Preemptively and non-preemptively transplanted patients show a comparable hypercoagulable state prior to kidney transplantation compared to living kidney donors.
ABSTRACT: To prevent renal graft thrombosis in kidney transplantation, centres use different perioperative anticoagulant strategies, based on various risk factors. In our centre, patients transplanted preemptively are considered at increased risk of renal graft thrombosis compared to patients who are dialysis-dependent at time of transplantation. Therefore these patients are given a single dose of 5000 IU unfractionated heparin intraoperatively before clamping of the vessels. We questioned whether there is a difference in haemostatic state between preemptively and non-preemptively transplanted patients and whether the distinction in intraoperative heparin administration used in our center is justified. For this analysis, citrate samples of patients participating in the VAPOR-1 trial were used and several haemostatic and fibrinolytic parameters were measured in 29 preemptively and 28 non-preemptively transplanted patients and compared to 37 living kidney donors. Sample points were: induction anaesthesia (T1), 5 minutes after reperfusion (T2) and 2 hours postoperative (T3). At T1, recipient groups showed comparable elevated levels of platelet factor 4 (PF4, indicating platelet activation), prothrombin fragment F1+2 and D-dimer (indicating coagulation activation) and Von Willebrand Factor (indicating endothelial activation) compared to the donors. The Clot Lysis Time (CLT, a measure of fibrinolytic potential) was prolonged in both recipient groups compared to the donors. At T3, F1+2, PF4 and CLT were higher in non-preemptively transplanted recipients compared to preemptively transplanted recipients. Compared to donors, non-preemptive recipients showed a prolonged CLT, but comparable levels of PF4 and D-dimer. In conclusion pre-transplantation, preemptively and non-preemptively transplanted patients show a comparable enhanced haemostatic state. A distinction in intraoperative heparin administration between preemptive and non-preemptive transplantation does not seem justified.
Project description:BACKGROUND AND OBJECTIVES:Long wait times for deceased donor kidneys and low rates of preemptive wait-listing have limited preemptive transplantation in the United States. We aimed to assess trends in preemptive deceased donor transplantation with the introduction of the new Kidney Allocation System (KAS) in 2014 and identify whether key disparities in preemptive transplantation have changed. DESIGN, SETTING, PARTICIPANTS, & MEASUREMENTS:We identified adult deceased donor kidney transplant recipients in the United States from 2000 to 2018 using the Scientific Registry of Transplant Recipients. Preemptive transplantation was defined as no dialysis before transplant. Associations between recipient, donor, transplant, and policy era characteristics and preemptive transplantation were calculated using logistic regression. To test for modification by KAS policy era, an interaction term between policy era and each characteristic of interest was introduced in bivariate and adjusted models. RESULTS:The proportion of preemptive transplants increased after implementation of KAS from 9.0% to 9.8%, with 1.10 (95% confidence interval [95% CI], 1.06 to 1.14) times higher odds of preemptive transplantation post-KAS compared with pre-KAS. Preemptive recipients were more likely to be white, older, female, more educated, hold private insurance, and have ESKD cause other than diabetes or hypertension. Policy era significantly modified the association between preemptive transplantation and race, age, insurance status, and Human Leukocyte Antigen zero-mismatch (interaction P<0.05). Medicare patients had a significantly lower odds of preemptive transplantation relative to private insurance holders (pre-KAS adjusted OR, [aOR] 0.26; [95% CI, 0.25 to 0.27], to 0.20 [95% CI, 0.18 to 0.22] post-KAS). Black and Hispanic patients experienced a similar phenomenon (aOR 0.48 [95% CI, 0.45 to 0.51] to 0.41 [95% CI, 0.37 to 0.45] and 0.43 [95% CI, 0.40 to 0.47] to 0.40 [95% CI, 0.36 to 0.46] respectively) compared with white patients. CONCLUSIONS:Although the proportion of deceased donor kidney transplants performed preemptively increased slightly after KAS, disparities in preemptive kidney transplantation persisted after the 2014 KAS policy changes and were exacerbated for racial minorities and Medicare patients.
