Evaluation of the Effectiveness of Screening for Iliac Arterial Calcification in Kidney Transplant Candidates.

BACKGROUND Peripheral vascular disease and iliac arterial calcification are prevalent in kidney transplant candidates and jeopardize graft outcomes. We report our experience with computed tomography (CT) screening for iliac arterial calcification. MATERIAL AND METHODS We retrospectively reviewed electronic medical records of 493 renal transplant candidates from protocol initiation in 2014. Non-contrast CT was performed or retrospectively reviewed if any of the following criteria were present: diabetes, ESRD >6 years, 25 pack-years of smoking or current smoker, diagnosis of peripheral vascular disease, parathyroidectomy, and coronary artery disease intervention. Differences in evaluation and transplant outcomes between groups were compared with chi-squared analysis. Multivariate logistic regression identified predictive criteria for presence of iliac arterial calcification. RESULTS Of 493 candidates evaluated, CTs were reviewed in 346 (70.2%). Iliac arterial calcification was identified in 119 screened candidates (34.4%). Of candidates with iliac arterial calcification identified on CT, 16 (13.4%) were excluded for CT findings, and 9 (7.6%) had their surgical management plan changed. Overall, 91 (76.5%) candidates with iliac arterial calcification on CT were approved, compared to 203 (89.4%) without calcification (P<0.001). The percentage of screened patients with iliac arterial calcification on CT increased with increasing age (P<0.0005). Age and diabetes mellitus were predictive of calcification. CONCLUSIONS Many kidney transplant candidates are at risk for iliac arterial calcification, although such calcification does not prevent transplantation for most candidates who have it. Algorithmic pre-operative screening has clinical value in determining transplant candidacy and potentially improving postoperative outcomes in patients requiring kidney transplantation.

The impact of intraoperative fluid management during laparoscopic donor nephrectomy on donor and recipient outcomes.

BACKGROUND: Intraoperative fluid management during laparoscopic donor nephrectomy (LDN) may have a significant effect on donor and recipient outcomes. We sought to quantify variability in fluid management and investigate its impact on donor and recipient outcomes. METHODS: A retrospective review of patients who underwent LDN from July 2011 to January 2016 with paired kidney recipients at a single center was performed. Patients were divided into tertiles of intraoperative fluid management (standard, high, and aggressive). Donor and recipient demographics, intraoperative data, and postoperative outcomes were analyzed. RESULTS: Overall, 413 paired kidney donors and recipients were identified. Intraoperative fluid management (mL/h) was highly variable with no correlation to donor weight (kg) (R = 0.017). The aggressive fluid management group had significantly lower recipient creatinine levels on postoperative day 1. However, no significant differences were noted in creatinine levels out to 6 months between groups. No significant differences were noted in recipient postoperative complications, graft loss, and death. There was a significant increase (P < 0.01) in the number of total donor complications in the aggressive fluid management group. CONCLUSIONS: Aggressive fluid management during LDN does not improve recipient outcomes and may worsen donor outcomes compared to standard fluid management.

Resident perceptions and evaluations of fellow-led and resident-led surgical services.

BACKGROUND: The impact of fellowship training on general surgery residency has remained challenging to assess. Surgical resident perceptions of fellow-led and resident-led surgical services have not been well described. METHODS: Retrospective cross-sectional data were collected from residents' service evaluations from 7/2014 through 7/2017. Surgical services were categorized as resident-led or fellow-led. 31 variables were evaluated and collapsed into 7 factors including clinical experience, educational experiences, clinical staff, workload, feedback, treatment of residents, and overall rotation. RESULTS: Among all PGY levels, fellow-led surgical services were rated significantly higher (p < 0.05) regarding clinical experience, clinical staff, treatment of residents, and overall rotation. PGY1-2 residents rated resident-led services significantly higher in the area of educational experiences, while PGY 3 residents rated resident-led services higher in the area of workload. However, PGY4-5 residents rated fellow-led services significantly higher in all 7 categories. Individual fellow-led services were rated significantly higher for various categories at different PGY levels. CONCLUSIONS: Surgical residents appear to value the educational experiences of fellow-led services. Each fellow-led service may ultimately provide unique educational opportunities and resources for different PGY levels.

