Kidney retransplantation outcomes in adults aged 70 and older: Analysis of risk factors and survival.

BACKGROUND: An increasing number of older patients are undergoing kidney transplant. Because of a finite longevity, more patients will be faced with failing allografts. At present there is a limited understanding of the benefits and risks associated with kidney retransplantation in this challenging population. METHODS: We performed a retrospective analysis of the Organ Procurement and Transplantation Network database of all adults ≥70 undergoing kidney retransplant from January 1, 2014 to December 31, 2022. We examined patient and graft survival of retransplanted patients compared to first time transplants. We also analyzed the risk factors that impacted the survival. RESULTS: During the study period there has been a significant rise in the number of retransplants performed, with 631 patients undergoing the procedure. Although clinically insignificant, overall graft, and patient survival rates were slightly lower in the retransplant group compared to the primary transplant group. With retransplant, patient survival was 91.3%, 75.6%, and 56.9% compared to 93.4%, 81.4%, and 64.4% with primary transplant at 1, 3, and 5 years, respectively. With retransplant, graft survival was 89.5%, 73.5%, 57.4% compared to 91.5%, 79.0%, and 63.6% in a primary transplant group at 1, 3, and 5 years, respectively. Multivariable analysis showed that factors predicting poor survival included longer time on dialysis before retransplantation and decreased functional capacity. No survival difference was noted between recipients of deceased versus living donor kidneys. Patients who underwent retransplantation before initiating dialysis had better patient and graft survival. CONCLUSION: Patients aged ≥70 achieve satisfactory outcomes following kidney retransplantation, highlighting that chronologic age should not preclude this medically complex population from this life-saving procedure. Improvement in functional status and timely retransplantation are the key factors to successful outcome.

Tocilizumab for treatment of chronic active antibody-mediated rejection in kidney transplant recipients.

BACKGROUND: The optimal treatment for chronic active antibody-mediated rejection (ca-AMR) remains unclear. Tocilizumab (TCZ), a monoclonal antibody against IL-6, has been proposed as a therapeutic option. We reported our experience treating ca-AMR with TCZ either as the first line option or as a rescue therapy. METHODS: We studied 11 adult kidney transplant recipients with biopsy-proven ca-AMR and preserved kidney function (eGFR 57 ± 18) who were treated with TCZ (8 mg/kg IV monthly). All biopsies were prompted by abnormal surveillance biomarker testing with DSA and/or dd-cfDNA. Clinical monitoring included dd-cfDNA and DSA testing every 3 months during the treatment with TCZ. RESULTS: In this cohort, ca-AMR was diagnosed at a median of 90 months (range 14-224) post-transplant, and 4 of 11 patients had DSA negative ca-AMR. Patients received a minimum of 3 months of TCZ, with 6 patients receiving at least 12 months of TCZ. Dd-cfDNA was elevated in all patients, with a median 2.24% at the start of TCZ treatment. After 6 months of TCZ treatment, 8/11 patients had dd- cfDNA <1%, and 3/11 had values <0.5%. Among those who completed at least 12 months of TCZ, dd-cfDNA decreased by 29% at 6 months (p = .05) and 47% by 12 months (p = .04). DSA also stabilized and, by 12 months, was reduced by 29% (p = .047). Graft function remained stable with no graft loss during treatment. There was a nonsignificant trend towards proteinuria reduction. During the course of treatment with tocilizumab, two patients experienced moderate to severe infections. CONCLUSIONS: In our early short-term experience, TCZ appears to reduce graft injury as measured by dd-cfDNA and modulate the immune response as evident by a modest reduction in immunodominant DSA MFI. Allograft function and proteinuria also stabilized.

Transplant tourism complicated by life-threatening New Delhi metallo-ß-lactamase-1 infection.

Transplant tourism, which is the practice of traveling to other countries for transplant, continues to be a major problem worldwide. We describe a patient who traveled to Pakistan and underwent commercial kidney transplant. He developed life-threatening infections from New Delhi metallo-ß-lactamase-1-producing Enterobacter cloacae and Rhizopus oryzae, resulting in a necrotizing kidney allograft infection and subsequent external iliac artery rupture. He survived after a prolonged course of nonstandardized antimicrobial therapy, including a combination of aztreonam and ceftazidime-avibactam, and aggressive surgical debridement with allograft nephrectomy. The early timing of infection with these unusual organisms localized to the allograft suggests contamination and substandard care at the time of transplant. This case highlights the challenges of caring for these infections and serves as a cautionary tale for the potential complications of commercial transplant tourism.

