How to increase kidney transplant activity throughout Europe : an advocacy review by the European Kidney Health Alliance

Kidney transplantation offers better outcomes and quality of life at lower societal costs compared with other options of renal replacement therapy. In this review of the European Kidney Health Alliance, the current status of kidney transplantation throughout Europe and suggestions for improvement of transplantation rates are reported. Although the European Union (EU) has made considerable efforts in the previous decade to stimulate transplantation activity, the discrepancies among European countries suggest that there is still room for improvement. The EU efforts have partially been neutralized by external factors such as economic crises or legal issues, especially the illicit manipulation of waiting lists. Hence, growth in the application of transplantation throughout Europe virtually remained unchanged over the last few years. Continued efforts are warranted to further stimulate transplantation rates, along with the current registration and data analysis efforts supported by the EU in the Effect of Differing Kidney Disease Treatment Modalities and Organ Donation and Transplantation Practices on Health Expenditure and Patient Outcomes project. Future actions should concentrate on organization, harmonization and improvement of the legal consent framework, population education and financial stimuli

Patient-reported factors influencing the choice of their kidney replacement treatment modality

International audienceBACKGROUND: Access to various kidney replacement therapy (KRT) modalities for patients with end-stage kidney disease differs substantially within Europe. METHODS: European adults on KRT filled out an online or paper-based survey about factors influencing and experiences with modality choice (e.g. information provision, decision-making and reasons for choice) between November 2017 and January 2019. We compared countries with low, middle and high gross domestic product (GDP). RESULTS: In total, 7820 patients [mean age 59 years, 56% male, 63% on centre haemodialysis (CHD)] from 38 countries participated. Twenty-five percent had received no information on the different modalities, and only 23% received information >12 months before KRT initiation. Patients were not informed about home haemodialysis (HHD) (42%) and comprehensive conservative management (33%). Besides nephrologists, nurses more frequently provided information in high-GDP countries, whereas physicians other than nephrologists did so in low-GDP countries. Patients from low-GDP countries reported later information provision, less information about other modalities than CHD and lower satisfaction with information. The majority of modality decisions were made involving both patient and nephrologist. Patients reported subjective (e.g. quality of life and fears) and objective reasons (e.g. costs and availability of treatments) for modality choice. Patients had good experiences with all modalities, but experiences were better for HHD and kidney transplantation and in middle- and high-GDP countries. CONCLUSION: Our results suggest European differences in patient-reported factors influencing KRT modality choice, possibly caused by disparities in availability of KRT modalities, different healthcare systems and varying patient preferences. Availability of home dialysis and kidney transplantation should be optimized

Work status and work ability of patients receiving kidney replacement therapy: results from a European survey

International audienceBACKGROUND: Employment is important for the quality of life and financial security of patients of working age receiving kidney replacement therapy (KRT). We aimed to examine self-reported work status and general, physical and mental work ability and to determine associations between demographic, disease-related, work-related and macroeconomic factors and employment. . METHODS: Europeans from 37 countries, ages 19-65 years, treated with dialysis or kidney transplantation, filled out the web-based or paper-based cross-sectional EDITH kidney patient survey between November 2017 and January 2019. We performed descriptive analyses and multivariable generalized logistic mixed models. RESULTS: Of the 3544 patients, 36.5% were employed and working [25.8% of dialysis patients, 53.9% of kidney transplant recipients (KTRs)]. The mean general work ability was 5.5 out of 10 (dialysis: 4.8, KTRs: 6.5). Non-working patients (all: 4.1, dialysis: 3.9, KTRs: 4.7) scored lower than working patients (all: 7.7, dialysis 7.3, KTRs: 8.0). Working dialysis patients scored lower on physical and mental work ability (7.1 and 8.1) than working KTRs (8.0 and 8.4; P < 0.001). Impaired physical work ability (42.7%) was more prevalent than impaired mental work ability (26.7%). Male sex, age 40-49 years, higher education, home dialysis or kidney transplantation as current treatment, treatment history including kidney transplantation, absence of diabetes mellitus, better general work ability and higher country gross domestic product were positively associated with employment (P < 0.05). CONCLUSIONS: Low employment rates and impaired work ability were prevalent among European patients receiving KRT. Demographic, disease-related, work-related and macro-economic factors were associated with employment

Interfractional renal and diaphragmatic position variation during radiotherapy in children and adults: is there a difference?

