Preformed Angiotensin II Type-1 Receptor Antibodies Are Associated With Rejection After Kidney Transplantation: A Single-Center, Cohort Study.

Antibodies against angiotensin II type-1 receptors (AT1R) have been increasingly recognized in association with rejection and poor allograft outcomes. Our goal was to define the prevalence of preformed antibodies against AT1R and evaluate the association with renal allograft outcomes in a consecutive cohort of 150 transplant recipients. IgG antibodies against AT1R were measured by enzyme-linked immunosorbent assay using cryopreserved serum samples obtained for HLA testing at the time of transplantation. Results were categorized as negative if <10 U/mL (44%), intermediate from 10 to 17 U/mL (38%), or strongly positive if >17 U/mL (18%). The presence of AT1R antibodies was inversely associated with age, dialysis status, and diabetes. We found a strong association between the presence of AT1R antibodies and acute cellular rejection using multivariate analyses, odds ratio 3.86 (95% CI, 1.03-14.47) for intermediate titers and 9.99 (95% CI, 2.6-38.4) for strongly positive titers. There was no association with HLA sensitization or C4d-positive antibody-mediated rejection. We did not observe a significant association with graft failure, allograft function, or proteinuria. Preformed AT1R antibodies are prevalent and highly associated with acute cellular rejection early after transplant, independent of anti-HLA antibodies. The presence of AT1R antibodies correlates with recipient characteristics that may denote stronger immune responses. Future studies are needed to evaluate the mechanism and causative effect of AT1R antibodies.

Are we underestimating the quality of aviremic hepatitis C-positive kidneys? Time to reconsider.

Kidney Donor Risk Index (KDRI) introduced in 2009 included hepatitis C serologic but not viremic status of the donors. With nucleic acid amplification testing (NAT) now being mandatory, further evaluation of these donors is possible. We conducted a retrospective matched case-control analysis of adult deceased donor kidney transplants performed between December 5, 2014 to December 31, 2016 with the KDRI score and hepatitis C virus antibody (HCV Ab) and NAT testing status obtained from the United Network for Organ Sharing database. The 205 aviremic HCV Ab+ NAT - kidney transplants were compared to KDRI matched control kidneys that were HCV Ab-NAT-. The aviremic HCV kidneys were recovered from donors who were significantly younger, more likely to be white, and less likely to have hypertension and diabetes. The majority of the recipients of the aviremic HCV kidneys when compared to matched controls were HCV positive: 90.2% vs 4.3%. The recipients were significantly older, were on dialysis for a shorter time, and were transplanted sooner. The graft survival of aviremic HCV kidneys was similar (P < .08). If the HCV status of the aviremic kidneys was assumed to be negative, 122 more kidneys could have been allocated to patients with estimated posttransplant survival <20. Seven kidneys would no longer have Kidney Donor Profile Index >85%. Further policies might consider these findings to appropriately allocate these kidneys.

Unintended Consequences in Use of Increased Risk Donor Kidneys in the New Kidney Allocation Era.

BACKGROUND: The new kidney allocation system (KAS) intends to allocate the top 20% of kidneys to younger recipients with longer life expectancy. We hypothesized that the new KAS would lead to greater allocation of Public Health Service (PHS) increased-risk donor organs to younger recipients. METHODS: Analyses of the Organ Procurement and Transplantation Network data of patients who underwent primary deceased kidney transplantation were performed in pre- and post-KAS periods. RESULTS: The allocation of PHS increased-risk kidney allografts in various age groups changed significantly after implementation of the new KAS, with an increased proportion of younger individuals receiving increased-risk kidneys (7% vs 10% in age group 20-29 y and 13% vs 18% in age group 30-39 y before and after KAS, respectively; P < .0001). This trend was reversed in recipients 50-59 years old, with 31% in the pre-KAS period compared with 26% after KAS (P < .0001). CONCLUSIONS: The new KAS resulted in a substantial increase in allocation of PHS increased-risk kidneys to candidates in younger age groups. Because increased-risk kidneys are generally underutilized, future efforts to optimize the utilization of these organs should target younger recipients and their providers.

