Abstract
Background
The relationship between muscle strength and chronic kidney disease (CKD) in children is unknown. This study aims to quantify the association between grip strength (GS) and kidney function and to explore factors associated with grip strength in children and adolescents with CKD.
Methods
We included 411 children (699 GS assessments) of the Chronic Kidney Disease in Children (CKiD) study. They were matched by age, sex, and height to a healthy control from the National Health and Nutrition Examination Survey to quantify the relationship between GS and CKD. Linear mixed models were used to identify factors associated with GS among CKD patients.
Results
Median GS z-score was − 0.72 (IQR − 1.39, 0.11) among CKD patients with CKD stages 2 through 5 having significantly lower GS than CKD stage 1. Compared with healthy controls, CKiD participants had a decreased GS z-score (− 0.53 SD lower, 95% CI − 0.67 to − 0.39) independent of race/ethnicity and body mass index. Factors associated with reduced GS included longer duration of CKD, pre-pubertal status, delayed puberty, neuropsychiatric comorbidities, need of feeding support, need for alkali therapy, and hemoglobin level. Decreased GS was also associated with both a lower frequency and intensity of physical activity.
Conclusions
CKD is associated with impaired muscle strength in children independent of growth retardation and BMI. Exposure to CKD for a prolonged time is associated with impaired muscle strength. Potential mediators of the impact of CKD on muscle strength include growth retardation, acidosis, poor nutritional status, and low physical activity. Additional studies are needed to assess the efficacy of interventions targeted at these risk factors.
Keywords: Children, Chronic kidney disease, Muscle strength, Outcomes, Quality of life
Introduction
Chronic kidney disease (CKD) in children is associated with a significant increase in morbidity and mortality compared with that in healthy children. The average life expectancy of pediatric patients with CKD initiating renal replacement therapy (RRT) in childhood and reaching adulthood is only 38 years for those receiving dialysis and 63 years for those with a kidney transplant [1].
Loss of muscle strength in adults is associated with the development of CKD, and many studies have investigated the role of CKD complications (metabolic acidosis, inflammation) and treatments (dialysis) in the loss of muscle mass [2]. In adults, many markers of muscle loss have been associated with poor quality of life and an increased risk of malnutrition, cardiovascular complications, hospitalization, and death [3, 4]. Consistent with previously published results in adults [5, 6], a recent study from the Chronic Kidney Disease in Children (CKiD) study showed an association between decreased muscle mass and progression of CKD [7]. However, it has been previously demonstrated that muscle mass and function are not affected by the same risk factors and can evolve differently. In a study involving hemodialysis patients, muscle mass was reduced, and muscle strength was lower than in healthy controls matched on muscle mass. Yet, muscle strength was only moderately correlated with muscle atrophy [8]. Similarly, a recent study of CKD patients with a median GFR of 31 mL/min/1.73 m2 demonstrated a loss of muscle size and impaired muscle quality, which was associated with decreased muscle function [9].
Grip strength is associated with total muscle strength in children and is a validated tool to evaluate isometric muscle strength [10]. A decreased grip strength has been reported in small cohorts of children with nephrotic syndrome or stage 5 CKD [11] and in children receiving peritoneal dialysis [12]. However, no study to date has examined the association between muscle strength and CKD in a large cohort of pediatric patients with mild-to-moderate CKD. The objectives of this study were to quantify the association between grip strength and kidney function and to explore factors associated with grip strength in children and adolescents with CKD.
Materials and methods
Study population and variables
CKiD is a prospective cohort study that enrolled patients aged 1 to 16 years with mild-to-moderate CKD (GFR estimated between 30 and 90 mL/min/1.73 m2) conducted at 54 pediatric nephrology centers in North America. The CKiD study design and conduct were approved by an observational monitoring board appointed by the National Institute of Diabetes and Digestive and Kidney Diseases and by the Institutional Review Boards of each participating center. Demographic and clinical data including anthropometrics, pubertal stage, assessment of physical activity, and creatinine and cystatin C to estimate the glomerular filtration rate [13] were collected at baseline and at annual follow-up visits. Body mass index was used to define obesity (BMI > 2 standard deviation scores (SDS)), overweight (1 SDS < BMI ≤ 2SDS), and thinness (BMI < − 2 SDS).
