Fatigability and the Role of Neuromuscular Impairments in Chronic Kidney Disease

Abstract

<b><i>Background:</i></b> The combination of neuromuscular impairments plus psychosocial aspects of chronic kidney disease (CKD) may predispose these patients to greater risk for experiencing increased levels of fatigability. There has been extensive clinical and scientific interest in the problem of fatigue in CKD and end-stage kidney disease (ESKD) patients, whereas less attention has been directed to understanding fatigability. Accordingly, the primary purposes of this review are to (1) discuss fatigue and fatigability and their potential interactions in patients with CKD and ESKD, (2) provide evidence for increased fatigability in CKD and ESKD patients, (3) examine how commonly experienced neuromuscular impairments in CKD and ESKD patients may contribute to the severity of performance fatigability, and (4) highlight preliminary evidence on the effects of exercise as a potential clinical treatment for targeting fatigability in this population. <b><i>Summary:</i></b> Fatigue is broadly defined as a multidimensional construct encompassing a subjective lack of physical and/or mental energy that is perceived by the individual to interfere with usual or desired activities. In contrast, fatigability is conceptualized within the context of physical activity and is quantified as the interactions between reductions in objective measures of performance (i.e., performance fatigability) and perceptual adjustments regulating activity performance (i.e., perceived fatigability). We propose herein a conceptual model to extend current understandings of fatigability by considering the interactions among fatigue, perceived fatigability, and performance fatigability. Neuromuscular impairments reported in patients with CKD and ESKD, including reductions in force capacity, skeletal muscle atrophy, mitochondrial dysfunction, abnormal skeletal muscle excitability, and neurological complications, may each contribute to the greater performance fatigability observed in these patients. <b><i>Key Messages:</i></b> Considering the interactions among fatigue, perceived fatigability, and performance fatigability provides a novel conceptual framework to advance the understanding of fatigability in CKD and ESKD patients. Measures of fatigability may provide valuable clinical insights into the overall health status of CKD and ESKD patients. Existing data suggest that CKD and ESKD patients are at greater risk of experiencing increased fatigability, partly due to neuromuscular impairments associated with reduced kidney function. Further investigations are warranted to determine the potential clinical role fatigability measures can play in monitoring the health of CKD and ESKD patients, and in identifying potential treatments targeting fatigability in this patient population.

Fatigue and Quality of Life in Children with Chronic Kidney Disease

“…Fatigue, both physical and cognitive, is a frequent symptom of chronic diseases. Fatigue is well-described in adult CKD, as a result of physical and mental disorders that accompany the disease [ 8 , 9 , 10 ]. Moreover, fatigue constitutes a well-recognized feature of frailty syndrome, which is defined as a decline in resistance to minor stress events due to reduced biological reserves, resulting in increased vulnerability to falls, fractures, hospitalization, and mortality [ 21 ].…”

“…Our findings are in accordance with Roumelioti ME et al’s study, where children with measured GFR 40- < 50, 30- < 40, or <30 presented 2.07, 2.35, and 2.59 higher odds of experiencing the “low energy” symptom than children with GFR ≥ 50 [ 12 ]. The “General Fatigue” symptom is probably the consequence of multiple CKD-related factors, involving chronic uremia, renal anemia, muscle and protein energy wasting, bone mineral disorders, and cardiovascular disease, which are highly encountered in CKD 5D patients [ 8 , 9 , 10 ]. Moreover, we remarked that “General Fatigue” symptom prevalence was not observed in KTx patients, highlighting the need for the implementation of strategies aimed at reducing the dialysis vintage in the pediatric population.…”

“…Moreover, skeletal muscle deficit, due to metabolic acidosis, chronic inflammation, increased protein catabolism, malnutrition, and mineral bone disorders, induce chronic fatigability in these patients [ 9 ]. Neurological complications, especially nerve dysfunctions, mostly observed in patients with CKD stage 5 on chronic dialysis (CKD 5D), may enhance performance fatigability [ 10 ]. Other dialysis-related factors, including mode and frequency of dialysis, may also affect the prevalence of this condition in CKD 5D patients [ 8 ].…”

Neural Drive Impairment in Chronic Kidney Disease Patients Is Associated with Neuromuscular Fatigability and Fatigue

“…Non-dialysis-dependent CKD is commonly associated with a reduction in muscle mass and function. Surprisingly, very few studies have investigated neuromuscular function during a standardized task (9). Heiwe et al (14) performed a time-to-task failure test of quadriceps muscles in CKD patients.…”

“…MVF significantly improves fatigue description in CKD patients with low degree of fatigue. A better understanding of the relationship between neuromuscular fatigability and self-reported fatigue is needed to allow us to target therapeutic approaches (9,13). No matter the time period used or normalization, only in CKD patients was there a significant relationship between the RER and the reduced motivation subscale.…”