Simultaneous Liver and Kidney Transplantation in Patients Aged 70 y and Older: Proceed With Caution.

Background: The number of elderly patients aged 70 y and older with liver and kidney failure is increasing, mainly because of increasing prevalence of metabolic dysfunction-associated steatohepatitis. At present, limited data are available on the outcomes of elderly patients who fit the criteria for dual organ transplantation since the implementation of the simultaneous liver and kidney (SLK) allocation policy. Methods: We performed a retrospective analysis of the Organ Procurement and Transplantation Network database of adults aged 18 y and older undergoing SLK and kidney transplantation only from August 11, 2017, to December 31, 2022. We examined patient and graft survivals and compared the outcomes of the recipients aged 70 y and older undergoing SLK transplantation to those who received kidney transplant alone and kidney after liver transplant. Results: During the study period, there has been a significant rise in the number of patients aged 70 y and older undergoing SLK transplantation, with 6 patients undergoing SLK transplantation in 2017 and 63 in 2021. Patients aged 70 y and older had significantly lower survival with 82.9% at 1 y and 66.5% at 3 y compared with 89.3% and 78.8% in the 50-69 y age group and 93.2% and 88.6% in the 18-49 y age group, respectively. Overall, kidney allograft survival was significantly lower in the 70 y and older group, with 80.9% at 1 y and 66.4% at 3 y compared with 91.1% and 75.5%, respectively, in those undergoing kidney transplant alone. There was no difference in kidney allograft survival in those undergoing SLK and kidney after liver transplantation. Conclusions: Although the outcomes are inferior in recipients of SLK transplant aged 70 y and older, chronologic age should not preclude them from undergoing transplantation. Kidney transplantation after liver transplantation could be considered to avoid futile transplants.

Impact of Obesity on Kidney Transplant Outcomes in Older Adults.

BACKGROUND: The prevalence of obesity in older patients undergoing kidney transplantation is increasing. Older age and obesity are associated with higher risks of complications and mortality post-transplantation. The optimal management of this group of patients remains undefined. METHODS: We retrospectively analyzed the United Network for Organ Sharing database of adults ≥70 years of age undergoing primary kidney transplant from January 1, 2014, to December 31, 2022. We examined patient and graft survival stratified by body mass index (BMI) in 3 categories, <30 kg/m2, 30 to 35 kg/m2, and >35 kg/m2. We also analyzed other risk factors that impacted survival. RESULTS: A total of 14,786 patients ≥70 years underwent kidney transplantation. Of those, 9,731 patients had a BMI <30 kg/m2, 3,726 patients with a BMI of 30 to 35 kg/m2, and 1,036 patients with a BMI >35 kg/m2. During the study period, there was a significant increase in kidney transplants in patients ≥70 years old across all BMI groups. Overall, patient survival, death-censored graft survival, and all-cause graft survival were lower in obese patients compared with nonobese patients. Multivariable analysis showed worse patient survival and graft survival in patients with a BMI of 30 to 35 kg/m2, a BMI >35 kg/m2, a longer duration of dialysis, diabetes mellitus, and poor functional status. CONCLUSION: Adults ≥70 years should be considered for kidney transplantation. Obesity with a BMI of 30 to 35 kg/m2 or >35 kg/m2, longer duration of dialysis, diabetes, and functional status are associated with worse outcomes. Optimization of these risk factors is essential when considering these patients for transplantation.

Development and First Clinical Use of an Extracorporeal Artificial Multiorgan System in Acute-on-Chronic Liver Failure Patients.