For participants over 6 years of age between 2013 and 2017, grip strength was assessed in the 3rd year following study entry and once every 2 years thereafter. Grip strength was measured using a manual dynamometer, with 3 tests per hand. The maximum strength for each hand and the sum of both hands were recorded. Combined grip strength values were normalized for sex and age based on norms derived from the National Health and Nutrition Examination Survey (NHANES), expressed as standard deviation scores (SDS) [14] and used in the analysis. All participants included in the CKiD study with at least one grip strength assessment were included in our analyses.
Statistical analysis
At the first visit with grip strength measured, continuous characteristics have been summarized using medians and interquartile ranges and categorical characteristics have been summarized using percentages. We assessed the correlation between eGFR and grip strength using the coefficient of correlation of Pearson. The median grip strength were compared between CKD severity group (defined according to the KDIGO guidelines (16) using a Kruskal–Wallis test). In children with more than one grip strength assessment during follow-up, we quantified the association between the change in GFR (ΔGFR) and the change in GS z-score (ΔGS) using the Pearson correlation coefficient.
To assess whether grip strength was reduced in children with CKD, we compared the 555 visits contributed by the 411 CKiD participants to 555 healthy children from the 2013–2014 NHANES study individually matched on age, sex, and height. Grip strength was assessed with the same method in NHANES as CKiD. Differences in continuous characteristics between the CKiD and NHANES populations were assessed using a Wilcoxon rank sum test; differences in categorical characteristics were assessed using a Pearson chi-square test. Grip strength in CKD patients and healthy NHANES controls were compared after adjusting for race and body mass index using a multivariable linear mixed model which accounted for the repeated measurements contributed by CKiD participants and for the individual matching of CKiD participants to NHANES. We also performed a sensitivity analysis after excluding patients with neuropsychiatric diseases and their controls.
We performed a set of explanatory analyses using a series of univariable mixed linear models to identify potential CKD complications (e.g., need for feeding support, need for alkali therapy, or anemia) that were associated with decreased grip strength. We also studied the association between grip strength z-score and measures of physical activity (number of days with various intensity of physical activity over the 7 days before the study visit) using univariable mixed linear models. Statistical analyses were performed using SAS 9.4 and a p value less than 0.05 was considered statistically significant.
Results
Association between GFR and grip strength in children with CKD
The CKiD study population included 411 participants that underwent a total of 699 visits with grip strength assessment (180 with one grip strength assessment, 174 with two, and 57 with three). Median age at first grip strength assessment was 14 (interquartile range [IQR] 11; 17) years; 62% were male, 68% had non-glomerular CKD, and the median (IQR) eGFR was 57 (43; 71) mL/min/1.73 m2 (Table 1). Median grip strength z-score was − 0.72 (IQR − 1.39; 0.11) SD. The correlation between eGFR and grip strength z-score was weak (r = 0.07, p = 0.05). The correlation between eGFR and grip strength z-score was slightly stronger in patients with non-glomerular diseases (r = 0.12, p = 0.006); there was no correlation in patients with glomerular diseases (r = − 0.04, p = 0.62). Differences were found in grip strength z-score by CKD stage (Fig. 1); while patients with CKD stage 1 had a conserved grip strength (median = − 0.10 [− 0.88; 0.83] SD), patients with CKD stages 2–5 had a lower grip strength compared with those with CKD stage 1 (median = − 0.73 [− 1.41; 0.06] SD). Among children with longitudinal assessment of grip strength, the mean time between the first and the last grip strength assessment was 2.5 years (SD 0.9), the mean eGFR decline was − 2.5 (SD 16.5) mL/min/1.73 m2 per year, and the mean difference in grip strength z-score was 0.03 (SD 0.4). We did not found any correlation between the change in GFR and the change in grip strength z-score (r = − 0.005, p = 0.75). The correlation between the change in GFR and the change in grip strength z-score and patients’ individual grip-strength z-score trajectories stratified by progression status are presented in supplemental Figs. 1 and 2, respectively.
