Characterizing the risk of human leukocyte antigen-incompatible living donor kidney transplantation in older recipients.

Older compatible living donor kidney transplant (CLDKT) recipients have higher mortality and death-censored graft failure (DCGF) compared to younger recipients. These risks may be amplified in older incompatible living donor kidney transplant (ILDKT) recipients who undergo desensitization and intense immunosuppression. In a 25-center cohort of ILDKT recipients transplanted between September 24, 1997, and December 15, 2016, we compared mortality, DCGF, delayed graft function (DGF), acute rejection (AR), and length of stay (LOS) between 234 older (age ≥60 years) and 1172 younger (age 18-59 years) recipients. To investigate whether the impact of age was different for ILDKT recipients compared to 17 542 CLDKT recipients, we used an interaction term to determine whether the relationship between posttransplant outcomes and transplant type (ILDKT vs CLDKT) was modified by age. Overall, older recipients had higher mortality (hazard ratio: 1.632.072.65, P < .001), lower DCGF (hazard ratio: 0.360.530.77, P = .001), and AR (odds ratio: 0.390.540.74, P < .001), and similar DGF (odds ratio: 0.461.032.33, P = .9) and LOS (incidence rate ratio: 0.880.981.10, P = 0.8) compared to younger recipients. The impact of age on mortality (interaction P = .052), DCGF (interaction P = .7), AR interaction P = .2), DGF (interaction P = .9), and LOS (interaction P = .5) were similar in ILDKT and CLDKT recipients. Age alone should not preclude eligibility for ILDKT.

Delayed graft function and acute rejection following HLA-incompatible living donor kidney transplantation.

Incompatible living donor kidney transplant recipients (ILDKTr) have pre-existing donor-specific antibody (DSA) that, despite desensitization, may persist or reappear with resulting consequences, including delayed graft function (DGF) and acute rejection (AR). To quantify the risk of DGF and AR in ILDKT and downstream effects, we compared 1406 ILDKTr to 17 542 compatible LDKT recipients (CLDKTr) using a 25-center cohort with novel SRTR linkage. We characterized DSA strength as positive Luminex, negative flow crossmatch (PLNF); positive flow, negative cytotoxic crossmatch (PFNC); or positive cytotoxic crossmatch (PCC). DGF occurred in 3.1% of CLDKT, 3.5% of PLNF, 5.7% of PFNC, and 7.6% of PCC recipients, which translated to higher DGF for PCC recipients (aOR = 1.03 1.682.72 ). However, the impact of DGF on mortality and DCGF risk was no higher for ILDKT than CLDKT (p interaction > .1). AR developed in 8.4% of CLDKT, 18.2% of PLNF, 21.3% of PFNC, and 21.7% of PCC recipients, which translated to higher AR (aOR PLNF = 1.45 2.093.02 ; PFNC = 1.67 2.403.46 ; PCC = 1.48 2.243.37 ). Although the impact of AR on mortality was no higher for ILDKT than CLDKT (p interaction = .1), its impact on DCGF risk was less consequential for ILDKT (aHR = 1.34 1.621.95 ) than CLDKT (aHR = 1.96 2.292.67 ) (p interaction = .004). Providers should consider these risks during preoperative counseling, and strategies to mitigate them should be considered.

Center-level Variation in HLA-incompatible Living Donor Kidney Transplantation Outcomes.

