Beje Thomas

Mobile Health Medication Adherence and Blood Pressure Control in Renal Transplant Recipients: A Proof-of-Concept Randomized Controlled Trial

Background Mobile phone based programs for kidney transplant recipients are promising tools for improving long-term graft outcomes and better managing comorbidities (eg, hypertension, diabetes). These tools provide an easy to use self-management framework allowing optimal medication adherence that is guided by the patients’ physiological data. This technology is also relatively inexpensive, has an intuitive interface, and provides the capability for real-time personalized feedback to help motivate patient self-efficacy. Automated summary reports of patients’ adherence and blood pressure can easily be uploaded to providers’ networks helping reduce clinical inertia by reducing regimen alteration time. Objective The aim of this study was to assess the feasibility, acceptability, and preliminary outcomes of a prototype mobile health (mHealth) medication and blood pressure (BP) self-management system for kidney transplant patients with uncontrolled hypertension. Methods A smartphone enabled medication adherence and BP self-management system was developed using a patient and provider centered design. The development framework utilized self-determination theory with iterative stages that were guided and refined based on patient/provider feedback. A 3-month proof-of-concept randomized controlled trial was conducted in 20 hypertensive kidney transplant patients identified as non-adherent to their current medication regimen based on a month long screening using an electronic medication tray. Participants randomized to the mHealth intervention had the reminder functions of their electronic medication tray enabled and received a bluetooth capable BP monitor and a smartphone that received and transmitted encrypted physiological data and delivered reminders to measure BP using text messaging. Controls received standard of care and their adherence continued to be monitored with the medication tray reminders turned off. Providers received weekly summary reports of patient medication adherence and BP readings. Results Participation and retention rates were 41/55 (75%) and 31/34 (91%), respectively. The prototype system appears to be safe, highly acceptable, and useful to patients and providers. Compared to the standard care control group (SC), the mHealth intervention group exhibited significant improvements in medication adherence and significant reductions in clinic-measured systolic blood pressures across the monthly evaluations. Physicians made more anti-hypertensive medication adjustments in the mHealth group versus the standard care group (7 adjustments in 5 patients versus 3 adjustments in 3 patients) during the 3-month trial based on the information provided in the weekly reports. Conclusions These data support the acceptability and feasibility of the prototype mHealth system. Further trials with larger sample sizes and additional biomarkers (eg, whole blood medication levels) are needed to examine efficacy and effectiveness of the system for improving medication adherence and blood pressure control after kidney transplantation over longer time periods. Trial Registration Clinicaltrials.gov NCT01859273; http://clinicaltrials.gov/ct2/show/NCT01859273 (Archived by WebCite at http://www.webcitation.org/6IqfCa3A3).

Takotsubo cardiomyopathy in two men receiving bevacizumab for metastatic cancer

Bevacizumab is a monoclonal antibody that inhibits vascular endothelial growth factor (VEGF). It is a novel chemotherapeutic agent currently approved as part of combination chemotherapy for metastatic colorectal cancer, non-small cell lung cancer, and breast cancer (Hurwitz et al 2004; Sandler et al 2006; Traina et al 2007). Arterial thrombosis, including cerebral infarction, transient ischemic attacks, myocardial infarction, and angina are common, occurring in 4.4% of patients whose regimen includes bevacizumab (versus 1.9% on regimen without bevacizumab) (Genetech, Inc. 2008). This series will review two cases of patients exposed to bevacizumab who subsequently developed ST elevations on electrocardiogram (ECG) and elevated cardiac biomarkers. Both patients underwent cardiac catheterization, which demonstrated apical ballooning and akinesis in a distribution discordant with the observed (noncritical) atherosclerotic lesions. Both patients had recovery of left ventricular function within 30 days. The clinical presentation, including ECGs and findings on catheterization as well as the rapid recovery of ventricular function, is consistent with the diagnosis of takotsubo cardiomyopathy. Takotsubo cardiomyopathy was first described in 1991, but the pathophysiology and exact mechanism of injury remain largely unknown. These two cases are notable for their occurrence in men and the association with treatment of metastatic cancer including bevacizumab.

