Muscle mass and plasma myostatin after exercise training: a substudy of Renal Exercise (RENEXC)-a randomized controlled trial.

BACKGROUND: Sarcopenia increases as renal function declines and is associated with higher morbidity and mortality. Myostatin is a negative regulator of muscle growth. Its expression in response to exercise is unclear. In this prespecified substudy of the Renal Exercise (RENEXC) trial, we investigated the effects of 12 months of exercise training on sarcopenia, muscle mass and plasma myostatin and the relationships between physical performance, muscle mass and plasma myostatin. METHODS: A total of 151 non-dialysis-dependent patients (average measured glomerular filtration rate 23 ± 8 mL/min/1.73 m2), irrespective of age or comorbidity, were randomly assigned to either strength or balance in combination with endurance training. Body composition was measured with dual-energy X-ray absorptiometry. Plasma myostatin was analysed using enzyme-linked immunosorbent assay kits. RESULTS: After 12 months, the prevalence of sarcopenia was unchanged, leg and whole-body lean mass increased significantly in the balance group and was unchanged in the strength group. Whole fat mass decreased significantly in both groups. There were no significant between-group differences in sarcopenia or body composition. Plasma myostatin levels increased significantly in both groups, with a significant difference in favour of the strength group. Plasma myostatin was significantly positively related to muscle mass and physical performance at baseline, but these relationships were attenuated after 12 months. CONCLUSIONS: Exercise training seems to be effective in preventing sarcopenia and maintaining muscle mass in non-dialysis-dependent patients with chronic kidney disease (CKD). However, the role of plasma myostatin on muscle mass and physical performance in patients with CKD warrants further study.

Twelve months of exercise training did not halt abdominal aortic calcification in patients with CKD - a sub-study of RENEXC-a randomized controlled trial.

BACKGROUND: Arteriosclerosis is prevalent in patients with chronic kidney disease (CKD). Our aims were to investigate (1) the effects of 12 months of either balance- or strength- both in combination with endurance training on abdominal aortic calcification (AAC); on some lipids and calcific- and inflammatory markers; and (2) the relationships between the change in AAC score and these markers in non-dialysis dependent patients with CKD stages 3 to 5. METHODS: One hundred twelve patients (mean age 67 ± 13 years), who completed 12 months of exercise training; comprising either balance- or strength training, both in combination with endurance training; with a measured glomerular filtration rate (mGFR) 22.6 ± 8 mL/min/1.73m2, were included in this study. AAC was evaluated with lateral lumbar X-ray using the scoring system described by Kauppila. Plasma fetuin-A, fibroblast growth factor 23 (FGF23) and interleukin 6 (IL6) were measured with Enzyme-linked immunosorbent assay (ELISA) kits. RESULTS: After 12 months of exercise training, the AAC score increased significantly in both groups; mGFR and lipoprotein (a) decreased significantly in both groups; parathyroid hormone (PTH) and 1,25(OH)2D3 increased significantly only in the strength group; fetuin-A increased significantly only in the balance group. Plasma triglycerides, total cholesterol, high-density lipoprotein cholesterol, low-density lipoprotein cholesterol, FGF23, phosphate, calcium, IL6, C-reactive protein (CRP), albumin were unchanged. The increase in AAC score was positively related to ageing and the levels of baseline triglycerides and lipoprotein (a). CONCLUSIONS: Exercise training did not prevent the progression of AAC; it might have contributed to the reduced levels of lipoprotein (a) and unchanged levels of calcific- and inflammatory markers in these patients with non-dialysis dependent CKD. Hypertriglyceridemia, high levels of lipoprotein (a) and ageing emerged as longitudinal predictors of vascular calcification in these patients. TRIAL REGISTRATION: NCT02041156 at www.ClinicalTrials.gov. Date of registration: January 20, 2014. Retrospectively registered.

Sarcopenia and relationships between muscle mass, measured glomerular filtration rate and physical function in patients with chronic kidney disease stages 3-5.

