Acute Renal Responses to Moderate-Intensity Aerobic Exercise with Non-traditional markers of Renal Health and Function in Healthy Individuals: A Pilot Study

Aerobic exercise elicits a multitude of physiological improvements in both healthy and diseased populations. However, acute changes in renal function with aerobic exercise remain difficult to quantify by traditional marker serum creatinine (sCr) to estimate glomerular filtration rate (eGFR). Recently, novel biomarkers cystatin C (CyC) and urine epidermal growth factor (uEGF) have been introduced as more reliable markers of renal health and function to be used in conjunction with sCr to assess changes in renal health and function in mid-spectrum CKD. Potentially, greater changes in novel markers of renal health and function similar to mid-spectrum CKD can be observed in healthy individuals. PURPOSE: To determine if an acute bout of moderate-intensity aerobic exercise can transiently alter novel markers of renal health and function in healthy individuals. METHODS: Thirty-nine participants (n = 18 men; n = 21 women; age 32.5 + 12.6 yr; height 171.1 + 11.4 cm; weight 78.7 + 15.6 kg; BMI 27.1 + 5.8) completed a single acute bout of moderate-intensity (50-65% HRR) aerobic exercise. Blood and urine samples were collected pre-exercise and 15 minutes post-exercise by the same technician under standardized conditions and stored at -60 ºC until project completion. Serum creatinine (sCR), urine creatinine (uCr), urine epidermal growth factor (uEGF), uEGF/uCr ratio (uEGFR), cystatin C (CyC) and eGFR - modification of diet in renal disease (MDRD) and the CKD-EPI- responses were analyzed using a paired sample t-test. RESULTS: Relative to pre-exercise measures: sCR (p = 0.38), uEGF (p = 0.35), and uEGFR (p = 0.09) remained unchanged, whereas, uCr (p = 0.045) and CyC (p = 0.00) significantly changed post-exercise. There was a difference in uEGF pre- to post-exercise, but the standard deviation was large, likely preventing this from being significant. In contrasts MDRD (p = 0.04) significantly increased while CKD-EPI (p = 0.22) had no significant changes. CONCLUSION: Acute changes in traditional and novel biomarkers of renal health and function in healthy individuals remain unclear after an acute bout of moderate-intensity aerobic exercise. Further investigation focused on sampling time and exercise intensity is needed to solidify the current understanding of renal health and function

Is Age an Independent Factor in Assessing Renal Health and Function in Healthy Individuals? A Pilot Study

Estimated glomerular filtration rate (eGFR) is a measure of renal filtration and clearance of serum creatinine and is conventionally used to characterize the progressive decline in renal function. Assessment of renal function and health is traditionally believed to be age-dependent. However, in the absence of cardiometabolic diseases (hypertension, diabetes, hyperlipemia, etc.), this may not be the case. Recently, novel markers of renal health and function support the notion that age is a secondary factor influencing renal decline. PURPOSE: To determine the magnitude of age as an influencing factor involved in the decline of renal function with novel markers of renal health and function in the absence of cardiometabolic risk factors. METHODS: Thirty-nine participants (n = 18 men; n = 21 women; age 32.5 + 12.6 yr; height 171.1 + 11.4 cm; weight 78.7 + 15.6 kg; BMI 27.1 + 5.8; SBP 120 + 11.2; DBP 78 + 6.6; CHOL 173 + 30; and GLU 96 + 7) completed a single health assessment to quantify renal health and function. Blood and urine samples were collected by the same technician under standardized conditions and stored at -60 ºC until project completion. Serum creatinine (sCR), urine creatinine (uCr), urine epidermal growth factor (uEGF), uEGF/uCr ratio (uEGFR), cystatin C (CyC) and eGFR - modification of diet in renal disease (MDRD) and the CKD-EPI - responses were analyzed and compared in age groups (20s, 30s, 40s, 50s) using 4 (group) by 1 (sample) ANOVAs. RESULTS: There were no significant differences in markers of renal health and function between any age group. sCR (p = 0.90), uCr (p = 0.17), uEGF (p = 0.15), CyC (p = 0.32), uEGFR (p = 0.28), MDRD (p = 0.17), and CKD-EPI (p = 0.83). CONCLUSION: In healthy individuals, changes in renal health and function appear to be independent of age in the absence of cardiometabolic diseases. Indicating renal health and function could potentially be maintained throughout adulthood, middle age, and possibly attenuated in the senior years with the continued absence of cardiometabolic diseases

