Faculty Bibliography

Transplanting hepatitis C viremic donor organs into hepatitis C virus (HCV)-negative recipients is becoming increasingly common; however, practices for posttransplant direct-acting antiviral (DAA) treatment vary widely. Protracted insurance authorization processes for DAA therapy often lead to treatment delays.

Antibody responses among immunocompromised solid organ transplant recipients (SOT) infected with Severe Acute Respiratory Syndrome Coronavirus-2 (SARS-CoV-2) may be diminished compared to the general population and have not been fully characterized. We conducted a cohort study at our transplant center to investigate the rate of seroconversion for SARS-CoV-2 IgG antibodies among SOT recipients who were diagnosed with Coronavirus disease 2019 (COVID-19) and underwent serum SARS-CoV-2 IgG enzyme-linked immunosorbent assay (ELISA) testing. The 61 patients who were included in the final analysis underwent initial SARS-CoV-2 IgG testing at a median of 62 days (Interquartile range 55.0-75.0) from symptom onset. Note that, 51 of 61 patients (83.6%) had positive SARS-CoV-2 IgG results, whereas 10 (16.4%) had negative IgG results. Six (60%) out of 10 seronegative patients underwent serial IgG testing and remained seronegative up to 17 weeks post-diagnosis. Use of belatacept in maintenance immunosuppression was significantly associated with negative IgG antibodies to SARS-CoV-2 both in univariate and multivariate analyses (Odds ratio 0.04, p = .01). In conclusion, the majority of organ transplant recipients with COVID-19 in our study developed SARS-CoV-2 antibodies. Further longitudinal studies of the durability and immunologic role of these IgG responses and the factors associated with lack of seroconversion are needed.

The current kidney allocation system (KAS) preferentially allocates kidneys from blood type A2 or A2B (A/A2B) donors to blood type B candidates. We used national data to evaluate center-level performance of A2/A2B to B transplants, and organ procurement organization (OPO) reporting of type A or AB donor subtyping, in 5-year time periods prior to (2009-2014) and following (2015-2019) KAS implementation. The number of centers performing A2/A2B to B transplants increased from 17 pre-KAS to 76 post-KAS, though this still represents only a minority of centers (7.3% pre-KAS and 32.6% post-KAS). For high-performing centers, the median net increase in A2/A2B to B transplants was 19 cases (range -2-72) per center in the 5 years post-KAS. The median net increase in total B recipient transplants was 21 cases (range -17-119) per center. Despite requirements for performance of subtyping, in 2019 subtyping was reported on only 56.4% of A/AB donors. This translates into potential missed opportunities for B recipients, and even post-KAS up to 2322 A2/A2B donor kidneys may have been allocated for transplantation as A/AB. Further progress must be made both at center and OPO levels to broaden implementation of A2/A2B to B transplants for the benefit of underserved recipients.

Purpose: Assessment and early detection of allograft injury in simultaneous pancreas and kidney (SPK) transplant recipients has clear benefits for optimizing treatment and intervention. Donor-derived cell-free DNA (dd-cfDNA) is an established biomarker for surveillance of kidney transplant recipients and an increasing body of evidence supports its utility in SPK transplantation.
Method(s): SPK patients were monitored prospectively with dd-cfDNA (AlloSure, CareDx Brisbane), initiated at the discretion of the treating physician. dd-cfDNA was drawn concomitantly with standard of care laboratory testing including serum creatinine, amylase, lipase, DSA and BK PCR. Pancreatic graft dysfunction was defined by elevations in serum amylase and lipase or dysregulated glucose control.
Result(s): A total of 9 SPK patients were identified with a total of 49 AlloSure ddcfDNA results. Median patient age was 48 years (range 26-56). There were 5 females (56%) recipients, 2 Caucasian (22%), 3 Black (33%) and 4 Hispanic (44%) recipients. 6 SPK patients had stable graft function and 3 SPK patients developed pancreatic graft dysfunction. The median AlloSure dd-cfDNA level in stable SPK patients was 0.18% (IQR 0.12-0.39%, Figure 1). One SPK recipient with stable pancreatic enzymes had an AlloSure dd-cfDNA level of 1.3% in the setting of sub-therapeutic tacrolimus levels, which normalized with titration of immunosuppression. Of the 3 SPK recipients with pancreatic graft dysfunction, 1 patient had an AlloSure ddcfDNA level of 3.5% associated with clinical allograft rejection. AlloSure dd-cfDNA levels decreased to 0.14% within 1 month of empiric treatment. The remaining 2 SPK recipients with graft dysfunction had paired AlloSure dd-cfDNA levels of 0.42% and 0.52%. These patients were subsequently diagnosed with a bowel obstruction and partial splenic vein thrombosis as the cause for graft dysfunction.
Conclusion(s): In stable SPK recipients, AlloSure dd-cfDNA levels remain low during the post-transplant course. In this case series, AlloSure dd-cfDNA was able to differentiate allograft injury associated with rejection from alternative etiologies of graft dysfunction. Elevated dd-cfDNA levels associated with rejection and subtherapeutic immunosuppression decreased following intervention. Further studies are required to further define reference values and response to intervention. (Table Presented)

