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Successful A2 to B Deceased Donor Kidney Transplant after Desensitization for High-Strength Non-HLA Antibody Made Possible by Utilizing a Hepatitis C Positive Donor [Case Report]

Karpel, H Charli; Ali, Nicole M; Lawson, Nikki; Tatapudi, Vasishta S; Friedlander, Rex; Philogene, Mary Carmelle; Montgomery, Robert A; Lonze, Bonnie E
Desensitization using plasma exchange can remove harmful antibodies prior to transplantation and mitigate risks for hyperacute and severe early acute antibody-mediated rejection. Traditionally, the use of plasma exchange requires a living donor so that the timing of treatments relative to transplant can be planned. Non-HLA antibody is increasingly recognized as capable of causing antibody-mediated renal allograft rejection and has been associated with decreased graft longevity. Our patient had high-strength non-HLA antibody deemed prohibitive to transplantation without desensitization, but no living donors. As the patient was eligible to receive an A2 ABO blood group organ and was willing to accept a hepatitis C positive donor kidney, this afforded a high probability of receiving an offer within a short enough time frame to attempt empiric desensitization in anticipation of a deceased donor transplant. Fifteen plasma exchange treatments were performed before the patient received an organ offer, and the patient was successfully transplanted. Hepatitis C infection was treated posttransplant. No episodes of rejection were observed. At one-year posttransplant, the patient maintains good graft function. In this case, willingness to consider nontraditional donor organs enabled us to mimic living donor desensitization using a deceased donor.
PMCID:7094197
PMID: 32231847
ISSN: 2090-6943
CID: 4371402

Single And Double Lung Transplantation Have Equivalent Survival for Idiopathic Pulmonary Fibrosis

Ranganath, Neel K; Malas, Jad; Phillips, Katherine G; Lesko, Melissa B; Smith, Deane E; Angel, Luis F; Lonze, Bonnie E; Kon, Zachary N
BACKGROUND:Several studies have described improved survival with double lung transplantation (DLT) compared to single lung transplantation (SLT) in pulmonary fibrosis. To avoid the innate selection bias of including patients exclusively listed for SLT or DLT, this study analyzed those deemed appropriate for either procedure at time of listing. METHODS:All consecutive adult lung transplants for idiopathic pulmonary fibrosis (IPF) provided by the Scientific Registry of Transplant Recipients were retrospectively reviewed (2007-2017). Isolated lobar transplants (N=11), or patients listed only for SLT (N=1834) or DLT (N=2372) were excluded. Group stratification was based on the ultimate procedure (SLT vs DLT). Group propensity matching was performed based on 24 recipient/donor characteristics. Recipient demographics, donor demographics, and outcomes were compared between groups. RESULTS:During the study period, 45% (974/2179) and 55% (1205/2179) of patients ultimately received SLT and DLT, respectively. After propensity matching, 466 matched patients remained in each group. SLT patients were less likely to require prolonged (>48 hours) ventilator support than DLT patients. There was also a trend towards reduced rates of post-transplant renal failure and hospital length of stay in SLT recipients. Whether analyzed by time of listing or time of transplant, survival was similar between groups. CONCLUSIONS:In recipients concurrently listed for SLT and DLT, overall survival was similar regardless of the eventual procedure. These data suggests that the previously purported survival advantage for DLT may purely represent selection bias, and should not preclude the use of SLT in appropriately-selected IPF patients.
PMID: 31445911
ISSN: 1552-6259
CID: 4054102

Risk factors and outcomes associated with early airway dehiscence following lung transplantation [Meeting Abstract]

