Renal Protective Effect of Everolimus in Liver Transplantation: A Prospective Randomized Open-Label Trial.

Renal dysfunction is associated with poor long-term outcomes after liver transplantation. We examined the renal sparing effect of everolimus (EVR) compared to standard calcineurin inhibitor (CNI) immunosuppression with direct measurements of renal function over 24 months. METHODS: This was a prospective, randomized, open-label trial comparing EVR and mycophenolic acid (MPA) with CNI and MPA immunosuppression. An Investigational New Drug Application (IND # 113882) was obtained with the Food and Drug Administration as EVR is only approved for use with low-dose tacrolimus. Serum creatinine, 24-hour urine creatinine clearance, iothalamate clearance, Cockcroft-Gault creatinine clearance (CrCl), and Modification of Diet in Renal Disease estimated glomerular filtration rate were prospectively measured at 4 study visits. Nonparametric statistical tests were used for analyses, including the Mann-Whitney U test for continuous outcomes and Pearson's chi-square test for binary outcomes. Effect size was measured using Cohen's d. Patients also completed quality of life surveys using the FACT-Hep instrument at each study visit. Comparison between the 2 groups was performed using the Student t test. RESULTS: Each arm had 12 subjects; 4 patients dropped out in the EVR arm and 1 in the CNI arm by 24 months. Serum creatinine (P = 0.015), Modification of Diet in Renal Disease estimated glomerular filtration rate (P = 0.013), and 24-hour urine CrCL (P = 0.032) were significantly better at 24 months with EVR. Iothalamate clearance showed significant improvement at 12 months (P = 0.049) and a trend toward better renal function (P = 0.099) at 24 months. There was no statistical significance with Cockcroft-Gault CrCl. Adverse events were not significantly different between the 2 arms. The EVR group also showed significantly better physical, functional, and overall self-reported quality of life (P = 0.01) at 24 months. CONCLUSIONS: EVR with MPA resulted in significant long-term improvement in renal function and quality of life at 24 months after liver transplantation compared with standard CNI with MPA immunosuppression.

Endovascular Stenting of Portal Vein for Graft Rescue after a Pancreas Transplant Venous Graft Thrombosis: A Case Report.

Venous thrombosis of pancreas transplant allografts often leads to graft loss. It is an worrisome complication and difficult to treat, forming the most common nonimmunological cause of graft loss. Multiple risk factors have been implicated in the development of venous thrombosis of pancreas transplant. Color Doppler ultrasonography enables early diagnosis of venous thrombosis, thus increasing the possibility of graft-rescue treatments. Endovascular management of pancreatic transplant vascular complications is scant and in the form of case reports. We report a case of early detection of pancreatic graft venous thrombosis that was treated successfully by catheter-directed thrombolysis mechanical thrombectomy, percutaneous transluminal angioplasty, and stenting of portal vein.

Association Between Delayed Graft Function and Incisional Hernia after Renal Transplant.

OBJECTIVES: Incisional hernias can occur after any abdominal operation, including after renal transplant. Several risk factors have been identified in nonimmunosuppressed surgical patients. We aimed to identify whether specific risk factors correlated with the development of incisional hernias after renal transplant. The existence of associations between these risk factors and postoperative complications was also reviewed. MATERIALS AND METHODS: We reviewed 969 kidney transplants performed between February 2000 and January 2011. Thirty-nine kidney transplant recipients who were treated with rapamycin were excluded. The following potential risk factors were evaluated: recipient age, sex, body mass index at transplant, delayed graft function, diabetes, albumin, postoperative platelet count, drain placement, donor body mass index, donor type, warm ischemic time, and cold ischemic time. We performed univariate and multivariate logistic regression tests. RESULTS: In our patient group, a total of 52 (5.4%) transplants were complicated by incisional hernia. On univariate analysis, we found that delayed graft function (P = .001) and infection (P < .001) were statistically significant predictors for development of incisional hernia. Multivariate analyses revealed that delayed graft function and length of stay remained statistically significant predictors. CONCLUSIONS: Delayed graft function and length of stay are significant predictors of incisional hernia after kidney transplant.

De Novo Thrombotic Microangiopathy Immediately After Kidney Transplant in Patients Without Apparent Risk Factors.

