Objective Fatigue is among the most common and burdensome symptoms in patients with end-stage kidney disease (ESKD) undergoing maintenance hemodialysis, yet its metabolic drivers are not well defined. The aim of our study was to evaluate amino acid profiles in relation to dialysis-related fatigue. Methods In a post hoc analysis of 115 adults with ESKD receiving hemodialysis, fatigue was measured on dialysis and non-dialysis day using the validated Brief Fatigue Inventory (BFI) test. Twenty-four plasma amino acid were measured pre- and post-dialysis. Differences in amino acid concentrations and metabolic pathways were evaluated across global BFI score categories (low, intermediate, high) on each day. Ordinal logistic regression examined associations between amino acids and shifts in global BFI score categories from dialysis to non-dialysis days. Results On dialysis day, levels of tyrosine (p=0.01), asparagine (p=0.02), and ornithine (p=0.03) were lower in participants with high global BFI scores. Pathway-level analyses demonstrated lower branched-chain amino acid and essential amino acid pathway activity with high global BFI scores. On non-dialysis day, no differences in individual amino acids and metabolic pathways across global BFI score categories were observed. Aspartic acid (p=0.01), glycyl-histidine (p=0.04), and alanine, aspartate, and glutamate metabolism pathway (p=0.04) were associated with a shift toward lower global BFI score categories from dialysis to non-dialysis days. Conclusions Fatigue in hemodialysis patients is linked to specific amino acid and metabolic changes on dialysis days, but not on non-dialysis days. These findings support exploring amino acid-targeted interventions, especially when fatigue is most severe.
Objective Nutrition disorders and nutrition related conditions contribute to increased morbidity, mortality, and poor quality of life in hemodialysis (HD) patients. This study investigates the prevalence and overlap between these conditions in HD patients. Methods This cross-sectional multicenter study included adult HD patients from the Netherlands. Body composition was assessed using single-frequency bioimpedance analysis (SF-BIA), multi-frequency bioimpedance analysis (MF-BIA), or bioimpedance spectroscopy (BIS). Muscle strength was estimated by handgrip strength. Nutrition disorders and nutrition related conditions were assessed using: Global Leadership Initiative on Malnutrition (GLIM), Protein-Energy Wasting (PEW), Subjective Global Assessment (SGA), Patient-Generated SGA (PG-SGA), European Working Group on Sarcopenia in Older People (EWGSOP2) and the Sarcopenic Obesity Global Leadership Initiative (SOGLI) consensus. Overlap was identified using VENN diagrams. Results Of the 128 HD patients included, 59% were classified as malnourished based on GLIM criteria, with reduced muscle mass being the most prevalent phenotypic indicator (83%). PEW was present in 38%, sarcopenia according to EWGSOP2 in 23%, and sarcopenic obesity per SOGLI in 5%. Moderate-to-severe malnutrition was present in 47% of patients using the SGA (n = 89) and in 98% using PG-SGA (n = 39). GLIM showed the greatest overlap with other frameworks. Conclusion This study reveals a high prevalence of malnutrition, PEW, and sarcopenia among HD patients. These results highlight the need for muscle-oriented screening and provide novel insight into the coexistence of nutrition disorders and nutrition related conditions in this population. Given the overlap with other frameworks, GLIM appears to be a promising approach for diagnosing malnutrition in HD patients.
Purpose This study aims to elucidate the role of indoxyl sulfate (IS) and soluble (pro)renin receptor [s(P)RR] in sarcopenia among maintenance hemodialysis (MHD) patients, integrating clinical observations with in vitro mechanistic investigations. Methods A single-center cross-sectional study enrolled 141 MHD patients to analyze correlations between serum IS, s(P)RR, and sarcopenia parameters. Multivariate logistic regression was conducted to determine independent predictors of sarcopenia in MHD patients. Mechanistic insights were derived from C2C12 myotube experiments, including myostatin (MSTN) knockdown and renin-angiotensin system (RAS) inhibition, to evaluate IS- and s(P)RR-induced mitochondrial dysfunction, oxidative stress, and atrophy. Results Sarcopenic patients exhibited elevated IS and s(P)RR levels and impaired physical performance. s(P)RR independently predicted sarcopenia. In vitro, IS upregulated s(P)RR, suppressed peroxisome proliferator-activated receptor-γ coactivator-1α (PGC1α) and nuclear respiratory factor-1 (Nrf-1), and induced mitochondrial dysfunction, oxidative stress, and myotube atrophy, which were rescued by s(P)RR inhibition. Recombinant s(P)RR suppressed PGC1α and Nrf-1 expression, exacerbating mitochondrial damage and atrophy in C2C12 myotubes, which were reversed by PGC1α overexpression. MSTN knockdown attenuated IS-induced myotube atrophy, oxidative stress, and PGC1α downregulation, effects reversed by s(P)RR. Similarly, RAS blockade ameliorated IS-induced myotube atrophy and s(P)RR upregulation, and restored PGC1α expression. Conclusion Clinical data reveal significant associations between IS, s(P)RR, and sarcopenia in MHD patients. In vitro experiments further indicate that the IS-s(P)RR-PGC1α/Nrf-1 axis, with MSTN and the RAS as key mediators, contributes to muscle atrophy via mitochondrial dysfunction and oxidative stress. s(P)RR emerges as a novel diagnostic biomarker and a modifiable target, providing a foundation for further translational studies.