Ranganath, N; Malas, J; Phillips, K G; Bittle, G J; Lesko, M B; Angel, L F; Lonze, B E; Kon, Z N
Objective: Anastomotic complications occur in 77%-18% of lung transplants, but no large multi-institutional analyses to determine risk factors for airway dehiscence (AD) exist. Using national registry data, we compared pre-operative recipient/donor risk factors and post-operative outcomes in patients with and without AD.
Method(s): Data on adult lung transplants between 2007 and 2017 were provided by the Scientifc Registry of Transplant Recipients. Recipient/donor demographics were compared with regards to AD, and multivariable logistic regression identifed independent risk factors for AD. Kaplan-Meier curves and log-rank tests described mortality and graft survival.
Result(s): Two hundred and seventy-fve/18,122 recipients (1.5%) experienced AD. These recipients were more often male (71.6% vs. 59.6%, P < 0.001), obese (20.1% vs. 15.6%, P = 0.041), transplanted from intensive care unit (17.5% vs. 1 1 . 0 % , P = 0.001), and mechanically ventilated (11.6% vs. 6.9%, P = 0.002). AD was not associated with recipient steroid use (51.9% vs. 47.7%, P = 0.194) or lung disease diagnosis group. Donor diabetes (8.0% vs. 7.0%, P = 0.482) and donor smoking (7.4% vs. 9.0%, P = 0.449) were also not associated with AD. Patients with AD were more likely to have received bilateral lungs (78.5% vs. 68.3%, P < 0.001) and less likely to have received a single left lung (6.5% vs. 17.3%, P < 0.001). Cold ischemia time between 2 and 4 hours was less common in the AD group (17.2% vs. 23.7%, P = 0.013). Multivariable analysis revealed recipient obesity and donor gunshot death as independent predictive factors for AD, while donor age >40 and single left lung transplant were negative predictive factors (Table SA10-1). Mortality and graft failure were both signifcantly higher in the AD group (Fig. SA10-1).
Conclusion(s): We identifed independent risk factors for AD and confrmed poor post-operative outcomes. However, many known impediments to wound healing such as chronic steroid use, diabetes, and smoking did not appear to be associated with AD
EMBASE:632150686
ISSN: 1559-0879
CID: 4523902

Safety and Efficacy of Imlifidase in Highly-Sensitized Kidney Transplant Patients: Results from a Phase 2 Study. [Meeting Abstract]

Jordan, S. C.; Legendre, C.; Desai, N.; Lorant, T.; Bengtsson, M.; Laxmyr, L.; Lonze, B.; Vo, A.; Wood, K. J.; Kjellman, C.; Montgomery, R. A.
ISI:000474897601029
ISSN: 1600-6135
CID: 4026392

Early airway dehiscence: Risk factors and outcomes with the rising incidence of extracorporeal membrane oxygenation as a bridge to lung transplantation

Malas, Jad; Ranganath, Neel K; Phillips, Katherine G; Bittle, Gregory J; Hisamoto, Kazuhiro; Smith, Deane E; Lesko, Melissa B; Angel, Luis F; Lonze, Bonnie E; Kon, Zachary N
BACKGROUND:Anastomotic complications occur in 7% to 18% of lung transplant recipients, among which airway dehiscence (AD) is particularly catastrophic. Using multi-institutional registry data, this study compared preoperative recipient/donor risk factors and outcomes in patients with and without AD and analyzed the effect of extracorporeal membrane oxygenation (ECMO) on the incidence of AD. METHODS:Data on adult lung transplants from 2007 to 2017 were provided by the Scientific Registry of Transplant Recipients. Patients receiving isolated lobar transplantation and patients with unknown AD status were excluded. Multivariable logistic regression identified independent risk factors for AD. Kaplan-Meier curves and log-rank tests describe mortality and graft survival. RESULTS:Of 18 122 lung transplants, 275 (1.5%) experienced AD. While the incidence of ECMO steadily increased from 0.7% to 5.9% over the study period, the incidence of AD remained relatively constant. Multivariable analysis revealed recipient male gender and prolonged ( > 48 hours) posttransplant mechanical ventilation as independent predictive factors for AD, while advanced donor age and single left lung transplant were protective factors. Recipient chronic steroid use, recipient diabetes, donor diabetes, and donor smoking history were not predictive of AD. Mortality and graft failure were significantly worse in the AD group. CONCLUSIONS:Despite increased ECMO utilization, the incidence of AD has remained stable. Multiple independent risk factors for AD were identified and poor postoperative outcomes confirmed. However, many known impediments to wound healing such as recipient chronic steroid use, recipient and donor diabetes, and donor smoking were not identified as risk factors for AD, reinforcing the critical role of technical performance.
PMID: 31334904
ISSN: 1540-8191
CID: 3986962

Impact of the Opioid Epidemic on Lung Transplantation: Donor, Recipient and Discard Characteristics