Multiple organ failure (MOF) is a common and deadly condition. Patients with liver cirrhosis with acute-on-chronic liver failure (AOCLF) are particularly susceptible. Excess fluid accumulation in tissues makes routine hemodialysis generally ineffective because of cardiovascular instability. Patients with three or more organ failures face a mortality rate of more than 90%. Many cannot survive liver transplantation. Extracorporeal support systems like MARS (Baxter, Deerfield, IL) and Prometheus (Bad Homburg, Germany) have shown promise but fall short in bridging patients to transplantation. A novel Artificial Multi-organ Replacement System (AMOR) was developed at the University of Washington Medical Center. AMOR removes protein-bound toxins through a combination of albumin dialysis, a charcoal sorbent column, and a novel rinsing method to prevent sorbent column saturation. It removes excess fluid through hemodialysis. Ten AOCLF patients with over three organ failures were treated by the AMOR system. All patients showed significant clinical improvement. Fifty percent of the cohort received liver transplants or recovered liver function. AMOR was successful in removing large amounts of excess body fluid, which regular hemodialysis could not. AMOR is cost-effective and user-friendly. It removes excess fluid, supporting the other vital organs such as liver, kidneys, lungs, and heart. This pilot study's results encourage further exploration of AMOR for treating MOF patients.

Intention-to-treat Analysis of Patients Aged 70 Years and Older Awaiting Kidney Transplantation in Post-Kidney Allocation System Era.

BACKGROUND: The US population is aging, and so the number of patients treated for end-stage renal disease is on the rise. In the United States, 38% of people over 65 y old have chronic kidney disease. There continues to be a reluctance of clinicians to consider older candidates for transplant, including early referrals. METHODS: We conducted a retrospective analysis of the Organ Procurement and Transplantation Network database of all adults ≥70 y old undergoing kidney transplants from December 1, 2014, to June 30, 2021. We compared patient and graft survival in candidates who were transplanted while on hemodialysis versus preemptive with a living versus deceased donor kidney transplant. RESULTS: In 2021, only 43% of the candidates listed for transplant were preemptive. In an intention-to-treat analysis from the time of listing, candidate survival was significantly improved for those transplanted preemptively versus being on dialysis (hazard ratio 0.59; confidence interval, 0.56-0.63). All donor types, donor after circulatory death, donor after brain death, and living donor, had a significant decrease in death over remaining on the waiting list. Patients who were on dialysis or transplanted preemptively with a living donor kidney had significantly better survival than those receiving a deceased donor kidney. However, receiving a deceased donor kidney significantly decreased the chance of death over remaining on the waiting list. CONCLUSIONS: Patients ≥70 y old who are transplanted preemptively, whether with a deceased donor or a living donor kidney, have a significantly better survival than those who are transplanted after initiating dialysis. Emphasis on timely referral for a kidney transplant should be placed in this population.

Maximizing utility of nondirected living liver donor grafts using machine learning.

Objective: There is an unmet need for optimizing hepatic allograft allocation from nondirected living liver donors (ND-LLD). Materials and method: Using OPTN living donor liver transplant (LDLT) data (1/1/2000-12/31/2019), we identified 6328 LDLTs (4621 right, 644 left, 1063 left-lateral grafts). Random forest survival models were constructed to predict 10-year graft survival for each of the 3 graft types. Results: Donor-to-recipient body surface area ratio was an important predictor in all 3 models. Other predictors in all 3 models were: malignant diagnosis, medical location at LDLT (inpatient/ICU), and moderate ascites. Biliary atresia was important in left and left-lateral graft models. Re-transplant was important in right graft models. C-index for 10-year graft survival predictions for the 3 models were: 0.70 (left-lateral); 0.63 (left); 0.61 (right). Similar C-indices were found for 1-, 3-, and 5-year graft survivals. Comparison of model predictions to actual 10-year graft survivals demonstrated that the predicted upper quartile survival group in each model had significantly better actual 10-year graft survival compared to the lower quartiles (p<0.005). Conclusion: When applied in clinical context, our models assist with the identification and stratification of potential recipients for hepatic grafts from ND-LLD based on predicted graft survivals, while accounting for complex donor-recipient interactions. These analyses highlight the unmet need for granular data collection and machine learning modeling to identify potential recipients who have the best predicted transplant outcomes with ND-LLD grafts.

Anti-GSTT1 antibodies and Null genotype correlate with histological changes of antibody mediated rejection in kidney transplantation.