Impact of screening for metabolic syndrome on the evaluation of obese living kidney donors.

BACKGROUND: We report our experience with metabolic syndrome screening for obese living kidney donor candidates to mitigate the long-term risk of CKD. METHODS: We retrospectively reviewed 814 obese (BMI≥30) and 993 nonobese living kidney donor evaluations over 12 years. Using logistic regression, we explored interactions between social/clinical variables and candidate acceptance before and after policy implementation. RESULTS: Obese donor candidate acceptance decreased after metabolic syndrome screening began (56.3%, 46.3%, p < 0.01), while nonobese candidate acceptance remained similar (59.6%, 59.2%, p = 0.59). Adjusting for age, gender, race, BMI, and number of prior evaluations, acceptance of obese candidates decreased significantly more than nonobese (p = 0.025). In candidates without metabolic syndrome, there was no significant change in how age, sex, race, or BMI affected a donor candidate's probability of acceptance. CONCLUSION: Metabolic syndrome screening is a simple stratification tool for centers with liberal absolute BMI cut-offs to exclude potentially higher-risk obese candidates.

Use of complement binding assays to assess the efficacy of antibody mediated rejection therapy and prediction of graft survival in kidney transplantation.

BACKGROUND: The Luminex® single antigen bead assay (SAB) is the method of choice for monitoring the treatment for antibody-mediated rejection (AMR). A ⩾50% reduction of the dominant donor-specific antibody (IgG-DSA) mean fluorescence intensity (MFI) has been associated with improved kidney allograft survival, and C1q-fixing DSA activity is associated with poor outcomes in patients with AMR. We aimed to investigate if C1q-DSA can be used as a reliable predictor of response to therapy and allograft survival in patients with biopsy-proven AMR. METHODS: We tested pre- and post-treatment sera of 30 kidney transplant patients receiving plasmapheresis and low-dose IVIG for biopsy-proven AMR. IgG-DSA and C1q-DSA MFI were measured and correlated with graft loss or survival. Patients were classified as nonresponders (NR) when treatment resulted in <50% reduction in MFI of IgG-DSA and/or C1q-DSA was detectable following therapy. RESULTS: Differences in the percentage of patients deemed NR depended upon the end-point criterion (73% by reduction in IgG-DSA MFI vs. 50% by persistent C1q-DSA activity). None of the seven patients with <50% reduction of IgG-DSA but non-detectable C1q-DSA-fixing activity after therapy experienced graft loss, suggesting that C1q-DSA activity may better correlate with response. Reduction of C1q-DSA activity predicted graft survival better than IgG-DSA in the univariate Cox analysis (20.1% vs. 5.9% in NR; log-rank P-value=0.0147). CONCLUSIONS: A rapid reduction of DSA concentration below the threshold required for complement activation is associated with better graft survival, and C1q-DSA is a better predictor of outcomes than IgG-DSA MFI reduction.

Long-Term Outcomes of Kidney Transplant Recipients with Bladder Dysfunction: A Single-Center Study.

BACKGROUND: Long-term outcomes of kidney transplantation recipients with bladder dysfunction or prior bladder surgery are not well characterized. MATERIAL AND METHODS: Electronic records of 1753 recipients of kidney-alone transplant between January 2000 and December 2008 were reviewed. We found that 1652 recipients had normal bladder function, 80 had bladder dysfunction, and 21 had bladder substitute or urinary diversion. Kaplan-Meier survival curves and multivariable regression modeling were performed to determine survival outcomes. RESULTS: Kaplan-Meier graft survival (p=.11) and patient survival (p=.18) were lower in recipients with bladder surgery but not statistically significant. Multivariate analysis demonstrated inferior graft survival (HR 3.57, 95% CI 1.06-12.1, p =0.04) and a trend towards inferior patient survival (HR 3.19, 95% CI .71-14.5, p=0.13) in reci-pients with bladder surgery. The major cause of graft failure was chronic rejection for normal function (17.1%) and bladder dysfunction (28.5%), and infection for bladder surgery (28.5%). Post-operative urinary infectious and surgical complications were higher in recipients with bladder dysfunction (35%) and substitutes (52.3%) compared with normal function (12.8%). CONCLUSIONS: Kidney transplant recipients with prior bladder surgery have an increased risk of graft failure and an increased risk of infectious urinary complications. These risks should be considered in recipient selection and post-transplant management.

