BACKGROUND.Kidneys from deceased donors with acute kidney injury (AKI) are more likely to be discarded because of concerns for poor outcomes after transplantation. The aim of this study was to ...determine the long-term outcomes of a large cohort of patients transplanted utilizing kidneys from deceased donors with AKI.
METHODS.All patients receiving a deceased donor kidney transplant during a recent 10-year period were included. Acute Kidney Injury Network (AKIN) criteria were used to classify the donors. Donor kidneys with >10% cortical necrosis or more than mild chronic changes were discarded. The primary outcome is the combined endpoint of death or graft loss.
RESULTS.The cohort included 1313 kidneys from 974 donors, AKIN stage 0 (no AKI) in 319 (24.3%), stage 1 in 370 (28.2%), stage 2 in 177 (13.5), and stage 3 in 447 (34.0%). Estimated 5-year graft survival (95% confidence interval) was 78.5% (72.5-84.5), 77.8% (72.8-82.1), 83.8% (76.8-88.9), and 84.6% (79.5-88.7) for AKIN donor stage 0 to 3, respectively (log-rank P = 0.10). After adjusting for baseline differences, the hazard ratio (95% confidence interval) for the combined endpoint for the AKIN stage 3 group (relative to AKIN 0 group) was 0.70 (0.45-1.10). Delayed graft function occurred in 44.6% and 75.4% of AKIN 2 and 3 groups, as compared to 33.9% and 33.5% in AKIN 0 and 1 (P < 0.001).
CONCLUSION.We conclude that transplanting selected kidneys from deceased donors with AKI with preimplantation biopsy showing <10% cortical necrosis and no more than mild chronic changes have excellent long-term graft survival.
Hepatocellular Carcinoma (HCC) is the most common liver malignancy and third leading cause of cancer death worldwide. For early- and intermediate-stage disease, liver-directed therapies for ...locoregional control, or down-staging prior to definitive surgical therapy with hepatic resection or liver transplantation, have been studied broadly, and are the mainstays of current treatment guidelines. As HCC incidence has continued to grow, and with more patients presenting with advanced disease, our current treatment modalities do not suffice, and better therapies are needed to improve disease-specific and overall survival. Until recently, sorafenib was the only systemic therapy utilized, and was associated with dismal results. The advent of immuno-oncology has been of significant interest, and has changed the paradigm of therapy for HCC. Lately, combination regimens including atezolizumab plus bevacizumab; durvalumab plus tremelimumab; and pembrolizumab plus Lenvatinib have shown impressive responses of between 25-35%; this is much higher than responses observed with single agents. Complete responses with checkpoint inhibitor therapy have been observed in advanced-stage HCC patients. These dramatic results have naturally led to several questions. Can or should checkpoint inhibitors, or other immunotherapy combinations, be used routinely before resection or transplant? Is there a synergistic effect of immunotherapy with locoregional therapy, and will pre-treatment increase disease-free survival after surgical intervention? Is it immunologically safe to use these therapies prior to transplantation? Much is still to be learned in terms of the dosing, timing, and overall utility of the use of immune checkpoint inhibitors for pre-transplant care and down-staging. More studies will be needed to understand the management of adverse events while maximizing the therapeutic window of these agents. In this review, we look at the current data on therapy with immune checkpoint inhibitors in advanced HCC, with a focus on pre-transplant treatment prior to liver transplant.
BACKGROUNDAs the population in the United States continues to age, an increase in the number of potential donation after circulatory death (DCD) donors with advanced chronological age can be ...expected. The aim of this study was to analyze a multi-institutional experience in liver transplantation using DCD donors 50 years or older.
METHODSAll DCD liver transplant (LT) performed at Mayo Clinic Florida, Mayo Clinic Rochester, and Mayo Clinic Arizona from 2002 to 2016 were included. Recipients of DCD LT were divided into 2 groupsthose with donors 50 years or older (N = 155) and those with donors younger than 50 years(N = 316).