Abnormal myofiber morphology and limb dysfunction in claudication

Background Peripheral artery disease (PAD), which affects an estimated 27 million people in Europe and North America, is caused by atherosclerotic plaques that limit blood flow to the legs. Chronic, repeated ischemia in the lower leg muscles of PAD patients is associated with loss of normal myofiber morphology and myofiber degradation. In this study, we tested the hypothesis that myofiber morphometrics of PAD calf muscle are significantly different from normal calf muscle and correlate with reduced calf muscle strength and walking performance. Methods Gastrocnemius biopsies were collected from 154 PAD patients (Fontaine stage II) and 85 control subjects. Morphometric parameters of gastrocnemius fibers were determined and evaluated for associations with walking distances and calf muscle strength. Results Compared with control myofibers, PAD myofiber cross-sectional area, major and minor axes, equivalent diameter, perimeter, solidity, and density were significantly decreased (P \u3c 0.005), whereas roundness was significantly increased (P \u3c 0.005). Myofiber morphometric parameters correlated with walking distances and calf muscle strength. Multiple regression analyses demonstrated myofiber cross-sectional area, roundness, and solidity as the best predictors of calf muscle strength and 6-min walking distance, whereas cross-sectional area was the main predictor of maximum walking distance. Conclusions Myofiber morphometrics of PAD gastrocnemius differ significantly from those of control muscle and predict calf muscle strength and walking distances of the PAD patients. Morphometric parameters of gastrocnemius myofibers may serve as objective criteria for diagnosis, staging, and treatment of PAD

Abnormal Accumulation of Desmin in Gastrocnemius Myofibers of Patients with Peripheral Artery Disease: Associations with Altered Myofiber Morphology and Density, Mitochondrial Dysfunction and Impaired Limb Function

Patients with peripheral artery disease (PAD) develop a myopathy in their ischemic lower extremities, which is characterized by myofiber degeneration, mitochondrial dysfunction and impaired limb function. Desmin, a protein of the cytoskeleton, is central to maintenance of the structure, shape and function of the myofiber and its organelles, especially the mitochondria, and to translation of sarcomere contraction into muscle contraction. In this study, we investigated the hypothesis that disruption of the desmin network occurs in gastrocnemius myofibers of PAD patients and correlates with altered myofiber morphology, mitochondrial dysfunction, and impaired limb function. Using fluorescence microscopy, we evaluated desmin organization and quantified myofiber content in the gastrocnemius of PAD and control patients. Desmin was highly disorganized in PAD but not control muscles and myofiber content was increased significantly in PAD compared to control muscles. By qPCR, we found that desmin gene transcripts were increased in the gastrocnemius of PAD patients as compared with control patients. Increased desmin and desmin gene transcripts in PAD muscles correlated with altered myofiber morphology, decreased mitochondrial respiration, reduced calf muscle strength and decreased walking performance. In conclusion, our studies identified disruption of the desmin system in gastrocnemius myofibers as an index of the myopathy and limitation of muscle function in patients with PAD

High-Fat Diet Augments the Effect of Alcohol on Skeletal Muscle Mitochondrial Dysfunction in Mice