Table 1.
Characteristics of 411 CKiD participants at first grip strength assessment (2013–2017)
| Characteristics | Median (IQR) or n (%) |
|---|---|
| Age (years) | 14 (11; 17) |
| Male sex | 253 (62%) |
| Race/ethnicity | |
| Hispanic White | 51 (12%) |
| Non-Hispanic White | 238 (58%) |
| Non-Hispanic Black | 73 (18%) |
| Asian | 11 (3%) |
| Other | 37 (9%) |
| History of hypertension | 199 (49%) |
| History of diabetes | 12 (3%) |
| Anemiaδ | 117 (28%) |
| Height SDS¥ | − 0.4 (− 1.1; 0.4) |
| Body mass index (kg/m2) | |
| Obese | 43 (11%) |
| Overweight | 86 (23%) |
| Normal | 240 (64%) |
| Thin | 7 (2%) |
| Glomerular CKD etiology | 131 (32%) |
| eGFR (mL/min/1.73 m2)¥ | 57 (43; 71) |
| CKD stage¥ | |
| Stage 1 | 32 (8%) |
| Stage 2 | 155 (38%) |
| Stage 3a | 108 (26%) |
| Stage 3b | 77 (19%) |
| Stage 4 | 37 (9%) |
| Stage 5 | 1 (<1%) |
Anemia was defined as a hemoglobin < 5th percentile using age- and sex-specific norms
Missing: height z-score n = 4, BMI n = 35, eGFR and CKD stage n = 1, history of hypertension n = 8, history of diabetes n = 4
Fig. 1.
Distribution of grip strength z-scores by CKD stage
Comparison of grip strength between CKD children and NHANES controls
Five hundred fifty-five of 699 participant-visits could be matched with a participant from NHANES (95 visits were excluded because of missing height and 49 because no exact match was found in NHANES). Overall, CKiD participants were more often Caucasians and were more likely overweight than NHANES (Table 2). Patients with CKD had a lower grip strength than controls matched for age, sex, and height (mean grip strength z-score − 0.61 (SD 1.1) in CKD vs. − 0.18 (SD 0.9) in non-CKD patients, p < 0.0001). Independent of CKD status, Hispanics and Asians had a lower grip strength compared with non-Hispanic whites, and obese and overweight patients had a higher grip strength z-score compared with normal weight patients; underweight patients tended to have a lower grip strength z-score (Table 3). Most importantly, after adjusting for race and body mass index, having CKD remained significantly associated with lower grip strength (− 0.53 [95% confidence interval − 0.67; − 0.39]). The effect of BMI was similar in both CKD patients and healthy controls (p = 0.67). The association between CKD and lower grip strength was unchanged after excluding patients with a known history of neuropsychological disease from the analysis (− 0.50 [95% confidence interval − 0.63; − 0.40]).
Table 2.
Characteristics of the CKiD participants and age-sex-height individually matched NHANES participants for 555 person-visits with grip strength data available
| Characteristics | CKiD (n = 555) | NHANES (n = 555) | p value |
|---|---|---|---|
| Age (years) | 14(11–17) | 14(11–17) | 1 |
| Male sex | 357 (64%) | 357 (64%) | 1 |
| Height (cm) | 158 (145; 168) | 158 (145; 168) | 1 |
| Race/ethnicity | <0.0001 | ||
| Hispanic White | 69 (12%) | 185 (33%) | |
| Non-Hispanic White | 337 (61%) | 148(31%) | |
| Non-Hispanic Black | 90 (16%) | 132 (24%) | |
| Asian | 11 (2%) | 62 (11%) | |
| Other | 48 (9%) | 28 (5%) | |
| Body mass index | < 0.0001 | ||
| Obese | 59(11%) | 106 (19%) | |
| Overweight | 128 (23%) | 98 (18%) | |
| Normal | 353 (64%) | 351 (63%) | |
| Thin | 9 (1%) | 0 (0%) |
Table 3.
