Holly B. Meadows

Early Aspirin Therapy May Reduce Hepatic Artery Thrombosis in Liver Transplantation

BACKGROUND Hepatic artery thrombosis (HAT) remains among the leading causes of early graft loss after liver transplantation. Our transplant center began using universal aspirin prophylactic therapy immediately posttransplantation in 2007. The aim of this study was to determine the safety and efficacy of early aspirin therapy on clinical outcomes. METHODS This large-scale, cross-sectional analysis included all adult liver transplantations performed between 2000 and 2009. Pediatric and multiorgan transplants were excluded. Patients were grouped and compared based on whether they received early initiation of aspirin 325 mg PO daily posttransplantation. RESULTS A total of 541 adult liver transplantations occurred during the study period; 439 had complete documentation and were analyzed. Clinical outcomes show aspirin patients had similar rates of early and late HAT, but had significantly lower early HAT, defined as HAT occurring within the first 30 days posttransplant, leading to graft loss. Other clinical outcomes were similar between groups including bleeding events and wound complications. CONCLUSIONS Immediate initiation of aspirin therapy after liver transplantation may reduce the rate of HAT leading to early graft loss, without increasing bleeding or other complication rates.

Improving Transplant Patient Safety Through Pharmacist Discharge Medication Reconciliation

Greater than 50% of medication errors are estimated to occur during transitions of care, and solid‐organ transplant recipients are at an increased risk for errors due to significant changes in their medication regimen following transplantation. This prospective, observational study with a historical control group was conducted to evaluate the discharge process for transplant recipients and determine if transplant pharmacist involvement would improve safety. During the prospective period, a total of 191 errors were made on discharge medication reconciliations (n = 64, mean rate 3.0 per patient); however, pharmacists prevented 119 of these errors (1.9 errors per patient). In the retrospective period, none of the 430 errors identified were prevented at the time of discharge (n = 128, p < 0.0001). The 72 errors not prevented at the time of discharge in the prospective cohort were identified by the pharmacist at the patients first clinic visit (1.1 errors per patient). In the historical cohort, all 430 errors made at discharge persisted until at least the time of the first clinic visit (3.4 errors per patient, p < 0.0001). This study demonstrates that transplant recipients are at a high risk for medication errors and that transplant pharmacist involvement leads to improved safety through the significant reduction of medication errors.

Prospective randomized controlled trial of rabbit antithymocyte globulin compared with IL-2 receptor antagonist induction therapy in kidney transplantation.

Objective:The aim of this study was to determine the safety and efficacy of induction with rabbit antithymocyte globulin (RATG) compared with interleukin-2 receptor antagonists in a racially diverse kidney transplant patient population under modern immunosuppression. Background:The optimal induction therapy in patients at risk for rejection, particularly black recipients, in the modern era of immunosuppression with flow cytometry-based cross-matching is unclear. Methods:This was a prospective, risk-stratified, randomized, single-center, open-label study of 200 consecutively enrolled patients in a large academic teaching center. Patients were randomized to receive either daclizumab or basiliximab versus RATG for induction in combination with tacrolimus, mycophenolate mofetil, and corticosteroids. Patients were stratified between groups to ensure equal numbers of black, retransplants, high panel reactive antibodies (PRAs) (>20%), and prolonged cold ischemic times (>24 hours) in each group. Primary outcome measure is treatment efficacy defined as the incidence of biopsy-proven acute rejection and estimated creatinine clearance. Patients were followed up for 12 months. Renal transplant recipients were included if they were adult (≥18 years old) and received an allograft from a deceased, living unrelated, or nonhuman leukocyte antigen identical living-related donor. Results:A total of 200 patients (n = 98 in the interleukin-2 receptor antagonists, and n = 102 in the RATG) were enrolled from February 2009 through July 2011. One-year acute rejection rates were low and similar between groups (10% in the interleukin-2 receptor antagonist group vs 6% in the RATG group; P = 0.30). Creatinine clearance was also similar between groups (interleukin-2 receptor antagonist group 56 ± 20 mL/min per 1.73 m2 vs RATG group 55 ± 22 mL/min per 1.73 m2; P = 0.73). Subanalysis of recipient race revealed that in blacks only RATG was protective against 6- and 12-month acute rejection, without an increased risk of infection. Induction did not affect rejection rates according to recipient calculated PRAs; however, RATG was associated with an increased risk of BK virus in low-PRA patients. Conclusions and Relevance:RATG induction provides improved protection against early acute rejection in black renal transplant recipients, whereas sensitized patients do not seem to demonstrate a similar benefit from this therapy. This study is registered at Clinicaltrials.gov (NCT00859131).