Thrombotic microangiopathy refers to a spectrum of conditions that share a common underlying pathologic mechanism that result in endothelial damage and microangiopathic hemolytic anemia. De novo thrombotic microangiopathy after kidney transplant is often triggered by immunosuppressive drugs, and studies most often implicate calcineurin inhibitors and/or mammalian target of rapamycin inhibitors; however, muromonab and alemtuzumab also reportedly cause thrombotic microangiopathy. In addition, thrombotic microangiopathy may be triggered by acute antibody-mediated rejection and infections like cytomegalovirus and parvovirus. Here, we present a case series of 3 patients without any apparent risk factors (eg, acute antibody-mediated rejection) who developed de novo thrombotic microangiopathy immediately following kidney transplant, but before the introduction of calcineurin inhibitors. Two of these 3 patients were successfully managed with plasma exchange, and calcineurin inhibitors were successfully introduced without the recurrence of thrombotic microangiopathy.

Dialysis within 24 hours of transplant does not improve graft function.

OBJECTIVES: Grafts from extended criteria donors, donors after cardiac death, and elderly donors have an increased risk of delayed graft function, lower graft survival, longer hospital stay, higher costs, and increased medical sequelae. A modifiable risk factor for delayed graft function may be the performance of dialysis on the same day as renal transplant. We reviewed our institutional experience to determine whether dialysis performed within 24 hours of engraftment increased the incidence or length of delayed graft function. MATERIALS AND METHODS: We retrospectively reviewed our kidney transplants performed between 2008 and 2012. Preemptive transplants, transplants associated with peritoneal dialysis, potassium > 5 mmol/L, or living donors, and cases with insufficient information were excluded. Data collected included demographic, biochemical, donor, operative, and outcome variables (length of stay, length of delayed graft function, rejection, and a composite unfavorable outcome comprising cardiac and infectious events). Transplants that were associated with hemodialysis within 24 hours before transplant (study group) were compared with the remainder of the cohort (control group). RESULTS: A total of 205 renal transplants were reviewed. There were 144 of 205 transplants (70.24%) in the study group, and the others comprised the control group. The rate of delayed graft function was 31% for the study group and 29% for control groups (P = .4959). Mean length of delayed graft function was 5.8 days for the study group and 6.1 days for control group (P = .7323). Delayed graft function risk factors such as donor age, terminal creatinine, and machine perfusion rate were similarly distributed across both groups. CONCLUSIONS: Normokalemic patients who did or did not undergo dialysis within 24 hours before transplant had equivalent incidence and duration of delayed graft function, graft outcomes, and patient outcomes. Therefore, dialysis within 24 hours before transplant is unnecessary in the setting of normokalemia.

Equal 3-Year Outcomes for Kidney Transplantation Alone in HCV-Positive Patients With Cirrhosis.

Kidney transplantation alone in clinically compensated patients with cirrhosis is not well documented. Current guidelines list cirrhosis as a contraindication for kidney transplantation alone. This is an Institutional Review Board-approved retrospective study. We report our experience with a retrospective comparison between transplants in hepatitis C virus-positive (HCV(+)) patients without cirrhosis and HCV(+) patients with cirrhosis. All of the patients were followed for at least a full 3-year period. All of the deaths and graft losses were recorded and analyzed using Kaplan-Meier methodology. One- and three-year cumulative patient survival rates for noncirrhotic patients were 91% and 82%, respectively. For cirrhotic patients, one- and three-year cumulative patient survival rates were 100% and 83%, respectively (P = NS). One- and three-year cumulative graft survival rates censored for death were 94% and 81%, and 95% and 82% for the noncirrhosis and cirrhosis groups, respectively (P = NS). Comparable patient and allograft survival rates were observed when standard kidney allograft recipients were analyzed separately. This study is the longest follow-up document in the literature showing that HCV(+) clinically ompensated patients with cirrhosis may undergo kidney transplantation alone as a safe and viable practice.

Risk factors for renal allograft compartment syndrome.