RESULTSGraft survival was similar between the DCD donors 50 years or older group and DCD donors younger than 50 group(P = 0.99). Graft survival at 1, 3, and 5 years was 87.0%, 75.6%, and 71.8% in the DCD donors 50 years or older group and 85.8%, 76.0%, and 70.4% in the DCD donors younger than 50 group.The rate of total biliary complications (32.3% vs 23.7%; P = 0.049) and of anastomotic strictures (16.1% vs 8.2%; P = 0.01) were higher in the DCD donors 50 years or older compared with the DCD donors younger than 50 group. No statistical significant difference in the rate of ischemic cholangiopathy (11.6% vs 7.6%; P = 0.15) was seen between the 2 groups. Due to homogeneous practice patterns at the involved institutions, additional Cox regression analysis using national data obtained from Scientific Registry of Transplant Recipients was used to evaluate predictors of graft failure in DCD donors 50 years or older. Significant predictors of graft failure includeda calculated Model for End-Stage Liver Disease score of 30 or higher (P < 0.001), mechanical ventilation at the time of transplant (P < 0.001), medical condition (in intensive care unit) (P = 0.002), and cold ischemia time (P < 0.001).
CONCLUSIONSThe present study demonstrates that acceptable graft and patient survival can be achieved with the usage of DCD LT with donors 50 years or older. Optimizing recipient selection criteria and minimizing cold ischemia time may further improve outcomes.
A 63-year-old man with compensated nonalcoholic steatohepatitis cirrhosis was referred for liver transplant evaluation because of new diagnosis of hepatocellular carcinoma (HCC). After 6 months of ...therapy, the patient demonstrated dramatic response with an AFP level of 19.6 ng/mL and no new HCC lesions on imaging (Figure 2). Because of decompensation likely related to CPIT, despite being within Milan criteria and qualifying for model for end-stage liver disease exception points of 23, the patient was carefully evaluated, considering the potential graft failure and rejection risk in the setting of recent CPIT use. Use of Thymoglobulin for induction in liver transplant recipients is considered off-label (it is only Food and Drug Administration–approved for prevention and treatment of rejection in kidney transplant recipients). Pilot evaluation of PD-1 inhibition in metastatic cancer patients with a history of liver transplantation:
Donation after cardiac death (DCD) and acute kidney injury (AKI) donors have historically been considered independent risk factors for delayed graft function (DGF), allograft failure, and inferior ...outcomes. With growing experience, updated analyses have shown good outcomes. There continues to be limited data, however, on outcomes specific to DCD donors who have AKI. Primary outcomes for this study were post–kidney transplant patient and allograft survival comparing two donor groups: DCD AKIN stage 2‐3 and DBD AKIN stage 2‐3. In comparing these groups, there were no short‐ or long‐term differences in patient (hazard ratio HR 1.07, 95% confidence interval CI 0.54‐1.93, P = .83) or allograft survival (HR 1.47, 95% CI 0.64‐2.97, P = .32). In multivariate models, the DCD/DBD status had no significant impact on the estimated GFR (eGFR) at 1 (P = .38), 2 (P = .60), and 3 years (P = .52). DGF (57.9% vs 67.9%, P = .09), rejection (12.1% vs 13.9%, P = .12), and progression of interstitial fibrosis/tubular atrophy (IFTA) on protocol biopsy (P = .16) were similar between the two groups. With careful selection, good outcomes can be achieved utilizing severe AKI DCD kidneys. Historic concerns regarding primary nonfunction, DGF resulting in interstitial fibrosis and rejection, and inferior outcomes were not observed. Given the ongoing organ shortage, increased effort should be undertaken to further utilize these donors.
With careful selection, good long‐term outcomes can be achieved using severe acute kidney injury kidneys from donation after cardiac death donors.
OBJECTIVE:To understand whether reduced lengths of stay after kidney transplantation were associated with excess health care utilization in the first 90 days or long-term graft and patient survival ...outcomes.
BACKGROUND:Reducing length of stay after kidney transplant has an unknown effect on post-transplant health care utilization. We studied this association in a cohort of 1001 consecutive kidney transplants.
