Patricia L. Gordon

Effects of Resistance Exercise Training and Nandrolone Decanoate on Body Composition and Muscle Function among Patients Who Receive Hemodialysis: A Randomized, Controlled Trial

Patients who are on hemodialysis commonly experience muscle wasting and weakness, which have a negative effect on physical functioning and quality of life. The objective of this study was to determine whether anabolic steroid administration and resistance exercise training induce anabolic effects among patients who receive maintenance hemodialysis. A randomized 2 x 2 factorial trial of anabolic steroid administration and resistance exercise training was conducted in 79 patients who were receiving maintenance hemodialysis at University of California, San Francisco-affiliated dialysis units. Interventions included double-blinded weekly nandrolone decanoate (100 mg for women; 200 mg for men) or placebo injections and lower extremity resistance exercise training for 12 wk during hemodialysis sessions three times per week using ankle weights. Primary outcomes included change in lean body mass (LBM) measured by dual-energy x-ray absorptiometry, quadriceps muscle cross-sectional area measured by magnetic resonance imaging, and knee extensor muscle strength. Secondary outcomes included changes in physical performance, self-reported physical functioning, and physical activity. Sixty-eight patients completed the study. Patients who received nandrolone decanoate increased their LBM by 3.1 +/- 2.2 kg (P < 0.0001). Exercise did not result in a significant increase in LBM. Quadriceps muscle cross-sectional area increased in patients who were assigned to exercise (P = 0.01) and to nandrolone (P < 0.0001) in an additive manner. Patients who exercised increased their strength in a training-specific fashion, and exercise was associated with an improvement in self-reported physical functioning (P = 0.04 compared with nonexercising groups). Nandrolone decanoate and resistance exercise produced anabolic effects among patients who were on hemodialysis. Further studies are needed to determine whether these interventions improve survival.

Resistance Training Increases Muscle Mitochondrial Biogenesis in Patients with Chronic Kidney Disease

BACKGROUND AND OBJECTIVES Muscle wasting, a common complication in chronic kidney disease (CKD), contributes to poor outcomes. Mitochondrial biogenesis is critical for the maintenance of skeletal muscle function and structural integrity. The present study--a secondary analysis from a published randomized controlled trial--examined the effect of resistance exercise training on skeletal muscle mitochondrial (mt)DNA copy number and determined its association with skeletal muscle phenotype (muscle mass and strength). DESIGN, SETTING, PARTICIPANTS, & MEASUREMENTS Twenty-three patients with moderate-to-severe CKD were randomized to resistance training (n = 13) or an attention-control (n = 10) group for 12 weeks. After a run-in period of a low-protein diet that continued during the intervention, mtDNA copy number in the vastus lateralis muscle was estimated by quantitative real-time PCR at baseline and 12 weeks. RESULTS Participants mean age was 64 +/- 10 (SD) years and median (interquartile range, IQR) GFR 27.5 (37.0) ml/min. There were no differences between groups at baseline. Median (IQR) mtDNA copy number was 13,713 (10,618). There was a significant increase in muscle mtDNA with exercise compared with controls (1306 [13306] versus -3747 [15467], P = 0.01). The change in muscle mtDNA copy number was positively correlated with previously reported changes in types I and II muscle fiber cross-sectional area. CONCLUSIONS In this pilot study, resistance training was highly effective in enhancing mitochondrial content in patients with moderate-to-severe CKD. This finding suggests that the mitochondrial dysfunction observed with chronic disease could potentially be restored with this exercise modality and should be investigated further.

Management of Osteoporosis in CKD Stages 3 to 5

Osteoporosis and chronic kidney disease (CKD) are both common conditions of older adults and both may be associated with substantial morbidity. However, biochemical and histologic changes that occur with progressive kidney disease require specific interventions, some of which may be concordant with osteoporosis management in the general population, whereas others may be less relevant or perhaps even harmful. In this article, we review the diagnosis of and management strategies for osteoporosis in individuals with CKD, placing these into perspective with the recently published KDIGO (Kidney Disease: Improving Global Outcomes) guidelines for treatment of CKD-mineral and bone disorder (CKD-MBD). Specifically, we highlight osteoporosis treatment recommendations by CKD stage and discuss new avenues for osteoporosis treatment that may be useful in individuals with CKD.

Association of 1,25-Dihydroxyvitamin D Levels With Physical Performance and Thigh Muscle Cross-sectional Area in Chronic Kidney Disease Stage 3 and 4

BACKGROUND Declines in 1,25-dihydroxyvitamin D (1,25(OH)₂D) levels and physical functioning follow the course of chronic kidney disease (CKD). Although the molecular actions of vitamin D in skeletal muscle are well known, and muscle weakness and atrophy are observed in vitamin D-deficient states, there is little information regarding vitamin D and muscle function and size in CKD. OBJECTIVE To examine associations of vitamin D with physical performance (PF) and muscle size. DESIGN Cross-sectional. SETTING CKD clinic. SUBJECTS Twenty-six patients (61 ± 13 years, 92% men) with CKD stage 3 or 4. MAIN OUTCOME MEASURES Gait speed, 6-minute walk, sit-to-stand time, 1-legged balance, and thigh muscle cross-sectional area (MCSA), measured by magnetic resonance imaging (MRI). RESULTS Overall, 73% were 25-hydroxyvitamin D (25(OH)D) deficient (n = 10) or insufficient (n = 9) (Kidney Disease Outcomes Quality Initiative guidelines). 25(OH)D level was associated with normal gait speed only (r = 0.41, P = .04). Normal and fast gait speed, the distance walked in 6 minutes, and sit-to-stand time were best explained by 1,25(OH)₂D and body mass index (P < .05 for all) and 1-legged stand by 1,25(OH)₂D (r = 0.40, P < .05) only. There were no associations of age, estimated glomerular filtration rate (eGFR), intact parathyroid hormone (iPTH), or albumin with any PF measures. MCSA was associated with eGFR (r = 0.54, P < .01) only. Variance in MCSA was best explained by a model containing 1,25(OH)₂D, plasma Ca²⁺, and daily physical activity (by accelerometry) (P < .05 for all). Once these variables were in the model, there was no contribution of eGFR. CONCLUSION These results suggest that 1,25(OH)₂D is a determinant of PF and muscle size in patients with stage 3 and 4 CKD.

Correlates of Physical Functioning and Performance Across the Spectrum of Kidney Function.

The aim of this study was to determine the extent to which poor physical functioning, low participation in physical activity, and muscle atrophy observed among patients on hemodialysis are evident in the earlier stages of chronic kidney disease (CKD). We enrolled adults in three groups: no CKD, Stages 3 to 4 CKD, and hemodialysis. Outcomes measured were physical activity, muscle size, thigh muscle strength, physical performance, and self-reported physical function. Patients with CKD had muscle area intermediate between the no CKD and hemodialysis groups, but they had low levels of physical activity that were similar to the hemodialysis group. Physical activity and muscle size were significantly associated with all outcomes. Kidney function was not significantly associated with muscle strength or physical performance after adjustment for physical activity and muscle size. In conclusion, interventions aimed to increase muscle mass and energy expenditure might have an impact on improving physical function of CKD patients.