A randomized crossover study comparing different tacrolimus formulations to reduce intrapatient variability in tacrolimus exposure in kidney transplant recipients

A high intrapatient variability (IPV) in tacrolimus exposure is a risk factor for poor long-term outcomes after kidney transplantation. The main objective of this trial was to investigate whether tacrolimus IPV decreases after switching patients from immediate-release (IR)-tacrolimus to either extended-release (ER)-tacrolimus or LifeCyclePharma (LCP)-tacrolimus. In this randomized, prospective, open-label, cross-over trial, adult kidney transplant recipients on a stable immunosuppressive regimen, including IR-tacrolimus, were randomized for conversion to ER-tacrolimus or LCP-tacrolimus, and for the order in which IR-tacrolimus and the once-daily formulations were taken. Patients were followed 6 months for each formulation, with monthly tacrolimus predose concentration assessments to calculate the IPV. The IPV was defined as the coefficient of variation (%) of dose corrected predose concentrations. Ninety-two patients were included for analysis of the primary outcome. No significant differences between the IPV of IR-tacrolimus (16.6%) and the combined once-daily formulations (18.3%) were observed (% difference +1.7%, 95% confidence interval [CI] -1.1% to -4.5%, p = 0.24). The IPV of LCP-tacrolimus (20.1%) was not significantly different from the IPV of ER-tacrolimus (16.5%, % difference +3.6%, 95% CI -0.1% to 7.3%, p = 0.06). In conclusion, the IPV did not decrease after switching from IR-tacrolimus to either ER-tacrolimus or LCP-tacrolimus. These results provide no arguments to switch kidney transplant recipients from twice-daily (IR) tacrolimus formulations to once-daily (modified-release) tacrolimus formulations when the aim is to lower the IPV.Personalised Therapeutic

Itching in dialysis patients: impact on health-related quality of life and interactions with sleep problems and psychological symptoms-results from the RENINE/PROMs registry

Background Itching (pruritus) is common in dialysis patients, but little is known about its impact on health-related quality of life (HRQOL), sleep problems and psychological symptoms. This study investigates the impact of itching in dialysis patients by looking into the persistence of itching, the effect of itching on the course of HRQOL and the combined effect of itching with sleep problems and with psychological symptoms on HRQOL. Methods Data were obtained from the RENINE/PROMs registry and included 2978 dialysis patients who completed patient-reported outcome measures between 2018 and 2020. Itching, sleep problems and psychological symptoms were assessed with the Dialysis Symptom Index (DSI) and HRQOL with the 12-item Short Form Health Survey. Effects of itching on HRQOL and interactions with sleep problems and psychological symptoms were investigated cross-sectionally and longitudinally using linear regression and linear mixed models. Results Half of the patients experienced itching and in 70% of them, itching was persistent. Itching was associated with a lower physical and mental HRQOL {-3.35 [95% confidence interval (CI) -4.12 to -2.59) and -3.79 [95% CI -4.56 to -3.03]}. HRQOL remained stable during 2 years and trajectories did not differ between patients with or without itching. Sleep problems (70% versus 52%) and psychological symptoms (36% versus 19%) were more common in patients with itching. These symptoms had an additional negative effect on HRQOL but did not interact with itching. Conclusions The persistence of itching, its impact on HRQOL over time and the additional effect on HRQOL of sleep problems and psychological symptoms emphasize the need for recognition and effective treatment of itching to reduce symptom burden and improve HRQOL.Clinical epidemiolog

Discussing results of patient-reported outcome measures (PROMs) between patients and healthcare professionals in routine dialysis care: a qualitative study

