Symptom Burden in Patients on Maintenance Hemodialysis: Prevalence and Severity 17 Years Apart.

Objectives: The aim of this study is to compare data from two cohorts separated by a 17-year interval. We assessed the prevalence and severity of symptoms with the "dialysis symptom index" in these two groups, recruited in 2007 and 2024, to determine how advancements in dialysis therapy have influenced the symptom burden's prevalence and severity. Methods: End-stage renal diseases patients receiving maintenance hemodialysis three times a week in the hemodialysis unit of the university hospital were recruited between February and March 2007. In May 2024, in the same unit, another population sample was recruited and studied, as in 2007. The Dialysis Symptom Index (DSI) was administered to each patient, during the dialysis treatment. The DSI is made up of 30 questions, each of which addresses a specific physical or emotional symptom. The total symptom burden score, representing the total number of symptoms reported as being present, and the total symptom severity score, which represents the sum of individual severity scores, were generated for each patient. Results: We studied 71 patients in 2007 and 61 patients in 2024. The demographic, clinical and laboratory characteristics of the two study populations did not differ significantly. The total symptom burden score did not differ significantly between 2007 and 2024. The prevalence of most symptoms was similar in the two groups. The prevalence of constipation, decreased interest in sex and difficulty in becoming sexually aroused was higher in 2024 than in 2007. The total symptom severity was similar in the two periods. The severity of most symptoms was similar in the two groups. The severity of decreased interest in sex and difficulty in becoming sexually aroused was higher in 2024 than in 2007. Conclusions: The present study shows that, 17 years apart, the prevalence and severity of the symptom burden in patients on maintenance hemodialysis did not change significantly. These results suggest that studies investigating the causes and the pathogenesis of symptoms of patients on maintenance hemodialysis are urgently needed in the next future, as well as studies on therapeutic strategies.

Interdialytic weight gain and low-salt diet in patients on chronic hemodialysis: A systematic review and meta-analysis.

OBJECTIVE: The present systematic review and meta-analysis aims to determine the difference in the interdialytic weight gain (IDWG) between low salt intake diet and normal/high salt intake diet or between nutritional counseling aimed at reducing diet salt intake and no nutritional counseling in patients on chronic hemodialysis. METHODS: Medline, PubMed, Web of Science, and the Cochrane Library were searched. Randomized, crossover or parallel studies and observational studies were considered for inclusion and: 1) included adult patients on chronic hemodialysis since at least 6 months; 2) compared normal salt intake diet with low salt intake diet on IDWG; 3) compared nutritional counseling aimed at reducing diet salt intake with no intervention on IDWG; 4) reported on IDWG. RESULTS: Eight articles (783 patients) were fully assessed for eligibility and included in the investigation. Meta-analysis showed frequencies of patients that increased their weight after dialysis more than 2.5 Kg (events) over total enrolled subjects for each group (control and experimental). As no significant heterogeneity was observed (I2 = 8%; p = 0.36), the pooled analysis was performed using a fixed-effect model. Funnel plot was generated and no obvious asymmetry was observed. The Overall Odds Ratio to get an event in the experimental group, in respect to controls, is 0.57 (0.33-0.97) (p = 0.04] with single studies OR ranging between 0.11 and 1.08. CONCLUSION: The present systematic review and meta-analysis suggest that the use of a low salt diet sodium or a nutritional counseling aimed at reducing diet salt intake is associated with a statistically significant reduction of the IDWG in patients on chronic hemodialysis.

Use of Proton Pump Inhibitors Is Not Associated with Post-Dialysis Fatigue and Time of Recovery after Dialysis in Patients on Maintenance Hemodialysis.

Objectives: To define if the use of proton pump inhibitors (PPI) is associated with PDF prevalence and characteristics and with time of recovery after dialysis in patients on maintenance hemodialysis. Methods: Patients were defined as experiencing PDF if they spontaneously offered this complaint when asked the open-ended question: "Do you feel fatigued after dialysis?". Time of recovery after dialysis (TIRD) was also assessed for each patient. Each patient was invited to rate the intensity, duration and frequency of PDF from 1 to 5. We defined if patients used PPI (no PPI use or PPI use), the type of used PPI, the dose of used PPI, and the duration of the use of PPI (<1 year or ≥1 year). Results: A total of 346 patients were studied: 259 used PPI (55 used omeprazole, 63 esomeprazole, 54 pantoprazole, 87 lansoprazole, and 7 rabeprazole) and 87 did not. Two hundred and thirty-two patients declared PDF and 114 did not. The median [min-max] TIRD was 210 min [0-1440]. The prevalence of PDF in PPI users and PPI non-users was 67% and 68%, respectively (p = 0.878). The median [min-max] TIRD did not differ significantly between PPI users and PPI non-users (180 [0-1440] and 240 [0-1440], respectively; p = 0.871). Median PDF intensity, duration, frequency, and severity did not differ significantly between PPI use and no use. The prevalence of PDF was similar among the different types of PPI use and did not differ with respect to PPI non-users. Duration of PPI exposure was <1 year in 40 patients and ≥1 year in 219 patients. The prevalence of PDF did not differ between the two exposures. The correlation matrix between PPI equivalent dose, PPI treatment duration and PDF frequency, PDF characteristics, and TIRD showed whether there was statistical significance. Conclusions: The use of PPI is not associated with PDF and time of recovery after dialysis in patients on maintenance hemodialysis.

An integrated multitool analysis contributes elements to interpreting unclassified factor IX missense variants associated with hemophilia B.

BACKGROUND: Dissection of genotype-phenotype relationships in hemophilia B (HB) is particularly relevant for challenging (mild HB) or for HB-associated but unclassified factor (F)IX missense variants. OBJECTIVE: To contribute elements to interpret unclassified HB-associated FIX missense variants by a multiple-level approach upon identification of a reported, but uncharacterized, FIX missense variant associated with mild HB. METHODS: Molecular modeling of wild-type and V92A FIX variants, expression studies in HEK293 cells with evaluation of protein (ELISA, western blotting) and activity (activated partial thromboplastin time-based/chromogenic assays) levels after recombinant expression, and multiple prediction tools. RESULTS: The F9(NM_000133.4):c.275T>C (p.V92A) variant was found in a mild HB patient (antigen, 45.4 U/dL; coagulant activity, 23.6 IU/dL; specific activity, 0.52). Newly generated molecular models showed alterations in Gla/EGF1-EGF2 domain conformation impacting Ca++ affinity and protein-protein interactions with activated factor XI (FXIa). Multitool analysis indicated a moderate impact on protein structure/function of the valine-to-alanine substitution, in accordance with patient and modeling data. Expression studies on the V92A variant showed a specific activity (0.49 ± 0.07; wild-type, 1.0 ± 0.1) recapitulating that of the natural variant, and pointed toward a moderate activation impairment as the main determinant underlying the p.V92A defect. The validated multitool approach, integrated with evidence-based data, was challenged on a panel (n = 9) of unclassified FIX missense variants, which resulted in inferred protein (secretion/function) outputs and HB severity. CONCLUSION: The rational integration of multitool and multiparameter analyses contributed elements to interpret genotype/phenotype relationships of unclassified FIX missense variants, with implications for diagnosis, management, and treatment of HB patients, and potentially translatable into other human disorders.