SSRI/SNRI Therapy is Associated With a Higher Risk of Gastrointestinal Bleeding in LVAD Patients.

BACKGROUND: Gastrointestinal bleeding (GIB) is common in left ventricular assist device (LVAD) patients. Serotonin release from platelets promotes platelet aggregation, and selective serotonin reuptake inhibitor/serotonin-norepinephrine reuptake inhibitor (SSRI/SNRI) therapy inhibits the transporter responsible for re-uptake. METHODS: We reviewed the records of LVAD (HeartMateII™, Abbott Medical, Lake Bluff, IL, USA and Heartware™, Medtronic, Minneapolis, MN, USA) patients at the Medical University of South Carolina and Johns Hopkins Hospital between January 2009 and January 2016. After exclusions, 248 patients were included for analysis. After univariate analysis, logistic regression multivariate analysis was performed to adjust for any demographic, cardiovascular, and laboratory data variables found to be associated with GI bleeding post-LVAD. RESULTS: Gastrointestinal bleeding occurred in 85 patients (35%) with 55% of GIBs due to arteriovenous malformations (AVMs). Of the total cohort, 105 patients received an SSRI or SNRI during LVAD support. Forty-four (44) SSRI/SNRI (41.9%) and 41 non-SSRI/SNRI (28.7%) patients had a GIB (RR 1.46, p = 0.03). Twenty-six (26) (24.8%) of the SSRI/SNRI patients had a GIB due to AVMs versus 21 (14.7%) of the non-SSRI/SNRI patients (RR 1.69, p = 0.05). In fully-adjusted multivariate regression analysis, SSRI/SNRI therapy was independently associated with GIB (OR 1.78, p = 0.045). For GIB, the number needed to harm (NNH) was 7.6. CONCLUSION: In conclusion, SSRI/SNRI therapy is independently associated with an increased risk of GIB in LVAD patients.

Effect of Angiotensin II Inhibitors on Gastrointestinal Bleeding in Patients With Left Ventricular Assist Devices.

BACKGROUND: Angiotensin II receptor activation may result in angiogenesis, and ultimately arteriovenous malformations (AVM), through transforming growth factor (TGF)-ß and angiopoietin-2 pathway activation. OBJECTIVES: The goal of this study was to determine whether angiotensin-converting enzyme (ACE) inhibitors or angiotensin receptor blockers (ARB) were associated with lower risk of major gastrointestinal bleeds (GIB) and AVM-related GIBs in continuous-flow left ventricular assist device (CF-LVAD) patients. METHODS: The authors reviewed HeartMate II CF-LVAD recipients between January 2009 and July 2016. Major GIBs were endoscopically confirmed requiring ≥2 U of packed red blood cells or resulting in death. ACE inhibitor/ARB dose was abstracted from medical records. ACE inhibitor/ARB exposure status was landmarked at 30 days post-operatively to avoid immortal time bias. Fine and Gray hazard models assessed the impact of ACE inhibitor/ARB therapy on major GIB and AVM-related GIB, whereas standard Cox regression assessed the impact on mortality, adjusting for baseline variables. RESULTS: One-hundred and eleven patients were included with a mean 2.1 ± 1.4 years follow-up. Patients who received an ACE inhibitor/ARB within 30 days post-operatively had a 57% reduction in the risk of major GIB (adjusted hazard ratio [aHR]: 0.43; 95% confidence interval [CI]: 0.19 to 0.97; p = 0.042) and a 63% reduction in the risk of AVM-related GIB (aHR: 0.37; 95% CI: 0.16 to 0.84; p = 0.017). When the mean daily post-operative lisinopril-equivalent ACE inhibitor/ARB dose was >5 mg, the risk of major GIB decreased in a dose-threshold manner (aHR: 0.28; 95% CI: 0.09 to 0.85; p = 0.025). CONCLUSIONS: ACE inhibitor/ARB therapy is associated with a protective effect of developing GIBs in CF-LVAD patients, with a dose threshold of >5 mg of daily lisinopril equivalence, possibly due to prevention of AVM formation.

Evaluation of anticoagulation and nonsurgical major bleeding in recipients of continuous-flow left ventricular assist devices.