Pre‐existing diabetes significantly increases the risk of graft failure and mortality following renal transplantation

The aim of this study was to examine the impact of pre‐existing diabetes mellitus (DM) on acute rejection, graft loss, and mortality following kidney transplant and whether glycemic control or cardiovascular disease (CVD) risk control with medications influenced outcomes. This was a cohort study of 1002 renal transplants conducted between 2000 and 2008. Patients were included if they received a kidney transplant within the allotted time and were at least 18 yr of age. Cox regression was used to assess acute rejection, graft failure, or death controlling for relevant sociodemographic, clinical, and post‐transplant variables. Five‐yr patient survival (83% vs. 93%, p < 0.001) and graft survival (74% vs. 79%, p = 0.005) were significantly lower in patients with pre‐existing DM. Sequential Cox regression models demonstrated that pre‐existing DM was consistently associated with a higher risk of death (HR 2.3–3.0, p < 0.01) and graft failure (HR 1.5–1.8, p < 0.04) in all models except after adjusting for CVD medication use (HR 1.9, p = 0.174 and HR 1.5, p = 0.210, respectively). These data suggest pre‐existing DM is a significant risk factor for graft failure and death following renal transplantation and aggressive CVD risk reduction with medications may be an important strategy to reduce mortality and graft failure.

Are Thiazide Diuretics Safe and Effective Antihypertensive Therapy in Kidney Transplant Recipients

Background/Aims: There are no published studies assessing the safety and efficacy of thiazides as antihypertensives in kidney transplantation (KTX). Methods: This was a longitudinal retrospective cohort study conducted in adult KTX recipients. Patients were grouped based on receiving thiazides following KTX. Safety and efficacy comparisons were made between thiazide recipients and unexposed patients, as well as change in blood pressure (BP) within thiazide patients. Results: 1,093 patients were included (thiazide group: 108, unexposed group: 985). Mean follow-up was 7.3 ± 4.5 years. Thiazide recipients were older (53 ± 11 vs. 48 ± 13 years, p < 0.001) and more likely to be female (52 vs. 41%, p = 0.023) and have pre-KTX hypertension (97 vs. 88%, p = 0.004) or diabetes (36 vs. 27%, p = 0.035). After controlling for baseline differences, safety analysis revealed thiazide recipients were not more likely to be readmitted to the hospital, but were at higher risk to develop hyperkalemia (56 vs. 38%, p < 0.001) or hypokalemia (28 vs. 18%, p = 0.010), with similar rates of hypotension, decreased estimated glomerular filtration rate, graft loss and death. Efficacy analysis demonstrated systolic (147 ± 17 to 139 ± 18 mm Hg, p < 0.001) and diastolic (79 ± 9 to 77 ± 11 mm Hg, p < 0.001) BPs were significantly reduced after thiazide initiation. Compared to unexposed patients, thiazide recipients had higher mean BPs during the entire follow-up (142/78 vs. 136/77, p < 0.001), with similar BPs while on thiazides and comparable rates of goal BPs (<130/80 mm Hg, 32 vs. 36%, p = 0.219). Conclusions: In KTX, based on long-term outcomes, thiazides appear to be safe and effective antihypertensives; in the short-term, thiazides may increase the risk of developing potassium disturbances.

The Impact of Cardiovascular Disease and Risk Factor Treatment on Ethnic Disparities in Kidney Transplant

There is limited data on the use of cardiovascular disease (CVD) risk factor medications following renal transplant, especially when comparing use across ethnicities. The aim of this study was to compare the incidence, treatment, and impact of CVD between ethnicities in kidney transplant recipients. This was a retrospective cohort study of adults who underwent transplant between 2000 and 2008 within our academic medical transplant center. Pediatrics, multiorgan transplants, and those lost to follow-up were excluded. Data collection included all transplant and sociodemographic characteristics, medication use, CVD risk factor management, and follow-up events, including acute rejection, graft loss, and death. A total of 987 patients were included and followed for a mean of 6.7 ± 3.0 years. The baseline demographics revealed black patients were equally likely to have preexisting CVD (24% vs 25%, P = .651), but more likely to have preexisting diabetes (35% vs 23%, P < .001) or hypertension (97% vs 94%, P = .029). Black patients had poorer treatment of CVD risk factors, with lower rates of control of diabetes (35% vs 51%, P < .05) and dyslipidemia (37% vs 42%, P < .05). Black renal transplant recipients who had preexisting CVD had reduced graft survival rates compared to white patients (10-year rate 50% vs 60%, P = .033), but similar rates of graft survival were found in those without CVD (10-year rate 70% vs 71% in white patients, P = .483). CVD is common in transplant recipients, with black patients having higher rates and poorer control of diabetes and dyslipidemia.