BACKGROUND: The presence of anti-Glutathione S-transferase T1 (GSTT1) antibodies (abs) has been hypothesized as a pathogenic contributor in antibody-mediated rejection (AMR). METHODS: We aimed to evaluate the relationship between genetic variants of GSTT1, anti-GSTT1 abs and AMR in a cohort of 87 kidney transplant (KTx) patients using Immucor's non-HLA Luminex assay. Patients were classified according to biopsy-proven AMR and HLA-DSA status: AMR with positive anti-HLA-DSAs (AMR/DSA+, n = 29), AMR but no detectable anti-HLA-DSAs (AMR/DSA-, n = 28) and control patients with stable allograft function and no evidence of rejection (n = 30). RESULTS: At an MFI cut-off of 3000, the overall prevalence of anti-GSTT1 abs was 18.3%. The proportion of patients with anti-GSTT1 abs was higher in the AMR/DSA- group (25%), compared to the control (13.3%) and AMR/DSA+ group (3.4%) (p = 0.06). Among patients with anti-GSTT1 abs, the MFI was higher in AMR/DSA- and GSTT1-Null patients. Of 81 patients who underwent GSTT1 genotyping, 19.8% were homozygotes for the null allele (GSTT1-Null). GSTT1-Null status in the transplant recipients was associated with the development of anti-GSTT1 abs (OR, 4.49; 95%CI, 1.2-16.7). In addition, GSTT1-Null genotype (OR 26.01; 95%CI, 1.63-404) and anti-GSTT1 ab positivity (OR 14.8; 95%CI, 1.1-190) were associated with AMR. Within AMR/DSA- patients, the presence of anti-GSTT1 abs didn't confer a higher risk of failure within the study observation period. CONCLUSION: The presence of anti-GSTT1 abs and GSTT1-Null genotype is associated with AMR, but do not appear to lead to accelerated graft injury in this cohort of early allograft injury changes, with a limited period of follow-up.

Combining donor-derived cell-free DNA and donor specific antibody testing as non-invasive biomarkers for rejection in kidney transplantation.

Donor specific anti-HLA antibodies (DSA) and donor-derived cell-free DNA (dd-cfDNA) have lead to substantial progress in the non-invasive monitoring of the renal allograft by being able to detect or rule out subclinical rejection and guide immunosuppressive changes. In this study we sought to analyze the clinical, de novo DSA (dnDSA) and histological determinants of dd-cfDNA levels. The study included a cohort of stable renal function kidney transplant (KT) recipients who underwent anti-HLA dnDSA and dd-cfDNA testing between September 2017-December 2019. Statistical models were constructed to detect association with predictors of dd-cfDNA levels and other clinical characteristics. 171 renal allograft recipients were tested for dd-cfDNA and dnDSA at a median 1.06 years posttransplant (IQR: 0.37-4.63). Median dd-cfDNA was 0.25% (IQR: 0.19-0.51), 18.7% of patients having a dd-cfDNA ≥ 1%. In a multivariate linear regression model the presence of dnDSA MFI ≥ 2500 was the best independent determinant of dd-cfDNA level (p < 0.001). Among patients tested, 54 had concurrent dd-cfDNA determination at the time of an allograft biopsy. dd-cfDNA had an AUC of 0.82 (95% CI 0.69-0.91; p < 0.001) and of 0.96 (95% CI 0.87-0.99) to discriminate any rejection and ABMR, respectively. After multivariate adjustment, the models that included ABMR (R = 0.82, R2 = 0.67, p < 0.001), or ptc (R = 0.79, R2 = 0.63, p < 0.001) showed the best correlation with dd-cfDNA level. We are confirming a strong association of dd-cfDNA with dnDSA and underlying alloimmune-mediated injury in renal allograft recipients in a cohort of patients with unsuspecting clinical characteristics for rejection and excellent allograft function. Our findings support the need for noninvasive biomarker surveillance in KT recipients and we propose that dd-cfDNA may complement dnDSA screening.

Donor-derived Cell-free DNA Complements De Novo Class II DSA in Detecting Late Alloimmune Injury Post Kidney Transplantation.

