Charles F. Bratton

Racial disparities in organ donation and why.

Purpose of reviewHigh prevalence of comorbidities such as diabetes, hypertension, obesity, hepatitis B and C, in minority groups, results in racial minorities being disproportionally represented on transplant waiting lists. Organ transplantation positively impacts patient survival but greater access is limited by a severe donor shortage. Recent findingsUnfortunately, minority groups also suffer from disparities in deceased and living donation. African-Americans comprise 12.9% of the population and 34% of the kidney transplant waiting list but only 13.8% of deceased donors. Barriers to minority deceased donation include: decreased awareness of transplantation, religious or cultural distrust of the medical community, fear of medical abandonment and fear of racism. Furthermore, African-Americans comprise only 11.8% of living donors. Barriers to minority living donation include: unwillingness to donate, medical comorbid conditions, trust or fear of medical community, loss to follow-up, poor coping mechanisms, financial concerns, reluctance to ask family members and friends, fear of surgery, and lack of awareness about living donor kidney transplantation. SummaryTransplant center-based education classes significantly and positively impact African-American concerns and beliefs surrounding living donation. Community and national strategies utilizing culturally sensitive communication and interventions can ameliorate disparities and improve access to transplantation.

Improved Patient Safety and Outcomes With a Comprehensive Interdisciplinary Improvement Initiative in Kidney Transplant Recipients

Although kidney transplant recipients at the authors’ institution had a short length of stay (LOS), delayed discharges and early readmissions were common; medication use and safety were at the core of these issues. A multidisciplinary quality improvement initiative was developed that targeted eliminating these issues. The team developed key initiatives including improved medication reconciliation, development of a diabetes management service, and improved discharge medication dispensing, delivery, education, and scrutiny. Follow-up analysis demonstrated reduced medication discrepancies by >2 per patient and obtaining 100% adherence with reconciliation. Pharmacists reviewed discharge medications, reaching 100% by study end, leading to a 40% reduction in medication safety issues. LOS remained short, and delayed discharges were reduced by 14%; 7-day readmission rates decreased by 50%. Acute rejection and infection rates also significantly decreased. In conclusion, a multidisciplinary quality improvement initiative can improve medication safety in kidney transplant patients, which can lead to improved clinical outcomes.

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.

Leflunomide efficacy and pharmacodynamics for the treatment of BK viral infection.

BACKGROUND AND OBJECTIVES BK virus is an infection in kidney transplantation patients jeopardizing graft survival. Unfortunately, there is no consensus on treatment of BK viremia and nephropathy. Leflunomide has been studied for the treatment of BK viremia and nephropathy, but there are limited data on the utility of leflunomide therapeutic drug monitoring. This study aimed to determine if a pharmacodynamic relationship exists between BK viral load reduction and leflunomide metabolite, A77 1726, serum concentrations. DESIGN, SETTING, PARTICIPANTS, & MEASUREMENTS This study was a retrospective, single-center, longitudinal analysis of patients identified with BK viremia with or without nephropathy. Patients were grouped according to whether they received leflunomide. All BK viral PCR and A77 1726 concentrations were analyzed to determine pharmacodynamics, and were correlated with clinical outcomes. RESULTS Of 76 patients identified, 52 received leflunomide therapy and 24 did not. Patients who received leflunomide were further analyzed according to A77 1726 concentrations and BK clearance; there was no difference in BK clearance. There was a lack of correlation between A77 1726 concentrations and log change in BK viral PCR concentration. Multivariate analysis demonstrated that mycophenolate mofetil discontinuation, BK viremia without nephropathy, and mean BK viral load were significantly associated with BK viral clearance; leflunomide use lacked this association. CONCLUSIONS Pharmacodynamic analysis revealed no association between A77 1726 concentrations and BK viral PCR reductions. Multivariate analysis demonstrated that leflunomide therapy was not associated with BK viral clearance. Randomized studies are needed to determine the utility of leflunomide for BK viremia and nephropathy.

