Nonadherence to immunosuppressive therapy after renal transplantation is associated with poor graft outcomes. We aimed to evaluate whether the use of the Adhere4U mobile medication manager application could improve adherence among renal transplant recipients ≥1 year posttransplantation. Adhere4U can provide medication reminders, monitor medication use, and provide information on immunosuppressants. We conducted a prospective randomized controlled study to compare the rate of nonadherence to index immunosuppressant (tacrolimus or cyclosporine) in a group using the Adhere4U app (mobile group) and in another group receiving conventional care (control group). The primary outcome was the nonadherence rate, which was evaluated using an electronic medication event monitoring system during the 6-month intervention period. Our secondary outcome included self-reported adherence using the Basel Assessment of Adherence to Immunosuppressive Medication Scale (BAASIS) and the visual analog scale (VAS) based on a 4-week recall on days 28, 90, and 180. Longitudinal data of repeated measures of self-rated adherence were analyzed using generalized estimating equations (GEE) to compare the between-group difference in adherence change over time. Between November 2013 and May 2015, 138 renal transplant recipients were randomly allocated to the control (n = 67) or the mobile group (n = 71). The overall nonadherence rate over the 6-month study period by electronic monitoring was 63.6%, with no between-group difference [mobile group, 65.0% (n = 39/60); control group, 62.1% (n = 36/58); odds ratio 1.14; 95% confidence interval 0.53–2.40; p = 0.89]. Self-rated nonadherence assessed using the BAASIS and VAS at baseline was 53.7% and 51.5%, respectively. Although the self-rated nonadherence by BAASIS of the mobile group was lower than the control group throughout the study period, there was no between-group difference in the change of nonadherence over time (χ2 = 2.82, df = 3, p = 0.42 by logistic GEE). There also was no significant between-group difference in the nonadherence by VAS (χ2 = 1.71, df = 3, p = 0.63 by logistic GEE) over time. The main limitation of this study was the low rate of patient engagement with the app among the mobile group. The rate of app use was 47.6% (31/65) at 28 days, 33.9% (19/56) at 90 days, and 11.5% (6/52) at 180 days. The Adhere4U application did not improve adherence to immunosuppressive therapy. Our evidence is limited by the high rate of attrition. Further studies on strategies to facilitate patient engagement with mobile interventions are warranted.

This study analyzed the association between medication adherence and the intrapatient variability (IPV) of tacrolimus concentrations among kidney transplant recipients through a post hoc analysis of the dataset from a recently conducted randomized controlled trial. Among 138 patients enrolled in the original trial, 92 patients with ≥ 5 months of medication event monitoring system (MEMS) use and ≥ 4 tacrolimus trough values were included in this post hoc analysis. The variability of tacrolimus trough levels was calculated using coefficient variation (CV) and mean absolute deviation. Adherence was assessed using MEMS and self-report via the Basal Assessment of Adherence to Immunosuppressive Medication Scale. There were no statistically significant differences in the CV [median 16.5% [interquartile range 11.6–25.5%] and 16.0% [11.5–23.5%], respectively, P = .602] between the nonadherent (n = 59) and adherent groups (n = 33). There was also no significant correlation between the CV and adherence detected by MEMS (taking adherence, ρ = − 0.067, P = .527; dosing adherence, ρ = − 0.098, P = .352; timing adherence, ρ = − 0.113, P = .284). Similarly, adherence measured by self-report did not significantly affect the IPV (P = .452). In this post hoc analysis, nonadherent behavior, measured through electronic monitoring or self-report, did not affect the IPV.

Background. High intrapatient variability (IPV) of tacrolimus (Tac) is increasingly recognized as a risk factor for poor graft outcomes in kidney transplantation. The timing of onset of its impact on kidney histologic lesions has not been investigated. Methods. We analyzed the adverse effect of Tac IPV using the coefficient of variability from 6 to 12 months posttransplantation on long-term outcomes in a cohort of 671 kidney recipients and on the evolution of chronic histologic lesions in a cohort of 212 recipients for whom paired protocol biopsies at 10 days and 1 year were available. Results. High IPV of Tac (cutoff value of coefficient of variability = median of 20.5%) was associated with an increased risk of graft loss (hazard ratio, 3.28; 95% confidence interval, 1.090–9.849; P = 0.035) in the entire cohort. At 1 year, the high Tac IPV group showed a significantly deteriorated chronicity score (F = 5.912, P = 0.016) compared with the low Tac IPV group in the Histology cohort after controlling for the 10-day scores. In a multivariate analysis, a high IPV of Tac was predictive of the chronicity score (odds ratio, 1.91; 95% confidence interval, 0.215–1.075; P = 0.003) at 1 year posttransplant. Conclusions. These data indicate that high IPV of Tac is associated with early deterioration of chronic histologic lesions as well as poorer long-term outcomes. Large prospective studies of Tac IPV usage as a clinical monitoring tool are needed in the future.

Engineering three-dimensional (3D) implantable tissue constructs is a promising strategy for replacing damaged or diseased tissues and organs with functional replacements. However, the efficient vascularization of new 3D organs is a major scientific and technical challenge since large tissue constructs or organs require a constant blood supply to survive in vivo. Current approaches to solving this problem generally fall into the following three major categories: (a) cell-based, (b) angiogenic factor-based, and (c) scaffold-based. In this review, we summarize state-of-the-art technologies that are used to develop complex, stable, and functional vasculature for engineered 3D tissue constructs and organs; additionally, we have suggested directions for future research.

Background: Immunosuppressive therapies are vital for solid organ transplant (SOT) recipients to ensure graft survival, but long-term use can lead to complications. This study aimed to comprehensively evaluate the complications associated with immunosuppressive agents across different types of major SOTs. Methods: In a retrospective cohort study using a national claims database, we analyzed adult SOT recipients who began immunosuppressive therapy from 2007 to 2018. We identified complications such as infections, acute kidney injury, hypertensive emergencies, chronic kidney disease, hypertension, diabetes, dyslipidemia, and osteoporosis. These outcomes were determined through diagnostic codes, medication usage data, and hospital or emergency department visits. Results: Among 30,997 transplants with three-year follow up, complication rates varied by transplant type. Pancreatic transplant recipients had the lowest complication rate (225.9 per 1000 patient-years), while lung transplant recipients experienced the highest rate (823.9 per 1000 patient-years). Serious infections and chronic kidney disease were most common 2 to 6 months post transplant. Other complications, like acute kidney injury, hypertensive emergencies, hypertension, diabetes, dyslipidemia, and osteoporosis, were predominantly observed in the first month. Opportunistic infections peaked between 7 months and 1 year after transplantation. Conclusions: This study emphasizes the varied complications related to immunosuppressive therapy among different SOT recipients, delineating specific timeframes for each complication and maintenance regimen.