We sought to evaluate the association between de novo donor-specific antibodies (dnDSAs) class and their mean fluorescence intensity (MFI) with donor-derived cell-free DNA (dd-cfDNA), aiming to further clarify the biomarker utility of these noninvasive tests in relation to renal allograft function and histology. METHODS: The study included kidney transplant recipients (n = 171) who underwent surveillance testing with DSA and dd-cfDNA as part of their clinical care between September 2017 and December 2019 at our center. RESULTS: We identified dnDSA in 43 patients (25%) at a median of 4.63 y (IQR, 1.5-7) posttransplant. The presence of DSA with MFI >2500 was associated with a median dd-cfDNA of 0.96% (IQR, 0.26-2.95) significantly higher than in patients with DSA MFI <2500 (0.28%; IQR, 0.19-0.39) or without detectable DSA (0.22%; IQR, 0.17-0.37; P < 0.001). Class II dnDSAs were the most prevalent dnDSA (88.3%), the majority with MFI >2500 (82.9%). Patients with DQ-dnDSAs (47.4%) had higher MFI and dd-cfDNA levels than other class II dnDSAs. By comparison, all patients that developed only class I DSAs had MFI <2500 and a low dd-cfDNA. In addition, the serum creatinine was 1.55 ± 0.48 mg/dL in those dnDSA-negative, 1.15 ± 0.37 mg/dL in those with dnDSA MFI <2500, and 1.53 ± 0.66 mg/dL in those with dnDSA MFI >2500 (P = 0.05). After multivariate adjustment, an elevated dd-cfDNA was independently associated with the presence of dnDSA with MFI ≥2500. We identified that both dd-cfDNA and dnDSAs were strongly associated with antibody-mediated rejection, whereas for individual Banff histological lesions, DSA MFIs ≥2500 had the strongest association with C4d staining score and dd-cfDNA >1% with microvascular inflammation. CONCLUSIONS: Our study identifies class II dnDSA as being strongly associated with late alloimmune injury post kidney transplant independent of allograft dysfunction and shows that dd-cfDNA may complement the clinical significance of dnDSAs.

Protective antibodies against human parainfluenza virus type 3 infection.

Human parainfluenza virus type III (HPIV3) is a common respiratory pathogen that afflicts children and can be fatal in vulnerable populations, including the immunocompromised. There are currently no effective vaccines or therapeutics available, resulting in tens of thousands of hospitalizations per year. In an effort to discover a protective antibody against HPIV3, we screened the B cell repertoires from peripheral blood, tonsils, and spleen from healthy children and adults. These analyses yielded five monoclonal antibodies that potently neutralized HPIV3 in vitro. These HPIV3-neutralizing antibodies targeted two non-overlapping epitopes of the HPIV3 F protein, with most targeting the apex. Prophylactic administration of one of these antibodies, PI3-E12, resulted in potent protection against HPIV3 infection in cotton rats. Additionally, PI3-E12 could also be used therapeutically to suppress HPIV3 in immunocompromised animals. These results demonstrate the potential clinical utility of PI3-E12 for the prevention or treatment of HPIV3 in both immunocompetent and immunocompromised individuals.

The biopsied donor liver: incorporating macrosteatosis into high-risk donor assessment.

To expand the donor liver pool, ways are sought to better define the limits of marginally transplantable organs. The Donor Risk Index (DRI) lists 7 donor characteristics, together with cold ischemia time and location of the donor, as risk factors for graft failure. We hypothesized that donor hepatic steatosis is an additional independent risk factor. We analyzed the Scientific Registry of Transplant Recipients for all adult liver transplants performed from October 1, 2003, through February 6, 2008, with grafts from deceased donors to identify donor characteristics and procurement logistics parameters predictive of decreased graft survival. A proportional hazard model of donor variables, including percent steatosis from higher-risk donors, was created with graft survival as the primary outcome. Of 21,777 transplants, 5051 donors had percent macrovesicular steatosis recorded on donor liver biopsy. Compared to the 16,726 donors with no recorded liver biopsy, the donors with biopsied livers had a higher DRI, were older and more obese, and a higher percentage died from anoxia or stroke than from head trauma. The donors whose livers were biopsied became our study group. Factors most strongly associated with graft failure at 1 year after transplantation with livers from this high-risk donor group were donor age, donor liver macrovesicular steatosis, cold ischemia time, and donation after cardiac death status. In conclusion, in a high-risk donor group, macrovesicular steatosis is an independent risk factor for graft survival, along with other factors of the DRI including donor age, donor race, donation after cardiac death status, and cold ischemia time.