Phillips, Katherine G; Ward, Alison F; Ranganath, Neel K; Malas, Jad; Lonze, Bonnie E; Moazami, Nader; Angel, Luis F; Kon, Zachary N
BACKGROUND:The national opioid epidemic may have expanded the donor pool for lung transplantation, but concerns remain regarding infectious risks and allograft function. This study compared donor/recipient characteristics, outcomes, and reasons for organ discard between overdose death donors (ODD) and all other mechanism-of-death donors. METHODS:Data on adult lung transplants from 2000-2017 were provided by the Scientific Registry of Transplant Recipients. Pulmonary allografts used in multiple organ transplantations were excluded. Donor/recipient demographics, outcomes, and organ discard were analyzed with regards to ODD since 2010. Discard analysis was limited to donors who had at least one organ transplanted but their pulmonary allografts discarded. RESULTS:From 2010-2017, 7.3% (962/13,196) of lung transplantations were from ODD, over a 3-fold increase from the 2.1% (164/7,969) in 2000-2007. ODD were younger but more likely to have a history of smoking, hepatitis C, or an abnormal bronchoscopy finding. Overall survival was similar between ODD and non-ODD groups. ODD of discarded pulmonary allografts were younger and more likely to be hepatitis C positive, but were less likely to have a history of smoking than their non-ODD counterparts. CONCLUSIONS:Rates of ODD utilization in lung transplantation have increased in accordance with the opioid epidemic, but there remains a significant pool of ODD pulmonary allografts with favorable characteristics that are discarded. With no significant difference in survival between ODD and non-ODD recipients, further expansion of this donor pool may be appropriate and pulmonary allografts should not be discarded based solely on ODD status.
PMID: 31323210
ISSN: 1552-6259
CID: 3978102

Impact of the Opioid Epidemic on Heart Transplantation: Donor Characteristics and Organ Discard

Phillips, Katherine G; Ranganath, Neel K; Malas, Jad; Lonze, Bonnie E; Gidea, Claudia G; Smith, Deane E; Kon, Zachary N; Reyentovich, Alex; Moazami, Nader
BACKGROUND:The national opioid epidemic has expanded the donor pool for heart transplantation, but concerns remain regarding infectious risk and allograft function. This study compared donor and recipient characteristics, outcomes, and reasons for organ discard between overdose-death donors (ODDs) and donors with all other mechanism of death. METHODS:Data on adult cardiac transplants from 2010 to 2017 were provided by the Scientific Registry of Transplant Recipients. Cardiac allografts used in multiple organ transplantations were excluded. Recipient and donor characteristics and organ discard were analyzed with regard to ODDs. Kaplan-Meier curves and log-rank tests described mortality survival. RESULTS:A total of 1,710 of 15,904 (10.8%) cardiac transplantations were from ODDs, approximately a 10-fold increase from 2000 (1.2%). ODDs were more frequently older than 40 years of age (87.2% vs 70.1%; p < 0.001), had higher rates of substance abuse, were more likely hepatitis C positive (1.3% vs 0.2%; p < 0.001), and less frequently required inotropic support at the time of procurement (38.4% vs 44.8%; p < 0.001). Overall survival was not different between the groups (p = 0.066). Discarded ODD allografts were more likely to be hepatitis C positive (30.8% vs 5.3%; p < 0.001) and to be identified as conveying increased risk by the Public Health Services (63.3% vs 13.2%; p < 0.001), but they were less likely to be discarded because of a diseased organ state (28.2% vs 36.1%; p < 0.001). CONCLUSIONS:Rates of ODDs have increased corresponding with the worsening opioid epidemic. Even though ODDs have higher rates of hepatitis C, cardiac allograft quality indices are favorable, and recipient outcomes are similar when compared with non-ODDs, a finding indicating that greater use of this donor pool may be appropriate.
PMID: 31178157
ISSN: 1552-6259
CID: 3929762

Clinical Experience with Heart Transplantation from Hepatitis C Positive Donors [Meeting Abstract]

Reyentovich, A.; Gidea, C.; Smith, D.; Lonze, B.; Pavone, J.; Katz, S.; Pan, S.; Rao, S.; Saraon, T.; Moazami, N.
ISI:000461365100095
ISSN: 1053-2498
CID: 3803772

Cardiac Allografts from Overdosed Donors: An Underutilized Resource? [Meeting Abstract]

