Patients with advanced chronic kidney disease and vascular calcification have a large hydrodynamic radius of secondary calciprotein particles.

BACKGROUND: The size of secondary calciprotein particles (CPP2) and the speed of transformation (T50) from primary calciprotein particles (CPP1) to CPP2 in serum may be associated with vascular calcification (VC) in patients with chronic kidney disease (CKD). METHODS: We developed a high throughput, microplate-based assay using dynamic light scattering (DLS) to measure the transformation of CPP1 to CPP2, hydrodynamic radius (Rh) of CPP1 and CPP2, T50 and aggregation of CPP2. We used this DLS assay to test the hypothesis that a large Rh of CPP2 and/or a fast T50 are associated with VC in 45 participants with CKD Stages 4-5 (22 without VC and 23 with VC) and 17 healthy volunteers (HV). VC was defined as a Kauppila score >6 or an Adragao score ≥3. RESULTS: CKD participants with VC had larger cumulants Rh of CPP2 {370 nm [interquartile range (IQR) 272-566]} compared with CKD participants without VC [212 nm (IQR 169-315)] and compared with HV [168 nm (IQR 145-352), P < 0.01 for each]. More CPP2 were in aggregates in CKD participants with VC than those without VC (70% versus 36%). The odds of having VC increased by 9% with every 10 nm increase in the Rh of CPP2, after adjusting for age, diabetes, serum calcium and phosphate [odds ratio 1.09, 95% confidence interval (CI) 1.03, 1.16, P = 0.005]. The area under the receiver operating characteristic curve for VC of CPP2 size was 0.75 (95% CI 0.60, 0.90). T50 was similar in CKD participants with and without VC, although both groups had a lower T50 than HV. CONCLUSIONS: Rh of CPP2, but not T50, is independently associated with VC in patients with CKD Stages 4-5.

Long-Term Patency of Arteriovenous Fistulae Salvaged by Balloon Angioplasty with and without Accessory Vein Embolization: A Retrospective Study.

PURPOSE: To investigate whether accessory vein embolization (AVE) improves long-term performance of salvaged nonmaturing arteriovenous fistulae (AVFs). MATERIALS AND METHODS: This retrospective review included 72 patients who underwent percutaneous balloon angioplasty for salvage of nonmaturing AVFs between 2008 and 2014. AVE was performed on 32 patients between 2008 and 2011 (mean age, 59 y [range, 33-85 y]; men, n = 21; women, n = 11; upper arm, n = 17; forearm, n = 15), whereas the procedure was not performed on 40 patients after 2011 (mean age, 62 y [range, 28-85 y]; men, n = 26; women, n = 14; upper arm, n = 26; forearm, n = 14). Endpoints compared between groups included number of procedures required to achieve maturation, time to maturation, number of procedures required to maintain patency, and duration of primary and secondary patency after intervention. RESULTS: There was no statistically significant difference in number of procedures to achieve maturation (2.1 ± 1.4 vs 2.4 ± 1.2; P = .24) or time to maturation (26.1 d ± 56.2 vs 41.1 d ± 54.6; P = .072) between AVE and no embolization groups. Primary (P = .21) and secondary patency (P = .14) after intervention were not significantly different between groups. The number of procedures performed to maintain patency after maturation was significantly greater in the AVE group for patients with forearm AVFs (0.11 ± 0.098 vs 0.04 ± 0.064 per patient year; P = .039) but not for patients with upper arm AVFs. CONCLUSIONS: AVE of AVFs after balloon angioplasty does not lead to significantly improved long-term outcomes. Percutaneous salvage of nonmaturing AVFs in the forearm without AVE resulted in a decreased number of interventions to maintain patency.

Survey of Living Organ Donors' Experience and Directions for Process Improvement.

INTRODUCTION: Understanding living organ donors' experience with donation and challenges faced during the process is necessary to guide the development of effective strategies to maximize donor benefit and increase the number of living donors. METHODS: An anonymous self-administered survey, specifically designed for this population based on key informant interviews, was mailed to 426 individuals who donated a kidney or liver at our institution. Quantitative and qualitative methods including open and axial coding were used to analyze donor responses. FINDINGS: Of the 141 survey respondents, 94% would encourage others to become donors; however, nearly half (44%) thought the donation process could be improved and offered numerous suggestions. Five major themes arose: (1) desire for greater convenience in testing and scheduling; (2) involvement of previous donors throughout the process; (3) education and promotion of donation through social media; (4) unanticipated difficulties, specifically pain; and (5) financial concerns. DISCUSSION: Donor feedback has been translated into performance improvements at our hospital, many of which are applicable to other institutions. Population-specific survey development helps to identify vital patient concerns and provides valuable feedback to enhance the delivery of care.