Intraoperative portal vein blood flow predicts allograft and patient survival following liver transplantation.

BACKGROUND: We hypothesized that operative variables might predict survival following liver transplantation. METHODS: We examined perioperative variables from 469 liver transplants carried out at the University of Washington during 2003-2006. Logistic regression determined the variables' contributions to survival at 30, 90 and 365 days. RESULTS: Portal vein blood flow (>1 l/min) was significant to patient survival at 30, 90 and 365 days. Complete reperfusion was only a significant predictor of survival at 30 days. This provided model receiver operating characteristic (ROC) area under the curve (AUC) statistics of 0.93 and 0.87 for 30 and 90 days, respectively. At 365 days, hepatic artery blood flow (>250 ml/min) combined with portal vein blood flow was significantly predictive of survival, with an AUC of 0.74. A subset analysis of 110 transplants demonstrated improved 1-year survival with more aggressive vascular revisions. DISCUSSION: Portal vein blood flow is a significant predictor of survival after liver transplantation. Initially, the liver's survival is based on portal vein blood flow; however, subsequent biliary problems and patient demise result from both poor portal vein and inadequate hepatic artery blood flow.

The impact of consecutive operations on survival after liver transplantation.

The impact of surgeon fatigue on patient outcomes has not been previously studied. In order to assess the relationship of surgeon workload to patient outcome, we analyzed the impact of the interval between liver transplants and the cumulative number of liver transplants in a week on patient outcome. The outcomes of 390 liver transplants performed between 2003 and 2006 at the University of Washington Medical Center were analyzed. Overall 1-year patient/graft survival was significantly higher if the primary surgeon had >2 days between transplants (< or =2 days between transplants, 82.8%/81.5%, versus >2 days between transplants, 92.5%/91.2%, P < 0.003/0.004). Patient survival was also improved if a surgeon performed < or =3 liver transplants in 1 week versus > or =4 (90.4% versus 80.9%, P < 0.026). No other analyzed complication reached significance. Surgeon fatigue from successive transplants may potentially affect liver transplant survival. Call schedules should recognize the potential impact of workload on liver transplant outcome. Liver Transpl 15:907-914, 2009. (c) 2009 AASLD.

Should liver transplantation in patients with model for end-stage liver disease scores

Studies have shown that liver transplantation offers no survival benefits to patients with Model for End-Stage Liver Disease (MELD) scores or=18 years) listed for or undergoing primary liver transplantation in the United States for chronic liver disease from 1/1/2003 through 12/31/2007 with follow-up until 2/1/2008. The "Rule 14" policy gave a 3% improvement in overall patient survival over the present system at 1, 2, 3, and 4 years and predicted a 13% decrease in overall waitlist time for patients with MELD scores of 15 to 40. Patients with the greatest benefit from a "Rule 14" policy were those with MELD scores of 6 to 10, for whom a 17% survival advantage was predicted from waiting on the list versus undergoing transplantation. Our analysis supports changing the national liver allocation policy to not allow liver transplantation for patients with MELD

Burden of excess mortality after implementation of the new kidney allocation system may be borne disproportionately by middle-aged recipients.

Under the new kidney allocation system (KAS), implemented in 2014, the distribution of the best quality donor kidney grafts shifted between age groups, but it is unclear whether this change translates to meaningful differences in post-transplant outcomes. We conducted a retrospective cohort study of 20,345 deceased donor kidney transplant recipients before and 4,605 recipients after implementation of the KAS using data from the United Network of Organ Sharing. Overall, two-year mortality was greater among recipients in the post-KAS era compared with the pre-KAS era (6.31% vs 5.91% respectively, [p = 0.01]), and two-year graft loss was not significantly different between eras (9.95% and 9.65%, respectively [p = 0.13]). In analysis stratified by age group (18-45, 46-55, 56-65, and ≥66 years), relative risk of mortality was 1.48 (95% confidence interval [CI] 1.09-1.98) among recipients 46-55 years old and 1.47 (95% CI 1.18-1.81) among recipients 56-65 years old. Relative risk of all-cause graft loss was 1.43 (95% CI 1.20-1.70) among recipients 56-65 years old. There were no significant differences in relative risk of mortality or graft loss associated with the KAS era among other age groups. After adjustment for recipient characteristics and characteristics of the changing donor pool, relative risk of two-year mortality and graft loss associated with the post-KAS era was attenuated for recipients aged 46-55 and 56-65 years, but remained statistically significant. In this early analysis after implementation of the KAS, there is suggestion that increased risk of mortality and graft loss may be disproportionately borne by middle-aged recipients, which is only partially accounted for by changes in recipient and donor characteristics. These findings signal a need to continue to monitor the effects of the KAS to ensure that allocation practices both maximize utility of the kidney graft pool and respect fairness between age groups.