Project description:BACKGROUND:It is unknown whether the new kidney transplant allocation system (KAS) has attenuated the advantages of preemptive wait-listing as a strategy to minimize pretransplant dialysis exposure. METHODS:We performed a retrospective study of adult US deceased donor kidney transplant (DDKT) recipients between December 4, 2011-December 3, 2014 (pre-KAS) and December 4, 2014-December 3, 2017 (post-KAS). We estimated pretransplant dialysis durations by preemptive listing status in the pre- and post-KAS periods using multivariable gamma regression models. RESULTS:Among 65 385 DDKT recipients, preemptively listed recipients (21%, n = 13 696) were more likely to be white (59% vs 34%, P < 0.001) and have private insurance (64% vs 30%, P < 0.001). In the pre- and post-KAS periods, average adjusted pretransplant dialysis durations for preemptively listed recipients were <2 years in all racial groups. Compared to recipients who were listed after starting dialysis, preemptively listed recipients experienced 3.85 (95% Confidence Interval [CI] 3.71-3.99) and 4.53 (95% CI 4.32-4.74) fewer average years of pretransplant dialysis in the pre- and post-KAS periods, respectively (P < 0.001 for all comparisons). CONCLUSIONS:Preemptively wait-listed DDKT recipients continue to experience substantially fewer years of pretransplant dialysis than recipients listed after dialysis onset. Efforts are needed to improve both socioeconomic and racial disparities in preemptive wait-listing.
Project description:Introduction:Long wait times for kidney transplants have prompted investigation into strategies to decrease the discarding of potentially viable organs. Recent reports suggest that kidneys from hepatitis C virus (HCV)-infected donors may be transplanted into HCV-naive donors followed by direct-acting antiviral therapy. Methods:This was a pilot clinical trial to transplant kidneys from HCV-infected donors into HCV-naive recipients with preemptive use of elbasvir and grazoprevir for 12 weeks. The primary outcome was sustained virologic response 12 weeks after completion of therapy. Secondary outcomes were safety, quality of life, and early viral kinetics. Results:A total of 33 patients were screened, and 8 underwent kidney transplantation from a HCV-viremic donors from August 2017 to March 2019. The median donor kidney donor profile index was 31% (range, 29%-65%), and patients who underwent transplantation waited a median of 6.5 months (range, 1-19 months). None had detectable HCV viremia beyond 2 weeks post-transplantation, and all achieved sustained virologic response 12 weeks after therapy (SVR12). There were no study-related severe adverse events. One patient experienced early graft loss due to venous thrombosis, whereas the remaining 7 patients had excellent allograft function at 6 months. Conclusion:Preemptive elbasvir and grazoprevir eliminated HCV infection in HCV-naive patients who received a kidney transplant from an HCV-infected donor.
Project description:Cytomegalovirus (CMV) is one of the most common viral pathogens causing clinical disease in liver transplant recipients, and contributing to substantial morbidity and occasional mortality. CMV causes febrile illness often accompanied by bone marrow suppression, and in some cases, invades tissues including the transplanted liver allograft. In addition, CMV has been significantly associated with an increased predisposition to acute and chronic allograft rejection, accelerated hepatitis C recurrence, and other opportunistic infections, as well as reduced overall patient and allograft survival. To negate the adverse effects of CMV infection on transplant outcome, its prevention, whether through antiviral prophylaxis or preemptive therapy, is an essential component to the management of liver transplant recipients. Two recently updated guidelines have suggested that antiviral prophylaxis or preemptive therapy are similarly effective in preventing CMV disease in modest-risk CMV-seropositive liver transplant recipients, while antiviral prophylaxis is the preferred strategy over preemptive therapy for the prevention of CMV disease in high-risk recipients [CMV-seronegative recipients of liver allografts from CMV-seropositive donors (D+/R-)]. However, antiviral prophylaxis has only delayed the onset of CMV disease in many CMV D+/R- liver transplant recipients, and such occurrence of late-onset CMV disease was significantly associated with increased all-cause and infection-related mortality after liver transplantation. Therefore, a search for better strategies for prevention, such as prolonged duration of antiviral prophylaxis, a hybrid approach (antiviral prophylaxis followed by preemptive therapy), or the use of immunologic measures to guide antiviral prophylaxis has been suggested to prevent late-onset CMV disease. The standard treatment of CMV disease consists of intravenous ganciclovir or oral valganciclovir, and if feasible, reduction in pharmacologic immunosuppression. In one clinical trial, oral valganciclovir was as effective as intravenous ganciclovir for the treatment of mild to moderate CMV disease in solid organ (including liver) transplant recipients. The aim of this article is to provide a state-of-the art review of the epidemiology, diagnosis, prevention, and treatment of CMV infection and disease after liver transplantation.
