PhysIOpathology of NEuromuscular function rElated to fatigue in chronic Renal disease in the elderly (PIONEER): Study protocol

Background: Chronic Kidney Disease (CKD) is associated with reduced muscular strength resulting in profound fatigue. The physiopathology of these changes, their prevalence and evolution are still debated. Moreover, we have little data on elderly CKD patients. The present study protocol aims to 1) quantify the prevalence of low muscle strength (dynapenia) in a cohort of elderly patients with advanced CKD and to 2) characterize their force production coupled with electromyographic features and the symptoms of fatigue compared to a matched control group. Methods: This is a case-control, prospective, interventional study. Inclusion criteria: age ≥ 60 years; CKD Stage 3b-5; clinical stability (i.e. no hospitalization and ≤ 25% in creatinine increase in the previous 3 months). Controls with normal kidney function will be matched in terms of age, gender and diabetes mellitus (requisite: estimated glomerular filtration rate ≥ 60 ml/min/1.73m2 available in the last 6 months). Exclusion criteria for cases and controls: neuromuscular disease, life expectancy < 3 months. The handgrip strength protocol is an intermittent test consisting in 6 series of 9 repetitions of 3-s sub-maximum contractions at 40% of the maximum voluntary contraction (MVC) and 2 s of resting time between contractions. Each series is separated by one fast sub-maximum contraction and one MVC. Strength is assessed with a high-frequency handgrip dynamometer paired with surface electromyography. Symptoms of fatigue are assessed using MFI-20 and FACIT-F questionnaires. In order to reach a statistical power of 96%, we plan to enroll 110 subjects in each group. Discussion: The novelty of this study resides in the application of an already validated set of tests in a population in which this combination (dynamometer, electromyography and questionnaires) has not previously been explored. We expect a high prevalence of dynapenia and a higher fatigability in CKD patients. A positive correlation is expected between reported fatigue and fatigability. Better appreciation of the prevalence and the relationship between fatigability and a sensation of fatigue can help us target interventions in CKD patients to improve quality of life and survival. Trial registration: The study was approved by Ethical Committee EST III n°20.03.01 and was recorded as a Clinical Trial (NCT04330807) on April 2, 2020.