BACKGROUND: Desensitization protocols for HLA-incompatible living donor kidney transplantation (ILDKT) vary across centers. The impact of these, as well as other practice variations, on ILDKT outcomes remains unknown. METHODS: We sought to quantify center-level variation in mortality and graft loss following ILDKT using a 25-center cohort of 1358 ILDKT recipients with linkage to Scientific Registry of Transplant Recipients for accurate outcome ascertainment. We used multilevel Cox regression with shared frailty to determine the variation in post-ILDKT outcomes attributable to between-center differences and to identify any center-level characteristics associated with improved post-ILDKT outcomes. RESULTS: After adjusting for patient-level characteristics, only 6 centers (24%) had lower mortality and 1 (4%) had higher mortality than average. Similarly, only 5 centers (20%) had higher graft loss and 2 had lower graft loss than average. Only 4.7% of the differences in mortality (P < 0.01) and 4.4% of the differences in graft loss (P < 0.01) were attributable to between-center variation. These translated to a median hazard ratio of 1.36 for mortality and 1.34 of graft loss for similar candidates at different centers. Post-ILDKT outcomes were not associated with the following center-level characteristics: ILDKT volume and transplanting a higher proportion of highly sensitized, prior transplant, preemptive, or minority candidates. CONCLUSIONS: Unlike most aspects of transplantation in which center-level variation and volume impact outcomes, we did not find substantial evidence for this in ILDKT. Our findings support the continued practice of ILDKT across these diverse centers.

Hospital readmissions following HLA-incompatible live donor kidney transplantation: A multi-center study.

Thirty percent of kidney transplant recipients are readmitted in the first month posttransplantation. Those with donor-specific antibody requiring desensitization and incompatible live donor kidney transplantation (ILDKT) constitute a unique subpopulation that might be at higher readmission risk. Drawing on a 22-center cohort, 379 ILDKTs with Medicare primary insurance were matched to compatible transplant-matched controls and to waitlist-only matched controls on panel reactive antibody, age, blood group, renal replacement time, prior kidney transplantation, race, gender, diabetes, and transplant date/waitlisting date. Readmission risk was determined using multilevel, mixed-effects Poisson regression. In the first month, ILDKTs had a 1.28-fold higher readmission risk than compatible controls (95% confidence interval [CI] 1.13-1.46; P < .001). Risk peaked at 6-12 months (relative risk [RR] 1.67, 95% CI 1.49-1.87; P < .001), attenuating by 24-36 months (RR 1.24, 95% CI 1.10-1.40; P < .001). ILDKTs had a 5.86-fold higher readmission risk (95% CI 4.96-6.92; P < .001) in the first month compared to waitlist-only controls. At 12-24 (RR 0.85, 95% CI 0.77-0.95; P = .002) and 24-36 months (RR 0.74, 95% CI 0.66-0.84; P < .001), ILDKTs had a lower risk than waitlist-only controls. These findings of ILDKTs having a higher readmission risk than compatible controls, but a lower readmission risk after the first year than waitlist-only controls should be considered in regulatory/payment schemas and planning clinical care.

Outcomes of kidney transplants and risk of infection transmission from increased infectious risk donors.

Concern over transmission of viral infections has been reported to result in higher discard rates of high infectious risk kidneys (HIR) although data on actual viral transmission rates are lacking. At our center, we performed 89 HIR and 533 non-HIR kidney transplants (KTs) between 2004 and 2011. Follow-up screening labs in recipients of HIR kidneys tested for human immunodeficiency virus, hepatitis C virus, and hepatitis B virus did not reveal any cases of viral transmission over median follow-up of 4.3 years. Patient and graft outcomes were similar at 5 years between HIR and non-HIR KTs. An updated analysis of the Organ Procurement and Transplant Network (OPTN) registry of deceased-donor kidney transplants between 2008 and 2012 included 57 526 transplants was performed. Retrospective calculation of KDRI (kidney donor risk index) differed (P<.001) between all groups with median KDRI of 0.99 for HIR kidneys, 1.07 for non-HIR standard criteria donor kidneys, and 1.81 for non-HIR expanded criteria donor (ECD) kidneys. This was reflected in the significantly improved 5-year graft survival for HIR KTs when compared with non-HIR ECD KTs (84% vs 78%; P<.001). Our data can guide counseling of KT candidates about the safety and benefits of HIR kidneys.

Survival Benefit with Kidney Transplants from HLA-Incompatible Live Donors.