Background: Sarcopenia and poor physical function are common in patients with chronic kidney disease (CKD). Our aim was to investigate the relationships between muscle mass and measured glomerular filtration rate (GFR) and between muscle mass and strength and balance, respectively, in patients with CKD stages 3-5. Methods: This is a baseline data analysis of a randomized controlled clinical trial. A total of 148 adult patients with an estimated GFR <30 mL/min/1.72 m2, not on renal replacement therapy, irrespective of the number of comorbidities were included from the Department of Nephrology, Skåne University Hospital, Lund, from 2011 to 2016. Body composition was measured by dual-energy X-ray absorptiometry (DEXA). GFR was measured by iohexol clearance. Balance was measured by functional reach and the Berg balance test and strength by handgrip strength and isometric quadriceps strength. Results: Measured GFR ranged from 8 to 55 mL/min/1.73 m2. Lean mass (P < 0.05), fat mass (P < 0.05), appendicular skeletal muscle (P < 0.001) and appendicular skeletal muscle index (P < 0.05) were associated with GFR. Functional reach was associated with leg lean mass (P < 0.05) and the Berg balance test score was associated with trunk lean mass (P < 0.05). Handgrip strength was associated with arm lean mass (P < 0.001). Isometric quadriceps strength was associated with leg lean mass (P < 0.001). More men (44%) suffered from low muscle mass than women (22%), whereas more women (36%) suffered from low muscle strength than men (26%). However, when combining both, men (16%) suffered from sarcopenia to a greater extent than women (8%). Conclusions: Among patients with CKD stages 3-5, loss of lean body mass, especially appendicular skeletal muscle, was significantly related to GFR decline. Two important markers of physical function, balance and strength, were significantly related to muscle mass. Moreover, men were more prone to sarcopenia than women during kidney function decline.

Relationships between abdominal aortic calcification, glomerular filtration rate, and cardiovascular risk factors in patients with non-dialysis dependent chronic kidney disease
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BACKGROUND: Abdominal aortic calcification (AAC) is an established risk factor for cardiovascular events in patients with chronic kidney disease (CKD). We hypothesized that AAC is associated with a decline in glomerular filtration rate (GFR) as well as with some other cardiovascular risk factors. MATERIALS AND METHODS: This is a cross-sectional analysis of baseline data from a randomized controlled clinical trial (RENEXC). A total of 151 patients (aged 66 ± 14 years) with an average measured GFR (mGFR) of 22.5 ± 8.2 mL/min/1.73m2, not on renal replacement therapy, irrespective of number of comorbidities, were included. GFR was measured with iohexol clearance and estimated using cystatin C- and creatinine-based equations (eGFR). AAC was evaluated with lateral lumbar X-ray using the scoring system described by Kauppila. All patients underwent laboratory analyses, 24-hour ambulatory blood pressure monitoring, and standard echocardiography. Multiple linear regression analyses controlling for sex, age, cardiovascular comorbidities, and hypertension were performed. RESULTS: The prevalence of AAC in this group of patients was 73%, and 47% had severe calcification (AAC score ≥ 7). More men (76%) had AAC than women (69%). AAC score was associated with mGFR (p = 0.03), eGFR (p = 0.006), plasma albumin (p = 0.006), plasma phosphate (p = 0.01), pulse pressure (p = 0.004), left ventricular mass (LVM) (p = 0.02), left atrial volume (LAV; p < 0.001), and left atrial volume index (LAVI; p = 0.001). CONCLUSION: AAC was highly prevalent in CKD. The degree of calcification in the abdominal aorta was strongly associated with a decline in GFR, a decrease in plasma albumin, an increase in plasma phosphate, an increase in pulse pressure, and cardiac structural changes, such as an increase in LVM, LAV, and LAVI.
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Decline in measured glomerular filtration rate is associated with a decrease in endurance, strength, balance and fine motor skills.