Continuous-flow left ventricular assist device (LVAD) placement has become a standard of care in advanced heart failure treatment. Bleeding is the most frequently reported adverse event after LVAD implantation and may be increased by antithrombotic agents used for prevention of pump thrombosis. This retrospective cohort included 85 adult patients implanted with a Heartmate II LVAD. Major bleeding was defined as occurring >7 days after implant and included intracranial hemorrhage, events requiring 2 units of packed red blood cells within a 24-h period, and death from bleeding. Primary outcome was intensity of anticoagulation between patients with or without at least one incidence of nonsurgical major bleeding. Major bleeding occurred in 35 (41%) patients with 0.48 events per patient year and a median (IQR) time to first bleed of 134.5 (39.3, 368.5) days. The median (IQR) INR at time of bleed was 1.7 (1.4, 2.5). Median INR during follow-up did not differ between groups and patients with major bleeding were not more likely to have a supra-therapeutic INR. Patients who bled were more likely to have received LVAD for destination therapy, to have lower weight, worse renal function, and lower hemoglobin at baseline. Duration of LVAD support and survival were similar between groups with no difference in occurrence of thrombosis. Incidence of nonsurgical major bleeding was not significantly associated with degree of anticoagulation. Certain baseline characteristics may be more important than anticoagulation intensity to identify patients at risk for bleeding after LVAD implant. Modification of anticoagulation alone is not a sufficient management strategy and early intervention may be required to mitigate bleeding impact.

Belatacept in Solid Organ Transplant: Review of Current Literature Across Transplant Types.

Calcineurin inhibitors (CNIs) have been the backbone immunosuppressant for solid organ transplant recipients for decades. Long-term use of CNIs unfortunately is associated with multiple toxicities, with the biggest concern being CNI-induced nephrotoxicity. Belatacept is a novel agent approved for maintenance immunosuppression in renal transplant recipients. In the kidney transplant literature, it has shown promise as being an alternative agent by preserving renal function and having a minimal adverse effect profile. There are emerging studies of its use in other organ groups, particularly liver transplantation, as well as using with other alternative immunosuppressive strategies. The purpose of this review is to analyze the current literature of belatacept use in solid organ transplantation and discuss its use in current practice.

Morbid obesity and functional status as predictors of surgical complication after renal transplantation.

BACKGROUND: This study evaluated the impact of body mass index (BMI) and patient functional status on the risk for surgical complications after kidney transplant. METHODS: This retrospective cohort study of adult kidney transplant recipients grouped patients by baseline Karnofsky status (low function ≤ 70%) and further stratified by morbid obesity (BMI ≥ 35 kg/m2) to assess surgical complication risk. RESULTS: 736 patients were included with surgical complications occurring in 25%. Logistic regression analysis with interaction terms demonstrated that morbid obesity and low functional status conditionally impact risk with an OR of 2.8 [95% CI (1.1-7.3)]. Within the functional status cohort, BMI ≥35 kg/m2 was associated with increased risk of surgical complication, superficial wound infection, and DGF. Independent predictors for surgical complications included diabetes and morbid obesity with low functional status. There was no significant difference in graft loss or death across the cohorts. CONCLUSIONS: While neither morbid obesity nor poor functional status alone predicts increased complications, the combined presence is associated with significant increase in risk for surgical complications after renal transplantation.

Effectiveness of an Evidence-Based Induction Therapy Protocol Revision in Adult Kidney Transplant Recipients.

STUDY OBJECTIVE: Induction immunosuppression significantly improves graft outcomes after kidney transplantation, but protocols vary among transplant centers due to the lack of data identifying an optimal induction agent. The objective of this study was to assess the effectiveness of an evidence-based protocol change in induction therapy in adult kidney transplant recipients. DESIGN: Retrospective cohort study. SETTING: Large tertiary care academic medical center. PATIENTS: A total of 349 patients transplanted between August 2011 and December 2013 were included in the study. A protocol revision in 2012 reserved the use of lymphocyte-depleting induction therapy to a select group of traditionally high-risk patients based on the findings of a previous randomized controlled trial performed at this center. MEASUREMENTS AND MAIN RESULTS: The primary outcome was biopsy-proved acute rejection and graft loss. The use of nondepleting induction therapy increased significantly after the protocol revision, with no significant differences in rejection or infection rates identified between protocols. When comparing graft survival between the protocol cohorts, there was no significant difference. A cost-minimization analysis indicated that the revised protocol was associated with considerable medication cost savings. CONCLUSION: A protocol targeting the use of lymphocyte-depleting induction to a select group of high-risk recipients appears to have equivalent efficacy and safety and is less costly compared with a more traditional induction protocol.

