Comparison of a home-based (multi) systemic intervention to promoting Medication AdheRence and Self-management among kidney transplant recipients with care-as-usual: the MARS randomized controlled trial protocol

BACKGROUND: After kidney transplantation non-adherence and inadequate self-management undermine clinical outcomes and quality of life. Both have been demonstrated to be substantial in all age groups. However, interventions promoting adherence and self-management among kidney transplant recipients that have proven to be effective are scarce. In this study we aim to develop and test an intervention to optimize adherence and self-management. In this article we describe the background and design of the trial entitled 'promoting Medication AdheRence and Self-management among kidney transplant recipients' (MARS-trial)'. METHODS/DESIGN: This is a single-center, parallel arm randomized controlled trial. Nonadherent kidney transplant recipients aged 12 years or older are eligible for inclusion. Patients will be randomly assigned to either the experimental or a control group. The control group will receive care-as-usual. The experimental group will receive care-as-usual plus the MARS-intervention. The MARS-intervention is an outreaching intervention, based on the principles of (multi) systemic therapy which means involving the social network. A standardized intervention protocol is used for consistency but we will tailor the behavior change techniques used to the specific needs and determinants

Improving quality of life, emotional states and medical compliance in recipients of kidney transplants

Quality of Life (QOL) amongst transplant patients has become an issue as a means to optimize the use of scarce resources and improve outcome. The relationship between QOL, medical compliance, psychosocial states and QOL is presented as follows: Patient empowerment: Patient empowerment and compliance with medications in patients who experienced late acute rejection, was assessed using the Long-term Medication Behaviour Scale (LTMBS-scale). We demonstrated a relationship between late acute rejection and low confidence in taking medication and items relating to physical and psychological symptoms. Effect of psychotherapeutic program on emotional states after kidney transplantation: Recurring emotional states as recalled by patients during psychotherapy sessions (e.g. loss of QOL) were analysed and used to formulate effective group and individual psychotherapy intervention. The Beck Depression Inventory (BDI) was utilised as a measure of change before, during and after treatment. There was significant improvement in psychological states after therapy contemplated as follows, (i) fear of rejection, (ii) feelings of paradoxical loss (iii) psychological integration of the transplant. Randomised controlled study to determine the efficacy of individual or group psychotherapy amongst kidney transplant patients: Analysis of group and individual psychotherapy in recipients of kidney transplants versus control patients was conducted. Improvement appeared to be more significant in the individual therapy compared to group therapy (p= 0.01). In both the individual and group therapy arm, lowering of scores was progressive and sustained (p=O.OI). However, individual therapy resulted in the lowest BDI scores at the end of treatment period. Coming to terms with the 'imagined past': After a successful transplant, patients may present with feelings of paradoxical loss (e.g. grief or low mood). We propose that paradoxical loss should be considered in terms of an imagined past (loss of life goals which have never been actualised as a result of chronic illness). Feelings of loss present an obstacle to a good QOL after transplantation as low mood may lead to ambivalence and subsequently to non-compliance

Proteomics for rejection diagnosis in renal transplant patients: where are we now?

Rejection is one of the key factors that determine the long-term allograft function and survival in renal transplant patients. Reliable and timely diagnosis is important to treat rejection as early as possible. Allograft biopsies are not suitable for continuous monitoring of rejection. Thus, there is an unmet need for non-invasive methods to diagnose acute and chronic rejection. Proteomics in urine and blood samples has been explored for this purpose in 29 studies conducted since 2003. This review describes the different proteomic approaches and summarizes the results from the studies that examined proteomics for the rejection diagnoses. The potential limitations and open questions in establishing proteomic markers for rejection are discussed, including ongoing trials and future challenges to this topic

