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Pancreas Transplantation from Hepatitis C Viremic Donors to Uninfected Recipients

Lonze, Bonnie E; Baptiste, Gillian; Ali, Nicole M; Dagher, Nabil N; Gelb, Bruce E; Mattoo, Aprajita; Soomro, Irfana; Tatapudi, Vashista S; Montgomery, Robert A; Stewart, Zoe A
Despite utilization of hepatitis C viremic organs for hepatitis C naïve recipients (HCV D+/R-) in other solid organ transplants, HCV viremic pancreata remain an unexplored source of donor organs. This study reports the first series of HCV D+/R- pancreas transplants. HCV D+/R- had shorter wait list times compared to HCV D-/R-, waiting a mean of 16 days from listing for HCV positive organs. HCV D+/R- had a lower match allocation sequence than HCV D-/R-, and this correlated to receipt of organs with a lower Pancreas Donor Risk Index (PDRI) score. All HCV D+R- had excellent graft function with a mean follow up of 438 days and had undetectable HCV RNA levels by a mean of 23 days after initiation of HCV-directed therapy. The rates of infectious complications, re-operation, readmission, rejection, and length of stay were not impacted by donor HCV status. A national review of potential ideal pancreas donors found that 37% of ideal HCV negative pancreas allografts were transplanted, compared to only 5% of ideal HCV positive pancreas allografts. The results of the current study demonstrate the safety of accepting HCV positive pancreata for HCV naïve recipients and advocates for increased utilization of ideal HCV positive pancreas allografts.
PMID: 33346951
ISSN: 1600-6143
CID: 4726692

COVID-19 Antibodies and Outcomes among Outpatient Maintenance Hemodialysis Patients

Khatri, Minesh; Islam, Shahidul; Dutka, Paula; Carson, John; Drakakis, James; Imbriano, Louis; Jawaid, Imran; Mehta, Tapan; Miyawaki, Nobuyuki; Wu, Elain; Yang, Stephen; Ali, Nicole; Divers, Jasmin; Grant, Candace; Masani, Naveed
Background/UNASSIGNED:Patients on maintenance hemodialysis are particularly vulnerable to infection and hospitalization from severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). Due to immunocompromised patients and the clustering that occurs in outpatient dialysis units, the seroprevalence of COVID-19 antibodies in this population is unknown and has significant implications for public health. Also, little is known about their risk factors for hospitalization. Methods/UNASSIGNED:nasopharyngeal, real-time, reverse-transcriptase PCR (RT-PCR); SARS-CoV-2 IgG seropositivity; hospitalization; and mortality. Results/UNASSIGNED:<0.001) compared with those who tested negative. Higher positivity rates were also observed among those who took taxis and ambulettes to and from dialysis, compared with those who used personal transportation. Antibodies were detected in all of the patients with a positive PCR result who underwent serologic testing. Of those that were seropositive, 32% were asymptomatic. The hospitalization rate on the basis of either antibody or PCR positivity was 35%, with a hospital mortality rate of 33%. Aside from COPD, no other variables were more prevalent in patients who were hospitalized. Conclusions/UNASSIGNED:We observed significant differences in rates of COVID-19 infection within three outpatient dialysis units, with universal seroconversion. Among patients with ESKD, rates of asymptomatic infection appear to be high, as do hospitalization and mortality rates.
PMCID:8740990
PMID: 35373027
ISSN: 2641-7650
CID: 5219442

Impact of the COVID-19 Pandemic on Induction Immunosuppression Selection in Kidney Transplant Recipients in New York City [Meeting Abstract]

Weldon, Elaina; Khalil, Karen; Jonchhe, Srijana; Stern, Jeffrey; Lewis, Tyler; Ali, Nicole; Stewart-Lewis, Zoe
ISI:000605453000050
ISSN: 1600-6135
CID: 4816182

Evaluation and Transplantation of a SARS-CoV-2 Seropositive Kidney Candidate [Case Report]

Graves, Maya C; Mehta, Sapna A; Lonze, Bonnie E; Ali, Nicole M
The COVID-19 pandemic affected transplant center activity in areas with high number of cases such as New York City and prompted reevaluation of patients awaiting organ transplant diagnosed with SARS-CoV-2 infection. To resume safe transplantation at our center, we found it necessary to (1) identify transplant candidates with possible exposure to or history of COVID-19 infection, (2) outline a clinical and laboratory assessment to determine adequate clinical recovery from COVID-19 for transplantation, and (3) determine whether the possibility of perioperative COVID-19 transmission from the patient to staff would pose unacceptable risk. Here, we describe our center's approach to proceeding with transplantation in a SARS-CoV-2 seropositive living donor kidney transplant recipient and describe early posttransplant outcomes.
PMCID:7945674
PMID: 33747584
ISSN: 2090-6641
CID: 4836662