BACKGROUND: A report from a high-volume single center indicated a survival benefit of receiving a kidney transplant from an HLA-incompatible live donor as compared with remaining on the waiting list, whether or not a kidney from a deceased donor was received. The generalizability of that finding is unclear. METHODS: In a 22-center study, we estimated the survival benefit for 1025 recipients of kidney transplants from HLA-incompatible live donors who were matched with controls who remained on the waiting list or received a transplant from a deceased donor (waiting-list-or-transplant control group) and controls who remained on the waiting list but did not receive a transplant (waiting-list-only control group). We analyzed the data with and without patients from the highest-volume center in the study. RESULTS: Recipients of kidney transplants from incompatible live donors had a higher survival rate than either control group at 1 year (95.0%, vs. 94.0% for the waiting-list-or-transplant control group and 89.6% for the waiting-list-only control group), 3 years (91.7% vs. 83.6% and 72.7%, respectively), 5 years (86.0% vs. 74.4% and 59.2%), and 8 years (76.5% vs. 62.9% and 43.9%) (P<0.001 for all comparisons with the two control groups). The survival benefit was significant at 8 years across all levels of donor-specific antibody: 89.2% for recipients of kidney transplants from incompatible live donors who had a positive Luminex assay for anti-HLA antibody but a negative flow-cytometric cross-match versus 65.0% for the waiting-list-or-transplant control group and 47.1% for the waiting-list-only control group; 76.3% for recipients with a positive flow-cytometric cross-match but a negative cytotoxic cross-match versus 63.3% and 43.0% in the two control groups, respectively; and 71.0% for recipients with a positive cytotoxic cross-match versus 61.5% and 43.7%, respectively. The findings did not change when patients from the highest-volume center were excluded. CONCLUSIONS: This multicenter study validated single-center evidence that patients who received kidney transplants from HLA-incompatible live donors had a substantial survival benefit as compared with patients who did not undergo transplantation and those who waited for transplants from deceased donors. (Funded by the National Institute of Diabetes and Digestive and Kidney Diseases.).

Multimodality therapy and liver transplantation for hepatocellular carcinoma: a 14-year prospective analysis of outcomes.

BACKGROUND: Hepatocellular carcinoma is a major cause of death among patients with cirrhosis. A standardized approach of multimodality therapy with intent-to-treat by transplantation for all patients with hepatocellular carcinoma was instituted at our transplant center in 1997. Data were prospectively collected to evaluate the impact of multimodality therapy on posttransplant patient survival, tumor recurrence, and patient survival without transplantation. METHODS: All patients with hepatocellular carcinoma were eligible for multimodality therapy. Multimodality therapy consisted of hepatic resection, radiofrequency ablation, transarterial chemoembolization, transarterial chemoinfusion, yttrium-90 microsphere radioembolization, and sorafenib. RESULTS: Approximately 715 patients underwent multimodality therapy; 231 patients were included in the intent-to-treat with transplantation arm, and 484 patients were treated with multimodality therapy or palliative therapy because of contraindications for transplantation. A 60.2% transplantation rate was achieved in the intent-to-treat with transplantation arm. Posttransplant survivals at 1 and 5 years were 97.1% and 72.5%, respectively. Tumor recurrence rates at 1, 3, and 5 years were 2.4%, 6.2%, and 11.6%, respectively. Patients with contraindications to transplant had increased 1- and 5-year survival from diagnosis with multimodality therapy compared with those not treated (73.1% and 46.5% versus 15.5% and 4.4%, P<0.0001). CONCLUSIONS: Using multimodality therapy before liver transplantation for hepatocellular carcinoma achieved low recurrence rates and posttransplant survival equivalent to patients with primary liver disease without hepatocellular carcinoma. Multimodality therapy may help identify patients with less active tumor biology and result in improved disease-free survival and organ utilization.

Identification of biomarkers to assess organ quality and predict posttransplantation outcomes.