Assessment of Bleeding and Thrombosis Based on Aspirin Responsiveness after Continuous-Flow Left Ventricular Assist Device Placement.

Pump thrombosis (PT) is a severe complication of left ventricular assist device (LVAD) support. This study evaluated PT and bleeding after LVAD placement in patients responsive to a standard aspirin dose of 81 mg using platelet inhibition monitoring compared with initial nonresponders who were then titrated upward to achieve therapeutic response. Patients ≥ 18 years of age with initial placement of HeartMate II LVAD at our institution and at least one VerifyNow Aspirin test performed during initial hospitalization were included. The primary endpoints were bleeding and PT compared between initial aspirin responders and nonresponders. Of 85 patients, 19 (22%) were nonresponsive to initial aspirin therapy. Responders and nonresponders showed similar survival (p = 0.082), freedom from suspected/confirmed PT (p = 0.941), confirmed PT (p = 0.273), bleeding (p = 0.401), and incidence rates in PT and bleeding. Among the initial responders (<500 vs. 500-549 aspirin reaction units), there were no significant differences in survival (p = 0.177), freedom from suspected/confirmed PT (p = 0.542), confirmed PT (p = 0.159), bleeding (p = 0.879), and incidence of PT and bleeding. Platelet function testing may detect resistance to standard aspirin regimens used in LVAD patients. Dose escalation in initially nonresponsive patients to achieve responsiveness may confer a similar PT risk to patients initially responsive to standard aspirin dosing without increased bleeding risk.

Development of a Predictive Model for Drug-Related Problems in Kidney Transplant Recipients.

STUDY OBJECTIVE: Drug-related problems (DRPs) are associated with increased rates of infection, rejection, and graft loss in kidney transplant recipients. This study aimed to develop a model to predict which patients are at highest risk of DRPs to streamline pharmacists' workflow in a chronic kidney transplant clinic. DESIGN: Prospective observational study. SETTING: Chronic kidney transplant clinic at a large, tertiary care, academic hospital. PATIENTS: Two hundred thirty-seven adults seen in the kidney transplant clinic between September 16, 2015, and November 30, 2015, who were at least 90 days posttransplantation at the time of their clinic visit. MEASUREMENTS AND MAIN RESULTS: Prospective data detailing DRPs and a survey assessing baseline characteristics and patient-related outcomes were used to generate a predictive model to identify patients at risk of having six or more DRPs; the cutoff of six DRPs provided a threshold for identifying a subset of high-risk patients on whom the transplant pharmacists could focus their efforts. DRPs were categorized as nonadherence, overdosing or underdosing, duplication of therapy, preventable adverse drug reaction, missing medication, erroneous medication, conflicting provider information, undermonitoring or lack of monitoring, and wrong medication received. In total, 865 unique DRPs were identified, and the most common were erroneous medication, missing medication, and nonadherence, accounting for 38%, 21%, and 16% of the DRPs, respectively. A nine-variable model with a sensitivity of 62.5% and specificity of 66.7% (area under the receiver operating characteristic curve of 0.720) was developed to identify patients at risk of having six or more DRPs. The model included the following variables: age, Medicaid for prescription insurance, current employment status, medication affordability, difficulty or lack of difficulty obtaining medications from the pharmacy, negative impact of medications on quality of life, medication nonadherence, poor rating of current health status, and moderate or poor medication understanding. CONCLUSION: These results demonstrated that a straightforward, 5-minute survey completed by renal transplant recipients prior to their clinic visit may be capable of effectively determining those at risk of having six or more DRPs, potentially allowing use as a screening tool for transplant pharmacists' workflow prioritization. External validation is needed before this tool can be used in the outpatient setting.

Transplanting Sensitized Kidney Transplant Patients With Equivalent Outcomes Utilizing Stringent HLA Crossmatching.