Renal allograft compartment syndrome (RACS) is graft dysfunction secondary to intracompartment hypertension. The purpose of this study was to identify risk factors for RACS. We reviewed 7 cases of established RACS and all intra-abdominal placements of the kidney in order to include potential RACS. We also studied early graft losses in order to rule out a missed RACS. We compared the allograft length and width, recipient height, weight, body mass index, aberrant vessels, site of incision, and side of kidney with the remainder of the cohort as potential predictors of RACS. Among 538 transplants, 40 met the criteria for actual RACS or potential RACS. We uncovered 7 cases of RACS. Only kidney length and width were statistically significant (P = 0.041 and 0.004, respectively). The width was associated with a higher odds ratio than was length (2.315 versus 1.61). Increased allograft length and width should be considered as a potential risk for RACS.

Elimination of warm ischemia using the Ice Bag Technique does not decrease delayed graft function.

BACKGROUND: Warm ischemic time (WIT) in kidney transplantation has significant effects on graft survival, function, and postoperative morbidity. We utilized the Ice Bag Technique (IBT) to determine if eliminating WIT would decrease the incidence and length of delayed graft function (DGF) in our cohort. METHODS: We conducted a prospective study of 150 kidney transplants. We compared the elimination of WIT with IBT to traditional methods. Data was analyzed using non-parametric statistical tests. RESULTS: 66 of the 134 patients underwent transplantation using IBT. 28 right kidneys, 34 left kidneys, and 4 dual kidneys were implanted successfully. Patients with a body mass index (BMI) as high as 41 were transplanted. Kidneys with up to three arteries and two veins, and kidneys up to 15.5 by 9 cm in size were safely transplanted into either iliac fossa. Despite the complete elimination of WIT, there was no difference in DGF, length of DGF, length of stay graft rejection, graft survival, patient survival, or wound or urologic complications between groups (p > 0.05). CONCLUSIONS: The elimination of warm ischemic time using the IBT does not appear to reduce the incidence or length of DGF in this cohort. The technique may be useful for cases with prolonged anastomosis time (AT), but further studies with larger cohorts are required to determine whether it decreases DGF.

No benefit when placing drains after kidney transplant: a complex statistical analysis.

OBJECTIVES: This paper sought to determine if there were an association between drain placement and the incidence of wound complications. MATERIALS AND METHODS: A single-center institutional review board-approved retrospective study between 2001 to 2008, comparing 680 kidney transplant patients who either had a drain placed or were left undrained. Linear regression modeling was used to adjust the risk factors between the groups. Patients received calcineurin inhibitors, steroids, and a mycophenolate formulation. The incidence of early major and minor wound complications were captured. Minor wound complications were defined as seroma, lymphocele, and perigraft fluid collection, and major wound complications were defined as wound dehiscence, hematomas, evisceration, infections, wound necrosis, and hernias. Patients with incomplete data or those taking sirolimus were excluded. RESULTS: Six hundred eighty kidney transplant cases were reviewed. Four hundred seventy-nine received drains; 201 did not. Demographic analyses revealed that the drain group had a higher average value in age and body mass index. The drain group had a lower albumin and a lower mean platelet count after surgery. The number of patients without diabetes in the drain group numbered nearly twice as many as did those without drains. An attempt was made to statistically account for demographic differences. Seventy-eight of 479 drained patients (16.28%) and 24 of 201 no-drain patients (11.94%) had a wound complication. Minor wound complications were observed in 9 patients (1.88%) in the drain group and 6 in no-drain group (2.99%) (P = .3702). Major wound complications were observed in 58 patients in the drain group (12.18%) and 17 in the no-drain group (8.46%) (P = .1655). Drain placement had no effect on major or minor wound complications. CONCLUSIONS: Drain placement is not associated with major or minor wound complications in kidney transplants.

MELD predicts mortality in conservatively managed pneumatosis intestinalis in cirrhotics.