Coloduodenovesical Fistula After Simultaneous Pancreas-Kidney Transplant: Case Report and Review of the Literature.

BACKGROUND: Complicated diverticulitis after transplantation occurs in as many as 3.5% of cases and carries a 25% mortality rate. Diagnosis of complicated diverticulitis in this population can be challenging because of abnormal presentations caused by immunosuppression. Only 4 cases of fistulization after kidney transplantation are described in the literature; none occurred after simultaneous pancreas-kidney transplant. METHODS: We present a first case of a coloduodenovesical fistula in a patient 9 years after simultaneous pancreas-kidney transplant. The patient presented with intermittent episodes of elevated creatinine and recurrent urinary tract infection. The presence of fistula was strongly suspected in cystoscopy, but, despite extensive investigation, a fistula tract could not be identified. RESULTS: The patient ultimately underwent surgical exploration for positive cystoscopy examination, continuation of urinary complaints, and presence of multiple colonic diverticula in computed tomography scan. At surgical exploration, a fistula track was identified between the sigmoid colon and duodenal stump of the pancreas allograft. Subsequently, sigmoidectomy, bladder repair, and enteric conversion of the pancreas transplant were performed. CONCLUSIONS: Complications of diverticulitis should be considered in organ transplant recipients presenting with recurrent urinary infection and elevated creatinine, and surgical exploration might be indicated even if unable to well-define the fistula tract.

Sporadic Retroperitoneal Hemangioblastoma: Report of a Case and Review of the Literature.

We report a case of sporadic isolated hemangioblastoma arising from the retroperitoneum and provide a review of the scarce literature regarding this very rare tumor. Furthermore, we thoroughly describe the pathologic features and the broad differential diagnosis that should always be included in the study of any retroperitoneal soft tissue mass to arrive at the final diagnosis.

Landscape of Kidney Transplantation in Patients With Compensated Liver Disease: Results of a Survey of Transplant Surgeons in the United States.

BACKGROUND: The therapeutic options that provide the best long-term outcome for patients who have a combination of end-stage renal disease and compensated cirrhosis are unknown. METHODS: Given the paucity of data and the lack of clinical guidance in this area, a national survey was conducted in the form of an e-mail-based questionnaire addressed to the transplantation surgeons registered with the American Society of Transplant Surgeons. RESULTS: Of the 818 surgeons invited to participate in the survey, 167 (20%) responded. Twenty-one (12.6%) respondents indicated that their program performed <50 kidney transplantations per year, 49 (29.3%) reported performing 50 to 100 kidney transplantations per year, and the majority, 97 (58.1%) of respondents, performed >100 kidney transplantations per year. The majority, 116 (69.5%), believed that compensated cirrhotic patients with end-stage renal disease could be considered for renal transplantation alone, 45 (26.9%) respondents believed that compensated cirrhotic patients on dialysis could only be considered for simultaneous liver-kidney transplantation, and 6 (3.6%) believed that this population of patients was not suitable for kidney transplantation alone. CONCLUSIONS: Our findings suggest that there is a substantial heterogeneity of opinion among transplantation surgeons towards transplantation options for compensated cirrhotic patients. Further data is needed to define best practices and clinical guidelines.

Serum alkaline phosphatase and bilirubin are early surrogate markers for ischemic cholangiopathy and graft failure in liver transplantation from donation after circulatory death.

Liver transplantation with the use of donation after circulatory death (DCD) is associated with ischemic cholangiopathy (IC) often leading to graft loss. We hypothesized that serial postoperative analysis of alkaline phosphatase and bilirubin might identify patients who would later on develop ischemic cholangiopathy and/or graft loss, allowing early recognition and potentially retransplantation. The University of Washington DCD experience totals 89 DCD liver transplantations performed from 2003 to 2011 with Kaplan-Meier estimated 5-year patient and graft survival rates of 81.6% and 75.6%, respectively; 84/89 patients transplanted with DCD livers lived ≥ 60 days after transplantation and were analyzed. Serum bilirubin and alkaline phosphatase levels at 1 week, 2 week, 1 month, and 2 months after transplantation were analyzed. Two-month serum bilirubin and alkaline phosphatase proved to have the strongest associations with development of IC and graft failure. Two-month alkaline phosphatase of <100 U/L had a negative predictive value of 97% for development of IC. Two-month alkaline phosphatase demonstrated an inflection starting at >300 U/L strongly associated with development of IC (P < .0001). Serum bilirubin at 2 months was most strongly associated with graft failure within the 1st year with a strong inflection point at 2.5 mg/dL (P = .0001). All jaundiced recipients at 60 days after transplantation (bilirubin >2.5 mg/dL) developed graft failure within the 1st year (P < .0001). Use of these early surrogate markers could facilitate prioritization and early retransplantation for DCD liver recipients with allografts destined for failure.