Ischemic cholangiopathy following liver transplantation from donation after cardiac death donors.

The use of donation after cardiac death (DCD) donor hepatic allografts is becoming more widespread; however, there have been published reports of increased graft failure from specific complications associated with this type of allograft. The complication of ischemic cholangiopathy (IC) has been reported to occur more frequently after the use of DCD hepatic allografts. We report the results of 52 liver transplants from DCD donors and the factors that influenced the development of IC. We conducted a retrospective review of all DCD and donation after brain death (DBD) donor liver recipients from September 2003 through December 2006 at a single institution. Survival and complication rates were compared between the 2 groups. The Cox proportional hazards model was then used to identify recipient and donor factors that predict the development of IC in the DCD group. There was no difference in 1-year patient or graft survival rates between the 2 groups. There was no incidence of primary nonfunction from the DCD allografts. Hepatic artery complications and anastomotic bile duct complications were comparable in the 2 groups. There was, however, an increased risk for the development of IC in the DCD group (13.7% versus 1%, P = 0.001). Donor weight >100 kg and total ischemia times > or =9 hours, in donors older than 50 years of age, predicted the development of IC in the DCD group. In conclusion, there is a higher incidence of IC in recipients receiving DCD donor livers; however, patient and graft outcomes with DCD donors remain comparable to those with DBD donors. Careful donor selection may improve utilization of these grafts.

Identifying risk for recurrent hepatocellular carcinoma after liver transplantation: implications for surveillance studies and new adjuvant therapies.

The recurrence of hepatocellular carcinoma (HCC) is a major cause of mortality for patients transplanted with HCC. There currently exists no standard method for identifying those patients with a high risk for recurrence. Identification of factors leading to recurrence is necessary to develop an efficient surveillance protocol and address new potential adjuvant therapies. We conducted a retrospective review of 834 consecutive liver transplants from 1/1/1996 to 12/31/2005 (mean follow-up 1303 +/- 1069 days) at one institution and 352 consecutive transplants from 1/2/2002 to 12/31/2005 (mean follow-up 836 +/- 402 days) at a second institution. The test cohort comprised patients identified with HCC in their explanted livers from 1/1/2001 to 12/31/2005 at the first institution. Explant pathology and donor and recipient characteristics were reviewed to determine factors associated with HCC recurrence. These predictors were validated in the remaining liver transplant recipients. The test cohort had 116 patients with findings of HCC in their explanted livers. Twelve patients developed recurrent HCC. Stepwise logistic regression identified 4 independent significant explant factors predictive of recurrence. Size of one tumor (>4.5 cm), macroinvasion, and bilobar tumor were positive predictors of recurrence, whereas the presence of only well-differentiated HCC was a negative predictor. Designating each significant factor with points in relation to its odds ratio, a Predicting Cancer Recurrence Score (PCRS) with results ranging from -3 to 6 was developed that accurately determined risk of recurrence. These findings were then applied to the two validation cohorts, which confirmed the high predictive value of this model. In conclusion, patients transplanted for HCC with a PCRS of < or =0 have a low risk of recurrence. Patients with a PCRS of 1 or 2 have a moderate risk of recurrence, and those with a PCRS of > or =3 have a high risk for recurrence.

Splenic Subcapsular Hematoma After Endoscopic Retrograde Cholangiopancreatography in a Liver Transplant Recipient: Case Report and Literature Review.

Splenic injuries after an endoscopic retrograde cholangiopancreatography are a rare but lethal complication. We describe a subcapsular splenic hematoma requiring emergent splenectomy after an endoscopic retrograde cholangiopancreatography in a liver transplant recipient.