UNLABELLED: The increased disparity between organ supply and need has led to the use of extended criteria donors and donation after cardiac death donors with other comorbidities. METHODS: We have examined the preimplantation transcriptome of 112 kidney transplant recipient samples from 100 deceased-donor kidneys by microarray profiling. Subject groups were segregated based on estimated glomerular filtration rate (eGFR) at 1 month after transplantation: the GFR-high group (n=74) included patients with eGFR 45 mL/min per 1.73 m(2), whereas the GFR-low group (n=35) included patients with eGFR 45 mL/min or less per 1.73 m(2). RESULTS: Gene expression profiling identified higher expression of 160 probe sets (140 genes) in the GFR-low group, whereas expression of 37 probe sets (33 genes) was higher in the GFR-high group (P<0.01, false discovery rate <0.2). Four genes (CCL5, CXCR4, ITGB2, and EGF) were selected based on fold change and P value and further validated using an independent set of samples. A random forest analysis identified three of these genes (CCL5, CXCR4, and ITGB2) as important predictors of graft function after transplantation. CONCLUSIONS: Inclusion of pretransplantation molecular gene expression profiles in donor quality assessment systems may provide the necessary information for better donor organ selection and function prediction. These biomarkers would further allow a more objective and complete assessment of procured renal allografts at pretransplantation time.

Reduced expression of inflammatory genes in deceased donor kidneys undergoing pulsatile pump preservation.

BACKGROUND: The use of expanded criteria donor kidneys (ECD) had been associated with worse outcomes. Whole gene expression of pre-implantation allograft biopsies from deceased donor kidneys (DDKs) was evaluated to compare the effect of pulsatile pump preservation (PPP) vs. cold storage preservation (CSP) on standard and ECD kidneys. METHODOLOGY/PRINCIPAL FINDINGS: 99 pre-implantation DDK biopsies were studied using gene expression with GeneChips. Kidneys transplant recipients were followed post transplantation for 35.8 months (range = 24-62). The PPP group included 60 biopsies (cold ischemia time (CIT) = 1,367+/-509 minutes) and the CSP group included 39 biopsies (CIT = 1,022+/-485 minutes) (P<0.001). Donor age (42.0±14.6 vs. 34.1±14.2 years, P = 0.009) and the percentage of ECD kidneys (PPP = 35% vs. CSP = 12.8%, P = 0.012) were significantly different between groups. A two-sample t-test was performed, and probe sets having a P<0.001 were considered significant. Probe set level linear models were fit using cold ischemia time and CSP/PPP as independent variables to determine significant probe sets (P<0.001) between groups after adjusting for cold ischemia time. Thus, 43 significant genes were identified (P<0.001). Over-expression of genes associated with inflammation (CD86, CD209, CLEC4, EGFR2, TFF3, among others) was observed in the CSP group. Cell-to-cell signaling and interaction, and antigen presentation were the most important pathways with genes significantly over-expressed in CSP kidneys. When the analysis was restricted to ECD kidneys, genes involved in inflammation were also differentially up-regulated in ECD kidneys undergoing CSP. However, graft survival at the end of the study was similar between groups (P = 0.2). Moreover, the incidence of delayed graft function was not significant between groups. CONCLUSIONS/SIGNIFICANCE: Inflammation was the most important up-regulated pattern associated with pre-implantation biopsies undergoing CSP even when the PPP group has a larger number of ECD kidneys. No significant difference was observed in delayed graft function incidence and graft function post-transplantation. These findings support the use of PPP in ECD donor kidneys.

Substitution of tenofovir/emtricitabine for Hepatitis B immune globulin prevents recurrence of Hepatitis B after liver transplantation.