Differential rates of ischemic cholangiopathy and graft survival associated with induction therapy in DCD liver transplantation.

Transplantation utilizing donation after circulatory death (DCD) donors is associated with ischemic cholangiopathy (IC) and graft loss. The University of Washington (UW) DCD experience totals 89 DCD liver transplants performed between 2003 and 2011. Overall outcome after DCD liver transplantation at UW demonstrates Kaplan-Meier estimated 5-year patient and graft survival rates of 81.6% and 75.6%, respectively, with the great majority of patient and graft losses occurring in the first-year posttransplant from IC. Our program has almost exclusively utilized either anti-thymocyte globulin (ATG) or basiliximab induction (86/89) for DCD liver transplantations. Analysis of the differential effect of induction agent on graft survival demonstrated graft survival of 96.9% at 1 year for ATG versus 75.9% for basiliximab (p = 0.013). The improved survival did not appear to be from a lower rate of rejection (21.9% vs. 22.2%) but rather a differential rate of IC, 35.2% for basiliximab versus 12.5% for ATG (p = 0.011). Multivariable analysis demonstrated induction agent to be independently associated with graft survival and IC free graft survival when analyzed against variables including donor age, fWIT, donor cold ischemia time and transplant era.

A symptomatic de novo pheochromocytoma 23 years after liver transplantation: a case report and review of the literature.

We report a case of subacute onset of headaches and tremors with a newly discovered adrenal pheochromocytoma 23 years after an orthotopic liver transplantation and provide a review of the scarce literature regarding endocrine malignancies in liver transplant recipients. We describe the clinical presentation, diagnostic work-up, and management. This is the second case report in the literature of a de novo pheochromocytoma after solid organ transplantation. It shows that new-onset common symptoms in transplant recipients are always challenging and deserve a very thorough work-up until the cause of the symptoms is elucidated. A broad differential diagnosis should always be included in the study of any abnormalities in this patient population.

PD-L1 signal on liver dendritic cells is critical for Foxp3(+)CD4(+)CD25(+) Treg and liver tolerance induction in mice.

Allogeneic liver transplantation induces spontaneous tolerance in mice without a requirement for immunosuppression. The underling mechanisms remain unclear. Our recent studies indicated that Foxp3(+)CD25(+)CD4(+) regulatory T (Treg) cells play an important role in the induction of spontaneous transplant tolerance. How Treg cells are induced and their functional mechanisms to regulate the response remain undefined. In this study, we employed a mouse liver transplant model using PD-L1-/-, and Flt3L-/- mice to critically examine the role of liver dendritic cells (DCs) and the PD-L1 signal in Treg induction. Our results showed that liver DCs, which expressed a great number of PD-L1 molecules, induced more Foxp3(+)CD25(+)CD4(+) Treg in vitro upon coculture with allogeneic CD4 T cells compared with spleen DCs. The DCs from PD-L1-deficient mice failed to expand Foxp3(+)CD25(+)CD4(+) Treg in vitro. Adoptive transfer of Foxp3(+)CD25(+)CD4(+)Treg expanded from liver DCs prolonged heart allograft survival significantly greater than spleen cell controls. Moreover, liver grafts from Flt3L-/- and PD-L1-/- mice were rejected acutely in C3H recipients. Immunohistochemistry revealed reduced Foxp3(+) cells and significantly increased IL-2, IL-10, and IFN-γ producing elements in the liver grafts and recipient spleens of Flt3L-/- and PD-L1-/- donors. In conclusion, liver DCs play a critical role in the induction of Foxp3(+)CD25(+)CD4(+) Treg, which may mediate spontaneous acceptance of MHC-mismatched liver allografts in mice. The effects of DCs on Foxp3(+)CD25(+)CD4(+) Treg induction and expansion appear to depend on the PD-L1 signal.

