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Global kidney exchange should expand wisely

Roth, Alvin E; Marino, Ignazio R; Ekwenna, Obi; Dunn, Ty B; Paloyo, Siegfredo R; Tan, Miguel; Correa-Rotter, Ricardo; Kuhr, Christian S; Marsh, Christopher L; Ortiz, Jorge; Testa, Giuliano; Sindhwani, Puneet; Segev, Dorry L; Rogers, Jeffrey; Punch, Jeffrey D; Forbes, Rachel C; Zimmerman, Michael A; Ellis, Matthew J; Rege, Aparna; Basagoitia, Laura; Krawiec, Kimberly D; Rees, Michael A
PMID: 32430941
ISSN: 1432-2277
CID: 5126362

Addressing Racial Disparities in Live Donor Kidney Transplantation Through Education and Advocacy Training

King, Elizabeth A; Ruck, Jessica M; Garonzik-Wang, Jacqueline; Bowring, Mary G; Kumar, Komal; Purnell, Tanjala; Cameron, Andrew; Segev, Dorry L
Background/UNASSIGNED:The Live Donor Champion (LDC) program trains kidney transplant (KT) candidates and their family/friends ("champions") as educator-advocates for live donor KT (LDKT). This program was created to empower patients and champions, particularly African American (AA) waitlist candidates that historically had lower access to LDKT. We assessed changes in knowledge about and comfort discussing live donation and donor referral associated with LDC participation, both overall and by participant race. Methods/UNASSIGNED:We compared 163 adult KT candidates who were LDC participants from October 2013 to May 2016 with 489 matched controls, both overall and by race. We compared changes in comfort and knowledge post-LDC using rank-sum tests among participants by race. We compared time to first live donor referral for participants versus controls, by race, using Cox regression. Results/UNASSIGNED: < 0.001); the impact of LDC participation was similar among non-AAs and AAs (p-interaction = 0.6). Conclusions/UNASSIGNED:The LDC program increased knowledge, comfort, and live donor referral for non-AA and AA participants, underscoring the effectiveness in the program in promoting LDKT in a population with historically lower access to LDKT.
PMCID:7423916
PMID: 32851126
ISSN: 2373-8731
CID: 5126632

Outcome implications of benzodiazepine and opioid co-prescription in kidney transplant recipients

Lam, Ngan N; Schnitzler, Mark A; Axelrod, David A; Xiao, Huiling; McAdams-DeMarco, Mara; Segev, Dorry L; Massie, Allan B; Dharnidharka, Vikas R; Naik, Abhijit S; Muzaale, Abimereki D; Hess, Gregory P; Kasiske, Bertram L; Lentine, Krista L
The outcomes of benzodiazepine and opioid co-prescription are not well-defined in transplant populations. We examined linked national transplant registry and pharmaceutical records to characterize benzodiazepine and opioid use in the years before and after transplant in large US cohort of kidney transplant recipients (2007-2016; N = 98 620), and associations (adjusted hazard ratio, LCL aHRUCL ) with death and graft failure. Among the cohort, 15.6% filled benzodiazepine prescriptions in the year before transplant, and 14.0% filled benzodiazepine prescriptions in the year after transplant (short-acting, 9.5%; long-acting, 3.3%; both 1.1%). Use of short-acting benzodiazepines in the year before transplant was associated with a 22% increased risk of death in the year after transplant (aHR, 1.08 1.221.38 ), while use of all classes in the year after transplant was associated with increased risk of death from >1 to 5 years (aHR: short-acting 1.29 1.391.48 ; long-acting 1.12 1.251.40 ; both 1.46 1.742.07 ). Recipients who used benzodiazepines were also more likely to fill opioid prescriptions. Recipients who filled both classes of benzodiazepine and the highest level of opioids had a 2.9-fold increased risk of death compared to recipients who did not use either. Co-prescription of benzodiazepines and opioids in kidney transplant recipients is associated with increased mortality. Ongoing research is needed to understand mechanisms of risk relationships.
PMCID:7722087
PMID: 32510628
ISSN: 1399-0012
CID: 5126432

Outcomes of donor-derived superinfection screening in HIV-positive to HIV-positive kidney and liver transplantation: a multicentre, prospective, observational study