Purpose: As an early epicenter in the coronavirus pandemic, our center modified induction immunosuppression strategies for transplantation. We sought to determine if changes in induction immunosuppression secondary to the COVID-19 pandemic impacted the incidence of acute rejection.
Method(s): Adult kidney transplant recipients at NYU Langone Health between 09/2019 and 08/2020 were retrospectively identified. Patients who received a multiorgan transplant or whose induction regimen was changed due to clinical course were excluded. Patients transplanted before and after 3/17/2020 were grouped as pre-pandemic (PRE) and post-pandemic (POST), respectively, based on temporary interruption of transplantation. Induction immunosuppression discordance was identified by blind adjudication from a standard protocol. Reduced induction agent use (basiliximab given when pre-pandemic protocol indicated rabbit anti-thymocyte globulin (rATG)) was compared between groups using a Chi-square test. Biopsyproven acute rejection (BPAR) and the incidence of rejection was compared using a Poisson regression model.
Result(s): 203 kidney transplant recipients were retrospectively identified. 38 patients were excluded, leaving 165 patients for analysis. Median patient age was 57 years, 67% were male, and diabetes mellitus (35%) was the most common cause of renal disease. Discordance from protocol induction agent was 16% in the PRE group and 28% in the POST group (p=0.06). More patients received reduced induction with basiliximab in lieu of rATG in the POST group than the PRE group (26% vs. 7%, p=0.001). BPAR occurred in 5 PRE (5%) and 6 POST (11%) patients (p=0.19). The incidence of rejection was 0.13 and 0.75 rejection episodes/1,000-patient days for the PRE and POST groups, respectively; this was significantly different between the 2 time periods (unadjusted IRR 5.69, 95% CI 1.74-18.6, p=0.004).
Conclusion(s): More patients received reduced induction immunosuppression driven by the COVID-19 pandemic concerns. These COVID-related changes in immunosuppression may have contributed to a trend in increased acute rejection in a preliminary analysis

Purpose: The presentation of Coronavirus disease 2019 (COVID-19) ranges from mild illness to severe respiratory failure. Disease progression may differ in immunocompromised patients and immunocompetent hosts. Therefore, we aim to characterize COVID-19 clinical presentation and outcomes in solid organ transplant recipients (SOTRs) to identify initial clinical factors that may predict COVID-19 associated mortality.
Method(s): We prospectively reviewed baseline demographic and clinical characteristics among adult kidney, pancreas, liver, heart and lung transplant recipients diagnosed with COVID-19 between March 1, 2020 and May 5, 2020 at our transplant center in New York City. A series of chi-square and Fisher's exact tests were conducted to investigate the relationship between several predictor variables (baseline characteristics, symptoms at presentation, and baseline immunosuppression regimen) and 30-day mortality.
Result(s): 73 SOTRs (53 kidney, 8 liver, 7 heart, 3 lung, 2 heart/kidney) with SARSCoV-2 PCR-confirmed COVID-19 were included in the final analysis. Median age was 59 years (IQR 54-68) and 34.2% were female. Median time since transplant was 21 months (IQR 13-46.5). All patients were on baseline immunosuppresion as shown in table 1. The majority of patients were diagnosed in the Emergency Department. Most common presenting symptoms were cough (68.5%), gastrointestinal symptoms (54.8%) and dyspnea (45.2%) with median of 5 days from symptom onset to hospitalization. All patients had elevated inflammatory markers at time of diagnosis (median CRP 54 mg/L, median ferritin 704 ng/mL, median procalcitonin 0.11 ng/mL, median D-dimer 311 ng/mL). 84.1% of patients required supplemental oxygen, including intubation in 19.7%. 13 of 63 (21%) hospitalized patients died. Dyspnea on presentation was the only baseline or presenting patient factor found to be predictive of death (p =.004). When stratified by initial chest X-ray findings, dyspnea combined with abnormal chest X-ray predicted mortality (p=.021) while dyspnea with normal chest X-ray did not.
Conclusion(s): Presenting symptoms of dyspnea and radiographic signs of pneumonia on initial imaging predicted mortality among SOTRs with COVID-19 in our cohort. These findings can inform allocation of limited resources in COVID-19 management, including the triage and timing of COVID-19 directed therapies early in the illness course among different patient populations