RATIONALE:Patients on hemodialysis (HD) commonly report poor nutritional status, which is associated with negative clinical outcomes. The aim of the "Hemodialysis Anorexia Sarcopenia Protein-Energy Wasting" (H.A.S.PEW) study was to determine the prevalence of protein-energy wasting (PEW) syndrome, to explore associations between PEW, anorexia, and sarcopenia, as well as to assess the diagnostic accuracy of phase angle (PhA) from bioelectrical impedance analysis (BIA) in predicting PEW in patients on HD. METHODS:The H.A.S.PEW study was a single-center, cross-sectional study in patients undergoing HD. The International Society of Renal Nutrition and Metabolism (ISRNM) criteria were used for the diagnosis of PEW by using the PEW score index. Anorexia was diagnosed by Simplified Nutritional Appetite Questionnaire (SNAQ), sarcopenia was identified by European Working Group on Sarcopenia in Older People 2 (EWGSOP2) criteria and body composition was analyzed by BIA. RESULTS:A total of 190 patients (129 men; median age: 70.0 years, IQR: 58.0.-78.0) were evaluated. PEW was diagnosed in 14.7% of the patients, while 25.3% reported anorexia and 30.0% sarcopenia. Both anorexia (p < 0.001) and sarcopenia (p < 0.001) were positively associated with PEW. Patients with anorexia, sarcopenia or lower PhA values had significantly higher risk of PEW than those without anorexia, sarcopenia or with higher PhA [OR = 4.5 (1.96-10.40), p < 0.001; OR = 5.7 (2.42-13.32), p < 0.001; OR = 0.3 (0.15-0.42), p < 0.001, respectively). After adjusting for age, handgrip strength (HGS), C-reactive protein (CRP) levels, HD vintage, anorexia and sarcopenia, PhA continued to demonstrate a significant association with the development of PEW (ORadjust = 0.3, p < 0.001). Receiver Operating Characteristic (ROC) curve analysis revealed cut-off points of 4.25o for males and 4.10o for females, for the ability of PhA to identify PEW syndrome, while the agreement between PhA (PhA for the whole sample: ≤ 4.24o) and ISRNM criteria for PEW diagnosis was found to be moderate (κ = 0.414, p < 0.001). CONCLUSIONS:Anorexia and sarcopenia may increase the risk of PEW syndrome in HD patients. BIA-derived PhA seems to be a valid marker for PEW detection independently of anorexia and sarcopenia.
George Alan Kaysen, MD, PhD (1943-2026), was an internationally recognized physician-scientist whose work helped define our modern understanding of protein metabolism, inflammation, and nutritional disorders in kidney disease. Over a distinguished academic career that included leadership positions at the University of California, San Francisco, the Veterans Administration Medical Center in Martinez, and the University of California, Davis, he made foundational contributions to the study of albumin kinetics, lipoprotein metabolism, nephrotic-range proteinuria, dialysis-associated metabolic derangements, protein-energy wasting, sarcopenia, and frailty. He also played major leadership roles in the International Society of Renal Nutrition and Metabolism, serving in multiple council positions, as Secretary-Treasurer, as President-Elect, and as President. He was also a member of the Editorial Boards of the Journal of Renal Nutrition and several other journals. His scholarly impact was extraordinary: approximately 290 publications, more than 18,500 citations, and three publications cited more than 1,000 times. Dr. Kaysen's scientific leadership, mentorship, and service to the international renal nutrition community left a lasting legacy that continues to shape research, clinical practice, and professional collaboration.