AIM: Physical performance in chronic kidney disease affects morbidity and mortality. The aim was to find out which measures of physical performance are important in chronic kidney disease (CKD) and if there are associations with declining measured glomerular filtration rate (GFR). METHODS: Endurance was assessed by 6 min walk test (6-MWT) and stair climbing, muscular endurance by 30 s sit to stand, heel rises and toe lifts, strength by quadriceps- and handgrip-strength, balance by functional reach and Berg's balance scale, and fine motor skills by Moberg's picking-up test. GFR was measured by Iohexol clearance. RESULTS: The study comprised 101 patients with CKD 3b-5 not started dialysis, 40 women and 61 men, with a mean age of 67 ± 13 (range: 22 - 87) years. All measures of physical performance were impaired. A decrease in GFR of 10 mL/min per 1.73 m2 corresponded to a 35 metre shorter walking distance in the 6-MWT. Multivariable linear regression analysis showed significant relationships between decline in GFR and the 6-MWT (P = 0.04), isometric quadriceps strength left (P = 0.04), balance measured as functional reach (P = 0.02) and fine motor skills in the left hand as measured by Moberg's picking-up test (P = 0.01), respectively, after sex, age, comorbidity and the interaction between sex and age had been taken into account. CONCLUSION: Endurance, muscular endurance, strength, balance and fine motor skills were impaired in patients with CKD 3b-5. Walking capacity, isometric quadriceps strength, balance, and fine motor skills were associated with declining GFR. The left extremities were more susceptible to GFR, ageing and comorbidities and seem thus to be more sensitive.

Relationship between declining glomerular filtration rate and measures of cardiac and vascular autonomic neuropathy.

AIM: Cardiac and vascular autonomic neuropathy contributes to increased morbidity and mortality in patients with chronic kidney disease. The aim of this study was to analyze the effects of a decline in glomerular filtration rate (GFR) on heart rate variability (HRV) and nocturnal blood pressure dipping. METHODS: This cross-sectional study comprises 124 patients (46 women, 78 men; age 66 ± 14 years) with chronic kidney disease (CKD) 3-5, not on renal replacement therapy. GFR was measured with iohexol clearance, HRV with 24 h Holter electrocardiogram (ECG) and nocturnal dipping with 24 hour ambulatory blood pressure. RESULTS: The GFR was 22.5 ± 8.5 mL/min per 1.73 m2 . The main finding was a significant curvilinear association between the 24 h standard deviation of NN interval (24SDNN) in the HRV analysis and GFR (P = 0.01), logGFR (P = 0.006), diabetes mellitus (P = 0.05) and beta blocker treatment (0.03), respectively. The effect of diabetes mellitus on 24SDNN corresponded to a decline in GFR from 30 to 12 mL/min per 1.73 m2 . There were significant curvilinear associations between systolic nocturnal dipping (P = 0.02) and diastolic nocturnal dipping (P = 0.05), respectively, and diabetes mellitus but not with GFR or logGFR. CONCLUSION: In conclusion, cardiac sympathetic overdrive and decreased vagal control appear during CKD 4 and 5. The association with GFR is curvilinear. Diabetes mellitus was significantly associated with both cardiac and vascular autonomic neuropathy, as measured by heart rate variability and nocturnal blood pressure dipping, respectively. Knowing that arrhythmias, often due to sympathetic hyperactivity, are an important cause of sudden death in the dialysis population, this study contributes important knowledge on possible intervention thresholds.

Small distal muscles and balance predict survival in end-stage renal disease.