Safe use of highly steatotic livers by utilizing a donor/recipient clinical algorithm

The aim of this study was to assess the long‐term safety and clinical outcomes associated with the utilization of highly steatotic donor livers utilizing a specific donor/recipient matching algorithm. This was a prospective, observational, single‐center, 10‐yr follow‐up study. Highly steatotic livers were utilized according to a donor/recipient algorithm that guided the surgeon to use highly steatotic donor organs judiciously in low‐risk recipients. This study initially compared fat assessment based on frozen‐section Ehrlichs hematoxylin and eosin (H&E) to reperfusion biopsy fat assessment and demonstrated that H&E is an insensitive analysis to determine degree of steatosis. Patients were divided into three groups based on donor steatosis (group 1: <30% steatosis, group 2: 30–60% steatosis, group 3: >60% steatosis), and clinical outcomes were assessed. One hundred and sixteen patients were included in the analysis. Patients that received severely steatotic livers (>60% fat) showed increased reperfusion liver injury and delayed return of liver function in the early postoperative period, demonstrated by biochemical markers. However, there were no differences in primary non‐function, postoperative complications, length of stay, and patient and graft survival. Using rigorous donor/recipient matching through a detailed algorithm, these data demonstrate that normal liver allograft outcomes are not superior to those in highly steatotic grafts.

Long-term efficacy of induction therapy with anti-interleukin-2 receptor antibodies or thymoglobulin compared with no induction therapy in renal transplantation.

BACKGROUND Although the utility of antibody induction therapy has been demonstrated in clinical trials, the ideal regimen to use based on patient risk factors has not been fully elucidated. The objectives of this study were to determine the impact of either anti-interleukin-2 receptor antibodies (IL-2RA) or thymoglobulin induction therapies versus no induction therapy on acute rejection rates and on 3-year graft survival rates. METHODS This retrospective analysis compared 3 patient groups-those who did not receive induction, those who received IL-2RA induction, and those who received thymoglobulin induction. RESULTS Three hundred eleven patients were included in this study. Patients were well matched for demographic and immunologic characteristics in the noninduced and IL-2RA induction therapy groups; the thymoglobulin induction group included significantly higher risk patients. The acute rejection rates were significantly lower in the IL-2RA and thymoglobulin groups when compared with the no induction therapy group (28% vs 15% vs 41%, respectively; P = .001), which was confirmed with multivariate analysis. The 3-year graft loss rates (no induction 21% vs IL2-RA induction 19% vs thymoglobulin induction 25%; P > .50) and creatinine concentrations (no induction 1.8 +/- 0.7, IL-2RA induction 2.0 +/- 1.0, and thymoglobulin induction 1.9 +/- 1.2; P = .47) were similar between all groups. CONCLUSION The use of induction therapy significantly reduces the incidence of acute rejection. The use of thymoglobulin induction equalizes 3-year graft survival rates in high-risk patients to those seen in low-risk patients receiving either no induction or IL-2RA induction.

Significant racial differences in the key factors associated with early graft loss in kidney transplant recipients.