Association between CKD status and mean grip strength z-score adjusted by race and body mass index, N = 1110
| Characteristics | Difference in mean grip strength z-score | 95% confidence interval | p value |
|---|---|---|---|
| CKD | − 0.53 | − 0.67, − 0.39 | <0.0001 |
| Race | |||
| Hispanic White | − 0.41 | − 0.57, − 0.25 | <0.0001 |
| Non-Hispanic White | 0 (reference) | NA | NA |
| Non-Hispanic Black | 0.01 | − 0.17, 0.19 | 0.88 |
| Asian | − 0.50 | − 0.75, − 0.25 | <0.0001 |
| Other | − 0.14 | − 0.39, 0.11 | 0.29 |
| Body mass index | |||
| Obese | 0.52 | 0.34, 0.70 | <0.0001 |
| Overweight | 0.21 | 0.07, 0.35 | 0.005 |
| Normal | 0 (reference) | NA | NA |
| Thin | − 0.91 | −1.67, − 0.25 | 0.007 |
Association between grip strength, CKD complications, physical activity, and quality of life
Table 4 presents the univariable association between various CKD complications or associated conditions and grip strength z-score. We confirmed the previously reported association of grip strength with race/ethnicity, BMI, and the positive association of height z-score with grip strength. We observed a positive association between age and grip strength z-score (increase of 0.04 SD [0.02; 0.06] in grip strength per 1-year increase in age). A statistically significant negative association with grip strength z-score was also observed for duration of CKD (average decrease of 0.02 SD [95% CI − 0.04; − 0.01] in grip strength per additional year with CKD), pre-pubertal status (average decrease of 0.55 SD [95% CI − 0.60; − 0.20] in grip strength for Tanner stage 1 vs. 5), delayed puberty (− 0.62 SD [95% CI − 1.29; 0.05] in grip strength), neuropsychiatric comorbidities (− 0.56 SD [− 1.03; − 0.10]), need of feeding support (− 0.58 SD [− 0.95; − 0.21]), prescribed alkali therapy (− 0.40 SD [− 0.64;− 0.17]), and hemoglobin (− 0.07 SD [0.03; 0.11] per 1-g/dL decrease in hemoglobin). There was a trend towards an association between a decreased grip strength z-score and hyperparathyroidism and high-grade proteinuria. We did not find any association between inflammation (CRP) or FGF23 levels and grip strength z-score.
Table 4.
Univariable linear mixed models to quantify association of several factors with GS z-score among children with chronic kidney disease, n = 699 person-visits contributed by 411 CKiD participants
| Characteristics | Effect on mean grip strength z-score | 95% confidence interval | p value |
|---|---|---|---|
| Age (per year) | 0.04 | 0.02;0.06 | <0.0001 |
| Duration of CKD (in years) adjusted for age | − 0.02 | − 0.04; − 0.01 | 0.03 |
| Non-glomerular CKD etiology (vs. glomerular) | − 0.13 | − 0.33; 0.07 | 0.19 |
| Race | |||
| Hispanic White | − 0.44 | 0.71; − 0.16 | 0.002 |
| Non-Hispanic White | Reference | ||
| Non-Hispanic Black | 0.02 | − 0.23; 0.26 | 0.90 |
| Asian | − 1.17 | −1.73; − 0.61 | <0.0001 |
| Other | − 0.28 | − 0.59; 0.03 | 0.07 |
| Body mass index | |||
| Obese | 0.80 | 0.50; 1.11 | <0.0001 |
| Overweight | 0.27 | 0.05; 0.49 | 0.01 |
| Normal | Reference | ||
| Thin | −1.06 | −1.84; − 0.27 | 0.008 |
| Severe thinness | − 0.89 | − 2.45; 0.67 | 0.26 |
| Age-sex-specific height z-score, per 1 SDS increase | 0.52 | 0.45; 0.58 | <0.0001 |
| Tanner stage¥ | |||
| 1 | − 0.55 | − 0.60; − 0.20 | <0.0001 |
| 2 | − 0.57 | − 0.91; − 0.23 | 0.001 |
| 3 | − 0.33 | − 0.69; 0.03 | 0.07 |
| 4 | − 0.04 | − 0.37; 0.28 | 0.80 |
