Acute Responses in Agonists of uEGF to Moderate-Intensity and High-Intensity Interval Exercise in Mid-Spectrum CKD

Urine epidermal growth factor (uEGF) is a novel biomarker utilized in assessing renal health in various renal diseases, specifically chronic kidney disease (CKD). uEGF promotes multiple intracellular pathways, stimulating renal cell growth, survival, and replication. uEGF production is activated by multiple agonists that bind to the uEGF receptor. Aerobic exercise initiates the upregulation of several of these agonists to increase the production of uEGF. Depending on the mode and intensity of aerobic exercise, uEGF agonists may activate differently in CKD populations. PURPOSE: To determine the influence of an acute bout of steady-state exercise (SSE) and high-intensity interval exercise (HIIE) on concentrations of uEGF agonists (serum insulin-like growth factor 1 (IGF-1), angiotensin II receptor type 1 (AGTR-1), and transforming growth factor beta 1 (TGF-β1)) in mid-spectrum CKD. METHODS: Twenty participants (n = 6 men; n = 14 women; age 62.0 + 9.9 yr; weight 80.9 + 16.2 kg; body fat 37.3 + 8.5% of weight; VO2max 19.4 + 4.7 ml/kg/min) completed 30 min of SSE at 65% VO2reserve or HIIE by treadmill walking (90% and 20% of VO2reserve in 3:2 min ratio) in a randomized crossover design. Both exercise conditions averaged ~ 65% VO2reserve. Blood and urine samples were obtained under standardized conditions just before, 1hr, and 24hrs after exercise. uEGF (ng/mL), serum IGF-1 (ng/mL), AGTR-1 (ng/mL), and TGF-β1 (pg/mL) responses were analyzed using 2 (condition) by 3 (sample point) repeated measures ANOVAs and Pearson Correlations. RESULTS: Serum IGF-1 and AGTR-1 increased 1hr and 24hr post-exercise in both exercise conditions; however, statistical significance was not achieved (p = 0.28 and p = 0.09). Similarly, serum TGF-β1 decreased at 24hrs in both exercise conditions but statistically remained unaltered (p = 0.42). IGF-1 was significantly correlated to uEGF in both conditions at all three-time points (p = 0.03), while AGTR-1 was significantly correlated to uEGF at 1hr in HIIE. uEGF findings were previously reported in ACSM abstract (DOI: 10.1249/01.mss.0000560710.72569.11). CONCLUSION: Agonists of uEGF remained unaltered following an acute bout of SSE and HIIE in mid-spectrum CKD. Further research is needed to understand better uEGF response activation to aerobic exercise in mid-spectrum CKD

Metabolic Phenotypes and Chronic Kidney Disease: A Cross-Sectional Assessment of Patients from a Large Federally Qualified Health Center

The purpose of this study is to determine if renal function varies by metabolic phenotype. A total of 9599 patients from a large Federally Qualified Health Center (FQHC) were included in the analysis. Metabolic health was classified as the absence of metabolic abnormalities defined by the National Cholesterol Education Program Adult Treatment Panel III criteria, excluding waist circumference. Obesity was defined as body mass index >30 kg/m2 and renal health as an estimated glomerular filtration rate (eGFR) >60 mL/min/1.73 m2. Linear and logistic regressions were used to analyze the data. The metabolically healthy overweight (MHO) phenotype had the highest eGFR (104.86 ± 28.76 mL/min/1.72 m2) and lowest unadjusted odds of chronic kidney disease (CKD) (OR = 0.46, 95%CI = 0.168, 1.267, p = 0.133), while the metabolically unhealthy normal weight (MUN) phenotype demonstrated the lowest eGFR (91.34 ± 33.28 mL/min/1.72 m2) and the highest unadjusted odds of CKD (OR = 3.63, p < 0.0001). After controlling for age, sex, and smoking status, the metabolically unhealthy obese (MUO) (OR = 1.80, 95%CI = 1.08, 3.00, p = 0.024) was the only phenotype with significantly higher odds of CKD as compared to the reference. We demonstrate that the metabolically unhealthy phenotypes have the highest odds of CKD compared to metabolically healthy individuals

The Influence of an Acute Bout of Aerobic Exercise on Vascular Endothelial Function in Moderate Stages of Chronic Kidney Disease

Chronic kidney disease (CKD) is directly influenced by the deleterious effects of systemic inflammation and oxidative stress. The vascular endothelium may transiently respond to aerobic exercise and improve post-exercise vascular renal function in moderate stages of CKD. Brachial artery flow-mediated dilation (FMD) is a nitric-oxide-dependent measure of endothelial function that is transiently potentiated by exercise. The purpose of the study was to determine the acute influence of a single bout of high-intensity interval exercise (HIIE) or steady-state moderate-intensity exercise (SSE) on endothelial dysfunction in moderate stages of CKD. Twenty participants (n = 6 men; n = 14 women) completed 30 min of SSE (65%) and HIIE (90:20%) of VO2reserve in a randomized crossover design. FMD measurements and blood samples were obtained before, 1 h, and 24 h post-exercise. FMD responses were augmented 1 h post-exercise in both conditions (p < 0.005). Relative to pre-exercise measures, total antioxidant capacity increased by 4.3% 24 h post-exercise (p = 0.012), while paraoxonase-1 was maintained 1 h and elevated by 6.1% 24 h after SSE, but not HIIE (p = 0.035). In summary, FMD can be augmented by a single episode of either HIIE or SSE in moderate stages of CKD. Modest improvements were observed in antioxidant analytes, and markers of oxidative stress were blunted in response to either SSE or HIIE

M13 Bacteriophage Display Framework That Allows Sortase-Mediated Modification of Surface-Accessible Phage Proteins

We exploit bacterial sortases to attach a variety of moieties to the capsid proteins of M13 bacteriophage. We show that pIII, pIX, and pVIII can be functionalized with entities ranging from small molecules (e.g., fluorophores, biotin) to correctly folded proteins (e.g., GFP, antibodies, streptavidin) in a site-specific manner, and with yields that surpass those of any reported using phage display technology. A case in point is modification of pVIII. While a phage vector limits the size of the insert into pVIII to a few amino acids, a phagemid system limits the number of copies actually displayed at the surface of M13. Using sortase-based reactions, a 100-fold increase in the efficiency of display of GFP onto pVIII is achieved. Taking advantage of orthogonal sortases, we can simultaneously target two distinct capsid proteins in the same phage particle and maintain excellent specificity of labeling. As demonstrated in this work, this is a simple and effective method for creating a variety of structures, thus expanding the use of M13 for materials science applications and as a biological tool.United States. Army Research Office. (Institute for Collaborative Biotechnologies Grant W911NF-09-0001