METHODS:We retrospectively reviewed 2011–2015 data from a prospectively-maintained kidney transplant database from a single center.
RESULTS:A total of 1001 patients underwent kidney transplant, and were dismissed from the hospital in 3 groupsEarly ≤2 days (19.8%), Normal 3–7 days (79.4%) and Late >7 days (3.8%). 34.8% of patients had living donor transplants (Early 51%, Normal 31.4%, Late 18.4%, P < 0.001). Early patients had lower delayed graft function rates (Early 19.2%, Normal 32%, Late73.7%, P = 0.001). By the hospital dismissal group, there were no differences in readmissions or emergency room visits at 30 or 90 days. Glomerular filtration rate at 12 months and rates of biopsy-proven acute rejection were also similar between groups. The timing of hospital dismissal was not associated with the risk-adjusted likelihood of readmission. Early and Normal patients had similar graft and patient survival. Late dismissal patients, who had higher rates of cardiovascular complications, had significantly higher late mortality versus Normal dismissal patients in unadjusted and risk-adjusted models.
CONCLUSION:Dismissing patients from the hospital 2 days after kidney transplant is safe, feasible, and improves value. It is not associated with excess health care utilization or worse short or long-term transplant outcomes.
Patients with solid organ transplants (SOTs) have been excluded from programmed death protein-1 (PD-1)/programmed death ligand-1 (PD-L1) inhibitor clinical trials due to concern for allograft ...rejection. The use of immune checkpoint inhibitor therapy remains controversial in transplant patients.
A retrospective pilot evaluation was conducted to assess the safety and efficacy of PD-1 inhibitors in patients with liver transplantation (LT). The primary endpoint was the rate of allograft rejection. Secondary endpoints included overall response rate (ORR), progression free survival (PFS) and overall survival (OS). Translational objectives included evaluation of tumor PD-L1, tumor infiltrating lymphocytes (TILs) and allograft PD-L1 expression.
Seven metastatic cancer patients with a history of LT who received PD-1 inhibitor therapy were included hepatocellular carcinoma (HCC), n=5; melanoma, n=2. Rejection was observed in 2 of 7 patients. When rejection occurs it appears to be an early event with a median time to rejection of 24 days in our cohort. One patient achieved a complete response (CR), 3 patients had progressive disease (PD) and 3 patients discontinued therapy prior to restaging assessments. Two of five patients with available tissue had PD-L1 expression in the allograft and both developed rejection. One of five evaluable patients had abundant TILs. Two of five evaluable patients had PD-L1 tumor staining. The single patient with both abundant TILs and PD-L1 staining obtained a response. The median OS and PFS were 1.1 (0.3-21.1) and 1.8 (0.7-21.1) months, respectively.
In this pilot evaluation both preliminary efficacy (1 of 4) and allograft rejection (2 of 7) were exhibited in evaluable patients. Larger, prospective trials are needed to elucidate optimal patient selection.
There is controversy regarding the impact of delayed graft function (DGF) on kidney transplant outcomes. We hypothesize that the duration of DGF, rather than DGF itself, is associated with long-term ...kidney graft function.
We analyzed all deceased donor kidney transplants (DDKT) done at our center between 2008 to 2020. We determined factors associated with DGF duration. DGF duration was assessed at three 14-day intervals: < 14 DGF days, 14-27 DGF days, > 28 DGF days. We studied the impact of DGF duration on survival and graft function and resource utilization, including hospital length of stay and readmissions.
1714 DDKT recipients were included, 59.4% (n = 1018) had DGF. The median DGF duration was 10 days IQR (6,15). The majority of recipients (95%) had resolution of DGF within 28 days. Donor factors associated with DGF days were longer cold ischemia time, donor on inotropes, older age, donation after circulatory death, higher terminal creatinine, and hypertension. Recipient factors associated with increased DGF duration included male sex, length on dialysis before transplant, and higher body mass index. There were no differences in acute rejection events or interstitial fibrosis progression by 4 months when comparing DGF days. The median length of stay was 3 days. However, readmissions increased with increasing DGF duration. Death-censored graft survival was not associated with the length of DGF except when DGF lasted > 28 days.