Risk stratification of kidneys from donation after cardiac death donors and the utility of machine perfusion.

There has been a dramatic increase in the utilization of kidneys from donors after cardiac death (DCD). While these organs represent an opportunity to expand the donor pool, the assessment of risk and optimal perioperative management remains unclear. Our primary aim was to identify risk factors for objective outcomes, and secondarily, we sought to determine what impact pulsatile machine perfusion (PMP) had on these outcomes. From 1993 to November 2008, 6057 DCD kidney transplants were reported to the Organ Procurement and Transplantation Network database, with complete endpoints for delayed graft function (DGF) and graft survival (GS). Risk factors were identified using a multivariable regression analysis adjusted for recipient factors. Age (50 yr) [OR 1.81, p < 0.0001] and cold ischemia time (CIT) (>30 h) [OR 3.22, p < 0.0001] were the strongest predictors of DGF. The use of PMP decreased the incidence of DGF only when donor age was >60 yr and improved long-term graft survival when donor age was >50 yr. Donor warm ischemia time >20 min was also found to correlate with increased DGF. While the incidence of DGF in DCD kidneys is significantly higher, the only factors the transplant surgeon can control are CIT and the use of PMP. The data suggest that the use of PMP in DCD kidneys <50 yr old provides little clinical benefit and may increase CIT.

D-MELD, a simple predictor of post liver transplant mortality for optimization of donor/recipient matching.

Numerous donor and recipient risk factors interact to influence the probability of survival after liver transplantation. We developed a statistic, D-MELD, the product of donor age and preoperative MELD, calculated from laboratory values. Using the UNOS STAR national transplant data base, we analyzed survival for first liver transplant recipients with chronic liver failure from deceased after brain death donors. Preoperative D-MELD score effectively stratified posttransplant survival. Using a cutoff D-MELD score of 1600, we defined a subgroup of donor-recipient matches with significantly poorer short- and long-term outcomes as measured by survival and length of stay (LOS). Avoidance of D-MELD scores above 1600 improved results for subgroups of high-risk patients with donor age >/=60 and those with preoperative MELD >/=30. D-MELD >/=1600 accurately predicted worse outcome in recipients with and without hepatitis C. There is significant regional variation in average D-MELD scores at transplant, however, regions with larger numbers of high D-MELD matches do not have higher survival rates. D-MELD is a simple, highly predictive tool for estimating outcomes after liver transplantation. This statistic could assist surgeons and their patients in making organ acceptance decisions. Applying D-MELD to liver allocation could eliminate many donor/recipient matches likely to have inferior outcome.

Ureteral complications in renal transplantation: a comparison of the Lich-Gregoir versus the Taguchi technique.

OBJECTIVE: Modifications of the Lich-Gregoir extravesical ureteroneocystostomy have become the standard technique for management of the ureter during renal transplantation. We performed a comparative outcome examination of the standard Lich-Gregoir technique and the Taguchi or "one-stitch" technique. METHODS: We reviewed our experience at the University of Washington with the Taguchi (one-stitch, Minnesota) extravesical reimplant technique that involves tacking the distal ureter to the bladder mucosa with a single absorbable stitch. RESULTS: During a 3.5-year period, 330 renal transplants were performed and in 73 cases a Taguchi ureteral anastomosis was employed rather than the Lich-Gregoir technique (238 cases). The overall complication rate for the Taguchi technique was 23% (n = 16) as opposed to 7.1% for the Lich-Gregoir technique. When comparing the Taguchi to the Lich-Gregoir technique, there was a significant increase in hematuria and ureteral complications (P = .002, .012). In a multivariate analysis, the Taguchi technique was a significant risk factor for both hematuria and ureteral complications. CONCLUSIONS: In summary, our limited experience with Taguchi ureteroneocystostomy resulted in dramatically higher complication rates than the modified the Lich-Gregoir technique.