Pneumatosis intestinalis (PI) is a radiologic finding associated with multiple conditions and a high mortality rate (33-40%, 1-3). The current literature addressing PI is limited to an unselected population. This is the first study addressing the management of PI in cirrhotics, a population in which surgical intervention is particularly risky. While nonoperative management is acceptable in the general population, it is unknown whether the same is true when managing patients with underlying cirrhosis. We retrospectively identified cases of PI found on computed tomography (CT) scans performed on cirrhotics from 2004 to 2011. Chart review included comorbidities, hospital course, serum lactate levels, APACHE scores and MELD scores. Nine cirrhotics with PI were identified. Eight were managed conservatively. One patient with MELD score of 18 underwent exploration and died. In total, six patients died. The mean MELD score in patients who died was higher than in those who survived (28 vs. 14). Mortality was 100% in cirrhotic patients with PI whose MELD was greater than 16. Mean lactate levels (33 mg/dL vs. 21 mg/dL) and mean APACHE scores (28 vs. 15) were also higher in those who died. Serum bicarbonate levels and white blood cell counts were not consistently elevated. Our results suggest that the MELD score is an important predictor of mortality in cirrhotics with PI. Serum lactate and APACHE scores are also important markers. Larger studies are required to determine whether there is a role for operative management in cirrhotic patients with a MELD lower than 16.

Satisfactory outcomes with usage of extended criteria donor (ECD) kidneys in re-transplant recipients.

BACKGROUND: The use of extended criteria donor (ECD) kidneys have increased substantially and the benefit recognized in certain populations. Our institution has maintained a policy of aggressively utilizing ECD kidneys, even among those who have failed a previous transplant. Previous reports on the benefit of ECD in re-transplants have shown equivocal outcomes. We sought to determine if our experience would support or refute this finding. MATERIAL AND METHODS: This is a retrospective study of 19 ECD re-transplants between 2002 and 2010. We compared 1 and 3 year outcomes with 95 patients with standard criteria donor (SCD) re-transplant and 169 patients with first time transplant using ECD kidneys. Outcomes and demographics were evaluated including delayed graft function (DGF), HTN, DM, cold ischemia time (CIT), BMI, donor age and prior allograft nephrectomies using a Cox Proportional Hazard model. We compared patient and graft survival using the log rank test. RESULTS: Patient survival were similar among the first time ECD and ECD re-transplant groups at 1 year (p=0.9547) and at 3 years (p=0.8287). Graft survival was also similar between first time ECD and ECD re-transplant groups at 1 year (p=0.4781) and at 3 years (p=0.8519). As expected, SCD re-transplant had better outcomes than the other groups. CONCLUSIONS: 1 and 3 years graft and patient survival among first time ECD transplants and ECD re-transplants are similar. As the list of patients on dialysis is ever growing, it may be prudent to aggressively explore the utility of using ECD kidneys in re-transplant patients.

Seasonal variations in outcomes after kidney transplantation: UNOS review of 336,330 transplants.

INTRODUCTION: The "July effect" is a widely discussed phenomenon of worse patient outcomes at teaching hospitals in July due to inexperienced house staff. METHODS: We conducted a retrospective review of Organ Procurement and Transplantation Network data from Oct 1, 1987 to June 30, 2011, including longitudinal censored data of 360,330 transplantations. Demographic and comorbid variables for donors and recipients were collected. Primary outcomes were graft loss, patient death, and delayed graft function. Secondary outcomes were surgical complications, length of stay, and graft rejection. We compared survival indicators (1-month, 1-, 3-, and 5-year survival and median survival times) for both grafts and patients. We also analyzed death-censored graft survival. RESULTS: There were fewer July donors with diabetes (p = 0.003), hypertension (p = 0.000), and extended criteria (p<0.0001). Graft survival (p = 0.000), death-censored graft survival (p = 0.001), and patient survival (p = 0.002) were statistically higher in July. After adjusting the Cox model for extended criteria donors, there was no difference in outcomes (p>0.05 for graft, death-censored graft survival, and patient survival). CONCLUSION: We conclude that there is no July effect. Initially identified, superior outcomes in July may be attributed to more conservative allografts selection in the beginning of the academic year.

Evaluating safety and efficacy of rabbit antithymocyte globulin induction in elderly kidney transplant recipients.