The impact of diabetes mellitus and glycemic control on clinical outcomes following liver transplant for hepatitis C

Hepatitis C is the leading indication for liver transplantation in the USA and recurrence is universal. The impact of preexisting diabetes, new‐onset diabetes after transplant (NODAT), and glycemic control on fibrosis progression has not been studied. This retrospective longitudinal cohort study included adult liver recipients with hepatitis C transplanted between 2000 and 2011. Patients were divided into three groups: preexisting diabetes (n = 41), NODAT (n = 59), and no diabetes (n = 103). Patients with preexisting diabetes (70%) or NODAT (59%) were more likely to develop hepatitis C recurrence (≥stage 1 fibrosis), as compared to non‐diabetics (36%, p = 0.006). There was also a trend toward a higher incidence of at least Stage 2 fibrosis (36% and 48% vs. 23%, respectively; p = 0.063). Patients with tight glycemic control had a lower rate of Stage 2 fibrosis development (78% vs. 60%, p = 0.027), while those with good control (<150 mg/dL) also had lower rates of Stage 2 fibrosis (84% vs. 62%, p = 0.004). Multivariable analysis verified a decreased rate of recurrence for patients with blood glucose <138 mg/dL (p = 0.021), after controlling for confounders. These results demonstrate that diabetes is strongly associated with an increased risk of hepatitis C virus‐related fibrosis development and glycemic control may reduce the risk and severity of recurrence.

Incidence, risk factors, and outcomes of opportunistic infections in pediatric renal transplant recipients.

OIs present significant risks to patients following solid organ transplantation. The purpose of this study was to identify risk factors for the development of OIs after kidney transplantation in pediatric patients and to evaluate the impact of OIs on outcomes in this patient population. A single‐center retrospective longitudinal cohort analysis including pediatric patients 21 yr of age or younger transplanted from July 1999 to June 2013 at an academic medical center was conducted. Patients were excluded if they received multi‐organ transplant. A total of 175 patients were included in the study. Patients who developed OIs were more likely to be female and younger at the time of transplant. A six‐factor risk model for OI development was developed. Death, disease recurrence, and PTLD development were similar between groups but trended toward increased incidence in the OI group. Incidence of rejection was significantly higher in the OI group (p = 0.04). Patients who developed OIs had several important risk factors, including younger age, EBV‐negative serostatus, CMV donor (+)/recipient (−), biopsy‐proven acute rejection, ANC <1000, MMF dose >500 mg/m2, and any infection. Incidence of rejection was higher in the OI group, but rate of graft loss was not statistically different.

Prediction of medication non-adherence and associated outcomes in pediatric kidney transplant recipients.

Studies have continued to evaluate risk factors associated with post‐transplant non‐adherence in pediatric patients. However, many of these studies fail to evaluate how risk factors can be utilized to predict MNA. The aims of this study were to (i) determine salient risk factors associated with MNA to develop an adequate predictive risk model and (ii) assess transplant outcomes based on the presence of MNA in a large, diverse cohort of pediatric KTX recipients. One hundred and seventy‐five solitary pediatric KTX recipients transplanted from 1999 to 2013 were included. AA, males, older patients, those who lived in urban environments, had legal issues, and lived shorter distances from the transplant center were more likely to have MNA. Using logistic regression, a parsimonious model applying nine risk factors together was developed for predicting MNA, demonstrating a PPV of 69% and a NPV of 81%. Patients with MNA had more than twice the risk of biopsy proven acute rejection, 1.6 times the risk of hospitalization, and 1.8 times the risk of graft loss. Utilization of a predictive model to determine risk of MNA after pediatric KTX may offer clinicians the ability to efficiently and effectively monitor MNA following transplant.

Clinical and Economic Outcomes Associated with Medication Errors in Kidney Transplantation

BACKGROUND AND OBJECTIVES Modern immunosuppressant regimens have significantly decreased acute rejection rates, but may have increased the risk of graft loss driven by adverse drug reactions (ADRs) and medication errors (MEs). The objectives of this study were to determine the incidence and risk factors for MEs and ADRs and determine the association between transplant outcomes and these events. DESIGN, SETTING, PARTICIPANTS, & MEASUREMENTS This was a post hoc analysis of a prospective, randomized trial that included patients aged>18 years that received a solitary renal transplant at an academic medical center recruited between March 2009 and July 2011. Patients were divided into groups based on developing a clinical significant ME (CSME), defined as a significant ME that contributed to a hospital admission. RESULTS The mean study follow-up was 2.5 ± 0.7 years. There were a total of 233 MEs and 327 ADRs in the 200 patients included in the analysis, with 64% of the cohort experiencing at least one ME and 87% experiencing an ADR; 23 patients (12%) experienced a CSME. Patients that experienced CSMEs had a trend toward more post-transplant readmissions (median 1 [interquartile range (IQR), 0-5] versus 0 [0-2]; P=0.06), higher costs for readmissions (median