Federica Caccia

Background: Fabry disease (FD) is a rare, X‐linked lysosomal storage disorder affecting multiple organs, including the musculoskeletal system. The physical status of FD patients remains poorly characterized. This multicentre cross‐sectional study aimed to evaluate physical fitness and function in FD patients and investigate associations with sex, FD phenotype and treatment status. Methods: Adults (aged ≥ 18 years) with genetically confirmed FD were recruited. Demographic and laboratory data were collected. Physical fitness was assessed using cardiopulmonary exercise testing (VO ₂ peak) and body composition parameters (fat‐free mass index [FFMI], fat mass index [FM] and phase angle [PA]) via bioelectrical impedance analysis. Physical function was evaluated with performance tests (6‐min walk test, handgrip strength test, 30‐s chair‐stand test, short physical performance battery), muscle strength tests (isometric and isokinetic knee strength) and self‐report fatigue questionnaires. Statistical analyses were stratified by sex, phenotype (classic vs. late‐onset/Variants of Uncertain Significance [VUS]) and treatment status (enzyme replacement therapy [ERT]/chaperone‐treated versus untreated). Results: Forty‐two FD patients (13 males; mean age 46 ± 13.9 years) were enrolled. VO ₂ < 85% of predicted was more frequent in classic phenotype patients (53.8%) than in late‐onset/VUS (11.5%; p < 0.01). FFMI was lower in classic than late‐onset/VUS (16.8 ± 1.0 vs. 18.6 ± 2.1 kg/m ² ; p = 0.01). Treated males had lower PA than untreated males (4.8° ± 1.0° vs. 7.6° ± 0.9°; p = 0.04), and PA correlated with VO ₂ peak ( r = 0.879; p = 0.01). Among classic phenotype males, 74.3% scored below the 50th percentile in handgrip strength (26.1 ± 7.8 kg), and 60.9% performed below predicted values in the 30‐s chair‐stand test (12.4 ± 4.3 repetitions). Self‐reported fatigue scores were higher in classic versus late‐onset/VUS patients ( p = 0.05) and in treated patients compared to untreated patients ( p = 0.02). Conclusions: Classic FD phenotype, particularly in males, was associated with reduced exercise capacity, muscle mass and physical performance. These findings support the integration of cardiopulmonary exercise testing, physical functional assessments and body composition analysis into the routine evaluation of FD patients.

Kidney failure is strongly associated with psychological disorders, including anxiety, depression, and suicidal ideation. However, the prevalence of suicide risk in patients undergoing dialysis has not been fully established. We performed a systematic review and meta-analysis aimed at assessing the prevalence of suicide risk in adult patients on dialysis and any correlation with demographic and clinical parameters. Twelve unique cross-sectional studies involving 1259 adult patients on dialysis were included. All patients were receiving hemodialysis treatment. In univariate meta-regression analysis, no significant effect of age, sex, and percentage of patients with diabetes mellitus on the prevalence of suicide risk was found. Overall, the prevalence of suicide risk was 20.6%. It varied widely, ranging from 4.0% to 57.3%, depending on the tools used (i.e. clinical interviews or self-report questionnaires). Among studies with more or less than 40% of patients on dialysis with anxiety and depression, the prevalence of suicide risk was very similar (21.2% vs 20.4%, respectively). The prevalence of suicide risk was more than double in lower-income than in higher-income countries (33.5% vs 15.3%, respectively). The present systematic review and meta-analysis is a pioneering effort to identify the prevalence of suicide risk in patients on dialysis. It revealed a significant prevalence of suicide risk among hemodialysis patients, with a rate notably higher than that observed in the general population. This elevated risk is influenced by a complex combination of biological, psychological, and socio-economic factors.

Haemodialysis (HD) is a life-saving therapy for individuals with kidney failure. Post-filter haemodiafiltration (HDF) and high-flux HD are the most widely used treatment modalities. To date, five randomized controlled trials (RCTs) have been performed that compare all-cause and cardiovascular (CV) mortality between HDF and low- or high-flux HD in adults receiving maintenance dialysis for at least 1 year. RCTs, meta-analyses and pooled individual patient data analyses have been published on this topic. However, all of them are limited by the heterogeneity of inclusion criteria and significant methodological shortcomings, including informative selection bias and the exclusion of poorly performing patients from the HDF arm after randomization. Given this background, the European Dialysis Working Group of the European Renal Association presents a Consensus Statement on HDF and high-flux HD, addressing three key outcomes: survival, health-related quality of life, and biochemical endpoints. A separate section is dedicated to paediatric patients. We searched five large electronic databases to identify parallel or cross-over RCTs comparing HDF with high-flux HD on pre-defined outcome measures. Using a mini-Delphi method, we developed 22 key consensus points by combining meta-analyses, clinical experience, and expert opinion. They aim to inform and assist in decision making and are not intended to define a standard of care. The key summary point is that HDF appears to be associated with improved overall and CV survival, provided high convection volumes are achieved. The generalizability of these findings to the entire dialysis population depends on the patient's overall health and requires further study.