Previous studies have shown that chronic heavy alcohol consumption and consumption of a high-fat (HF) diet can independently contribute to skeletal muscle oxidative stress and mitochondrial dysfunction, yet the concurrent effect of these risk factors remains unclear. We aimed to assess the effect of alcohol and different dietary compositions on mitochondrial activity and oxidative stress markers. Male and female mice were randomized to an alcohol (EtOH)-free HF diet, a HF + EtOH diet, or a low-Fat (LF) + EtOH diet for 6 weeks. At the end of the study, electron transport chain complex activity and expression as well as antioxidant activity and expression, were measured in skeletal muscles. Complex I and III activity were diminished in muscles of mice fed a HF + EtOH diet relative to the EtOH-free HF diet. Lipid peroxidation was elevated, and antioxidant activity was diminished, in muscles of mice fed a HF + EtOH diet as well. Consumption of a HF diet may exacerbate the negative effects of alcohol on skeletal muscle mitochondrial health and oxidative stress

High-Fat Diet Augments the Effect of Alcohol on Skeletal Muscle Mitochondrial Dysfunction in Mice

Previous studies have shown that chronic heavy alcohol consumption and consumption of a high-fat (HF) diet can independently contribute to skeletal muscle oxidative stress and mitochondrial dysfunction, yet the concurrent effect of these risk factors remains unclear. We aimed to assess the effect of alcohol and different dietary compositions on mitochondrial activity and oxidative stress markers. Male and female mice were randomized to an alcohol (EtOH)-free HF diet, a HF + EtOH diet, or a low-Fat (LF) + EtOH diet for 6 weeks. At the end of the study, electron transport chain complex activity and expression as well as antioxidant activity and expression, were measured in skeletal muscles. Complex I and III activity were diminished in muscles of mice fed a HF + EtOH diet relative to the EtOH-free HF diet. Lipid peroxidation was elevated, and antioxidant activity was diminished, in muscles of mice fed a HF + EtOH diet as well. Consumption of a HF diet may exacerbate the negative effects of alcohol on skeletal muscle mitochondrial health and oxidative stress

Oxidative damage in the gastrocnemius of patients with peripheral artery disease is myofiber type selective

Background: Peripheral artery disease (PAD), a manifestation of systemic atherosclerosis that produces blockages in the arteries supplying the legs, affects approximately 5% of Americans. We have previously, demonstrated that a myopathy characterized by myofiber oxidative damage and degeneration is central to PAD pathophysiology. Objectives: In this study, we hypothesized that increased oxidative damage in the myofibers of the gastrocnemius of PAD patients is myofiber-type selective and correlates with reduced myofiber size. Methods: Needle biopsies were taken from the gastrocnemius of 53 PAD patients (28 with early PAD and 25 with advanced PAD) and 25 controls. Carbonyl groups (marker of oxidative damage), were quantified in myofibers of slide-mounted tissue, by quantitative fluorescence microscopy. Myofiber cross-sectional area was determined from sarcolemma labeled with wheat germ agglutinin. The tissues were also labeled for myosin I and II, permitting quantification of oxidative damage to and relative frequency of the different myofiber Types (Type I, Type II and mixed Type I/II myofibers). We compared PAD patients in early (N=28) vs. advanced (N=25) disease stage for selective, myofiber oxidative damage and altered morphometrics. Results: The carbonyl content of gastrocnemius myofibers was higher in PAD patients compared to control subjects, for all three myofiber types (p<0.05). In PAD patients carbonyl content was higher (p<0.05) in Type II and I/II fibers compared to Type I fibers. Furthermore, the relative frequency and cross-sectional area of Type II fibers were lower, while the relative frequencies and cross-sectional area of Type I and Type I/II fibers were higher, in PAD compared to control gastrocnemius (p<0.05). Lastly, the type II-selective oxidative damage increased and myofiber size decreased as the disease progressed from the early to advanced stage. Conclusions: Our data confirm increased myofiber oxidative damage and reduced myofiber size in PAD gastrocnemius and demonstrate that the damage is selective for type II myofibers and is worse in the most advanced stage of PAD