Purpose: Utilization of HCV viremic donor kidneys for transplant into HCV naive recipients has become more widespread, yet best practices governing the initiation, timing or duration of direct acting antiviral (DAA) therapy are lacking. Most published series describe DAA initiation weeks to months after transplant. However, fibrosing cholestatic hepatitis has been reported with delayed DAA initiation. Herein we report our center practice utilizing donor blood for HCV genotyping to expedite DAA insurance approval and minimize the duration of recipient viremia.
Method(s): Patients received education and DAA insurance benefits were ensured prior to listing for HCV+ organs. At the time of transplant, donor blood accompanying the kidney was used for HCV genotyping. Results were received within one week of transplant. Recipients were screened for HCV RNA by POD#4, and weekly for 12 weeks. Insurance authorization for DAA coverage was sought after both recipient viremia and donor HCV genotyping resulted. In 3 cases, donor viral load was insufficient for genotyping, and these recipients were genotyped once viremic.
Result(s): 80 hepatitis C naive patients received hepatitis C positive donor kidneys between July, 2018 and October, 2020. 17 donors were HCV Ab+/NAT-and 63 donors were HCV Ab+/NAT+. All recipients of NAT+ donor organs became viremic; 89% were genotype 1a or 3. The median time to DAA initiation was 10 days for cases with donor genotyping (IQR 8-13). In contrast, the median time to DAA initiation was 20 days for the 3 cases with recipient genotyping (IQR 18-24). Median time from transplant to clearance of HCV viremia was 38 days (IQR 30-47) (Table 1). SVR12 was achieved in all patients, and no cases of fibrosing cholestatic hepatitis have been observed. There were 2 needlestick exposures of patient family members, though no HCV transmission occurred.
Conclusion(s): Early HCV genotyping using donor blood results in expedited initiation of DAA therapy for recipients of HCV+ kidneys. Compared to published reports, our patients are clearing viremia at the time that most other centers' patients are initiating DAA therapy. Whether duration of viremia or peak viral load are associated with adverse allograft events such as acute rejection is not known. The advantages to a shortened duration of HCV viremia remain to be characterized, but may include a lower risk of fibrosing cholestatic hepatitis and lower risk of HCV exposure to family members and caregivers. Our practice of expedited genotyping using donor blood is immediately implementable at all centers performing these transplants. (Table Presented)

Purpose: Blood type B candidates on the deceased donor kidney waitlist have a lower transplantation rate and longer wait time than candidates of other blood types. The new national kidney allocation system (KAS), implemented in December 2014, prioritizes the allocation of kidneys from blood type A2 and A2B deceased donors to blood type B candidates to mitigate this disparity in access to transplantation. We analyzed our center's data to determine whether blood type A2/A2B to B transplantation is clinically feasible without the need for additional immunosuppression.
Method(s): We conducted a single-center retrospective cohort study to analyze the utilization and outcomes in A2/A2B to B deceased donor renal transplants. Data on adult, kidney-only recipients were extracted with custom reports from the United Network for Organ transplantation (UNOS) portal. We used multivariable Coxproportional hazards models to compare graft and patient survival in blood type A2/A2B to B deceased donor renal transplants to survival in blood type B to B transplants. We estimated Kaplan-Meier (KM) graft and patient survival functions.
Result(s): Since 2015, our center has performed 44 A2/A2B to B and 65 B to B kidney transplants. We followed the patients for a median of 712 days (IQR 343-1143). Recipients of A2/A2B to B and B to B kidney transplants were similar with respect to age, gender, estimated post-transplant survival (EPTS), calculated panel reactive antibody (CPRA), HLA ABDR mismatch, kidney donor profile index (KDPI), and the incidence of delayed graft function (DGF). A higher percentage of A2/A2B to B transplant recipients were Black/African American (22/44, 50%) than B to B transplant recipients (14/65, 21.5%). Blood type A2/A2B to B and B to B transplant recipients had similar 1-year graft (97.7% vs. 93.8%, p=0.34) and 1-year patient survival (97.7% vs. 98.5%, p=0.78) rates. Multivariable models adjusted for race/ ethnicity showed that death censored graft survival (adjusted HR=1.45, p=0.70, 95% CI=0.21 to 9.82) and patient survival (4.22, p=0.14, 95% CI=0.64 to 27.92) in A2/A2B to B transplant recipients were similar to the traditionally ABO blood type compatible B to B transplants.
Conclusion(s): The NYU Langone blood type A2/A2B to B transplantation adds to the body of evidence suggesting that blood type A2/A2B to B transplantation is clinically feasible. This provision of the KAS appears to be having its intended effect of increasing access to transplantation in blood type B candidates with no attendant compromise in overall patient or death censored graft survival