Inferior graft survival was observed only in recipients of DDKT with DGF lasting beyond 28 days. DGF lasting < 28 days had no impact on graft survival. Duration of DGF, rather than DGF itself, is associated with graft survival.
Retrospective study approved by Mayo Clinic IRB number ID: 20-011561.
Cardiovascular disease (CVD) is a leading cause of post–liver transplant death, and variable care patterns may affect outcomes. We aimed to describe epidemiology and outcomes of inpatient CVD care ...across US hospitals. Using a merged data set from the 2002‐2011 Nationwide Inpatient Sample and the American Hospital Association Annual Survey, we evaluated liver transplant patients admitted primarily with myocardial infarction (MI), stroke (cerebrovascular accident CVA), congestive heart failure (CHF), dysrhythmias, cardiac arrest (CA), or malignant hypertension. Patient‐level data include demographics, Charlson comorbidity index, and CVD diagnoses. Facility‐level variables included ownership status, payer‐mix, hospital resources, teaching status, and physician/nursing‐to‐bed ratios. We used generalized estimating equations to evaluate patient‐ and hospital‐level factors associated with mortality. There were 4763 hospitalizations that occurred in 153 facilities (transplant hospitals, n = 80). CVD hospitalizations increased overall by 115% over the decade (P < 0.01). CVA and MI declined over time (both P < 0.05), but CHF and dysrhythmia grew significantly (both P < 0.03); a total of 19% of hospitalizations were for multiple CVD diagnoses. Transplant hospitals had lower comorbidity patients (P < 0.001) and greater resource intensity including presence of cardiac intensive care unit, interventional radiology, operating rooms, teaching status, and nursing density (all P < 0.01). Transplant and nontransplant hospitals had similar unadjusted mortality (overall, 3.9%, P = 0.55; by diagnosis, all P > 0.07). Transplant hospitals had significantly longer overall length of stay, higher total costs, and more high‐cost hospitalizations (all P < 0.05). After risk adjustment, transplant hospitals were associated with higher mortality and high‐cost hospitalizations. In conclusion, CVD after liver transplant is evolving and responsible for growing rates of inpatient care. Transplant hospitals are associated with poor outcomes, even after risk adjustment for patient and hospital characteristics, which may be attributable to selective referral of certain patient phenotypes but could also be related to differences in quality of care. Further study is warranted.
Outcomes of both donation after cardiac death (DCD) liver and kidney transplants are improving. Experience in simultaneous liver–kidney transplant (SLK) using DCD donors, however, remains limited. In ...an updated cohort (2010‐2018), outcomes of 30 DCD SLK and 131 donation after brain death (DBD) SLK from Mayo Clinic Arizona and Mayo Clinic Minnesota were reviewed. The Model for End‐Stage Liver Disease score was lower in the DCD SLK group (23 vs 29, P = .01). Kidney delayed graft function (DGF) rates were similar between the 2 groups (P = .11), although the duration of DGF was longer for DCD SLK recipients (20 vs 4 days, P = .01). Liver allograft (93.3% vs 93.1%, P = .29), kidney allograft (93.3% vs 93.1%, P = .91), and patient (96.7% vs 95.4%, P = .70) 1‐year survival rates were similar. At 1 year, there were no differences in the estimated glomerular filtration rate (57.7 ± 18.2 vs 56.3 ± 17.7, P = .75) or progression of fibrosis (ci) on protocol kidney biopsy (P = .67). A higher incidence of biliary complications was observed in the DCD SLK group, with ischemic cholangiopathy being the most common (10.0% vs 0.0%, P = .03). The majority of biliary complications resolved with endoscopic management. With appropriate selection, DCD SLK recipients can have results equivalent to those of DBD SLK recipients.
This 2‐center study demonstrates that, with appropriate selection, simultaneous liver–kidney transplants from donation after cardiac death donors can achieve good long‐term patient and allograft survival, excellent long‐term renal function, and a low incidence of ischemic cholangiopathy.
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