BACKGROUND/AIMS: Survival for patients on renal replacement therapy (RRT) has been shown to correlate to the level of physical activity and exercise capacity. We examined whether composite measures of functional status at the start of RRT predict survival. METHODS: In this retrospective study, the same physiotherapist, using a standardized battery of tests for functional status, tested 134 patients at the start of RRT. RESULTS: At the end of the observation period, 112 patients (84%) were still alive. Age (p < 0.0001), co-morbidity (p = 0.028), hand grip strength (right: p = 0.0065; left: p = 0.0039), standing heel rise (right: p = 0.011; left: p = 0.004) and functional reach (p = 0.015) were significant predictors of survival. After adjustment for sex, age and co-morbidity, hand grip strength left (p = 0.023) was a significant predictor of survival. CONCLUSION: Hand grip strength, standing heel rise and functional reach at the start of RRT seem to affect survival. A 50% reduction in hand grip strength left was associated with an almost 3-fold increase in mortality. Deterioration of function in small distal muscles and balance may be early signs of uraemic myopathy. A relatively simple and clinically feasible battery of tests can help detect patients at risk.

Bone mineral density after exercise training in patients with chronic kidney disease stages 3 to 5: a sub-study of RENEXC-a randomized controlled trial.

Background: We evaluated the effects of 12 months of exercise training on bone mineral density (BMD) in patients with chronic kidney disease (CKD) stages 3-5 not on kidney replacement therapy (KRT). Methods: A total of 151 patients were randomized to 12 months of either balance or strength training, both together with endurance training. Some 112 patients completed and 107 (69 men, 38 women) were analysed, with a mean age 66 ± 13.5 years and 31% having diabetes. The exercise training was self-administered, prescribed and monitored by a physiotherapist. Total body, hip and lumbar BMD, T score and Z score were measured at baseline and after 12 months using dual energy X-ray absorptiometry. Results: Both groups showed increased physical performance. The prevalence of osteoporosis and osteopenia was unchanged. The strength group (SG) decreased total body BMD (P < .001), the balance group (BG) increased total body T score (P < .05) and total body Z score (P < .005). Total body ΔT score was negative in the SG and unchanged in the BG (P < .005). Total body ΔZ score was negative in the SG and positive in the BG (P < .001). The proportion of progressors measured by ΔT (P < .05) and ΔZ scores (P < .05) was significantly lower in the BG compared with the SG. In multivariate logistic regression analysis, belonging to the BG was the only factor with a lower risk of deterioration of total body BMD, T and Z scores. Conclusions: Twelve months of balance training together with endurance training seemed to be superior to strength training in maintaining and improving BMD in patients with CKD not on KRT.

Central venous stenosis after subclavian versus internal jugular dialysis catheter insertion (CITES) in adults in need of a temporary central dialysis catheter: study protocol for a two-arm, parallel-group, non-inferiority randomised controlled trial.

BACKGROUND: The right internal jugular vein is currently recommended for temporary central dialysis catheters (tCDC) based on results from previous studies showing a lower incidence of central vein stenosis compared to the subclavian vein. Data is however conflicting, and there are several advantages when the subclavian route is used for tCDCs. This prospective, controlled, randomised, non-inferiority study aims to compare the incidence of post-catheterisation central vein stenosis between the right subclavian and the right internal jugular routes. METHODS: Adult patients needing a tCDC will be included from several hospitals and randomised to either subclavian or internal jugular vein catheterisation with a silicone tCDC. Inclusion continues until 50 patients in each group have undergone a follow-up CT venography. The primary outcome is the incidence of post-catheterisation central vein stenosis detected by a CT venography performed 1.5 to 3 months after removal of the tCDC. Secondary outcomes include between-group comparisons of (I) the patients' experience of discomfort and pain, (II) any dysfunction of the tCDC during use, (III) catheterisation success rate and (IV) the number of mechanical complications. Furthermore, the ability to detect central vein stenosis by a focused ultrasound examination will be evaluated using the CT venography as golden standard. DISCUSSION: The use of the subclavian route for tCDC placement has largely been abandoned due to older studies with various methodological issues. However, the subclavian route offers several advantages for the patient. This trial is designed to provide robust data on the incidence of central vein stenosis after silicone tCDC insertion in the era of ultrasound-guided catheterisations. TRIAL REGISTRATION: Clinicaltrials.gov; NCT04871568. Prospectively registered on May 4, 2021.