Background: There is continued and significant debate regarding the salient etiologies associated with graft loss and racial disparities in kidney transplant recipients. Methods: This was a longitudinal cohort study of all adult kidney transplant recipients, comparing patients with early graft loss (<5 years) to those with graft longevity (surviving graft with at least 5 years of follow-up) across racial cohorts [African-American (AA) and non-AA] to discern risk factors. Results: 524 patients were included, 55% AA, 151 with early graft loss (29%) and 373 with graft longevity (71%). Consistent within both races, early graft loss was significantly associated with disability income [adjusted odds ratio (AOR) 2.2, 95% CI 1.1-4.5], Kidney Donor Risk Index (AOR 3.2, 1.4-7.5), rehospitalization (AOR 2.1, 1.0-4.4) and acute rejection (AOR 4.4, 1.7-11.6). Unique risk factors in AAs included Medicare-only insurance (AOR 8.0, 2.3-28) and BK infection (AOR 5.6, 1.3-25). Unique protective factors in AAs included cardiovascular risk factor control: AAs with a mean systolic blood pressure <150 mm Hg had 80% lower risk of early graft loss (AOR 0.2, 0.1-0.7), while low-density lipoprotein <100 mg/dl (AOR 0.4, 0.2-0.8), triglycerides <150 mg/dl (AOR 0.4, 0.2-1.0) and hemoglobin A1C <7% (AOR 0.2, 0.1-0.6) were also protective against early graft loss in AA, but not in non-AA recipients. Conclusions: AA recipients have a number of unique risk factors for early graft loss, suggesting that controlling cardiovascular comorbidities may be an important mechanism to reduce racial disparities in kidney transplantation.

Clinical outcomes associated with the early postoperative use of heparin in pancreas transplantation.

Background Graft thrombosis following pancreas transplantation is the leading non-immunologic cause of graft loss. Routine systemic anticoagulation is controversial because of an increased bleeding risk. Methods This was a retrospective, single-center analysis including all pancreas transplants performed over 9 years evaluating the use of low-dose heparin in the early postoperative period. Clinical outcomes were partial and complete graft thrombosis within 30 days, bleeding events, relaparotomy rates, and 30-day graft and patient survival. Multivariate regression analysis was performed to identify risk factors for early graft loss resulting from thrombosis. Results One hundred fifty-two patients were included, 52 in the heparin group. The overall complete thrombosis rate was 13.1%, 10% in those who received heparin, and 15% in those who did not. Partial thrombosis was higher in the heparin group (10% vs. 3%). Higher relaparotomy rates were seen in the heparin group (29% vs. 22%); however, bleeding events were similar between groups. Graft and patient survival at 30 days were similar between groups; however, there was a trend toward higher graft survival in the heparin group. Heparin showed a trend toward a protective benefit for early graft loss resulting from thrombosis in all multivariate regression models. Conclusion These data suggest low-dose heparin early in the postoperative period may provide a protective benefit in the prevention of early graft loss resulting from thrombosis, without an increased risk of bleeding.

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.

Improving the Perioperative Value of Care for Vulnerable Kidney Transplant Recipients

BACKGROUND The increased use of marginal donors, an aging recipient population, and Diagnosis-Related Group (DRG) cost restraints place significant pressures on kidney transplant centers to maintain financial viability while sustaining high quality outcomes. We engaged in a quality initiative in delayed graft function (DGF) kidney transplant recipients aimed at improving safe and efficient discharge. STUDY DESIGN This was a retrospective analysis of national databases comparing the perioperative outcomes and costs for our transplant center and national benchmark values for kidney recipients undergoing transplantation between October 2008 and March 2012. During this time, we developed and implemented quality initiatives aimed at improving health care value for kidney transplant recipients, and focused efforts particularly in patients who developed DGF. Pediatric patients and multiorgan transplant recipients were excluded. RESULTS There were 583 kidney transplants performed at our institution; these were compared with 37,712 transplants available from national data. Rates of DGF increased at our institution from 6% to 25% but were steady at 27% nationally. The quality initiatives improved hospital length of stay (LOS) in DGF patients from an average of 8 days initially to 4 days at study end, which reduced overall LOS from 3.6 ± 1.5 days to 3.3 ± 0.8 days (p = 0.021); national LOS was consistent at a mean of 10 days; hospital costs decreased by 42% at our institution, while national rates rose by 12%. Our institutional 30-day readmission rates in all patients and those with DGF were significantly lower than national rates across the entire study period (9% vs 15% and 12% vs 18%, respectively). CONCLUSIONS These results demonstrate that health care value can be significantly improved in kidney transplant recipients, particularly in DGF patients, by implementing a multidisciplinary initiative aimed at safely and efficiently discharging patients.