Assisted maturation of native fistula in two patients with a continuous flow left ventricular assist device.

Patients who receive a left ventricular assist device (LVAD) are prone to develop end-stage renal disease. Primary arteriovenous fistula (AVF) maturation in these patients may be unsuccessful secondary to the nonpulsatile flow with an LVAD. Two patients with LVADs are described in whom assisted maturation aided long-term AVF patency.

Robotic-Assisted Management of Ureteral Complications in Post-Renal Transplant Patients: A Case Series and Literature Review.

Introduction: Urologic complications are thought to be the most common surgical complication of renal transplantation. Ureteral pathology, including stenosis, urine leak, and vesicoureteral reflux, predominates. Although endourologic and interventional radiological management may be utilized, failure rates remain relatively high and surgical reconstruction remains the definitive management. Robotic ureteral reconstruction has been demonstrated to provide patient benefit in nontransplant populations, but the literature on transplant reconstruction is very limited. This study reports an additional series of patients with a focus on surgical technique, as well as reviews the available evidence for robotic reconstruction for post-transplant ureteral complications. Methods: All institutional patients undergoing robotic-assisted reconstruction for post-transplant ureteral complications for the years 2019-2022 were included. Intra- and postoperative variables, patient demographics, and follow-up data were obtained retrospectively from parsing of patient records. Statistics were tabulated descriptively. Results: Eleven patients underwent ureteral reconstruction. Of the 11, 9 (81%) were male with a mean age of 51.9 years (16-70) and BMI of 33.8 (24.3-49.1). The most common (10/11) indication for reconstruction was stricture; the most common (10/11) technique used was Lich-Gregoir reimplantation. Mean operative time was 288 minutes (143-500). There were no intra- or immediate postoperative complications. Median length of stay was 2 days (1-22). There were two incidences of mortality at 2 and 5 months postoperatively unrelated to surgery. There were four readmissions within 30 days, three for urinary tract infection (UTI) and one for a pelvic abscess which required washout. The remainder of the cohort has been followed for a mean of 14.6 months (6-41) without any incidences of graft loss or recurrence of ureteral pathology. Conclusions: Robotic-assisted ureteral reconstruction is a technically challenging but highly feasible technique that may provide the benefits of minimally invasive surgery while still allowing definitive reconstruction. Centers with extensive robotic capabilities should consider the technique.

Diabetes mellitus impacts risk of macrovascular invasion in patients undergoing transplantation for hepatocellular carcinoma.

BACKGROUND: Diabetes mellitus (DM) is identified as a negative prognostic indicator in hepatocellular carcinoma (HCC), though the basis for this is unknown. METHODS: This is a retrospective analysis of a prospectively collected database of 191 HCC patients treated at the University of Rochester Medical Center (URMC) with orthotopic liver transplantation between 1998-2008. Clinical characteristics were compared between patients with and without DM prior to liver transplantation and logistic regression analyses were conducted to assess the effect of DM on clinical outcomes including vascular invasion. RESULTS: Eighty-four of 191 (44%) transplanted patients had DM at time of transplantation. An association of DM with invasive disease was found among transplanted HCC patients where histologically confirmed macrovascular invasion was found in 20.2% (17/84) of diabetics compared to 9.3% of non-diabetics (10/107) (p=0.032). This difference also remained significant when adjusting for tumor size, number of nodules, age, obesity and etiologic risk factors in multivariate logistic regression analysis (OR=3.2, p=0.025). CONCLUSIONS: DM is associated with macrovascular invasion among a cohort of transplanted HCC patients.

Robotic Assisted Transplant Nephrectomy: Case Series and Training Model for Improving Adoption.