COVID-19 antibody responses in solid organ transplant recipients [Meeting Abstract]

Zervou, F; Ali, N; Neumann, H J; Pellett, Madan R; Mehta, S A
Background: Studies to date indicate that most adults develop IgG antibody to severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) within 6 weeks of COVID-19 symptom onset. The seroconversion rate of solid organ transplant recipients (SOTR) following COVID-19 is unknown. Elucidation of humoral immune responses following COVID-19 in SOTR may inform risk of reinfection and the development of safe and effective vaccines for immunocompromised hosts.
Method(s): We assessed the frequency of SARS-CoV-2 IgG detection among adult SOTR diagnosed with COVID-19 by nasopharyngeal PCR assays between 3/1/2020 and 6/5/2020. SARS-CoV-2 IgG was detected in serum using the Abbott IgG assay at the manufacturer's recommended cut-off. Our primary objective was the frequency of SARS-CoV-2 IgG seropositivity after COVID-19. A secondary objective was to identify clinical factors associated with seroconversion. The mean age and nadir absolute lymphocyte count (ALC) were calculated between seropositive and negative SOTR and compared by Student's t-test.
Result(s): Among 93 SOTR diagnosed with COVID-19, 19 died before SARSCoV- 2 IgG testing could be performed, and 18 had testing pending as of abstract submission. 56 SOTR (44 kidney, 5 heart, 4 liver, 1 lung, and 1 heart-kidney recipients) completed testing and were included in the analysis. Median age was 58 years (IQR 49.5-67), and all received maintenance immunosuppression at the time of COVID-19 diagnosis with median nadir ALC during illness of 400 (IQR 200-600). SARS-CoV-2 IgG testing was performed at a median of 60 days (IQR 50-70) from symptom onset, the shortest interval being 16 days. 47 out of 56 SOTR tested positive for SARS-CoV-2 IgG. The likelihood of seroconversion was not different between those who were tested at < or >= 60 days from symptom onset (p=0.26), nor did it vary significantly by age (p =0.59), gender (p=0.53) or nadir ALC (p =0.28).
Conclusion(s): 83% of evaluated SOTR with COVID-19 disease had detectable SARS-CoV-2 IgG in serum at a median of 60 days after symptom onset. Studies are ongoing to identify variables associated with poor antibody response among the nearly 20% of SOTR in this cohort who failed to seroconvert. The significance of seroconversion on risk of reinfection and vaccine immunogenicity remains to be determined
EMBASE:634732194
ISSN: 2328-8957
CID: 4841502

Outpatient management of kidney transplant recipients with suspected COVID-19-Single-center experience during the New York City surge

Mehta, Sapna A; Leonard, Jeanette; Labella, Pauline; Cartiera, Katarzyna; Soomro, Irfana; Neumann, Henry; Montgomery, Robert A; Ali, Nicole M
Data describing the clinical progression of coronavirus disease 2019 (COVID-19) in transplant recipients are limited. In New York City during the surge in COVID-19 cases, a systematic approach to monitoring and triaging immunocompromised transplant patients was required in the context of strained healthcare resources, limited outpatient testing, and heightened hospital exposure risks. Public health guidance at the onset of the COVID-19 outbreak recommended outpatient monitoring of mildly symptomatic patients without specific recommendations for special populations such as transplant recipients. We developed and implemented a systematic monitoring algorithm for kidney transplant recipients at our transplant center who reported mild symptoms suggestive of COVID-19. We describe the outcomes of the first 44 patients monitored through this algorithm. A total of 44 kidney transplant recipients thought to be symptomatic for COVID-19 disease were followed for a minimum of 14 days. The majority of mildly symptomatic patients (34/44) had clinical progression of disease and were referred to the emergency department where they all tested PCR positive and required hospitalization. More than half of these patients presented with hypoxia requiring supplemental oxygen, 39% were intubated within 48 hours, and 53% developed acute kidney injury but did not require dialysis. There were 6 deaths. During surge outbreaks, kidney transplant patients with even mild symptoms have a high likelihood of COVID-19 disease and most will worsen requiring hospitalization for supportive measures. Earlier outpatient testing and hospitalization may improve COVID-19 outcomes among transplant recipients.
PMID: 32578324
ISSN: 1399-3062
CID: 4514502