Project description:BACKGROUND:Hearts and lungs from donors with hepatitis C viremia are typically not transplanted. The advent of direct-acting antiviral agents to treat hepatitis C virus (HCV) infection has raised the possibility of substantially increasing the donor organ pool by enabling the transplantation of hearts and lungs from HCV-infected donors into recipients who do not have HCV infection. METHODS:We conducted a trial involving transplantation of hearts and lungs from donors who had hepatitis C viremia, irrespective of HCV genotype, to adults without HCV infection. Sofosbuvir-velpatasvir, a pangenotypic direct-acting antiviral regimen, was preemptively administered to the organ recipients for 4 weeks, beginning within a few hours after transplantation, to block viral replication. The primary outcome was a composite of a sustained virologic response at 12 weeks after completion of antiviral therapy for HCV infection and graft survival at 6 months after transplantation. RESULTS:A total of 44 patients were enrolled: 36 received lung transplants and 8 received heart transplants. The median viral load in the HCV-infected donors was 890,000 IU per milliliter (interquartile range, 276,000 to 4.63 million). The HCV genotypes were genotype 1 (in 61% of the donors), genotype 2 (in 17%), genotype 3 (in 17%), and indeterminate (in 5%). A total of 42 of 44 recipients (95%) had a detectable hepatitis C viral load immediately after transplantation, with a median of 1800 IU per milliliter (interquartile range, 800 to 6180). Of the first 35 patients enrolled who had completed 6 months of follow-up, all 35 patients (100%; exact 95% confidence interval, 90 to 100) were alive and had excellent graft function and an undetectable hepatitis C viral load at 6 months after transplantation; the viral load became undetectable by approximately 2 weeks after transplantation, and it subsequently remained undetectable in all patients. No treatment-related serious adverse events were identified. More cases of acute cellular rejection for which treatment was indicated occurred in the HCV-infected lung-transplant recipients than in a cohort of patients who received lung transplants from donors who did not have HCV infection. This difference was not significant after adjustment for possible confounders. CONCLUSIONS:In patients without HCV infection who received a heart or lung transplant from donors with hepatitis C viremia, treatment with an antiviral regimen for 4 weeks, initiated within a few hours after transplantation, prevented the establishment of HCV infection. (Funded by the Mendez National Institute of Transplantation Foundation and others; DONATE HCV ClinicalTrials.gov number, NCT03086044.).
Project description:BACKGROUND:Racial disparities persist in access to kidney transplantation. Racial differences in preemptive referral, or referral prior to dialysis start, may explain this discrepancy. METHODS:Patient-level data on kidney transplant referrals (2005-2012) from all Georgia transplant centers were linked to the United States Renal Data System to examine racial disparities in preemptive referral, waitlisting, and living donor transplant. Adjusted logistic regression and Cox proportional hazard models determined the associations between race (African American vs white) and preemptive referral, and placement on the waitlist and receipt of a living donor kidney, respectively. RESULTS:Among 7752 adults referred for transplant evaluation, 20.38% (n = 1580) were preemptively referred. The odds of African Americans being preemptively referred for transplant evaluation were 37% (OR = 0.63; [95% CI: 0.55 0.71]) lower than white patients. Among preemptively referred patients, there was no racial difference (African Americans compared to white patients. HR = 0.96; [95% CI: 0.88, 1.04]) in waitlisting. However, African Americans were 70% less likely than white patients to receive a living donor transplant (HR = 0.30; [95% CI: 0.21, 0.42]). CONCLUSION:Racial disparities in transplant receipt may be partially explained by disparities in preemptive referral. Interventions to reduce racial disparities in kidney transplant access may need to be targeted earlier in the disease process.
Project description:In recent years, the opioid epidemic and new hepatitis C virus (HCV) treatments have changed the landscape of organ procurement and allocation. We studied national trends in solid organ transplantation (2000?2016), focusing on graft utilization from HCV seropositive deceased donors in the pre-2014 (2000?2013) versus current (2014?2016) eras with a retrospective analysis of the United Network for Organ Sharing database. During the study period, HCV seropositive donors increased from 181 to 661 donors/year. The rate of HCV seropositive donor transplants doubled from 2014 to 2016. Heart and lung transplantation data were too few to analyze. A higher number of HCV seropositive livers were transplanted into HCV seropositive recipients during the current era: 374 versus 124 liver transplants/year. Utilization rates for liver transplantation reached parity between HCV seropositive and non-HCV donors. While the number of HCV seropositive kidneys transplanted to HCV seropositive recipients increased from 165.4 to 334.7 kidneys/year from the pre-2014 era to the current era, utilization rates for kidneys remained lower in HCV seropositive than in non-HCV donors. In conclusion, relative underutilization of kidneys from HCV seropositive versus non-HCV donors has persisted, in contrast to trends in liver transplantation.