Introduction: Open transplant nephrectomy for failed renal allograft is an invasive procedure associated with significant perioperative morbidity and mortality. Minimally invasive surgical approaches have improved a variety of patient outcomes for many surgeries. Thus, robotic assisted transplant nephrectomy (RATN) potentially offers significant patient benefit. Although previously reported, there remains a paucity of data on RATN outcomes and techniques. Methods: Four perfused, high-fidelity hydrogel models were created using previously described techniques and used for simulated RATN. Subsequently performed institutional cases were included for analysis. Intra- and postoperative variables along with patient demographics were retrospectively obtained through parsing of patient records. Results: Simulated nephrectomy time was 67.33 minutes (35.75 - 98.91). Five patients underwent RATN. There were four male and one female patients. The average age was 47 years. The most common indication was abdominal pain secondary to rejection (3/5). Mean blood loss was 188 mL; mean operative time was 243 minutes, and mean length of stay was 4.5 days. Intraoperatively there were two incidences of small cystotomies. One patient was readmitted within 30 days for intraabdominal abscess. Conclusion: This study adds to the growing literature around RATN, demonstrating the feasibility of the technique and reporting good outcomes for this cohort.

Page phenomenon in a transplanted kidney: is it salvageable?

A male in his late 70s with a history of an uncomplicated kidney transplantation 20 years prior was brought to the Emergency Department after experiencing blunt abdominal trauma following a motor vehicle collision. Imaging revealed a large perinephric haematoma, a retroperitoneal haematoma and multiple fractures. He was admitted to the intensive care unit where a renal haematoma was found to be expanding with ultrasonography (US) and developed renal dysfunction including anuria and hyperkalemia. His creatinine rose to twice his baseline and Doppler US showed elevated resistive indices, confirming extrinsic compression and causing a Page phenomenon. An open surgical exploration through the upper aspect of his Gibson incisional scar was performed followed by evacuation of the haematoma. An intraoperative US was done demonstrating good flow in the renal vessels. His postoperative course was uncomplicated and was discharged home with renal function back to baseline. On follow-up, he continued to have a good renal function.

Assessing the Effectiveness of a Primary Care Provider Office-Based Intervention for Increasing Organ Donor Registration Rates in Two New York State Counties.

Introduction: Despite strong public support, organ donor registration rates (RR) continue to lag while need only grows. In the United States, the traditional registration site is the Department of Motor Vehicles (DMV), however Primary care provider (PCP) offices have been considered as alternate locations for increasing RR. Methods: Twelve PCP offices across 2 New York Counties were subjected to a control week where participants received only a registration opportunity and an intervention week with the addition of a motivational poster and informational brochure. Zip code level sociodemographic data were obtained for each site. RR from the DMV over the same period served as historical control. Results: There were 1292 participants in the control phase and 1099 in the experimental phase. New registration rate for the control was 33.8% (289/897); experimental phase 7.88% (61/769); DMV registration 21.02% (1902/9050). The intervention was associated with a significant decrease in registrations (OR 0.181 (95% CI 0.135-0.244, P < 0.001)). Offices were clustered based on sociodemographic factors and regressed in 2 clusters. Lower educational attainment was associated with lower registration in the first but not second cluster (OR = 0.948 (0.923-0.974, P < 0.001)). Conclusions: This study provided evidence that PCP offices were a feasible site for organ donor registration and calls into question the efficacy of written materials-only interventions for increasing organ donor RR. It reiterated the negative effect of lower educational attainment on registration and suggested future studies focus on more active methods of engagement.

High mortality in orthotopic liver transplant recipients who require hemodialysis.

Acute renal failure is a significant risk factor for death in patients with liver failure. The goal of this study was to analyze the impact of peri-transplant dialysis on the long-term mortality of liver transplant recipients. We performed a single-center, retrospective cohort study of 743 adult liver transplants; patients who received first liver transplants were divided into four groups: those who received more than one dialysis treatment (hemodialysis [HD], continuous veno-venous hemodialysis [CVVH]) pre-orthotopic liver transplantation (OLT), post OLT, pre- and post OLT, and those not dialyzed. There was no statistically significant difference in the mean survival time for patients who were not dialyzed or dialyzed only pre-OLT. Mean survival times were markedly reduced in patients dialyzed post OLT or both pre- and post OLT compared with those never dialyzed. Mortality risk in a Cox proportional hazards model correlated with hemodialysis post OLT, intra-operative vasopressin or neosynephrine, donor age >50 yr, Cr >1.5 mg/dL at transplant, and need for subsequent retransplant. Risk of post-OLT dialysis was correlated with pre-OLT dialysis, intra-operative levophed, pre-OLT diabetes, African American race, pre-OLT Cr >1.5, and male gender. We conclude that renal failure requiring hemodialysis post liver transplant, irrespective of pre-transplant dialysis status, is a profound risk factor for death in liver transplant recipients.