OBJECTIVES: The optimal immunosuppression regimen for elderly kidney transplant recipients is poorly defined. We sought to evaluate the short-term efficacy and safety of thymoglobulin in geriatric recipients of deceased-donor kidneys. MATERIALS AND METHODS: A single-center, retrospective analysis was undertaken between elderly (≥ 65 years) (n=137) and nonelderly (n=276) kidney transplant recipients who received rabbit antithymocyte globulin induction and calcineurin inhibitor, mycophenolic acid, and prednisone maintenance. RESULTS: The mean age was 70 versus 52 years. Fewer elderly patients had an earlier transplant or panel reactive antibodies > 20%, but had more machine perfused, older, and extended criteria donor kidneys. Elderly patients received lower rabbit antithymocyte globulin (5.4 vs 5.6 mg/kg; P = .04) and initial mycophenolic acid doses (1620 vs 1774 mg; P = .002), and experienced less delayed graft function (31.1% vs 50.0%; P < .001). Death-censored graft survival and graft function at 3 years and biopsy-proven acute rejection at 1 year were comparable; however, there was lower 3-year patient survival in elderly patients. Donor age was the only factor associated with reduced patient survival. Rates of malignancy, infection, or thrombocytopenia were similar; however, leukopenia occurred less frequently in elderly patients (11.7% vs 19.9%; P = .038). CONCLUSIONS: Elderly kidney transplant recipients receiving rabbit antithymocyte globulin did not experience different short-term graft survival, graft function or rates of infection, malignancy or hematologic adverse reactions than did nonelderly patients; they experienced fewer episodes of delayed graft function, but had lower 3-year patient survival.

Soft tissue sarcoma at a dialysis access site in a transplant recipient.

Soft tissue sarcomas typically present as soft, painless masses on an extremity. Here, we present a patient with metastatic soft tissue sarcomas at his dialysis access site. This association with dialysis access has not been documented previously. A 62-year-old man presented with a nonhealing wound on his left upper extremity after excision of a pseudoaneurysmal arteriovenous fistula. The patient had received a second kidney transplant that was functioning well. Immunosuppression included tacrolimus, mycophenolate mofetil, and prednisone. He was induced with thymoglobulin twice. A biopsy was performed showing a high-grade pleomorphic sarcoma. A magnetic resonance image of his left upper extremity showed an 11 × 5.5 × 3 cm mass abutting the biceps and brachialis muscles. Also, we discovered several lesions in the axilla and the left side of the neck, which were suspicious for metastases. A positron emission tomography-computed tomography scan confirmed a left upper extremity soft tissue mass, with marked fluorodeoxyglucose uptake, in abnormally enlarged axillary, and supraclavicular lymph nodes of the left thorax, consistent with metastases. The patient underwent chemotherapy and radiation therapy. Soft tissue sarcomas are rare. A high index of suspicion is needed to make a diagnosis. This is the first reported case of a soft tissue sarcoma discovered at a dialysis access site. As with all malignancies, early diagnosis is key to patient survival. Thorough physical examinations and increased vigilance by physicians caring for immunosuppressed patients is invaluable.

Early allograft biopsies performed during delayed graft function may not be necessary under thymoglobulin induction.

OBJECTIVES: Delayed graft function affects up to 50% of kidney transplant recipients. Some guidelines recommend surveillance biopsies beginning 7 days after engraftment. This may be unnecessary with anti-thymocyte globulin induction. MATERIALS AND METHODS: We conducted a retrospective study of deceased-donor renal transplant recipients with delayed graft function. RESULTS: One hundred eleven patients met the inclusion criteria. The incidence of rejections during delayed graft function was 2.7%. They were diagnosed between 9 and 11 days after transplant. The subsequent incidence of rejection at 12-month follow-up was 13.5% (n=15). The median time to rejection after transplant was 10 weeks. Fourteen of 15 patients had subtherapeutic immunosuppression. The only risk factor associated with later rejection after delayed graft function was use of donors after cardiac death. CONCLUSIONS: Early rejection during delayed graft function with anti-thymocyte globulin induction and maintenance immunosuppression with tacrolimus, mycophenolate mofetil, and steroids is rare. When later rejection occurs, it is at a median of 10 weeks after a transplant. Two of the 3 early rejections were antibody mediated. Later rejections were associated with subtherapeutic immunosuppression and donors after cardiac death. Biopsies need not be performed during the early postoperative period when anti-thymocyte globulin is used with tacrolimus, mycophenolate mofetil, and steroids.

Operative start times and complications after kidney transplantation.

