaluating caregiver-partners as potential donors. Methods/UNASSIGNED:To quantify these potential benefits, we surveyed caregiver-partners of dialysis patients and kidney transplant (KT) recipients (N = 99) at KT evaluation or post-KT. Using validated tools, we assessed relationship satisfaction and caregiver burden before or after their patient-partner's dialysis initiation and before or after their patient-partner's KT. Results/UNASSIGNED: = 0.3). Conclusions/UNASSIGNED:These benefits in caregiver burden and relationship quality support special consideration for spouses and partners in risk-assessment of potential kidney donors, particularly those with risk profiles slightly exceeding center thresholds.

RATIONALE & OBJECTIVE:Intact cognition is generally a prerequisite for navigating through and completing evaluation for kidney transplantation. Despite kidney transplantation being contraindicated for those with severe dementia, screening for more mild forms of cognitive impairment before referral is rare. Candidates may have unrecognized cognitive impairment, which may prolong evaluation, elevate mortality risk, and hinder access to kidney transplantation. We estimated the burden of cognitive impairment and its association with access to kidney transplantation and waitlist mortality. STUDY DESIGN:Prospective cohort study. SETTING & PARTICIPANTS:3,630 participants (January 2009 to June 2018) with cognitive function measured (by the Modified Mini-Mental State Examination [3MS]) at kidney transplantation evaluation at 1 of 2 transplantation centers. PREDICTORS:Cognitive impairment (3MS score<80). OUTCOMES:Listing, waitlist mortality, and kidney transplantation. ANALYTICAL APPROACH:We estimated the adjusted chance of listing (Cox regression), risk for waitlist mortality (competing-risks regression), and kidney transplantation rate (Poisson regression) by cognitive impairment. Given potential differences in cause of cognitive impairment among those with and without diabetes, we tested whether these associations differed by diabetes status using a Wald test. RESULTS:=0.02). Among candidates without diabetes, those with cognitive impairment were at 2.47 (95% CI, 1.31-4.66) times greater risk for waitlist mortality; cognitive impairment was not associated with this outcome among candidates with diabetes. LIMITATIONS:Single measure of cognitive impairment. CONCLUSIONS:Cognitive impairment is associated with a lower chance of being placed on the waitlist, and among patients without diabetes, with increased mortality on the waitlist. Future studies should investigate whether implementation of screening for cognitive impairment improves these outcomes.