BACKGROUND: Hepatitis B immune globulin (HBIg) with or without nucleos(t)ide analogue (NA) inhibitors has been shown to prevent recurrence of hepatitis B virus (HBV) following orthotopic liver transplantation (OLT). However, the use of HBIg has many disadvantages. AIMS: The present study was performed to determine if converting patients from HBIg ± NA to combination NA therapy could prevent recurrence of HBV. METHODS: Twenty-one recipients without evidence of HBV recurrence on HBIg ± NA for ≥ 6 months were enrolled. Patients received their last injection of HBIg at the time they initiated tenofovir disoproxil fumarate/emtricitabine (TDF/FTC; Truvada(®) ) and were followed up for 31.1 ± 9.0 [range 15-47] months. RESULTS: After 1 year, 3 patients (14%) had detectable HBsAg, one of whom was non-compliant. Two of 3 with recurrence cleared HBsAg by last follow-up on TDF/FTC; the non-compliant patient became HBV DNA-undetectable with re-institution of TDF/FTC. TDF/FTC saved $12,469/year over our standard-of-care, monthly intramuscular HBIg/lamivudine. There was no evidence of a general adverse effect of TDF/FTC on renal function. However, 3 patients developed reversible acute renal failure; on renal biopsy, 1 had possible TDF/FTC-induced acute tubular necrosis. CONCLUSIONS: Substitution of TDF/FTC for HBIg prevented recurrence of HBV DNA in 100% (20/20) of patients who were compliant with the medication and led to substantial cost savings over HBIg-containing regimens.

Graft-versus-host disease after solid organ transplantation: a single center experience and review of literature.

BACKGROUND: Graft-versus-host disease (GVHD) is an uncommon cause of morbidity and mortality after solid organ transplantation that is most likely under-diagnosed. We describe our single center experience with three cases of GVHD diagnosed over a period of 15 years in a total of 2,271 solid organ transplant recipients. CASE REPORTS: We describe three case reports: (1) a 3-week old neonate who developed GVHD 16 months after living-related liver transplant, (2) a 14-year old adolescent who developed GVHD 4 months following an unrelated cadaveric pancreas transplant and; (3) a 27-year old male who developed GVHD 18 days after simultaneous kidney-pancreas transplant from an unrelated donor. GVHD was confirmed through skin biopsies, engraftment profile from bone marrow biopsy and variable number tandem repeat analysis. Treatment strategies included use of corticosteroids and sirolimus monotherapy, corticosteroids and mesenchymal stromal cell therapy and reduction of immunosuppression. We observed that African-American race, sexual and HLA mismatching and cytomegalovirus infection may be high risk factors for development of GVHD following solid organ transplant. CONCLUSIONS: GVHD continues to be a rare but fatal complication following solid organ transplantation that demands a high index of clinical suspicion for diagnosis and management. Future approaches may focus on early recognition of risk factors and improving treatment protocols using a combination of mesenchymal stromal cell transplantation with pharmacotherapy.

Pretransplant transcriptome profiles identify among kidneys with delayed graft function those with poorer quality and outcome.

Robust biomarkers are needed to identify donor kidneys with poor quality associated with inferior early and longer-term outcome. The occurrence of delayed graft function (DGF) is most often used as a clinical outcome marker to capture poor kidney quality. Gene expression profiles of 92 preimplantation biopsies were evaluated in relation to DGF and estimated glomerular filtration rate (eGFR) to identify preoperative gene transcript changes associated with short-term function. Patients were stratified into those who required dialysis during the first week (DGF group) versus those without (noDGF group) and subclassified according to 1-month eGFR of >45 mL/min (eGFR(hi)) versus eGFR of ≤45 mL/min (eGFR(lo)). The groups and subgroups were compared in relation to clinical donor and recipient variables and transcriptome-associated biological pathways. A validation set was used to confirm target genes. Donor and recipient characteristics were similar between the DGF versus noDGF groups. A total of 206 probe sets were significant between groups (P < 0.01), but the gene functional analyses failed to identify any significantly affected pathways. However, the subclassification of the DGF and noDGF groups identified 283 probe sets to be significant among groups and associated with biological pathways. Kidneys that developed postoperative DGF and sustained an impaired 1-month function (DGF(lo) group) showed a transcriptome profile of significant immune activation already preimplant. In addition, these kidneys maintained a poorer transplant function throughout the first-year posttransplant. In conclusion, DGF is a poor marker for organ quality and transplant outcome. In contrast, preimplant gene expression profiles identify "poor quality" grafts and may eventually improve organ allocation.