Ureteral complications after hand-assisted laparoscopic living donor nephrectomy.

BACKGROUND: Urological complications, namely ureteral leak and obstruction, remain a major source of morbidity after renal transplantation. Given that the existing literature on ureteral complications pertains mostly to deceased as opposed to living donors, we aimed to assess the risk factors for ureteral complications solely after living donor nephrectomy. METHODS: We identified 480 consecutive cases of renal transplantation after hand-assisted laparoscopic living donor nephrectomy at our institution from January 2008 to February 2013. We determined the incidence of ureteral complications and assessed the association with a number of perioperative factors, including age, sex, race, and body mass index of both the donor and recipient; arterial and ureteral anatomy; procurement by transplant surgeon versus urologist; history of previous renal transplantations; technique of ureteral anastomosis; use of ureteral stent; total ischemia time; serum creatinine on discharge; and need for temporary posttransplant hemodialysis. RESULTS: Among 480 renal transplantations after living donor nephrectomy, ureteral complications occurred in 18 (3.7%), including ureteral leak in 10 (2.1%) and ureteral stricture in 8 (1.6%). Only two factors were significantly associated with ureteral complications on multivariate analysis: increased donor age and no placement of ureteral stent. CONCLUSIONS: Ureteral complications of renal transplants after living donor nephrectomy are uncommon. The use of a ureteral stent is protective against ureteral complications and increased donor age is associated with an increased incidence of ureteral complications.

CC Chemokine receptor 5 deficiency does not prevent local immune responses to adenovirus vector in islet transplant recipients.

BACKGROUND: CC chemokine receptor 5 (CCR5) plays an important role in mediating inflammation. We examined the effect of CCR5 on the immune response to adenovirus vectors and graft function in islet transplant model. MATERIALS AND METHODS: Syngeneic wild-type (WT) or CCR5-deficient (KO) mouse islets transduced with adenovirus encoding ß-gal were transplanted under the renal capsule. After transplant, blood glucose, glucose tolerance, graft cellular infiltration, transgene and chemokine/receptor expression, and systemic anti-adenoviral/-ß-gal immune response were evaluated. RESULTS: Diabetes was reversed in 1 d in both WT and KO untransduced recipients, while islets transduced with adenovirus failed to reverse diabetes until 10 d post-transplant in WT recipients or even longer (>15 d) in KO recipients (P < 0.05). A profound infiltration of CD4(+), CD8(+) cells and macrophages was observed in both WT and KO transduced grafts at 25 d. Though transgene expression was significantly reduced, insulin and ß-gal expression persisted over 3 mo. Glucose tolerance was impaired in all grafts in KO recipients compared with untransduced grafts in WT recipients at 25 d post-transplant, but was equivalent at 3 mo. Early expression of CCR2 mRNA was increased in transduced grafts in both WT and KO recipients. No systemic antivector immunity was demonstrated in any recipient group. CONCLUSIONS: Transduction of islets with adenovirus causes significant local inflammation in islet grafts and impairs early graft function in CCR5-deficient recipients, but long-term graft function is preserved. Thus, CCR5 absence does not prevent the local immune response to adenovirus transduction, and vector-associated graft dysfunction is not mediated by CCR5.

The high-risk recipient: the Eighth Annual American Society of Transplant Surgeons' State-of-the-Art Winter Symposium.