Project description:Adenovirus (ADV) infections after hematopoietic cell transplantation (HCT) range in severity from self-limited to fatal. We have previously reported high mortality rates in CD34(+) selected T cell-depleted (TCD) HCT recipients using symptomatic testing and culture methods for ADV detection. We report rates and outcomes of ADV viremia in 215 adult recipients of TCD HCT using the CliniMACS CD34(+) selection system. This was a prospective observational study of adults transplanted from March 21, 2012 through November 30, 2014 at Memorial Sloan-Kettering Cancer Center. TCD was performed using CliniMACS CD34(+) cell selection. Patients were monitored for ADV by whole blood PCR assay from +14 to +100 days post-transplant. ADV viremia was defined as ?1 PCR above the lower limit of quantitation. ADV disease was defined per European Group for Blood and Marrow Transplantation guidelines. Treatment for ADV was at the clinician's discretion. Competing risk regression analyses were used to identify predictors for ADV viremia and overall survival. The median age was 55 years (range, 22 to 72); 215 patients underwent TCD. All patients received myeloablative conditioning. Eighteen patients (8% of cohort) had ADV viremia at a median onset of 57 days (interquartile range [IQR], 23 to 79) and with a median viral load at first detection of 2.6 log10 copies/mL (IQR, 2.5 to 4.0). The median maximal viral load was 4.5 log10 copies/mL (IQR, 3.5 to 5.9). No significant risk factor was identified for ADV viremia by univariate analysis. Six patients (3% of total cohort, 33% of viremic patients) developed ADV disease (3 colitis, 2 nephritis/cystitis, 1 pneumonitis). ADV viremia preceded onset of ADV disease a median of 11 days from the first positive quantitative PCR (range, +3 to +37) except in 1 patient with nephritis. Overall, 12 of 18 viremic patients (67%) received antiviral treatment (5 cidofovir only, 7 brincidofovir ± cidofovir). All patients with ADV disease were treated, and 6 patients were preemptively treated for ADV. Among the 18 viremic patients, 8 (44%) died during the study period, and, of those, 4 (22%) died of ADV. Early ADV viremia was infrequent (8%) among adult HCT recipients of CD34(+) selected allografts. Among viremic patients, rate of ADV disease was 33% and ADV attributable mortality was 22%. Further studies are needed to assess the impact of preemptive treatment with brincidofovir on improving outcomes of ADV infections in this patient population.
Project description:OBJECTIVE:The shortage of available donor organs is an unsolvable concern leading to an expansion in the donor criteria for organ transplantation. Here, we describe our experience and assess the outcomes in recipients who obtained a graft from a donor with bacterial infections in deceased donor liver transplantation (DDLT). METHODS:All DDLTs between January 1991 and February 2017 were retrospectively reviewed. Patients were categorised into two groups based on the recipients who obtained a graft from a donor with (group I) or without (group II) evidence of bacterial infections. Outcomes and bacterial infections were compared between the two groups of recipients. RESULTS:Overall, a total of 285 DDLTs were performed from 248 donors consisting of 48 split liver grafts and 208 whole liver grafts. Of those, 98 recipients (group I, 34.3%) were transplanted with a graft from 78 donors with positive bacterial cultures. Donor sputum cultures had the highest rate of positive bacterial growth, accounting for 26.6% of donors. Overall survival (OS) was not significantly different between the two groups (p=0.9746). The OS rates at 1 and 3 years were 73.5% and 69.2%, respectively, in the group I recipients versus 68.8% and 62.4% in the group II recipients. Importantly, no hospital mortality was related to donor-derived bacterial infections. CONCLUSION:Transmission of bacteria from the donor to the recipient is infrequent in DDLT. Therefore, potential donors with positive bacterial infections should not be excluded for organ transplantation to increase organ availability and ameliorate the organ shortage.
Project description:Myeloproliferative neoplasms (MPN) encounter thromboses due to multiple known risk factors. Heparin-induced thrombocytopenia (HIT) is a thrombotic syndrome mediated by anti-platelet factor 4 (PF4)/heparin antibodies with undetermined significance for thrombosis in MPN. We hypothesized that anti-PF4/heparin Ab might occur in MPN and promote thrombosis.Anti-PF4/heparin antibodies were analyzed in 127 MPN patients including 76 PV and 51 ET. Screening, validation testing, and isotype testing of anti-PF4/heparin Ab were correlated with disease characteristics.Anti-PF4/heparin antibodies were detected in 21% of PV and 12% of ET versus 0.3-3% in heparin-exposed patients. Validation testing confirmed anti-PF4/heparin immunoglobulins in 15% of PV and 10% of ET. Isotype testing detected 9.2% IgG and 5.3% IgM in PV and exclusively IgM in ET. IgG-positive PV patients encountered thromboses in 57.1% suggesting anti-PF4/heparin IgG may contribute to higher risk for thrombosis in MPN. Overall, 45% of PV patients experienced thromboses with 11.8% positive for anti-PF4/heparin IgG versus 7.1% in PV without thrombosis.Anti-PF4/heparin antibodies occur endogenously and more frequently in MPN than upon heparin exposure. Thrombotic risk increases in anti-PF4/heparin IgG-positive PV reflecting potential implications and calling for larger, confirmatory cohorts. Anti-PF4/heparin IgG should be assessed upon thrombosis in PV to facilitate avoidance of heparin in anti-PF4/heparin IgG-positive PV.