Response to antiviral therapy in liver transplant recipients with recurrent hepatitis C viral infection: a single center experience.

INTRODUCTION: Recurrence of hepatitis C virus (HCV) in hepatic allograft is a major concern after successful liver transplant (LTx). AIM: To examine the response rate to pegylated interferon (PEG-IFN) and ribavirin in post-LTx patients with HCV recurrence. PATIENTS AND METHODS: Between January 2003 and September 2006, 60 patients with biopsy proven HCV recurrence (46 males and 14 females) received PEG-IFN 2a (n = 40) or IFN 2b (n = 20) with ribavirin. All patients were followed until July 2007. RESULTS: Fourteen patients (23.3%) tolerated antiviral therapy for less than six months and 10 (16.7%) discontinued therapy between six and 11 months. PEG-IFN dose was reduced in 21 (35%) patients and ribavirin dose was reduced in 16 (26.7%) patients. Overall, 55% patients achieved end of treatment response (EOT) and 35% sustained virological response (SVR). Mean Hepatitis Activity Index and Fibrosis Score pre-therapy was 5.8 +/- 1.9 and 1.7 +/- 1.3 and post-therapy, it was 4.4 +/- 2.1 and 2.4 +/- 1.6, respectively. Overall, three yr patient and graft survival was 73.9% and 69.2%, respectively. The patients with SVR had significantly lower viral load compared with other groups (p = 0.028). CONCLUSION: PEG-IFN and ribavirin therapy achieved 55% EOT and 35% SVR; 60% patients tolerated therapy. Biochemical response was observed in all groups of patients irrespective of virological response.

Development of a High-Fidelity Robot-Assisted Kidney Transplant Simulation Platform Using Three-Dimensional Printing and Hydrogel Casting Technologies.

Introduction and Objective: Despite the adoption of robotic donor nephrectomy, the steep learning curve of robotic recipient transplantation has hindered the implementation of a complete robot-assisted kidney transplantation (RAKT). We sought to develop a high-fidelity perfused full immersion nonbiohazardous platform for RAKT simulation training. Methods: A three-dimensional (3D) computer-aided design (CAD) model consisting of a kidney, pelvicaliceal system, renal artery, and vein was created from a CT scan of a donor patient. 3D printed casts designed from the CAD model were injected with various polyvinyl alcohol hydrogel formulations to fabricate an anatomical kidney phantom and surrounding abdominal cavity. The process was repeated using a recipient's CT scan to create the recipient pelvic model containing a bony pelvis, pelvic musculature, iliac arteries and veins, and bladder. Donor and recipient models each contained structures to simulate the perfused vascular and ureterovesical anastomosis. A board-certified transplant surgeon completed a robotic training curriculum, including four RAKT simulation procedures, from procurement of the donor kidney to final retroperitonealization. Metrics from the simulations (e.g., arterial, venous, ureterovesical, and total anastomosis times) were recorded and compared with surgical times from published data. Results: The average time for the nephrectomies was 67.33 (±31.58) minutes. The average total anastomosis time was 60.85 (±9.73) minutes with 20.37 (±3.87), 20.17 (±4) and 15.1 (±2.35) minutes for arterial, venous, and ureterovesical anastomosis, respectively. The recorded arterial and venous anastomosis times were within published times for competency (Δ = 2.47 and Δ = 2.87, respectively), whereas the uterovesical time was within the mastery range (Δ = 0.45). Conclusions: Using a combination of 3D printing and hydrogel casting technologies, a high fidelity perfused full-immersion nonbiohazardous simulation platform for RAKT was developed. The utilization of this platform has the potential to replace the early cases in a learning curve while decreasing the barriers to utilization for transitioning transplant surgeons.

Liver grafts from donors with central nervous system tumors: a single-center perspective.