The evolution of organ transplantation has produced results so successful that many transplant programs commonly see recipients with medical risks, which in the past, would have prohibited transplantation. The Eighth Annual American Society of Transplant Surgeons State-of-the-Art Winter Symposium focused on the high-risk recipient. The assessment of risk has evolved over time, as transplantation has matured. The acceptance of risk associated with a given candidate today is often made in consideration of the relative value of the organ to other candidates, the regulatory environment, and philosophical notions of utility, equity, and fairness. In addition, transplant programs must balance outcomes, transplant volume, and the costs of organ transplantation, which are impacted by high-risk recipients. Discussion focused on various types of high-risk recipients, such as those with coronary artery disease, morbid obesity, and hepatitis C; strategies to reduce risk, such as down-staging of hepatocellular carcinoma and treatment of pulmonary hypertension; the development of alternatives to transplantation; and the degree to which risk can or should be used to define candidate selection. These approaches can modify the impact of recipient risk on transplant outcomes and permit transplantation to be applied successfully to a greater variety of patients.

Immunity to islet grafts transduced with adenovirus vectors does not inhibit long-term islet function.

Adenoviral gene transfer is a potential ex vivo gene therapy for islet transplantation. However, the immunogenicity of adenoviral vectors can potentially impair vector efficacy in transplants where long-term gene expression is required. We investigated the effect of this antiviral immunity on vector expression and islet graft function. Syngeneic murine islets transduced with adenovirus encoding beta-galactosidase (AdCMVnt-betagal) were transplanted under the renal capsule. At different time points after transplant, blood glucose and glucose tolerance, intragraft cellular infiltration and IgG, IgM productions, and expression of transgene, cytokines and chemokines/receptors were assessed. Splenocytes and sera were analyzed to evaluate the systemic anti-adenoviral immune response. Diabetes was reversed in 1 day in recipients of a marginal amount (200) of untransduced islets, while AdCMVnt-betagal-transduced islets failed to reverse diabetes until 10 days post-transplant (p

Single center review of femoral arteriovenous grafts for hemodialysis.

INTRODUCTION: It is unclear how to manage high risk hemodialysis patients who present with an indwelling catheter. The National Kidney Foundation Practice Guidelines urge prompt removal of the catheter, but the guidelines do not specifically address the problem of patients whose only option is a femoral arteriovenous (AV) graft. METHODS: This study was a retrospective review of all patients who underwent femoral AV graft placement for hemodialysis access between January 1, 1996 and January 1, 2003 at the University of Michigan Health System (UMHS). Graft patency is reported according to the standards developed by the Society of Vascular Surgery and the American Association of Vascular Surgeons. RESULTS: Thirty patients were identified who had undergone femoral AV graft placement. The mean follow-up was 23 months (range 1-75 months). The patients had had significant medical co-morbidities and multiple previous access operations (mean 3; interquartile range 1-5). The 1-year secondary graft patency rate was 41%, the 2-year rate was 26%, and the 3-year rate was 21%. Infection was the cause of final graft loss in eight patients (50% of the grafts losses, 27% of the total grafts placed.) Among those who died (n=14), the mean time from femoral graft placement to death was 31.2+/-27.5 months. The patient survival was quite low: at 1 year 81%, at 2 years 68%, and at 3 years 54%. CONCLUSIONS: These complex patients who have exhausted their upper extremity hemodialysis options do poorly following femoral AV graft placement. Consideration should be given to long-term catheter-based access in some of these patients.

Long-term follow-up of percutaneous transhepatic balloon cholangioplasty in the management of biliary strictures after liver transplantation.