OBJECTIVE:Patients on maintenance hemodialysis commonly develop protein-energy wasting, sarcopenia, and disabling fatigue. Whether ketoanalogue (KA) supplementation, low-intensity intradialytic resistance exercise, or the two combined can improve physical function over a short period is uncertain. METHODS:In a single-centre, 12-week randomised trial, 100 prevalent hemodialysis patients were allocated 1:1:1:1 to KA only, KA plus exercise, exercise only, or control. The primary outcome was the 30-second sit-to-stand test (STS-30). Secondary outcomes were fatigue (MFIS), handgrip strength, bioimpedance skeletal muscle index (SMI), and quadriceps ultrasound total thickness. Between-group inference used baseline-adjusted 2×2 factorial ANCOVA with a KA-by-exercise interaction term, which tests whether the effect of one intervention depends on whether the other is present. Simple effects were estimated when the interaction was significant. RESULTS:Ninety-five patients completed follow-up. The four arms were similar at baseline in age, sex, dialysis vintage, comorbidities, and daily protein intake (0.65-0.77 g/kg), confirming successful randomisation. KA had a significant main effect on STS-30 (+1.34 reps; 95% CI 0.41-2.28; p=0.005) and on quadriceps thickness (+2.85; 95% CI 0.98-4.72; p=0.003), with no KA-by-exercise interaction. The exercise's main effect on STS-30 was not significant. For handgrip, KA alone and exercise alone each improved performance, but combining them did not produce additive gains (significant interaction, p<0.001). Fatigue and SMI showed no significant between-group effects; these findings are considered exploratory CONCLUSION: Twelve weeks of KA supplementation was associated with improved functional performance and preservation of quadriceps muscle thickness relative to non-supplemented patients in hemodialysis patients with low baseline protein intake. The low-intensity intradialytic exercise prescription tested did not, on its own, improve STS-30.
Objective: Knowledge, attitude, and practices (KAPs) related to dietary habits play a critical role in managing disease progression in chronic kidney disease (CKD) patients, yet these aspects remain understudied. This study focused on developing, validating, and assessing the utility of a tailored KAP questionnaire specifically designed for CKD patients. Methods: This prospective study was conducted from November 2022 to November 2023 among CKD stage 3 to nondialytic stage 5 patients attending a nephrology outpatient department. A multiple-choice KAP questionnaire, developed with input from 10 nephrologists, included 33 knowledge items (diet 23, disease 10), 33 attitude items on a Likert scale, and 11 practice items on dietary intake. Validity was assessed in a pilot group of 30 CKD patients. A total of 199 patients aged 18-60 years were enrolled and randomized into three diet groups: normal protein intake (0.8-1.0g/kg/day), low protein intake (0.6 g/kg/day), and very low protein intake with ketoanalogues supplementation (0.3 g/kg/day). Baseline demographic, socioeconomic, dietary data, and KAP scores were recorded, followed by dietary counseling. KAP scores were reassessed at 6 months and compared to baseline. Results: Among 199 enrolled CKD patients (60% male, 74.7% literate), postcounselling KAP scores showed significant improvements: knowledge increased from 29.5 +/- 21.3 to 53.3 +/- 19.8, attitude from 108.8 +/- 16.2 to 133.9 +/- 20.2, and practice from 17.0 +/- 3.2 to 20.1 +/- 2.8 (P < .05). In addition, all KAP components and estimated glomerular filtration rate significantly improved across different CKD stages following the 6-month dietary intervention. Conclusion: The validated KAP questionnaire revealed significant improvements in knowledge, attitude, and practice over 6 months following dietary counseling. These findings underscore the necessity of integrating dietary counseling into the management of CKD at all stages.
OBJECTIVE:To evaluate the nutritional status of maintenance hemodialysis (MHD) patients in a large Chinese region. METHODS:A multicenter cross-sectional investigation was carried out. All MHD patients received dialysis treatment from April to June 2024 in dialysis centers selected by convenience sampling within a large Chinese region were recruited. Demographic characteristics, physical parameters, and laboratory indices were collected. Protein-energy wasting (PEW) was adopted as a standard for malnutrition assessment and was analyzed in accordance with geographical subgroups. A multivariate logistic regression model was conducted to identify the influencing factors of PEW. RESULTS:In this study, the data of 4,618 MHD patients from 86 dialysis centers were analyzed. The prevalence rate of PEW was 33.2% (1,531/4,618). Subgroup analysis indicated that the prevalence rate was the highest in the Southern region, reaching 37% (535/1,446), and there were significant differences among different areas (Χ2 = 19.992, P = .001). However, the primary manifestations were all characterized by the reduced muscle mass and muscle strength. Multivariate logistic regression analysis demonstrated that age (oddrs ratio [OR] = 1.026, 95% confidence interval [CI]: 1.021-1.032, P < .01), sex (OR = 1.185, 95% CI: 1.038-1.352, P = .012), dialysis frequency (OR = 0.842, 95% CI: 0.731-0.969, P = .017), and hemodiafiltration frequency (OR = 0.936, 95% CI: 0.896-0.978, P = .003) were independent influencing factors of PEW. CONCLUSIONS:This study revealed the prevalence and manifestations of PEW among MHD patients in the large Chinese region as well as differences and related factors in different areas. It offered certain evidence for monitoring the nutritional status and future nutritional interventions of MHD patients in this region.