Traditionally, patients who die with a malignancy have been excluded from donation. However, it has become a common practice to accept organs from donors that have low-grade tumors or tumors with low metastatic potential. The aim of this study was to analyze our experience with the use of liver grafts from donors with central nervous system (CNS) tumors. A retrospective review of 1173 liver transplants performed between 1992 and 2006 identified 42 donors diagnosed with a CNS tumor. Thirty-two tumors were malignant, and 10 tumors were benign. Forty-two liver transplant recipients received livers from these donors. All patients were followed until May 2007 with a mean follow-up of 29 +/- 17 months. Among 42 donors, there were 28 males and 14 females. The mean donor risk index was 1.78 +/- 0.39. Twenty (47.6%) of the CNS tumors were glioblastoma multiforme (astrocytoma grade IV), 11 (26.2%) were other astrocytomas, and 1 (2.4%) was an anaplastic ependymoma. Twenty (62.5%) neoplasms were grade IV tumors, 8 (25%) were grade II tumors, and 4 (12.5%) were grade III tumors. Over 80% of the patients had at least 1 kind of invasive procedure violating the blood-brain barrier. The rate of recurrence for the entire group was 2.4% (all CNS tumors). There were 7 (7.2%) deaths in all. The most common cause of death was sepsis (n = 3, 7.2%). There was no difference in survival between recipients of grafts from donors with CNS tumors and recipients of grafts from donors without CNS tumors (1 year: 82% versus 83.3%, P = not significant; 3 years: 77.4% versus 72%, P = not significant). In conclusion, in our experience, despite violation of the blood-brain barrier and high-grade CNS tumors, recurrence was uncommon. Grafts from these donors are often an overlooked source of high-quality organs from younger donors and can be appropriately used, particularly in patients who, despite low Model for End-Stage Liver Disease scores, carry a high risk of mortality.

Incidence of abdominal wall numbness post-liver transplantation and its complications.

Liver transplantation (LTx) is a life-saving procedure for end-stage liver disease. However, LTx remains a major surgical procedure with a significant amount of morbidity and mortality. Several different types of post-LTx complications have been studied and reported; however, the numbness of the abdominal skin between the subcostal incision and the umbilicus and its associated complications have not been studied in a large patient population. The aim of this study was to report the incidence of numbness in the abdominal skin post-LTx and its implications in routine life. One hundred and one post-LTx patients were questioned in the clinic about numbness. There were 52 male patients and 49 female patients with a mean age of 51.9 +/- 11.3 years at the time of LTx, and the mean time from transplant was 35.0 +/- 29.5 months (range, 3-113 months). The implications were recorded. All 101 patients (100%) had an area of numbness between the subcostal incision and the umbilicus. Four of these patients had an area of superficial-to-deep burns from hot food (accidentally dropped on the abdomen), heating pads, or a hot cup of tea. One patient had ecchymosis from blunt trauma during gardening. Out of 36 diabetic patients, more than 24 patients were insulin-dependent and used the area for subcutaneous insulin injections. In addition, some of the 43 hepatitis C virus-positive patients used the area for subcutaneous interferon therapy. In conclusion, 100% of the patients had persistent numbness up to 9 years following LTx. Five percent of the patients developed thermal injuries or blunt trauma complications that could have been prevented with better education and awareness. More then 24% of the patients used the area for subcutaneous injections of insulin and/or interferon.

Minimizing morbidity of organ donation: analysis of factors for perioperative complications after living-donor nephrectomy in the United States.

BACKGROUND: Expansion of living kidney donation through liberalizing acceptance criteria invites a renewed focus on safety and outcomes. Wide variability exists in reported donor complications, and associated risk factors are ill defined. Use of administrative data can overcome the bias of single-center studies and identify variables associated with untoward events. METHODS: The study population consisted of 3074 living kidney donors from 28 centers during 2004 and 2005. Data from a large healthcare registry were used to retrospectively identify the study cohort. Perioperative complications were identified using ICD-9-CM coding and classified according to the Clavien system. Logistic regression models were constructed to identify donor and center factors associated with complications. RESULTS: There were no perioperative deaths. The overall complication rate was 10.6% and major complications defined by Clavien grade >or=3 was 4.2%. The prevalence of tobacco use, obesity, and hypertension, was 7.8%, 2.4%, and 2.3%, respectively. Age >50 (odds ratio [OR]=1.81, 95% confidence interval [95% CI]=1.25-2.61), tobacco use (OR=1.41, 95% CI=1.02-1.94), obesity (OR=1.92, 95% CI=1.06-3.46), and annual center volume 50 increases complications; however, the risk of major morbidity is small. Use of administrative data represents an important tool to facilitate the reconciliation of an increased need for organ donors with the concern for donor safety.