Increasing access to integrated ESKD care as part of Universal Health Coverage

The global nephrology community recognizes the need for a cohesive strategy to address the growing problem of end-stage kidney disease (ESKD). In March 2018, the International Society of Nephrology hosted a summit on integrated ESKD care, including 92 individuals from around the globe with diverse expertise and professional backgrounds. The attendees were from 41 countries, including 16 participants from 11 low- and lower-middle–income countries. The purpose was to develop a strategic plan to improve worldwide access to integrated ESKD care, by identifying and prioritizing key activities across 8 themes: (i) estimates of ESKD burden and treatment coverage, (ii) advocacy, (iii) education and training/workforce, (iv) financing/funding models, (v) ethics, (vi) dialysis, (vii) transplantation, and (viii) conservative care. Action plans with prioritized lists of goals, activities, and key deliverables, and an overarching performance framework were developed for each theme. Examples of these key deliverables include improved data availability, integration of core registry measures and analysis to inform development of health care policy; a framework for advocacy; improved and continued stakeholder engagement; improved workforce training; equitable, efficient, and cost-effective funding models; greater understanding and greater application of ethical principles in practice and policy; definition and application of standards for safe and sustainable dialysis treatment and a set of measurable quality parameters; and integration of dialysis, transplantation, and comprehensive conservative care as ESKD treatment options within the context of overall health priorities. Intended users of the action plans include clinicians, patients and their families, scientists, industry partners, government decision makers, and advocacy organizations. Implementation of this integrated and comprehensive plan is intended to improve quality and access to care and thereby reduce serious health-related suffering of adults and children affected by ESKD worldwide

Psychological adjustment to lung transplantation

Lung transplantation (LTx) is an effective treatment for end-stage lung failure. Despite great advances in transplant medicine over the last few decades, LTx does not result in complete recovery of health, as transplant recipients continue to be confronted by various health problems that must be psychologically processed and overcome. Many suffer from frequent emotional distress and psychological disorders that can negatively influence their ability to cope with their new organ, negatively impacting both their adherence to immunosuppressive therapy and health-related quality of life (HRQoL). Therefore, it is both clinically and scientifically relevant to assess the postoperative HRQoL and mental health of LTx recipients to identify those at risk for poor post-transplant outcomes and to improve patients’ symptom experience. This manuscript consists of three studies that review psychological adjustment to lung transplantation in terms of HRQoL and psychosocial outcomes via three different approaches. Study 1 is a systematic review of the literature to compile and interpret the evidence on measures to assess HRQoL and psychological outcomes following LTx, summarizing psychological outcomes in studies published between 1994 and 2013. Of 371 articles, 63 studies were selected for final review. Considerable heterogeneity was found in methodology, operational concepts and applied outcome measures in the existing literature on HRQoL and psychological outcomes after LTx. Nevertheless, eligible studies generally point to significant improvements in both mental health and HRQoL post-transplant. A huge opportunity for future research lies in the development of guidelines to aid in the selection of outcome measures to assess psychological outcomes of lung transplant recipients. The second study investigated the psychosocial outcome trajectories of 40 lung transplant recipients related to psychological distress and HRQoL over their first six months posttransplant. Three distinctive clusters were identified: (1) patients with optimal postoperative trajectories (35%); (2) patients with good postoperative trajectories (42%); and (3) patients with poor postoperative trajectories (23%). The last group tended to be older, to suffer from more severe disease, to have more co-morbid conditions, and to have had a prolonged ICU and/or hospital stay. Disease severity, length of stay, and HRQoL two weeks post-transplant were strong predictors of psychological distress and impaired HRQoL at six months of follow-up. The results underscore the psychosocial needs of patients with poor post-transplant trajectories. The third study qualitatively analyzed patient experiences with transplantation and their adjustment to normal life within the first six months post-transplant. ‘Physical benefits’, ‘fear of rejection’, ‘gratitude towards the donor’, and ‘side effects’ were the most frequently named themes with respect to the transplantation process, new lungs, donor and medication regimen. Most themes remained unchanged over time. While comments about ‘intensive care unit delirium’ and ‘worries regarding donated organ quality’ diminished significantly over time, mentions of ‘restrictions in everyday life’ increased significantly. Gender comparison revealed only marginal differences in the response categories. Improvements in physical function during the early postoperative phase may be limited by the onset of clinical complications, fear of rejection and infections, medication side effects, and restrictions in everyday life. Generally, studies on HRQoL and psychological outcomes after lung transplantation have been limited by lost to follow-up, cross-sectional designs, small sample sizes and, great variability in the use of validated and non-validated outcome measures, such that comparisons between different studies are difficult. One area of future research is the development of consensus guidelines to aid in the selection of outcome measures to assess HRQoL and psychological outcomes among LTx patients. In addition, longitudinal studies, including pre- vs. post-transplant assessment with adequately-sized samples are needed to further investigate outcome profiles and identify additional outcome predictors in these patients

Adipose-derived stem/stromal cells in kidney transplantation: Status quo and future perspectives

