James N. Fleming

Evaluation of Low- Versus High-dose Valganciclovir for Prevention of Cytomegalovirus Disease in High-risk Renal Transplant Recipients.

Background Despite proven efficacy of prolonged cytomegalovirus (CMV) prophylaxis using valganciclovir 900 mg/day, some centers use 450 mg/day due to reported success and cost savings. This multicenter, retrospective study compared the efficacy and safety of 6 months of low-dose versus high-dose valganciclovir prophylaxis in high-risk, donor-positive/recipient-negative, renal transplant recipients (RTR). Methods Two hundred thirty-seven high-risk RTR (low-dose group = valganciclovir 450 mg/day [n = 130]; high-dose group = valganciclovir 900 mg/day [n = s7]) were evaluated for 1-year CMV disease prevalence. Breakthrough CMV, resistant CMV, biopsy-proven acute rejection (BPAR), graft loss, opportunistic infections (OI), new-onset diabetes after transplantation (NODAT), premature valganciclovir discontinuation, renal function and myelosuppression were also assessed. Results Patient demographics and transplant characteristics were comparable. Induction and maintenance immunosuppression were similar, except for more early steroid withdrawal in the high-dose group. Similar proportions of patients developed CMV disease (14.6% vs 24.3%; P = 0.068); however, controlling CMV risk factor differences through multivariate logistic regression revealed significantly lower CMV disease in the low-dose group (P = 0.02; odds ratio, 0.432, 95% confidence interval, 0.211–0.887). Breakthrough and resistant CMV occurred at similar frequencies. There was no difference in renal function or rates of biopsy-proven acute rejection, graft loss, opportunistic infections, or new-onset diabetes after transplantation. The high-dose group had significantly lower mean white blood cell counts at months 5 and 6; however, premature valganciclovir discontinuation rates were similar. Conclusions Low-dose and high-dose valganciclovir regimens provide similar efficacy in preventing CMV disease in high-risk RTR, with a reduced incidence of leukopenia associated with the low-dose regimen and no difference in resistant CMV. Low-dose valganciclovir may provide a significant cost avoidance benefit.

Mobile Health in Solid Organ Transplant: The Time Is Now

Despite being in existence for >40 years, the application of telemedicine has lagged significantly in comparison to its generated interest. Detractors include the immobile design of most historic telemedicine interventions and the relative lack of smartphones among the general populace. Recently, the exponential increase in smartphone ownership and familiarity have provided the potential for the development of mobile health (mHealth) interventions that can be mirrored realistically in clinical applications. Existing studies have demonstrated some potential clinical benefits of mHealth in the various phases of solid organ transplantation (SOT). Furthermore, studies in nontransplant chronic diseases may be used to guide future studies in SOT. Nevertheless, substantially more must be accomplished before mHealth becomes mainstream. Further evidence of clinical benefits and a critical need for cost‐effectiveness analysis must prove its utility to patients, clinicians, hospitals, insurers, and the federal government. The SOT population is an ideal one in which to demonstrate the benefits of mHealth. In this review, the current evidence and status of mHealth in SOT is discussed, and a general path forward is presented that will allow buy‐in from the health care community, insurers, and the federal government to move mHealth from research to standard care.

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 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

The Impact of Health Care Appointment Non-Adherence on Graft Outcomes in Kidney Transplantation

18,091 [IQR,

Racial comparisons of everolimus pharmacokinetics and pharmacodynamics in adult kidney transplant recipients.

3023-

Tacrolimus Trough Concentration Variability and Disparities in African American Kidney Transplantation

56,268] versus