<p><b>Background:</b> Pediatric safety margins are generally based on data from adult studies; however, adult-based margins might be too large for children. The aim of this study was to quantify and compare interfractional organ position variation in children and adults.</p> <p><b>Material and methods:</b> For 35 children and 35 adults treated with thoracic/abdominal irradiation, 850 (range 5–30 per patient) retrospectively collected cone beam CT images were registered to the reference CT that was used for radiation treatment planning purposes. Renal position variation was assessed in three orthogonal directions and summarized as 3D vector lengths. Diaphragmatic position variation was assessed in the cranio-caudal (CC) direction only. We calculated means and SDs to estimate group systematic (Σ) and random errors (σ) of organ position variation. Finally, we investigated possible correlations between organ position variation and patients’ height.</p> <p><b>Results:</b> Interfractional organ position variation was different in children and adults. Median 3D right and left kidney vector lengths were significantly smaller in children than in adults (2.8, 2.9 mm vs. 5.6, 5.2 mm, respectively; <i>p</i> < .05). Generally, the pediatric Σ and σ were significantly smaller than in adults (<i>p</i> < .007). Overall and within both subgroups, organ position variation and patients’ height were only negligibly correlated.</p> <p><b>Conclusions:</b> Interfractional renal and diaphragmatic position variation in children is smaller than in adults indicating that pediatric margins should be defined differently from adult margins. Underlying mechanisms and other components of geometrical uncertainties need further investigation to explain differences and to appropriately define pediatric safety margins.</p

Quantification of renal and diaphragmatic interfractional motion in pediatric image-guided radiation therapy:A multicenter study

Background and purpose: To quantify renal and diaphragmatic interfractional motion in order to estimate systematic and random errors, and to investigate the correlation between interfractional motion and patient-specific factors. Material and methods: We used 527 retrospective abdominal-thoracic cone beam CT scans of 39 childhood cancer patients ( Results: Inter-patient organ motion varied widely, with the largest movements in the CC direction. Values of Sigma in LR, CC, and AP directions were 1.1, 3.8, 2.1 mm for the right, and 1.3, 3.0, 1.5 mm for the left kidney, respectively. The sigma in these three directions was 1.1, 3.1, 1.7 mm for the right, and 1.2, 2.9, 2.1 mm for the left kidney, respectively. For the diaphragm we estimated Sigma = 5.2 mm and sigma = 4.0 mm. No correlations were found between organ motion and height. Conclusions: The large inter-patient organ motion variations and the lack of correlation between motion and patient-related factors, suggest that individualized margin approaches might be required. (C) 2015 Elsevier Ireland Ltd. All rights reserved

R-CODOX-M/R-IVAC versus DA-EPOCH-R in patients with newly diagnosed Burkitt lymphoma (HOVON/SAKK): final results of a multicentre, phase 3, open-label, randomised trial.