Kidney transplantation (KT) is the gold standard treatment of end-stage renal disease. Despite progressive advances in organ preservation, surgical technique, intensive care, and immunosuppression, long-term allograft survival has not significantly improved. Among the many peri-operative complications that can jeopardize transplant outcomes, ischemia-reperfusion injury (IRI) deserves special consideration as it is associated with delayed graft function, acute rejection, and premature transplant loss. Over the years, several strategies have been proposed to mitigate the impact of IRI and favor tolerance, with rather disappointing results. There is mounting evidence that adipose stem/stromal cells (ASCs) possess specific characteristics that could help prevent, reduce, or reverse IRI. Immunomodulating and tolerogenic properties have also been suggested, thus leading to the development of ASC-based prophylactic and therapeutic strategies in pre-clinical and clinical models of renal IRI and allograft rejection. ASCs are copious, easy to harvest, and readily expandable in culture. Furthermore, ASCs can secrete extracellular vesicles (EV) which may act as powerful mediators of tissue repair and tolerance. In the present review, we discuss the current knowledge on the mechanisms of action and therapeutic opportunities offered by ASCs and ASC-derived EVs in the KT setting. Most relevant pre-clinical and clinical studies as well as actual limitations and future perspective are highlighted

Neuropsychological functioning post-renal transplantation: A prospective comparison of a steroid avoidance and a steroid maintenance protocol in relation to chronic prednisone therapy

Thirty-nine participants, 17 in a chronic steroid group (CS) and 22 in a steroid avoidance group (SA) were compared with regard to their cognitive performance. It was predicted that participants in the SA group would outperform those in the CS group on the domains of declarative memory and complex attention. For participants in the CS group, age and prednisone duration but not dose were predicted to significantly contribute to the score on the declarative memory composite score. Group-wise comparisons were not significant for the domains of declarative memory, complex attention, or processing speed. The CS group outperformed the SA group on the domain of simple attention. Regression analysis, for the CS group, indicated that duration of dialysis prior to transplant accounted for a significant portion of the variance in the declarative memory composite score. After controlling for months since transplant, prednisone dose also accounted for approximately 26% of the variance in the declarative memory score. Patients maintained on 5 mg of prednisone performed relatively worse than those maintained on 2.5 mg with regard to declarative memory. The clinical and theoretical significance of the findings relative to recent literature is discussed

Mathematical framework for human SLE Nephritis: disease dynamics and urine biomarkers

<p>Abstract</p> <p>Background</p> <p>Although the prognosis for Lupus Nephritis (LN) has dramatically improved with aggressive immunosuppressive therapies, these drugs carry significant side effects. To improve the effectiveness of these drugs, biomarkers of renal flare cycle could be used to detect the onset, severity, and responsiveness of kidney relapses, and to modify therapy accordingly. However, LN is a complex disease and individual biomarkers have so far not been sufficient to accurately describe disease activity. It has been postulated that biomarkers would be more informative if integrated into a pathogenic-based model of LN.</p> <p>Results</p> <p>This work is a first attempt to integrate human LN biomarkers data into a model of kidney inflammation. Our approach is based on a system of differential equations that capture, in a simplified way, the complexity of interactions underlying disease activity. Using this model, we have been able to fit clinical urine biomarkers data from individual patients and estimate patient-specific parameters to reproduce disease dynamics, and to better understand disease mechanisms. Furthermore, our simulations suggest that the model can be used to evaluate therapeutic strategies for individual patients, or a group of patients that share similar data patterns.</p> <p>Conclusions</p> <p>We show that effective combination of clinical data and physiologically based mathematical modeling may provide a basis for more comprehensive modeling and improved clinical care for LN patients.</p

Anxiety, depression, and perceived barriers to adherence among parents of pediatric transplant patients

Before being listed for an organ transplant, pediatric patients and families undergo a psychosocial pre-transplant evaluation to determine familial strengths and risk factors that may impact the success of transplant. Adherence is considered to be one of the primary factors in the survival of the transplanted organ and existing research has suggested a link between parental functioning and post-transplant adherence. To better understand the relationship between parental mental health and perceived barriers to adherence, this study examined whether parental symptoms of anxiety and depression significantly predicted parent and patient perceived barriers to adherence in the pre-transplant phase (n=65 parents and n=55 patients). Results of linear regression analyses indicated parental depression significantly predicted parent perceived barriers to adherence. This study underscored the importance of assessing parental depression in the pre-transplant evaluation and suggested that facilitating interventions to support adherence and patient and family functioning was important throughout the transplant proces