Pharmacokinetics of tacrolimus in living donor liver transplant and deceased donor liver transplant recipients.

INTRODUCTION: Hepatic dysfunction is an important determinant of the clearance of tacrolimus; however, the impact of reduced hepatic mass in living donor liver transplant (LDLT) patients on the drug exposure and clearance of tacrolimus is not known. AIM.: The aim of the present study is to compare the dosage, concentration and pharmacokinetics parameters of tacrolimus between LDLT and deceased donor liver transplant (DDLT) recipients. PATIENTS AND METHODS: Daily doses used and trough concentrations measured were compared in 12 LDLT and 12 DDLT patients. Multiple blood samples were taken over one dosing interval after oral tacrolimus administration, and pharmacokinetics differences were compared. RESULTS: The mean tacrolimus dosage in first 14 postoperative days was (0.06 mg/kg/day) for LDLT and (0.09 mg/kg/day) for DDLT (P=0.0001). Despite the lower doses used, mean trough concentration was significantly greater in LDLT as compared with DDLT (8.8+/-2.5 ng/mL vs. 6.79+/-1.5 ng/mL, respectively, P=0.013). On the day of the pharmacokinetic study, minimum Concentration (Cmin), 12-hr postdose concentration (Clast), and average concentration (Cavg) were significantly greater in LDLT as compared with DDLT (LDLT: 6.6+/-2.4 ng/mL, 7.2+/-1.8 ng/mL, 8.9+/-3.0 ng/mL; DDLT: 4.3+/-1.0 ng/mL, 4.9+/-1.6 ng/mL, 5.9+/-1.4 ng/mL, P=0.02, 0.04, and 0.02, respectively). Dose normalized AUC was 37.7% greater and clearance, 47.5% lower in LDLT as compared with DDLT. CONCLUSION: Although not statistically significant, the dose normalized AUC was 37.7% greater and clearance 47.5% lower in LDLT as compared with DDLT. An initial tacrolimus dose reduction of about 30-40% may be prudent in LDLT compared with DDLT recipients.

Stratifying risk of biliary complications in adult living donor liver transplantation by magnetic resonance cholangiography.

BACKGROUND: Accurate preoperative assessment of biliary anatomy in live donor hepatectomy may be helpful to assess the suitability of a graft and to stratify risk of biliary complications. METHODS: A retrospective review of existing data among donor and recipients of 36 living donor transplants was performed to assess role of preoperative magnetic resonance cholangiography (MRC) for defining biliary anatomy and to stratify risk of biliary complications. RESULTS: Thirty-six living liver donors underwent MRC, and subsequently right lobectomy. Intraoperative cholangiography and biliary exploration revealed that 24 donors (66.6%) had conventional and 12 (33.3%) had aberrant biliary anatomy. Intraoperative cholangiography demonstrated a strong correlation with MRC (P=0.001) and intraoperative findings (P=0.001). MRC had specificity and positive predictive value of 100%. The risk of developing biliary complication was 5.9 times higher if the biliary anatomy was of any type other than A (P=0.03, CI 1.06-32.9) after controlling for donor age, recipient age, and type of anastomosis. CONCLUSION: MRC reliably identified variant biliary anatomy. The preoperative MRC demonstrated congruence with the intraoperative cholangiogram and with the intraoperative findings. MRC is helpful in predicting risk of biliary complications in recipients, and identifies donors who would otherwise be excluded intraoperatively by cholangiography, thus limiting the risk of an unnecessary operation.

Pharmacokinetics of mycophenolic acid in live donor liver transplant patients vs deceased donor liver transplant patients.