OBJECIVES: Elevated panel reactive antibody levels have been traditionally associated with increased acute rejection rate and decreased long-term graft survival after kidney transplant. In this study, our objective was to determine patient and allograft outcomes in sensitized kidney transplant recipients with advanced HLA antibody detection and stringent protein sequence epitope analyses. MATERIALS AND METHODS: This was a subanalysis of a prospective, risk-stratified randomized controlled trial that compared interleukin 2 receptor antagonist to rabbit antithymocyte globulin induction in 200 kidney transplant recipients, examining outcomes based on panel reactive antibody levels of < 20% (low) versus ≥ 20% (high, sensitized). The study was conducted between February 2009 and July 2011. All patients underwent solid-phase single antigen bead assays to detect HLA antibodies and stringent HLA epitope analyses with protein sequence alignment for virtual crossmatching. Delayed graft function, acute rejection rates, and graft loss were the main outcomes measured. RESULTS: Both the low (134 patients) and high (66 patients) panel reactive antibody level cohorts had equivalent induction and maintenance immunosuppression. Patients in the high-level group were more likely to be female (P < .001), African American (P < .001), and received a kidney from a deceased donor (P = .004). Acute rejection rates were similar between the low (rate of 8%) and high (rate of 9%) panel reactive antibody groups (P = .783). Delayed graft function, borderline rejection, graft loss, and death were not different between groups. Multivariate analyses demonstrated delayed graft function to be the strongest predictor of acute rejection (odds ratio, 5.7; P = .005); panel reactive antibody level, as a continuous variable, had no significant correlation with acute rejection (C statistic, 0.48; P = .771). CONCLUSIONS: Appropriate biologic matching with single antigen bead assays and stringent epitope analyses provided excellent outcomes in sensitized patients regardless of the induction therapy choice.

Predicting and preventing readmissions in kidney transplant recipients.

A lack of research exploring post-transplant process optimization to reduce readmissions and increasing readmission rates at our center from 2009 to 2013 led to this study, aimed at assessing the effect of patient and process factors on 30-d readmission rates after kidney transplantation. This was a retrospective case-control study in adult kidney transplant recipients. Univariate and multivariate analyses were utilized to assess patient and process determinants of 30-d readmissions. 384 patients were included; 30-d readmissions were significantly associated with graft loss and death (p = 0.001). Diabetes (p = 0.049), pharmacist identification of poor understanding or adherence, and prolonged time on hemodialysis prior to transplant were associated with an increased risk of 30-d readmissions. After controlling for risk factors, readmission rates were only independently predicted by pharmacist identification of patient lack of understanding or adherence regarding post-transplant medications and dialysis exposure for more than three yr (OR 2.3, 95% CI 1.10-4.71, p = 0.026 and OR 2.1, 95% CI 1.22, 3.70, respectively), both of which were significantly modified by history of diabetes. Thirty-d readmissions are attributable to both patient and process-level factors. These data suggest that a lack of post-transplant medication knowledge in high-risk patients drives early hospital readmission.

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/m(2), and any infection. Incidence of rejection was higher in the OI group, but rate of graft loss was not statistically different.

Developing an Anti-Xa-Based Anticoagulation Protocol for Patients with Percutaneous Ventricular Assist Devices.

Because of the complexities associated with anticoagulation in temporary percutaneous ventricular assist device (pVAD) recipients, a lack of standardization exists in their management. This retrospective analysis evaluates current anticoagulation practices at a single center with the aim of identifying an optimal anticoagulation strategy and protocol. Patients were divided into two cohorts based on pVAD implanted (CentriMag (Thoratec; Pleasanton, CA) / TandemHeart (CardiacAssist; Pittsburgh, PA) or Impella (Abiomed, Danvers, MA)), with each group individually analyzed for bleeding and thrombotic complications. Patients in the CentriMag/TandemHeart cohort were subdivided based on the anticoagulation monitoring strategy (activated partial thromboplastin time (aPTT) or antifactor Xa unfractionated heparin (anti-Xa) values). In the CentriMag/TandemHeart cohort, there were five patients with anticoagulation titrated based on anti-Xa values; one patient developed a device thrombosis and a major bleed, whereas another patient experienced major bleeding. Eight patients received an Impella pVAD. Seven total major bleeds in three patients and no thrombotic events were detected. Based on distinct differences between the devices, anti-Xa values, and outcomes, two protocols were created to guide anticoagulation adjustments. However, anticoagulation in patients who require pVAD support is complex with constantly evolving anticoagulation goals. The ideal level of anticoagulation should be individually determined using several coagulation laboratory parameters in concert with hemodynamic changes in the patient's clinical status, the device, and the device cannulation.