En bloc kidney transplantation from pediatric donors: comparable outcomes with living donor kidney transplantation.

BACKGROUND: En bloc kidneys from pediatric donors have been considered suboptimal for transplantation to adult recipients and their outcomes have rarely been compared with living donor kidney transplantation (LDKT). Traditionally, there has been hesitancy in transplanting en bloc kidneys from donors weighing less than 10 kg due to high risk of technical complications. METHODS: Retrospective chart reviews were performed to compare outcomes after pediatric en bloc (n=20, mean donor weight 11.4 kg), standard criteria deceased (n=249), and living donor (n=215) kidney transplantation in adult recipients at our center. The outcomes after en bloc transplantation from young donors weighing less than or equal to 10 kg were compared with those from 11 to 15 kg donors. RESULTS: The 5-year graft survival after en bloc, standard deceased, and LDKT were 92%, 70%, and 88%, respectively (P=ns). There were no vascular complications, and urine leak was seen in 1 of 20 en bloc transplants. The 1-year serum creatinine of 1.1±0.2 mg/dL in recipients from less than or equal to 10 kg donors was comparable with 0.9±0.5 mg/dL in 11 to 15 kg group (P=ns). CONCLUSIONS: Excellent long-term outcome after pediatric en bloc kidney transplantation from donors weighing less than or equal to 15 kg are comparable with those after LDKT. By using meticulous surgical technique and judicious recipient selection criteria, technical graft losses can be minimized when using en bloc pediatric kidneys from donors weighing less than or equal to 10 kg. Use of pediatric en bloc kidneys should be encouraged continuously to address the problem of organ shortage.

Gene expression changes are associated with loss of kidney graft function and interstitial fibrosis and tubular atrophy: diagnosis versus prediction.

BACKGROUND: Loss of kidney graft function due to interstitial fibrosis (IF) and tubular atrophy (TA) is the most common cause of kidney allograft loss. METHODS: One hundred one allograft tissues (26 samples with IF/TA, 17 normal allografts, and an independent biopsy group collected at 3 month [n=34] posttransplantation) underwent microarray analysis to identify early detection/diagnostic biomarkers of IF/TA. Profiling of 24 allograft biopsies collected at or after 9-month posttransplantation (range 9-18 months) was used for validation. Three-month posttransplantation biopsies were classified as IF/TA nonprogressors (group 1) or progressors (group 2) using graft function and histology at 9-month posttransplantation. RESULTS: We identified 2223 differentially expressed probe sets between IF/TA and normal allograft biopsies using a Bonferroni correction. Genes up-regulated in IF/TA were primarily involved in pathways related to T-cell activation, natural killer cell-mediated cytotoxicity, and programmed cell death. A least absolute shrinkage and selection operator model was derived from the differentially expressed probe sets, resulting in a final model that included 10 probe sets and had 100% training set accuracy. The N-fold crossvalidated error was 2.4% (sensitivity 95.8% and specificity 100%). When 3-month biopsies were tested using the model, all the samples were classified as normal. However, evaluating gene expression of the 3-month biopsies and fitting a new penalized model, 100% sensitivity was observed in classifying the samples as group1 or 2. This model was evaluated in the sample set collected at or after 9-month posttransplantation. CONCLUSIONS: An IF/TA gene expression signature was identified, and it was useful for diagnosis but not prediction. However, gene expression profiles at 3 months might predict IF/TA progression.