BACKGROUND: This study evaluated the efficacy of a protocol of initial balloon dilation for biliary strictures after liver transplantation. METHODS: Complete records from 96 patients with biliary strictures were retrospectively reviewed. Seventy-six patients received percutaneous transhepatic balloon cholangioplasty (PTBC) after initial placement of biliary drainage (percutaneous transluminal cholangiography [PTC]) tube. In most cases, three dilations were performed with a 4 to 8 week interval between procedures. Follow-up ranged from 6 months to 10 years. RESULTS: PTBC successfully treated strictures in 39 of 76 (51.3%) cases. Factors favoring successful PTBC included older age at transplant, shorter cold ischemic time, and single strictures. There were nine recurrent strictures after PTBC, all of which were successfully treated by nonoperative measures. The number of dilations performed affected both the likelihood of success and the long-term risk of stricture recurrence. Of the 37 PTBC failures, 14 underwent subsequent surgical revision. When both angiographic and surgical modalities were considered, treatment success was associated with first transplants, shorter cold ischemic time and operative time, and less intraoperative transfusion requirements. Factors associated with treatment failure included multiple, central hepatic duct, and intrahepatic strictures. PTC-tube independence was achieved in 51 of 76 (67%) patients using the combined approach of PTBC and surgery for PTBC failures. CONCLUSIONS: PTBC is an effective initial modality for treating posttransplant biliary strictures. Prolonged cold ischemic and operative times and multiple or peripheral strictures predispose to treatment failure. Solitary extrahepatic strictures that fail PTBC are salvageable with surgical revision with excellent results.

Adenovirus transduction induces expression of multiple chemokines and chemokine receptors in murine beta cells and pancreatic islets.

Adenoviral vectors are highly efficient for transferring genes to islets. However, the inflammatory and immune responses stimulated by adenovirus may be detrimental to islet survival. Given the role of chemokines and their receptors in inflammation, we analyzed their expression in isolated murine islets, in a murine beta cell line and in syngeneic islet grafts after adenovirus transduction (AdRSVLacZ). AdRSVLacZ transduction enhanced and induced the expression of a variety of chemokines. Transduced syngeneic transplanted islets showed significantly enhanced expression of multiple chemokines and receptors, including monocyte chemoattractant protein-1 (MCP-1), CC chemokine receptor 2 (CCR2) and regulated upon activation, normal T cell expressed and secreted (RANTES), compared with untransduced islet grafts. AdRSVLacZ-transduced islet grafts had significant mononuclear infiltrates, and in situ hybridization demonstrated intragraft expression of MCP-1, CCR2 and RANTES. Although adenovirus transduction did not impair in vitro insulin secretion, diabetes was reversed in only one of six recipients of a marginal mass of AdRSVLacZ-transduced islets, compared with six of six control recipients. In conclusion, multiple chemokines and chemokine receptors are expressed by murine islets constitutively and in response to adenovirus transduction. Adenovirus transduction impairs engraftment of marginal mass of transplanted islets. This is not because of direct vector toxicity of islet secretory capacity, but may be related to host innate immunity in response to adenovirus vector.

Long-term survival after liver transplantation in children with metabolic disorders.

BACKGROUND: Liver transplantation for inherited metabolic disorders aims to save the patient's life when the disorder is expected to progress to organ failure, and to cure the underlying metabolic defect. METHODS: We retrospectively analyzed 146 pediatric liver transplants (28 metabolic; 118 non-metabolic) performed between 1986 and 2000. RESULTS: Twenty-eight transplants were performed in 24 children with metabolic disease (8 females; 16 males; age range 3 months to 17 yr). Indications included alpha-1-antitrypsin deficiency (n = 8), two cases each of hyperoxaluria type 1, Wilson's disease, hereditary tyrosinemia type I, citrullinemia, methylmalonic acidemia, and one case each of propionic acidemia, Crigler-Najjar syndrome type I, neonatal hemachromatosis, hemophilia B, Niemann-Pick disease type B, and cystic fibrosis. Eighteen transplants were whole organ grafts and 10 were lobar or segmental. Auxiliary liver transplants were performed in two patients and three received combined liver-kidney transplants. There were three deaths from sepsis, two from chronic rejection, and one from fulminant hepatitis. Seven of 10 patients currently of school age are within 1 yr of expected grade and three who had pretransplant developmental delay have remained in special education. Actuarial survival rates at 5 and 10 yr are 78% and 68%, respectively, with mean follow-up in excess of 5 yr. These results compare favorably to 100 pediatric patients transplanted for non-metabolic etiologies (65% and 61%, respectively) (p= NS). CONCLUSIONS: Pediatric liver transplantation for metabolic disorders results in excellent clinical and biochemical outcome with long survival and excellent quality of life for most recipients.