Malnutrition and Sarcopenia in Adults With Chronic Kidney Disease in Tunisia

Background Malnutrition and sarcopenia are frequent and clinically relevant complications of chronic kidney disease (CKD). They are related but distinct conditions. Evidence evaluating GLIM-defined malnutrition and EWGSOP2-defined sarcopenia concurrently remains limited, particularly across both non-dialysis CKD and dialysis populations, and longitudinal data on changes in these phenotypes and their association with kidney, cardiovascular and mortality outcomes are scarce. No multicenter data are available in Tunisia. Design TUN-CKDN (Tunisian Chronic Kidney Disease Nutrition) is a national, multicenter, prospective, longitudinal cohort study sponsored by the Société Tunisienne de Néphrologie, Dialyse et Transplantation Rénale (STNDT). Eligible patients followed in participating nephrology centers will be consecutively included over a planned 6-month recruitment period. Participants will be followed at 2 and 5 years after inclusion (window of plus or minus 3 months). Objectives Primary objective: to estimate, at baseline, the prevalence of GLIM-defined malnutrition and EWGSOP2-defined sarcopenia in patients with CKD stages G3a to G5D. Secondary objectives: (1) to describe the baseline overlap between malnutrition and sarcopenia (isolated and combined phenotypes) and to characterize nutritional and inflammatory status using the Malnutrition-Inflammation Score (MIS); (2) to describe the persistence, resolution and new onset of malnutrition and sarcopenia between baseline and 2 years; (3) to investigate the association of baseline malnutrition and sarcopenia with initiation of maintenance kidney replacement therapy among participants not receiving dialysis at baseline, major adverse cardiovascular events (MACE) and all-cause mortality at 2 and 5 years. Baseline assessment Data will be collected in a standardized electronic case report form (DACIMA Clinical Suite) and will include: sociodemographic characteristics; medical history, comorbidities and lifestyle factors; physical activity and sitting time (IPAQ-SF); CKD characteristics and treatment, including dialysis modality; clinical assessment of volume status; anthropometry (height, current weight, previous weights at 3 and 6 months and beyond 6 months when available, reference body weight determined according to volume status and dialysis modality); body composition by segmental bioelectrical impedance analysis using the same device model across centers, with calf circumference as an alternative surrogate for GLIM when impedance is unavailable or not interpretable; clinical assessment of subcutaneous fat loss and muscle wasting; muscle strength by the five-times sit-to-stand test (5STS); physical performance by usual gait speed over 4 meters; laboratory parameters from routine care (performed within 7 days of the clinical examination, immediately before a midweek session in hemodialysis patients); dietary intake by standardized dietary history conducted by trained dietitians and analyzed with Nutrilog software using the CIQUAL 2020 food composition table; and nutritional prescriptions. Definitions Malnutrition will be diagnosed according to the GLIM criteria and their 2025 update (at least one phenotypic and one etiologic criterion) and graded as stage 1 (moderate) or stage 2 (severe). Sarcopenia will be classified according to EWGSOP2 as absent, probable, confirmed or severe, or not classifiable when muscle strength cannot be assessed; confirmation requires low muscle mass by bioelectrical impedance. The MIS (0 to 30) will be calculated as a complementary measure. Derived scores and classifications will be generated automatically in the eCRF according to predefined algorithms. Missing diagnostic data will not be imputed; phenotypes that cannot be determined will be classified as indeterminate. Follow-up At 2 years, participants alive and available will undergo the same nutritional and muscle reassessment (the detailed dietary survey is not repeated). At 2 and 5 years, vital status, cause of death, MACE (non-fatal myocardial infarction, non-fatal stroke and cardiovascular death), hospitalizations and, in participants not on dialysis at baseline, kidney function (creatinine, eGFR by CKD-EPI 2021, urinary albumin-to-creatinine ratio, KDIGO categories) and initiation of kidney replacement therapy will be recorded. Reported events will be confirmed by review of medical records. Sample size and analysis A total of 4,000 participants will be included (two-sided alpha 5%, 80% power, design effect 1.5 for clustering by center, 10% non-evaluable participants and 10% loss to follow-up at 5 years). Prevalences will be estimated with 95% confidence intervals accounting for clustering by center. Overlap will be described with four mutually exclusive phenotypes and Cohen's kappa. Changes at 2 years will be described with transition matrices and McNemar's test, weighted by the inverse probability of reassessment. Associations with outcomes will be analyzed with Cox models with shared frailty for center, with competing-risk models (Fine-Gray or cause-specific) for kidney replacement therapy and MACE. Three analyses are planned: cross-sectional at the end of recruitment, at 2 years and at 5 years. Ethics The study is observational and does not modify usual care. Written informed consent will be obtained from all participants. Data will be pseudonymized and processed in accordance with Tunisian data-protection requirements (INPDP).