Living donor liver transplantation for neonatal hemochromatosis using non-anatomically resected segments II and III: a case report.

INTRODUCTION: Neonatal hemochromatosis is the most common cause of liver failure and liver transplantation in the newborn. The size of the infant determines the liver volume that can be transplanted safely without incurring complications arising from a large graft. Transplantation of monosegments II or III is a standard method for the newborns with liver failure. CASE PRESENTATION: A three-week old African-American male neonate was diagnosed with acute liver failure secondary to neonatal hemochromatosis. Living-related liver transplantation was considered after the failure of intensive medical therapy. Intra-operatively a non-anatomical resection and transplantation of segments II and III was performed successfully. The boy is growing normally two years after the transplantation. CONCLUSION: Non-anatomical resection and transplantation of liver segments II and III is preferred to the transplantation of anatomically resected monosegements, especially when the left lobe is thin and flat. It allows the use of a reduced-size donor liver with intact hilar structures and outflow veins. In an emergency, living-related liver transplantation should be offered to infants with liver failure secondary to neonatal hemochromatosis who fail to respond to medical treatment.

Distinctive gene expression profiles characterize donor biopsies from HCV-positive kidney donors.

BACKGROUND: Because of the shortage of organs for transplantation, procurement of kidneys from extended criteria donors is inevitable. Frequently, donors infected with hepatitis C virus (HCV) are used. To elucidate an initial compromise of molecular pathways in HCV graft, gene expression profiles were evaluated. METHODS: Twenty-four donor allograft biopsies (n=12 HCV positive (+) and n=12 HCV negative (-)) were collected at preimplantation time and profiled using microarrays. Donors were age, race, gender, and cold and warm ischemia time matched between groups. Probe level data were read into the R programming environment using the affy Bioconductor package, and the robust multiarray average method was used to obtain probe set expression summaries. To identify probe sets exhibiting differential expression, a two sample t test was performed. Molecular and biologic functions were analyzed using Interaction Networks and Functional Analysis. RESULTS: Fifty-eight probe sets were differentially expressed between HCV (+) versus HCV (-) donors (P<0.001). The molecular functions associated with the two top scored networks from the analysis of the differentially expressed genes were connective tissue development and function and tissue morphology (score 34), cell death, cell signaling, cellular assembly, and organization (score 32). Among the differentially affected top canonical pathways, we found the role of RIG1-like receptors in antiviral innate immunity (P<0.001), natural killer cell signaling (P=0.007), interleukin-8 signaling (P=0.048), interferon signaling (P=0.0 11; INFA21, INFGR1, and MED14), ILK signaling (P=0.001), and apoptosis signaling. CONCLUSIONS: A unique gene expression pattern was identified in HCV (+) kidney grafts. Innate immune system and inflammatory pathways were the most affected.

Adult living donor versus deceased donor liver transplantation: a 10-year prospective single center experience.

It has been 4 years since the first, long-term (> 3 years) prospective comparison of adult-to-adult living donor liver transplantation (A2ALLTx) to adult deceased donor liver transplantation (ADDLTx) was reported. In this follow up, prospective, IRB approved, 10-year comparison of A2ALLTx to ADDLTx we expand on our initial observations. This data includes: age, gender, ethnicity, primary liver disease, waiting time, pretransplant CTP/MELD score, cold ischemia time (CIT), perioperative mortality, acute and chronic rejection, graft and patient survival, charges and post-transplant complications. In 10 years, 465 ADDLTx (81.3%) and 107 A2ALLTx (18.7%) were performed at VCUHS. Hepatitis C virus (HCV) was the most common reason for transplantation in both groups (54.5% vs. 48.2%). Data regarding overall patient and graft survival and retransplantation rates were similar. Comparison of patient/graft survivals, retransplantation rates in patients with and without HCV were not statistically different. A2ALLTx patients had less acute rejection (9.6% vs. 21.7%) and more biliary complications (27.1% vs. 17.6%). In conclusion, A2ALLTx is as durable a liver replacement technique as the ADDLTx. Patients with A2ALLTx were younger, had lower MELD scores, less acute rejection and similar histological HCV recurrence. Biliary complications were more common in A2ALLTx but were not associated with increased graft loss compared to ADDLTx.