The worldwide focus on work hour regulations and patient safety has led to the re-examination of the merits of night-time surgery, including kidney transplantation. The risks of operating during nontraditional work hours with potentially fatigued surgeons and staff must be weighed against the negative effects of prolonged cold ischemic time with resultant graft compromise. The aim of this study was to evaluate the impact of performing renal transplantation procedures during evening versus day time hours. The main outcome measures assessed between the day and night cohorts included comparisons of the postoperative complication rates and survival outcomes for both the renal allograft and the patient. A retrospective review of 633 deceased donor renal transplants performed at a single institution was analyzed. Three statistically significant results were noted, namely, a decrease in vascular complications in the nighttime cohort, an increase in urologic complications on subgroup analysis in the 3 AM to 6 AM cohort, and the 12 AM to 3 AM subgroup had the greatest odds of any complication. There was no statistical difference in either patient or graft survival over a twelve month period following transplantation. We conclude that although the complication rate varied among cohorts this was clinically insignificant and there was no overall clinically relevant impact on patient or graft survival.

Are hepatitis C-positive allografts in simultaneous pancreas-kidney transplantation underutilized?

BACKGROUND: A recent review reported that recipient HCV infection had no significant impact on acute rejection rates or patient survival in SPKT but the utilization of HCV(+) organs was negligible. Using the UNOS database, we sought to determine utilization rates for HCV(+) allografts in Simultaneous Pancreas-Kidney Transplantation (SPKT. MATERIAL/METHODS: The Organ Procurement and Transplant Network / United Network for Organ Sharing database was employed to obtain information regarding HCV(+) and HCV-negative (HCV(-)) SPKT recipients and the disposition of donor pancreata. RESULTS: Between 2000 and January 2011, 702 of 25,904 donors (2.7%) were HCV(+) and met otherwise ideal criteria. We identified 16 patients who received HCV(+) organs for SPKT between 1995 and 2010. Four had kidney allograft losses secondary to chronic rejection. Six had pancreatic allograft losses: one due to pancreatitis, one to infection, one to chronic rejection, one to acute rejection and two to graft thrombosis. None of the sixteen patients were subsequently listed for liver transplantation. Meanwhile, 702 HCV(+) donors between the age of 14 and 40 with a BMI less than 30 were identified. During that time period, only 8 simultaneous pancreas-kidney transplants using HCV(+) donor organs occurred. Therefore, 694 HCV(+) pancreata were not utilized for SPKT in that time span. CONCLUSIONS: 16 patients have undergone SPKT with HCV(+) organs. Aggressive use of HCV(+) organs for SPKT could potentially lead to earlier transplantation for HCV(+) recipients and allow HCV(-) organs to be available more quickly for HCV(-) recipients additional research of this topic is warranted.

Tc-99m-BrIDA hepatobiliary (HIDA) scan has a low sensitivity for detecting biliary complications after orthotopic liver transplantation in patients with hyperbilirubinemia.

BACKGROUND: Tc-99m-BrIDA hepatobiliary scans are noninvasive tests for detecting biliary leaks and obstructions. However, there is low sensitivity and specificity in patients with hyperbilirubinemia. Biliary complications (BC) are the Achilles heel of orthotopic liver transplantation (OLT). We questioned whether hyperbilirubinemia in liver transplant recipients rendered HIDA scanning less dependable. METHODS: HIDA findings were compared to endoscopic retrograde cholangiopancreatography, laparotomy, and clinical course. Results were categorized as follows: true positive (TP), true negative (TN), false positive (FP), false negative (FN), or nondiagnostic/inconclusive. We searched for variables associated with erroneous or nondiagnostic tests which we defined as all examinations determined to be FP, FN and/or nondiagnostic/inconclusive. RESULTS: Thirty-four patients underwent a HIDA scan. The sensitivity and specificity were 70 and 100%. The sensitivity of HIDA improved to 100% in patients with a total bilirubin (TB) <5 mg/dl. Inconclusive and FN patients had a total bilirubin >5 mg/dl. One FN had a TB <5 mg/dl, but was determined inconclusive due to the roux-en-Y. CONCLUSION: HIDA scans performed when the total bilirubin was <5 mg/dl had a high sensitivity and specificity for detecting biliary complications after OLT. However, when the total bilirubin exceeded 5 mg/dl, the specificity was still 100% but the numbers of nondiagnostic/inconclusive and FN exams were increased.