Postrenal transplant non-EBV multiple myeloma of donor origin.

Multiple myeloma occurring after solid organ transplantation is a rare condition, with only a few case reports found in the literature. We report a case of Epstein-Barr virus-negative, posttransplant multiple myeloma in a 67-year-old female, presenting 18 months after renal transplantation. Interestingly, fluorescence in situ hybridization analysis of the tumor revealed a Y chromosome in the majority of the cells, indicating that the neoplasm was derived from the donor kidney. To our knowledge, this represents the first reported case with these features.

Outcomes with the selective use of enteric exocrine drainage in pancreas transplantation.

BACKGROUND: Bladder drainage of the exocrine secretions of pancreas transplants has been the standard of practice as it affords the ability to monitor for rejection and is thought to be associated with decreased morbidity. Recently, there has been renewed interest in avoiding the urinary tract complications and metabolic derangements that accompany bladder drainage by draining pancreatic exocrine secretions into the jejunum (enteric drainage). We sought to determine whether enteric drainage of pancreas transplants is safe and offers advantages without compromise in graft function or longevity. METHODS: We retrospectively reviewed all pancreas transplants performed at the University of Washington between 2000 and 2003. Selection of the exocrine drainage method was based on the length of cold ischemia time and whether the pancreas was transplanted alone or in combination with a kidney. Pearson's chi-square and Fisher's Exact tests were used for statistical comparisons in complications or rejections between the groups. RESULTS: Thirty-four pancreas transplants were performed with exocrine drainage into the bladder used in 17 and enteric drainage in 17. The complication rate was 53% in the bladder-drained group and 41% (P=.49) in the enteric-drained group. The incidence of pancreas rejection was 24% in the bladder-drained versus 29% in the enteric-drained patients (P=.50). One graft failed, which was in the bladder cohort. CONCLUSIONS: We found comparable rejection and complication rates between groups. We conclude that enteric drainage is safe when used selectively, and entails no increased risks compared with bladder drainage.

Rescue of acute portal vein thrombosis after liver transplantation using a cavoportal shunt at re-transplantation.

BACKGROUND: Portal vein thrombosis is a rare but devastating complication following orthotopic liver transplantation. Fulminant liver failure ensues with acute portal vein thrombosis after transplantation limiting the treatment options. METHODS: We successfully re-transplanted a 46-year-old female patient who developed acute portal vein thrombosis 19 d after orthotopic liver transplantation. Vascular reconstruction included a cavoportal shunt to augment portal blood flow. RESULTS: Twelve months after re-transplantation this patient lives independently and enjoys excellent liver allograft function. CONCLUSIONS: Cavoportal shunt can augment portal blood flow in adult recipients of orthotopic liver transplants. This technique can be successfully employed during re-transplantation when portal blood flow is inadequate to maintain patency.

Urologic aspects of kidney-pancreas transplantation.

The population of pancreas transplant recipients is growing steadily, and urologists most likely will be confronted with their unique anatomy and metabolic complications. The principles of diagnosis and management of these patients can be applied to other transplant recipients (e.g., heart, lung, and liver) who also are maintained on life-long immunosuppression and in whom urologic pathology develops commensurate with the incidence in the general population.

Urological complications of pancreatic transplantation.

PURPOSE: Pancreas transplantation is increasingly being used in the treatment of type I insulin-dependent diabetes mellitus. Because bladder drainage of the exocrine pancreatic secretion is the procedure of choice, urological complications are frequent. As the number of these procedures increases the urologist will have an extended role in the management of the postoperative complications, the majority of which are urological. MATERIALS AND METHODS: The literature from 1985 on the complications related to pancreas transplants was reviewed. RESULTS: Approximately 50 to 60% of bladder drained pancreas transplant recipients will have a urological complication postoperatively. CONCLUSIONS: The increasing application of bladder drained pancreas transplantation in the treatment of type I insulin-dependent diabetes mellitus necessitates that the clinical urologist is familiar with the management of complications related to this procedure.