ObjectivesPatient-reported outcome measures (PROMs) provide insight into patients' experienced health and needs, and can improve patient-professional communication. However, little is known about how to discuss PROM results. This study aimed to provide in-depth knowledge of patients' and healthcare professionals' experiences with and perspectives on discussing PROM results as part of routine dialysis care.DesignA qualitative study was performed using an interpretive description approach. Individual semistructured interviews were conducted with 22 patients and healthcare professionals. Interviews focused on general and specific situations (eg, addressing sensitive topics or when no medical treatment is available). Interviews were transcribed verbatim and analysed inductively using thematic analysis.SettingParticipants were purposively sampled from eight dialysis centres across the Netherlands.ParticipantsInterviews were conducted with 10 patients receiving dialysis treatment and 12 healthcare professionals (nephrologists and nurses).ResultsPatients and healthcare professionals provided practical guidance for optimal discussion about PROM results. First, patients and healthcare professionals emphasised that PROM results should always be discussed and indicated how to create a suitable setting, adequately prepare, deal with time constraints and use PROMs as a tool for personalised holistic consultations. Second, patients should actively participate and healthcare professionals should take a guiding role. A trusting patient-professional relationship was considered a prerequisite and patient-professional interaction was described as a collaboration in which both contribute their knowledge, experiences and ideas. Third, follow-up after discussing PROM results was considered important, including evaluations and actions (eg, symptom management) structurally embedded into the multidisciplinary treatment process. These general themes also applied to the specific situations, for example: results should also be discussed when no medical treatment is available. Though, healthcare professionals were expected to take more initiative and a leading role when discussing sensitive topics.ConclusionsThis study provides insight into how to organise and conduct conversations about PROM results and lays the foundation for training healthcare professionals to optimally discuss PROM results in routine nephrology care. Further research is needed to provide guidance on follow-up actions in response to specific PROM results

“What matters to you?”: The relevance of patient priorities in dialysis care for assessment and clinical practice

Background: Dialysis patients are confronted with numerous, complex problems, which make it difficult to identify individual patient's most prominent problems. The objectives of this study were to (1) identify dialysis patients' most prominent problems from a patient perspective and (2) to calculate disease-specific norms for questionnaires measuring these problems. Methods: One hundred seventy-five patients treated with hemodialysis or peritoneal dialysis completed a priority list on several domains of functioning (e.g., physical health, mental health, social functioning, and daily activities) and a set of matching questionnaires assessing patient functioning on these domains. Patient priorities were assessed by calculating the importance ranking of each domain on the priority list. Subsequently, disease-specific norm scores were calculated for all questionnaires, both for the overall sample and stratified by patient characteristics. Results: Fatigue was listed as patients' most prominent problem. Priorities differed between male and female patients, younger and older patients, and home and center dialysis patients, which was also reflected in their scores on the corresponding domains of functioning. Therefore, next to general norm scores, we calculated corrections to the general norms to take account of patient characteristics (i.e., sex, age, and dialysis type). Conclusions: Results highlight the importance of having attention for the specific priorities and needs of each individual patient. Adequate disease-specific, norm-based assessment is not only necessary for diagnostic procedures but is an essential element of patient-centered care: It will help to better understand and respect individual patient needs and tailor treatment accordingly.Applied Ergonomics and DesignHR HealthExternenregistrati

Nurse practitioner care improves renal outcome in patients with CKD

Treatment goals for patients with CKD are often unrealized for many reasons, but support by nurse practitioners may improve risk factor levels in these patients. Here, we analyzed renal endpoints of the Multifactorial Approach and Superior Treatment Efficacy in Renal Patients with the Aid of Nurse Practitioners (MASTERPLAN) study after extended follow-up to determine whether strict implementation of current CKD guidelines through the aid of nurse practitioners improves renal outcome. In total, 788 patients with moderate to severe CKD were randomized to receive nurse practitioner support added to physician care (intervention group) or physician care alone (control group). Median follow-up was 5.7 years. Renal outcome was a secondary endpoint of the MASTERPLAN study. We used a composite renal endpoint of death, ESRD, and 50% increase in serum creatinine. Event rates were compared with adjustment for baseline serum creatinine concentration and changes in estimated GFR were determined. During the randomized phase, there were small but significant differences between the groups in BP, proteinuria, LDL cholesterol, and use of aspirin, statins, active vitamin D, and antihypertensive medications, in favor of the intervention group. The intervention reduced the incidence of the composite renal endpoint by 20% (hazard ratio, 0.80; 95% confidence interval, 0.66 to 0.98; P=0.03). In the intervention group, the decrease in estimated GFR was 0.45 ml/min per 1.73 m2 per year less than in the control group (P=0.01). Inconclusion, additionalsupport by nurse practitioners attenuatedthe declineof kidney function and improved renal outcome in patients with CKD. Copyrigh