Bonny, Tania S; Kirby, Charles; Martens, Craig; Rose, Rebecca; Desai, Niraj; Seisa, Michael; Petropoulos, Christos; Florman, Sander; Friedman-Moraco, Rachel J; Turgeon, Nicole A; Brown, Diane; Segev, Dorry L; Durand, Christine M; Tobian, Aaron A R; Redd, Andrew D
BACKGROUND:One of the primary risks of HIV-positive to HIV-positive organ transplantation is loss of virological control because of donor-derived HIV superinfection, which occurs when an HIV-positive individual becomes infected with a new distinct HIV strain. In this study, as part of the larger HIV Organ Policy Equity pilot study, HIV-positive to HIV-positive kidney and liver transplant recipients in the USA were examined for evidence of sustained donor-derived HIV superinfection. METHODS:In this multicentre, prospective, observational study, HIV-positive to HIV-positive kidney and liver transplant recipients were followed in three hospitals in the USA. Candidates with well controlled HIV infection on ART, no active opportunistic infections, and minimum CD4 T-cell counts (>100 cells per μL for liver and >200 cells per μL for kidney per federal guidelines) were eligible to receive a kidney or liver from deceased HIV-positive donors without active infections or neoplasm. Peripheral blood mononuclear cells were collected from donor-recipient pairs at the time of transplantation, and from recipients at several timepoints up to 3 years after transplantation. Donor samples were assessed for HIV RNA viral load, CD4 cell count, and antiretroviral drug-resistant mutations. Donor and recipient HIV proviral DNA, and viral RNA from the viraemic timepoint were sequenced using a site-directed next-generation sequencing assay for the reverse transcriptase and gp41 genes. Neighbour-joining phylogenetic trees and direct sequence comparison were used to detect the presence of HIV superinfection. This study is registered with ClinicalTrials.gov, NCT02602262. FINDINGS:14 HIV-positive to HIV-positive kidney and eight liver transplant recipients were followed from March, 2016, to July, 2019. 17 recipients had adequate viral sequences allowing for HIV superinfection assessment. Eight donors were suppressed (viral load <400 copies per mL), and none had multiclass drug-resistant mutations detected. None of the recipients examined had evidence of HIV superinfection. One recipient had a viraemic episode (viral load of 2 080 000 copies per mL) 3 years after transplantation as a result of non-adherence to ART. Only recipient viral sequences were detected during the viraemic episode, suggesting that the donor virus, if present, was not reactivated despite temporary withdrawal of ART. INTERPRETATION:These findings suggest that loss of HIV suppression due to donor-derived HIV superinfection might not be a significant clinical concern in carefully monitored ART suppressed HIV-positive organ recipients. FUNDING:US National Institute of Allergy and Infectious Diseases and National Cancer Institute.
PMCID:8073978
PMID: 32730756
ISSN: 2352-3018
CID: 5126542

National Trends in the Association of Race and Ethnicity With Predialysis Nephrology Care in the United States From 2005 to 2015