| 5 | Reference | ||
| Delayed puberty | − 0.62 | −1.29; 0.05 | 0.07 |
| Neuropsychiatric comorbidities | − 0.56 | −1.03; − 0.10 | 0.02 |
| Appetite (over the past week) | |||
| Very good | Reference | ||
| Good | 0.01 | −0.13; 0.16 | 0.90 |
| Fair | − 0.16 | − 0.39; 0.06 | 0.15 |
| Poor | − 0.26 | − 0.70; 0.16 | 0.21 |
| Very poor | 0.11 | − 0.88; 1.10 | 0.83 |
| Feeding support (NG tube/gastrostomy and/or supplements) | − 0.58 | − 0.95– 0.21 | 0.003 |
| Alkali therapy | − 0.40 | − 0.64; − 0.17 | 0.0008 |
| Current steroid treatment | 0.44 | 0.04; 0.84 | 0.03 |
| Proteinuria (uPC mg/mg) | Reference | ||
| ≤ 0.2 | Reference | ||
| 0.2–2.0 | − 0.10 | − 0.27; 0.09 | 0.30 |
| >2.0 | − 0.24 | − 0.63; 0.01 | 0.06 |
| iPTH >130 pg/mL (~ 2 N) | − 0.39 | − 0.78; 0.01 | 0.05 |
| CRP > 10 mg/L | − 0.03 | − 0.48; 0.42 | 0.90 |
| Hemoglobin (g/dL)¥ | 0.07 | 0.03; 0.11 | 0.0005 |
| FGF23 c-term¥ | 0.00 | 0.001; 0.001 | 0.22 |
| FGF-23 intact¥ | 0.00 | 0.00; 0.00 | 0.96 |
| History of broken bone¥ | 0.07 | −0.15; 0.28 | 0.54 |
Missing: Tanner stage N = 263, delayed puberty N = 209, appetite N = 32, hemoglobin N = 42, FGF 23 N = 425, broken bone N = 28, hemoglobin N = 42, height z-score N = 30
Association of grip strength with physical activity and quality of life in children with CKD
We observed a statistically significant association between grip strength z-score and both the frequency and intensity of physical activity (Table 5). The number of days with over 60 min of physical activity over the last week (p = 0.008), the number of day per week with vigorous activity (p = 0.0002), and the practice of vigorous activity for more than 10 min (p = 0.002) were all associated with a significantly higher grip strength z-score. We did not found any association between grip strength z-score and time spent playing videogames or watching television.
Table 5.
Association between physical activity assessment and grip strength z-score in children with CKD, N = 639 person-visits contributed by 388 CKiD participants
| Characteristics | Median (IQR) or N (%) | Mean effect per one unit increase in exercise | 95% confidence interval | p value |
|---|---|---|---|---|
| Number of days with > 60-min exercise over past 7 days | 5 [3–8] | 0.06 | 0.02 | 0.008 |
| Number of days with > 20-min sweating/breathing hard exercise over past 7 days | 3 [1–5] | 0.02 | 0.02 | 0.31 |
| Number of days with > 30-min non-sweating/breathing hard exercise over past 7 days | 4 [2–6] | − 0.02 | 0.02 | 0.24 |
| Number of sports team played during last 12 months | 0 [0–2] | 0.07 | 0.04 | 0.09 |
| Patients with vigorous activity for > 10 min | 353 (54%) | 0.36 | 0.11 | 0.002 |
| Number of days/week with vigorous activity | 1 [0–4] | 0.09 | 0.02 | 0.0002 |
Finally, mean (SD) quality-of-life scores were 76 (16) and 78 (14) for parent- and participant-reported quality of life, respectively. There was a significant positive association between grip strength z-score and both parent-reported (r = 0.11, p = 0.01) and patient-reported quality of life (r = 0.14, p = 0.02). However, after taking into account repeated measurements by patients, each one SD increase in grip strength was associated with only a 1.6 (SE 0.6) average increase in parent-reported quality-of-life score and an average increase of 1.5 (SE 0.6) in patient-reported quality-of-life score.