BACKGROUND Patients with newly diagnosed high-risk Burkitt lymphoma are treated with high-intensity immune-chemotherapy regimens such as R-CODOX-M/R-IVAC or with lower-intensity regimens such as DA-EPOCH-R. The aim of this study was to make a formal comparison between these regimens. METHODS This multicentre, phase 3, open-label, randomised study was done in 26 clinical centres in the Netherlands, Belgium, and Switzerland. Eligible patients were aged 18-75 years with newly diagnosed high-risk Burkitt lymphoma without CNS involvement. Patients were randomly assigned to two cycles of R-CODOX-M/R-IVAC (R-CODOX-M: rituximab 375 mg/m2 on day 1 and 9, cyclophosphamide 800 mg/m2 on day 1, cyclophosphamide 200 mg/m2 on days 2-5, vincristine 1·5 mg/m2 on days 1 and 8, doxorubicin 40 mg/m2 on day 1, and methotrexate 3000 mg/m2 on day 10; R-IVAC: rituximab 375 mg/m2 on days 3 and 7, iphosphamide 1500 mg/m2 on days 1-5, etoposide 60 mg/m2 on days 1-5, and cytarabin 2000 mg/m2 on day 1 and 2) or six cycles of DA-EPOCH-R (dose-adjusted etoposide 50-124 mg/m2 on days 1-4, prednisolone 120 mg/m2 on days 1-5, vincristine 0·4 mg/m2 on days 1-4, dose-adjusted cyclophosphamide 480-1866 mg/m2 on day 5, dose-adjusted doxorubicin 10-24·8 mg/m2 on days 1-4, rituximab 375 mg/m2 on days 1 and 5). Patients older than 65 years received a dose modified R-CODOX-M/R-IVAC. All drugs were intravenous except for prednisolone, which was oral. Patients also received four intrathecal CNS administrations with cytarabin (70 mg) and four with methotrexate (15 mg). Patients were stratified by centre, leukemic disease, and HIV-positivity. The primary endpoint was progression-fee survival. All analyses were done by modified intention-to-treat, excluding randomly assigned patients who were subsequently found to have CNS involvement or diagnosis other than Burkitt lymphoma at study entry. This study is registered with the European Clinical Trial Register, EudraCT2013-004394-27. FINDINGS Due to a slow accrual, the study was closed prematurely on Nov 15, 2021. Between Aug 4, 2014, and Sept 17, 2021, 89 patients were enrolled and randomly assigned to receive R-CODOX-M/R-IVAC (n=46) or DA-EPOCH-R (n=43). Five patients were excluded after random assignment (three in the R-CODOX-M/R-IVAC group [one diagnosis other than Burkitt lymphoma at study entry according to local pathology and two CNS involvement] and two in the DA-EPOCH-R group [one diagnosis other than Burkitt lymphoma at study entry according to local pathology and one CNS involvement]. 84 remaining patients were included in the modified intention-to-treat analysis. 73 (87%) of 84 patients were male, 76 (90%) presented with stage III or IV disease, and nine (11%) had HIV-positive Burkitt lymphoma. Median patient age was 52 years (IQR 37-64). With a median follow-up of 28·5 months (IQR 13·2-43·7), 2-year progression-free survival was 76% (95% CI 60-86%) in the R-CODOX-M/R-IVAC group and 70% (54-82%) in the DA-EPOCH-R group (hazard ratio 1·42, 95% CI 0·63-3·18; p=0·40). There were two deaths in the R-CODOX-M/R-IVAC group (one infection [treatment related] and one due to disease progression [not treatment related]) and one death in the DA-EPOCH-R group (COVID-19 infection [treatment related]). In the R-CODOX-M/R-IVAC group, four patients went off-protocol because of toxic effects, versus none in the DA-EPOCH-R group. Patients treated with R-CODOX-M/R-IVAC had more infectious adverse events (24 [56%] of 43 patients had at least one grade 3-5 infection vs 14 [34%] of 41 patients in the DA-EPOCH-R group). INTERPRETATION The trial stopped early, but the available data suggest that while DA-EPOCH-R did not result in superior progression-free survival compared with R-CODOX-M/R-IVAC, it was associated with fewer toxic effects and need for supportive care. DA-EPOCH-R appears to be an additional valid therapeutic option for patients with high-risk Burkitt lymphoma without CNS involvement. FUNDING The Dutch Cancer Society and the Schumacher-Kramer Foundation

T cell recognition of naturally presented epitopes of self-heat shock protein 70

Self-reactive T cells have shown to have a potential role as regulators of the immune system preventing or even suppressing autoimmunity. One of the most abundant proteins that can be eluted from human HLA molecules is heat shock protein 70 (HSP70). The aims of the current study are to identify HSP70 epitopes based on published HLA elution studies and to investigate whether T cells from healthy individuals may respond to such self-epitopes. A literature search and subsequent in silico binding prediction based on theoretical MHC binding motifs resulted in the identification of seven HSP70 epitopes. PBMCs of healthy controls proliferated after incubation with two of the seven peptides (H167 and H290). Furthermore H161, H290, and H443 induced CD69 expression or production of cytokines IFNγ or TNFα in healthy controls. The identification of these naturally presented epitopes and the response they elicit in the normal immune system make them potential candidates to study during inflammatory conditions as well as in autoimmune diseases