Ranganath, N K; Phillips, K G; Malas, J; Lonze, B E; Smith, D E; Kon, Z N; Gidea, C G; Reyentovich, A; Moazami, N
Purpose: The opioid epidemic has expanded the cardiac donor pool, but the concern for primary graft dysfunction (PGD) remains a barrier to wider utilization of these hearts. We analyzed donor characteristics in transplanted and discarded cardiac allografts from overdosed donors (ODD) to determine if viable ODD hearts are being unnecessarily discarded due to inappropriate bias. Method(s): Data on adult cardiac transplantation from 2010-2017 were provided by the SRTR. Eight donor characteristics associated with PGD were analyzed: age, gender, hypertension, high creatinine, cocaine abuse, inotropic support, LVEF, and cardiac arrest. Donor characteristics of transplanted and discarded hearts were compared between ODD and non-ODD. Result(s): ODD comprised 11% (1710/15904) of transplanted hearts and 7% (2600/32678) of discarded hearts. Among transplanted hearts, ODD more frequently were younger than 50 (98% vs 90%), did not have hypertension (86% vs 83%), and did not require inotropic support (62% vs 55%) compared to non-ODD; ODD less frequently were male (63% vs 70%), had no history of cocaine abuse (57% vs 84%), or had creatinine <=1.5 (62% vs 81%). Among discarded hearts, ODD more frequently were younger than 50 (87% vs 46%), had no history of hypertension (78% vs 49%), and did not require inotropic support (51% vs 41%); ODD less often had no history of cocaine abuse (50% vs 86%) or creatinine <=1.5 (61% vs 69%) (Table). Donors known to have at least 6 of 8 favorable qualities comprised 36% (942/2600) of discarded ODD hearts, compared to 28% (9152/32678) of discarded non-ODD hearts (p<0.001). The most common reasons given for discard of ODD hearts with favorable qualities were poor organ function (18%), refusal by all programs (16%), and lack of recipient (11%). Conclusion(s): ODD hearts with favorable qualities are being discarded at disproportionally higher rates than non-ODD hearts. Further studies and better documentation are needed to understand current discard practices and if further expansion into this donor pool is appropriate.
EMBASE:2001696439
ISSN: 1557-3117
CID: 3790552

Single and Double Lung Transplantation Have Equivalent Functional Status Outcomes at One Year [Meeting Abstract]

Ranganath, N K; Geraci, T C; Malas, J; Phillips, K G; Smith, D E; Lonze, B E; Lesko, M B; Angel, L F; Kon, Z N
Purpose: Controversy remains over the mortality benefit of single (SLT) versus double lung transplantation (DLT) in idiopathic pulmonary fibrosis (IPF). Independent of this controversy, hesitancy to perform SLT in this population exists on the basis of unclear one year functional status. We compared functional status at one year between IPF patients listed for both who ultimately received SLT or DLT. Method(s): All consecutive adult lung transplants for IPF provided by the Scientific Registry of Transplant Recipients were retrospectively reviewed (2007-2017). Isolated lobar transplants (n=4), patients listed only for SLT (n=1834) or DLT (n=2372), and patients with missing functional status data (n=715) were excluded. Group stratification was based on the ultimate procedure (SLT or DLT). Group propensity matching was performed based on 25 recipient/donor characteristics. We compared 'good functional status' defined as >70%, at one year. Result(s): During the study period, 45% (660/1464) and 55% (804/1464) of patients listed for both procedures ultimately received SLT and DLT, respectively. After propensity matching, 341 matched patients remained in each group. Donor and recipient characteristics were similar (Table). There was no statistically significant difference in 'good functional status' at one year between SLT (77%, 264/341) and DLT (81%, 275/341) (p=0.301). The same trend is present for patients younger than 50 who receive SLT (82%, 23/28) versus DLT (94%, 34/36) (p=0.225), and patients between 50 and 60 who receive SLT (78%, 86/110) versus DLT (84%, 97/115) (p=0.305). The opposite trend is noted in patients older than 70 who receive SLT (72%, 13/18) versus DLT (61%, 11/18) (p=0.725). Conclusion(s): In this cohort of lung transplant recipients listed for both SLT and DLT, functional status was statistically similar between groups, even in younger recipients. This data suggests that SLT should not be precluded in IPF patients on the basis of expected functional status at one year.
EMBASE:2001696071
ISSN: 1557-3117
CID: 3790602