Discussion
In this study, we demonstrated that children with CKD have lower muscle strength compared with healthy children independently of age, sex, race, and other factors known for impacting muscle strength such as height and BMI. However, despite the strong association between the presence of CKD and lower muscle strength, among CKD patients, we only found significant differences in grip strength in those with an eGFR < 90 mL/min per 1.73 m2 (stages 2 to 5) compared with > 90 (stage 1). This absence of a strong correlation between the severity of the CKD and the severity of grip strength reduction suggests that factors other than eGFR either mediate or modulate the impact of CKD on muscle strength.
Previous studies reported impaired muscle strength in adults and children with advanced CKD and end-stage renal disease (ESRD) [12,15]. However, there is a paucity of data in children prior to ESRD. Tenbrock et al. found decreased grip strength in 14 pediatric patients with an eGFR <60 mL/min/1.73 m2, including 6 transplanted patients and 1 patient on peritoneal dialysis [11]. They also found a strong correlation between patient age and grip strength, with younger patients having lower grip strength z-scores. Our study agrees with these findings and suggests that early and chronic exposure to CKD, more than severity of CKD, is associated with the loss of muscle strength. Indeed, we found that younger patients with non-glomerular diseases and longer duration of CKD were at a higher risk of impaired grip strength. Conversely, eGFR was only moderately associated with grip strength, and no association was observed between eGFR and grip strength in patients with glomerular diseases. Moreover, among patients with repeated measures, there was no correlation between eGFR decline and grip strength decline at the individual level. Whereas this could be explained by the moderate change in eGFR between grip strength assessments, it also potentially supports the important contribution of factors other than eGFR determining grip strength in children with CKD.
A strength of the CKiD cohort, besides providing longitudinal follow-up of participants, is the data collection on a large number of clinical and biological variables. This allowed us to explore the association of various complications or CKD-associated comorbidities with muscle strength. We observed that patients with growth retardation, who needed nutritional support, and with low physical activity have a higher prevalence of impaired muscle strength. The concept of frailty has become a focus in adults with chronic diseases, and evaluation has included assessment for decreased muscle strength, along with weight loss, decreased physical activity, exhaustion, and other markers of poor physical performance [16, 17]. In a recent study of pediatric liver disease patients, there was a strong association between frailty score and severity of disease [18]. Similarly, a recent study from the CKiD cohort reported a high prevalence of various frailty indicators (sub-optimal growth, low muscle mass, fatigue, and inflammation) in children with CKD and found an association between those indicators and various complications such as infection and hospitalization [19]. Our study demonstrates that different aspects of the frailty syndrome are correlated with each other in children with CKD. Hence, screening children with CKD for decreased muscle strength, low physical activity levels, weight loss, and other measures of frailty may identify children who could benefit from interventions. In fact, interventions are already available, including growth hormone for short stature, alkali therapy for acidosis, nutritional support for weight loss or poor growth, and exercise training to prevent muscle loss. Future efforts should test the ability of these interventions to reverse or prevent frailty in children with CKD.
The association of low physical activity with lower muscle strength raises the question of whether low physical activity is a cause or a consequence of impaired muscle strength [20, 21]. The design of our study precludes us from answering this question; however, it is likely that low physical activity at least participates in amplifying the loss of muscle strength. For example, studies in adults with ESRD have demonstrated that an exercise training program improves muscle strength [22–26]. In children, exercise training is beneficial in improving muscle strength in children with cerebral palsy [27] and glucose metabolism in overweight and obese children [28]. However, the effect of exercise training in children with CKD and ESRD, as well as the optimal exercise intervention, needs additional study.
The mechanisms mediating the decreased muscle strength observed in CKD remain poorly understood. Recently, Abramowitz et al. demonstrated increased muscle collagen content in humans with CKD, and found an association between collagen content and decreased muscle strength [29]. However, how CKD induces changes in muscle histology and function remains unknown. Previous studies suggested that inflammation [30] and impaired bone metabolism may mediate the association between CKD and low muscle strength. However, we did not find a significant relationship between inflammation markers (CRP) or markers of impaired bone metabolism (PTH, FGF23) with decreased grip strength, although there was a trend towards an association between high PTH and lower grip strength. Thus, these factors seem to be of secondary importance in the development of low muscle strength in children with CKD, but other studies using more specific markers of inflammation and bone metabolism are needed.