Purnell, Tanjala S; Bae, Sunjae; Luo, Xun; Johnson, Morgan; Crews, Deidra C; Cooper, Lisa A; Henderson, Macey L; Greer, Raquel C; Rosas, Sylvia E; Boulware, L Ebony; Segev, Dorry L
Importance:Predialysis nephrology care is associated with better survival among patients with end-stage kidney disease. Objective:To examine national trends in racial/ethnic disparities in receipt of predialysis nephrology care at least 1 year before dialysis initiation in the United States from 2005 to 2015. Design, Setting, and Participants:This national registry study assessed US registry data of 1 000 390 adults in the US Renal Data System who initiated maintenance dialysis treatment from January 1, 2005, to December 31, 2015, in multiple cross-sectional analyses. Multivariable logistic regression models were used to examine national trends in racial/ethnic disparities in receipt of predialysis nephrology care with adjustments for potential confounders. Data were analyzed April 17, 2020. Exposure:Race/ethnicity of the patients. Main Outcomes and Measures:Receipt of at least 12 months of predialysis nephrology care as determined by clinician-based documentation on the End Stage Renal Disease Medical Evidence Report Form CMS 2728. Results:Among 1 000 390 adults (57.2% male; 54.6% White, 27.8% Black, 14.0% Hispanic, and 3.6% Asian; mean [SD] age, 62.4 [15.6] years) who initiated maintenance dialysis in the United States from 2005 to 2015, 310 743 (31.1%) received at least 12 months of predialysis nephrology care. In 2005 to 2007, compared with White adults, the adjusted odds ratio for receipt of at least 12 months of predialysis nephrology care was 0.82 (95% CI, 0.80-0.84) among Black adults, 0.67 (95% CI, 0.65-0.69) among Hispanic adults, and 0.84 (95% CI, 0.80-0.89) among Asian adults; in 2014 to 2015, the adjusted odds ratio was 0.76 (95% CI, 0.74-0.78) among Black adults, 0.61 (95% CI, 0.60-0.63) among Hispanic adults, and 0.90 (95% CI: 0.86-0.95) among Asian adults. Conclusions and Relevance:In this cross-sectional study of more than 1 million US adults with end-stage kidney disease, racial and ethnic disparities in predialysis nephrology care did not substantially improve from 2005 to 2015. Study findings suggest that national strategies to address racial/ethnic disparities in predialysis nephrology care are needed.
PMCID:7453308
PMID: 32852554
ISSN: 2574-3805
CID: 5126642

Outcomes After Declining a Steatotic Donor Liver for Liver Transplant Candidates in the United States

Jackson, Kyle R; Bowring, Mary G; Holscher, Courtenay; Haugen, Christine E; Long, Jane J; Liyanage, Luckmini; Massie, Allan B; Ottmann, Shane; Philosophe, Benjamin; Cameron, Andrew M; Segev, Dorry L; Garonzik-Wang, Jacqueline
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.
PMCID:8547552
PMID: 32732838
ISSN: 1534-6080
CID: 5126562

Poor Outcomes in Kidney Transplant Candidates and Recipients With History of Falls

Chu, Nadia M; Shi, Zhan; Berkowitz, Rachel; Haugen, Christine E; Garonzik-Wang, Jacqueline; Norman, Silas P; Humbyrd, Casey; Segev, Dorry L; McAdams-DeMarco, Mara A
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.
PMCID:7237294
PMID: 32732854
ISSN: 1534-6080
CID: 5126572

Minimizing Risks of Liver Transplantation With Steatotic Donor Livers by Preferred Recipient Matching

Jackson, Kyle R; Motter, Jennifer D; Haugen, Christine E; Long, Jane J; King, Betsy; Philosophe, Benjamin; Massie, Allan B; Cameron, Andrew M; Garonzik-Wang, Jacqueline; Segev, Dorry L
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.
PMCID:7237292
PMID: 32732837
ISSN: 1534-6080
CID: 5126552

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

Jackson, Kyle R; Bowring, Mary G; Kernodle, Amber; Boyarsky, Brian; Desai, Niraj; Charnaya, Olga; Garonzik-Wang, Jacqueline; Massie, Allan B; Segev, Dorry L
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 0.210.25 , P < .001), and more likely to receive offers for donors 18-34 years old and KDPI < 35% (aIRR: 1.12 1.201.29 , 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 0.770.98 , 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.
PMCID:8555691
PMID: 32012451
ISSN: 1600-6143
CID: 5126162

Prescription patterns of opioids and non-steroidal anti-inflammatory drugs in the first year after living kidney donation: An analysis of U.S. Registry and Pharmacy fill records

Vest, Luke S; Sarabu, Nagaraju; Koraishy, Farrukh M; Nguyen, Minh-Tri; Park, Meyeon; Lam, Ngan N; Schnitzler, Mark A; Axelrod, David; Hsu, Chi Yuan; Garg, Amit X; Segev, Dorry L; Massie, Allan B; Hess, Gregory P; Kasiske, Bertram L; Lentine, Krista L
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 aORUCL ). 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 1.381.53 ), less than college education (aOR,1.19 1.311.43 ), smoking (aOR,1.33 1.451.58 ), and nephrectomy complications (aOR,1.11 1.291.49 ). 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.
PMCID:7449599
PMID: 32502285
ISSN: 1399-0012
CID: 5126412