Randomized Controlled Trial of Exercise in CKD-The RENEXC Study.

INTRODUCTION: Home-based, clinically feasible trials in non-dialysis-dependent patients with chronic kidney disease (CKD) are sparse. We compared the effects of 2 different exercise training programs on physical performance, and measured glomerular filtration rate (mGFR) and albuminuria level in patients with CKD stages 3 to 5. METHODS: This is a single-center, randomized controlled trial (RCT) comprising 151 patients (mGFR: 22 ± 8 ml/min per 1.73 m2; age 66 ± 14 years) randomized to either balance or strength training. Both groups were prescribed 30 minutes of exercise per day for 5 days per week for 12 months, comprising 60 minutes per week of endurance training and 90 minutes per week of either strength or balance exercises. The exercises were individually prescribed, and the intensity was monitored with Borg's rating of perceived exertion (RPE). RESULTS: There were no treatment differences for any of the primary outcomes measuring physical performance. The strength and balance groups showed significantly increased effect sizes after 12 months for the following: walking (31 m and 24 m, P < 0.001) and the 30-second sit-to-stand test (both: 1 time, P < 0.001); quadriceps strength (right/left: strength 1.2/0.8 kg*m, P < 0.003; balance 0.6/0.9, P < 0.01); functional reach (both: 2 cm, P < 0.01); and fine motor skills (open/closed eyes, right/left, both: between 0.3 and 4 seconds faster, P < 0.05). After 12 months, there was a significant treatment difference for albuminuria (P < 0.02), which decreased by 33% in the strength group. In both groups, mGFR declined by 1.8 ml/min per 1.73 m2. CONCLUSION: Our primary hypothesis that strength training was superior to balance training was not confirmed. Within groups, 12 months of exercise training resulted in significant improvements in most measures of physical performance. Measured GFR declined similarly in the 2 groups. The strength group showed a significant decrease in albuminuria.

Comparing effects of 4 months of two self-administered exercise training programs on physical performance in patients with chronic kidney disease: RENEXC - A randomized controlled trial.

BACKGROUND: Exercise training is recommended to patients with chronic kidney disease (CKD). However, the level of evidence is still low. This randomized controlled trial (RCT) compared two different and self-administered exercise training programs in a representative CKD population. METHODS: This single centre RCT included 151 non-dialysis dependent CKD patients, irrespective of age and comorbidity. Self-administered exercise training of 150 minutes per week was prescribed for 4 months and consisted of 60 minutes endurance training in combination with 90 minutes of either strength or balance training (strength versus balance group). Overall endurance (6-minute walk-test (6-MWT), stair climbing), muscular endurance (30-seconds sit-to-stand (30-STS), heel rises and toe lifts, handgrip (HGS) and isometric quadriceps (IQS) strength, balance (functional reach (FR) and Berg´s balance scale (BBS)) and fine motor skills (Moberg´s picking up test (MPUT)) were measured at baseline and after 4 months. Intention to treat analyses with mixed models was used. RESULTS: 53 women and 98 men, mean age 66 ± 14: range 19 to 87 years, eGFR 20 ± 7: range 8 to 48 ml/min/1.73m2 participated. The strength group (n = 76) improved significantly in 6-MWT, stair climbing, 30-STS, heel rises right and left, toe lifts right, IQS right and left, and MPUT with closed eyes with the right and left hand. The balance group (n = 75) improved significantly in heel rises right and left, IQS left, BBS and left-handed MPUT with open and closed eyes. A significant effect between the groups was found for IQS right. CONCLUSIONS: Two different exercise training programs, consisting of endurance in combination with either strength or balance exercise training, improved or maintained overall endurance, muscular strength and endurance, balance and fine motor skills after 4 months of 150 minutes/week self-administered exercise training in a representative CKD population, regardless of age and comorbidity.