The exposure of mycophenolic acid in live donor liver transplant patients (those receiving a partial hepatic volume) in comparison to deceased donor liver transplant patients (those receiving the whole hepatic volume) after administration of mycophenolate mofetil has not been reported earlier. The aim of the present study is to compare the pharmacokinetics parameters of mycophenolic acid and mycophenolic acid glucuronide in live donor liver transplant patients versus deceased donor liver transplant patients. Twelve live donor liver transplant and 12 deceased donor liver transplant recipients were studied over a dosing interval after intravenous administration of mycophenolate mofetil. The maximum concentration (Cmax) and the area under the plasma concentration versus time curve (AUC) for mycophenolic acid in live donor liver transplant patients were significantly higher than in deceased donor liver transplant patients (Cmax/AUC: live donor liver transplant patients: 16.1 +/- 6.6 microg/mL/43.9 +/- 12.6 microg/mL.h vs deceased donor liver transplant patients: 10.7 +/- 2.0 microg/mL/28.9 +/- 7.1 microg/mL.h; P = .046/.002). The volume of distribution was higher in the deceased donor liver transplant patients compared with live donor liver transplant patients. However, the mean plasma concentration at 12 hours (Clast), drug disposition rate constant, half-life (t 1/2), and mean residence time were similar in both groups. The mean plasma concentration of mycophenolic acid glucuronide was 1.4 to 2.0 times higher in deceased donor liver transplant patients compared with live donor liver transplant patients. These observations point to the need to use a lower dosage (approximately 30%) of mycophenolate mofetil in live donor liver transplant patients compared with deceased donor liver transplant patients.

Polysubstance abuse in liver transplant patients and its impact on survival outcome.

BACKGROUND: Alcohol-related end-stage liver disease was the most common reason for liver transplant in the 1990s. Currently, hepatitis C virus (HCV) is the most common reason for transplant. The major HCV risk factor is intravenous drug abuse, which often includes other forms of substance abuse. It is important to understand posttransplant survival outcomes in patients with multiple substance abuse and pretransplant factors that predict relapse. METHODS: The medical records of patients referred to the transplant psychiatrist were retrospectively reviewed to identify posttransplant patients with pretransplant multisubstance abuse issues including cannabis, cocaine, opioids, and alcohol. Survival outcomes and drug relapse were assessed in relation to demographic variables including age, race, sex, legal history, psychiatric diagnoses or need for psychiatric hospitalization, and substance abuse diagnosis. RESULTS: Twenty-seven patients with polysubstance abuse disorders were identified: substance abuse (n=41), substance dependence (n=33), and other (n=8); a mean of 3.03 substances was used per patient. Eight patients relapsed (29.6%) and 10 patients died (33%) between 2 and 60 months after transplant. Patients were divided into relapse and no-relapse groups, and 1-year patient survival rates in patients were 100% and 83.9%, respectively. No between-group differences were found for age, race, sex, legal history, psychiatric diagnoses or need for psychiatric hospitalization, or having first-degree relatives with substance abuse issues. CONCLUSIONS: The rate of recidivism was 26.9%; however, it did not affect survival. No predictors of relapse were identified. Patients with polysubstance abuse issues should not be categorically denied access to liver transplant. Further research regarding these issues is essential.

Tobacco Use is a Modifiable Risk Factor for Post-Transplant Biliary Complications.

PURPOSE: Biliary complications following liver transplantation are a significant source of morbidity, potentially leading to graft failure necessitating retransplantation. We sought to evaluate smoking as an independent risk factor for post-transplant biliary complications. METHODS: The clinical course of all adult primary deceased donor liver transplants at our center from 1992 to 2012 was reviewed. Eligible patients were assigned to cohorts based on their lifetime tobacco exposure: never smokers indicating 0 pack-year exposure and all others were ever smokers. Biliary complications were defined as strictures, leaks, or bilomas requiring intervention. Complication rates were analyzed using univariate regression models correlated with donor and recipient characteristics. Associations found during univariate analysis were included in the final multivariate Cox model. RESULTS: Eight hundred sixty-five subjects were followed for a median of 65 months; 482 (55.7%) of patients had a positive smoking history at the time of transplant. In univariate analysis, positive tobacco smoking history (HR = 1.36; p = 0.037) and increased time from quit date to transplantation (HR = 0.998; p = 0.011) were positive and negative predictors of biliary complication, respectively. Lifetime tobacco exposure remained a significant predictor of biliary complication on multivariate analysis (HR = 1.408; p = 0.023). CONCLUSIONS: Smoking status is an independent predictor of post-transplant biliary complications, and the data presented reinforces the importance of early smoking cessation in the pre-transplantation period.