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).

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.

Hypertension after Kidney Transplantation: A Pathophysiologic Approach

Post-transplant hypertension is associated with decreased graft and patient survival and cardiovascular morbidity. Unfortunately, post-transplant hypertension is often poorly controlled. Important risk factors include immunosuppressive medications, complications of the transplant surgery, delayed graft function, rejection, and donor and recipient risk factors. The effects of immunosuppressive medications are multifactorial including increased vascular and sympathetic tone and salt and fluid retention. The immunosuppressive agents most commonly associated with hypertension are glucocorticoids and calcineurin inhibitors. Drug therapy for hypertension should be based on the comorbidities and pathophysiology. Evidence-based approaches to defining and treating hypertension in renal transplant recipients are predominantly extrapolated from large-scale studies performed in the general population. Thus, there continues to be a need for larger studies examining the pathophysiology, diagnosis and treatment of hypertension in renal transplant recipients.

Critical analysis of valganciclovir dosing and renal function on the development of cytomegalovirus infection in kidney transplantation.

Cytomegalovirus (CMV) infection is one of the most common and important opportunistic infections following kidney transplantation. It causes significant morbidity and mortality. Valganciclovir (VGCV) is the drug of choice for prophylaxis to prevent CMV infection.

Evaluation of the Upper Esophageal Sphincter (UES) Using Simultaneous High-Resolution Endoluminal Sonography (HRES) and Manometry

The aim of this study was to characterize the motion, morphology, and pressure of the upper esophageal sphincter (UES). The UES and its surrounding structures were evaluated in seven normal subjects and four human cadavers, using simultaneous high-resolution endoluminal sonography and manometry. The UES musculature on ultrasound is a C-shaped structure with an angle of 107 ± 19°. The mean peak resting UES pressure was 74 mm Hg, with a total cross-sectional area (CSA) of 0.87 ± 0.33 cm2. During swallowing, the UES moved in an orad direction. Localizing the UES sonographically, the peak UES pressure in the cadavers was 19.7 ± 10.0 mm Hg. The UES has a greater muscular CSA and resting pressure than the upper esophageal body. In the cadaver studies, the UES was imaged in conjunction with a significant increase in pressure, indicating that the pressure is due to passive mechanical conformational changes.

BK Virus in the Kidney Transplant Patient

Abstract:BK virus, a member of the polyomavirus family, is a well-recognized cause of irreversible graft failure after kidney transplantation. Awareness of the relationship between BK infection and immunosuppression along with better understanding of its pathogenesis has contributed to increasing rates of its diagnosis. Current therapies are aimed at early diagnosis, limiting inflammation caused by the virus and elimination of the virus through different strategies. The epidemiology, pathogenesis and the different modalities of therapy available are discussed in this review along with the approach to retransplantation in the setting of graft failure from BK infection.

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.

Volume (3-dimensional) space-time reconstruction of esophageal peristaltic contraction by using simultaneous US and manometry

BACKGROUND Conventional 3-dimensional endoluminal US was modified to evaluate peristaltic contractions in the esophagus. METHODS Two-dimensional US images and simultaneous intraluminal pressures were acquired during peristaltic contractions by locating the transducer at fixed positions in the esophagus in 6 normal volunteers during swallowing. Three-dimensional images were reconstructed by using a computer-based 3-dimensional algorithm with time as the x axis. RESULTS The peristaltic contraction sequence was viewed as a 3-dimensional US image. The geometric configuration of the esophagus, the muscle thickness, and corresponding pressures were evaluated. The 3-dimensional images demonstrate 4 phases of the peristaltic contraction sequence. CONCLUSIONS Three-dimensional time-resolved reconstruction of endoluminal US images of the esophagus and simultaneous recording of manometric data allow visualization of geometric changes and correlation with pressure changes during peristaltic contraction. Four phases of the peristaltic contraction sequence are demonstrated clearly on the 3-dimensional space-time images.