Effect of hyponatraemia on outcomes following orthotopic liver transplantation.

BACKGROUND: Hyponatraemia increases risk of adverse outcomes following orthotopic liver transplantation (OLT), but it is unclear whether improvement of pretransplant hyponatraemia ameliorates post-transplant complications. AIMS: To assess impact of pretransplant hyponatraemia on post-transplant outcomes. METHODS: We performed a retrospective analysis of 213 patients with cirrhosis who underwent liver transplantation. Patients with serum sodium 130 mEq/L at transplantation ('resolved hyponatraemia'; n=56) and to those without history of hyponatraemia before transplantation ('never hyponatraemic'; n=123). Primary endpoint was survival at 180 days post-OLT. Secondary outcomes included time until discharge alive, complications during hospitalization, length of time ventilated and length of post-transplant intensive care unit stay. RESULTS: There was no survival difference at 180 days post-OLT between groups. After transplantation, patients with either hyponatraemia at OLT or resolved hyponatraemia had longer time until discharge alive and had higher rates of delirium, acute renal failure, acute cellular rejection and infection than those who were never hyponatraemic. As compared with patients with hyponatraemia at OLT, those with resolved hyponatraemia were more likely to be discharged alive within 3 weeks, but other outcomes, including survival, did not differ significantly. CONCLUSIONS: We conclude that hyponatraemia at any time before liver transplantation is associated with adverse post-transplant outcome, even when hyponatraemia has resolved.

Incidence of prolonged length of stay after orthotopic liver transplantation and its influence on outcomes.

Orthotopic liver transplantation (OLT) is the only effective treatment for end-stage liver disease. Although most patients do well and are discharged promptly, some require prolonged length of stay (PLOS). The prevalence of PLOS, associated factors, and their impact on survival are not well defined. We reviewed our adult OLT database for patients who survived > 30 days. PLOS was defined as hospitalization > 30 days following OLT. Of 521 OLT recipients, 68 (13%) had PLOS with a median duration of 50 days versus only 10 days for patients discharged within 30 days. Significant differences in pre-OLT variables between patients with and without PLOS included the mean wait list time (P = 0.001), hospitalization at the time of OLT (P = 0.001), and prior OLT (P = 0.041). Factors independently associated with PLOS included intensive care unit status at the time of OLT [odds ratio (OR), 4; 95% confidence interval (CI), 1.6-10.4], OLT prior to Model for End-Stage Liver Disease implementation (OR, 2.27; 95% CI, 1.04-5.26), in-hospital post-OLT bacterial infection (OR, 9.34; 95% CI, 4.65-18.86), gastrointestinal bleeding (OR, 4.34; 95% CI, 1.4-14.08), renal failure (OR, 10.86; 95% CI, 5.07-23.25), and allograft rejection (OR, 3.7; 95% CI, 1.23-11.11). One-year graft survival and patient survival were significantly less in those with PLOS (for both, P < 0.0001). Among PLOS patients, factors independently associated with increased 1-year mortality were donor age (OR, 1.07; 95% CI, 1.009-1.13), primary diagnosis of hepatitis C virus (OR, 6.89; 95% CI, 1.40-34.48), in-hospital post-OLT bacterial infection (OR, 13.3; 95% CI, 2.11-83.33), and cardiac complications (OR, 20.4; 95% CI, 1.51-250; c-statistic for the model, 0.85). In conclusion, PLOS following OLT is associated with a significant decrease in survival despite a marked increase in cost and resource utilization. Efforts to modify those factors that contribute to PLOS may reduce this event, improve survival, and reduce OLT-associated costs.