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.

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 $18,091 [IQR, $3023-$56,268] versus $0 [$0-$15,991]; P<0.01), and overall length of stay (median 5.0 days [IQR, 2.0-14.0] versus 0.0 days [IQR, 0.0-5.5]; P<0.01) after the CSME event. CSME patients were also more likely to experience graft failure (22% versus 10%; P=0.05). CONCLUSIONS: Significant MEs commonly occur in renal transplant recipients and are associated with an increased risk of deleterious clinical outcomes, including subsequent hospital days, costs, and graft loss.

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).

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 diabetes on ethnic disparities seen in kidney transplantation.

Graft failure rates following kidney transplant is disproportionately higher in African American (AA) renal transplant recipients. The aim of our study was to measure the impact of diabetes and other known confounding risk factors on this disparity. This was a long-term cohort study of adult kidney transplant recipients between 2000 and 2008 comparing AA transplant recipients to White recipients. 987 patients were included and patients were followed for up to 12 years post-transplant. Univariate analysis demonstrated AA recipients were more likely to have diabetes (35% vs 23%, P<.001), hypertension (97% vs 94%, P=.029), human leukocyte antigen mismatches (4 vs 3, P<.001), and receiving dialysis for a longer period prior to transplant (3.9 vs 2.0 yrs, P<.001). AA patients were also less likely to receive a living donor transplant (7% vs 31%, P<.001). Multivariable modeling established both AA ethnicity (HR 1.32 [95% CI 1.04-1.68]) and pre-existing diabetes (1.58 [95% CI 1.25-2.00]) as important predictors of graft failure. Diabetes was a significant modifier on the influence of AA ethnicity as a risk factor for graft loss (19% HR reduction); tight glycemic control, which was less common in AA recipients (35% vs 51%, P=.013), additionally attenuated the ethnic disparities seen in graft loss (28% risk reduction). In the final fully adjusted model, which included sociodemographic, immunologic, and cardiovascular risk factor as variables, the influence of AA ethnicity on graft failure was essentially nullified (HR 1.09 [.81-1.48]). In conclusion, AA ethnicity continues to be an important risk factor for graft loss, which can be significantly attenuated by controlling for pre-existing diabetes, glycemic control, and other transplant and cardiovascular variables.

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.

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 use of activated recombinant factor VII in a patient with fulminant hepatic failure requiring placement of an intracranial pressure monitor.

OBJECTIVE: To evaluate the use of recombinant activated factor VII (rFVIIa) in a patient with fulminant hepatic failure (FHF) requiring placement of an intracranial pressure monitor. CASE SUMMARY: A 21-year-old female with no significant medical history was admitted to an outside hospital with elevated results of liver function tests. Subsequently, the patient was diagnosed with autoimmune hepatitis. Systemic corticosteroids were started, but her condition continued to decompensate. She was transferred to our tertiary care facility 5 days after initial presentation. The liver function test results remained elevated (eg, total bilirubin 27 mg/dL), and international normalized ratio (INR) was 3.57. The medical team decided to place an intracranial pressure monitor, with the neurosurgery team's goal being an INR less than 1.5 before placement of the monitor. After multiple units of fresh frozen plasma (FFP) failed to lower the patient's INR, rFVIIa 40 µg/kg was administered. A rapid decrease of the INR allowed the neurosurgery team to perform the procedure without complications. DISCUSSION: The use of rFVIIa allowed for decrease of this patient's INR after multiple units of FFP had failed to correct it. The utility of INR as a marker of coagulopathy in fulminant hepatic failure has been debated, but it is currently used as the standard laboratory test prior to invasive procedures, as in the case presented here. CONCLUSIONS: The use of rFVIIa for rapid decrease of INR in a patient with FHF prior to an invasive procedure was safe and efficacious. When considering the use of rFVIIa, clinicians should be aware of the risk of thrombosis. In our experience, and in the limited literature on the matter, rFVIIa 40 µg/kg appears to be an appropriate dose for decrease of the INR. Further studies are needed to confirm this finding.