Utilization of HCV+ pancreas donors signif cantly shortens the wait time for HCV-recipients [Meeting Abstract]

Baptiste, G; Lonze, B; Dagher, N; Gelb, B; Ali, N; Montgomery, R; Lewis, Z S
Background: Clinical trials have demonstrated the safety of utilizing hepatitis C viremic donors (HCV+) to expand the donor pool through transplantation into hepatitis C naive recipients (HCV-). However, there has been a lack of enthusiasm to of er HCV+ pancreas grafts to HCV- recipients. We of ered HCV- pancreas patients the option to list for HCV+ donor organs.
Material(s) and Method(s): Patients undergoing pancreas transplant evaluation had informed consent by a transplant physician to receive HCV+ donor organs. We ensured patients had pharmacy coverage for post-transplant HCV anti-retroviral therapy prior to listing. In our early experience, 4 of our 8 transplant recipients elected to list for HCV+ donor organs.
Result(s): In the first 8 months, the average time to transplant from listing was 41 days for patients with standard listing and 21 days for patients listing for HCV+ organs (p<0.05). Of note, 2 of the 4 HCV- recipients were blood type AB and had shorter match time due to their blood type. For all HCV+ donors, COD was anoxia/drug OD, all were HCV antibody and NAT positive, PHS IR, and national imports, with average rank of 3 on the match run. All HCV- donors were local donors with average rank of 21 on the match run. HCV+ donors were younger (28 years) in contrast to HCV- donors (35 years). All recipients have excellent graft function with no signif cant dif erences in complications, LOS, or readmissions.
Conclusion(s): Utilization of HCV+ pancreas donors has allowed our patients increased access to high quality pancreas donors with signif cantly shorter wait times
EMBASE:631496848
ISSN: 1600-6143
CID: 4400302

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

IdeS (Imlifidase): A Novel Agent That Cleaves Human IgG and Permits Successful Kidney Transplantation Across High-strength Donor-specific Antibody

Lonze, Bonnie E; Tatapudi, Vasishta S; Weldon, Elaina P; Min, Elijah S; Ali, Nicole M; Deterville, Cecilia L; Gelb, Bruce E; Benstein, Judith A; Dagher, Nabil N; Wu, Ming; Montgomery, Robert A
OBJECTIVES/OBJECTIVE:The presence of a donor-specific positive crossmatch has been considered to be a contraindication to kidney transplantation because of the risk of hyperacute rejection. Desensitization is the process of removing hazardous preformed donor-specific antibody (DSA) in order to safely proceed with transplant. Traditionally, this involves plasmapheresis and intravenous immune globulin treatments that occur over days to weeks, and has been feasible when there is a living donor and the date of the transplant is known, allowing time for pre-emptive treatments. For sensitized patients without a living donor, transplantation has been historically difficult. SUMMARY OF BACKGROUND DATA/BACKGROUND:IdeS (imlifidase) is an endopeptidase derived from Streptococcus pyogenes which has specificity for human IgG, and when infused intravenously results in rapid cleavage of IgG. METHODS:Here we present our single-center's experience with 7 highly sensitized (cPRA98-100%) kidney transplant candidates who had DSA resulting in positive crossmatches with their donors (5 deceased, 2 living) who received IdeS within 24 hours prior to transplant. RESULTS:All pre-IdeS crossmatches were positive and would have been prohibitive for transplantation. All crossmatches became negative post-IdeS and the patients underwent successful transplantation. Three patients had DSA rebound and antibody-mediated rejection, which responded to standard of care therapies. Three patients had delayed graft function, which ultimately resolved. No serious adverse events were associated with IdeS. All patients have functioning renal allografts at a median follow-up of 235 days. CONCLUSION/CONCLUSIONS:IdeS may represent a groundbreaking new method of desensitization for patients who otherwise might have no hope for receiving a lifesaving transplant.
PMID: 30004918
ISSN: 1528-1140
CID: 3192712

Early Graft Function Correlates with Survival Benefit in Kidney Transplant Recipients with Peripheral Vascular Disease. [Meeting Abstract]

Min, E.; Tatapudi, V.; Ali, N.; Gelb, B.; Dagher, N.; Benstein, J.; Montgomery, R.; Lonze, B.
ISI:000431965403170
ISSN: 1600-6135
CID: 3140532