Finally, we observed that a decreased grip strength was associated with a decrease quality of life in children with CKD. Similar association has been reported in other children with chronic diseases but did not report the absolute change in PEDSQL score associated with muscle strength increase [31]. Indeed, Varni et al. demonstrated that the minimal clinically important difference in PEDSQL score was 4 and 4.5 points for patient-reported and parent-reported QOL, respectively [32]. In our study, a one SD increase in grip strength was associated with a 1.6 unit increase in PEDSQL score. Thus, despite this association, muscle strength does not seem to be a major factor impacting the quality of life of children with CKD and intervention aiming at improving muscle strength is unlikely to result in a clinically meaningful improvement of the patients’ quality of life.
This study is the first to demonstrate an association between CKD and poor muscle strength in children from a large and well-phenotyped cohort. However, our study has several limitations. The amount of longitudinal grip strength data available was low, with few patients experiencing a large eGFR decrease between assessments, which limited our power in testing for an association between eGFR decline and muscle strength decline. Similarly, the limited number of measurement in patients with advanced CKD (stage 4 or 5) may account for the absence of significant association between CKD severity and grip strength impairment. While the use of data from NHANES allowed us to compare our patients to well-matched healthy children, the lack of many potential mediators or confounders in the NHANES data precluded us from determining how these factors might affect the association between CKD and grip strength. We performed an exploratory analysis looking at CKD complications associated with grip strength, but further studies are needed to establish independent risk factors of impaired muscle strength in children with CKD.
Conclusion
CKD is associated with impaired muscle strength in children independently of growth retardation and BMI status. Exposure to CKD at a young age and for a prolonged time is associated with impaired muscle strength. Potential mediators of the impact of CKD on muscle strength include growth retardation, acidosis, poor nutritional status/low BMI, and low physical activity. Further studies are needed to assess the efficacy of interventions targeted at these risk factors.
Supplementary Material
Acknowledgments
Data in this manuscript were collected by the Chronic Kidney Disease in Children (CKiD) prospective cohort study with clinical coordinating centers (principal investigators) at Children’s Mercy Hospital and the University of Missouri – Kansas City (Bradley Warady, MD) and Children’s Hospital of Philadelphia (Susan Furth, MD, PhD), Central Biochemistry Laboratory (George Schwartz, MD) at the University of Rochester Medical Center, and data coordinating center (Alvaro Munoz, PhD and Derek Ng, PhD) at the Johns Hopkins Bloomberg School of Public Health. The CKiD study is supported by grants from the National Institute of Diabetes and Digestive and Kidney Diseases, with additional funding from the Eunice Kennedy Shriver National Institute of Child Health and Human Development, and the National Heart, Lung, and Blood Institute (U01-DK-66143, U01-DK-66174, U24-DK-082194, U24-DK-66116). The CKiD website is located at https://statepi.jhsph.edu/ckid.
Funding information This study was supported by a grant from the French Society of Pediatrics-Evian Societe Danone Eaux France and the Barry Warshaw Fund for Pediatric Nephrology Fellows at Emory University and the Children’s Healthcare of Atlanta and Emory University’s Pediatric Biomarkers Core.
Footnotes
Electronic supplementary material The online version of this article (https://doi.org/10.1007/s00467-019-04461-x) contains supplementary material, which is available to authorized users.
Compliance with ethical standards
The CKiD study (NCT00327860) was approved by an external study monitoring board appointed by the National Institute of Diabetes and Digestive and Kidney Diseases and by the institutional review board of each participating center, including Children’s National Health System. Informed consent of all individual participants included in the study was obtained by each center, and the study was conducted in accordance with the Declaration of Helsinki.
Conflict of interest The authors declare that they have no conflict of interest.
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