Estimated proximal tubule fluid phosphate concentration and renal tubular damage biomarkers in early stages of chronic kidney disease.

INTRODUCTION: An increase in proximal tubule fluid phosphate concentration is caused by increased serum fibroblast growth factor 23 (FGF23) levels, which resulted in renal tubular damage in a mouse model of chronic kidney disease (CKD). However, few human studies have supported this concept. This study aimed to explore the association among estimated proximal tubule fluid phosphate concentration (ePTFp), serum FGF23 levels, and renal tubular damage biomarkers in middle-aged and older populations with mild decline in renal function. METHODS: This cross-sectional study included 218 participants aged ≥45 with CKD stages G2-G4. Anthropometric measurements, blood tests, spot urine biomarkers, renal ultrasonography, cardiovascular assessment, smoking status, and medication usage were obtained in the morning in fasted states. The ePTFp was calculated using serum creatinine, urine phosphate, and creatinine concentrations. Urinary ß2-microglobulin and liver-type fatty acid-binding protein (L-FABP) levels were evaluated to assess renal tubular damage. RESULTS: ePTFp, serum FGF23, urinary ß2-microglobulin, and urinary L-FABP levels increased with CKD stage progression (stages G2, G3, and G4). However, serum and urine phosphate concentrations were comparable across the CKD stages. Univariate analysis revealed a stronger correlation of ePTFp with serum FGF23, urinary ß2-microglobulin, and urinary L-FABP levels than with the corresponding serum and urine phosphate concentrations. Multivariate analyses demonstrated that increased ePTFp was independently associated with elevated serum FGF23 and urinary ß2-microglobulin levels, even after adjusting for potential covariates, including the estimated glomerular filtration rate and urinary albumin-to-creatinine ratio. CONCLUSIONS: Our results are consistent with the concept in mouse model and suggest that increased ePTFp are associated with increased serum FGF23 levels and renal tubular damage during the early stages of CKD.

Impact of Plant and Animal Protein-Based Meals on Serum Fibroblast Growth Factor-23 Levels in Healthy Young Men: A Randomized Crossover Trial.

Fibroblast growth factor-23 (FGF23) is a phosphaturic hormone secreted by osteocytes in response to dietary phosphate intake. An increase in FGF23 level is an indicator of excess phosphate intake relative to the residual nephron number. Therefore, avoiding excessive phosphate intake and inhibiting the elevation of serum FGF23 levels are important to preserve the number of functional nephrons. This randomized crossover trial aimed to determine the potential differences in the impacts on serum FGF23 levels between plant protein and animal protein-based meals in individuals with normal renal function. Nine young men were administered plant (no animal protein) or animal protein-based meals (70% of their protein was from animal sources) with the same phosphate content. The test meals consisted of breakfast, lunch, and dinner. Blood samples were collected in the morning, after overnight fasting, and before and after eating the test meals (for two consecutive days at the same hour each day). Furthermore, a 24-h urine sample was obtained on the day the test meal was consumed. No significant interactions were found among serum phosphate, calcium, and 1,25-dihydroxyvitamin D levels. However, after eating plant protein-based meals, serum FGF23 levels decreased and serum intact parathyroid hormone levels increased (interaction, p<0.05). Additionally, urine 24-h phosphate excretion tended to be lower in individuals consuming plant protein-based meals than in those consuming animal protein-based meals (p=0.06). In individuals with normal renal function, plant protein-based meals may prevent an increase in serum FGF23 levels and kidney damage caused by phosphate loading.

Combined effects of sleep and objectively-measured daily physical activity on arterial stiffness in middle-aged and older adults.

Although sleep quality and physical activity (PA) may influence on arterial stiffness, the combined effects of these two factors on arterial stiffness remain unknown. A total of 103 healthy middle-aged and older men and women (aged 50-83 years) with no history of cardiovascular disease and depression were included in this study. Arterial stiffness was measured using carotid-femoral pulse wave velocity (cfPWV), brachial-ankle PWV (baPWV), and femoral-ankle PWV (faPWV). Poor sleepers were defined as those with a Pittsburgh Sleep Quality Index score of >5.5. Using an accelerometer for seven consecutive days, low levels of PA were defined as low moderate-to-vigorous-intensity PA (MVPA) <19.0 min/day and low step counts <7100 steps/day, respectively. Poor sleepers with low PA levels, as determined by MVPA and daily steps, showed higher cfPWV, but not faPWV or baPWV, in middle-aged and older adults. Furthermore, in the analysis of covariance (ANCOVA) analyses adjusted for age, obesity, dyslipidemia, and sedentary behavior, the cfPWV result remained significant. Our study revealed that the coexistence of poor sleep quality and decreased PA (low MVPA or daily steps) might increase central arterial stiffness in middle-aged and older adults. Therefore, adequate sleep (good and sufficient sleep quality) and regular PA, especially at appropriate levels of MVPA (i.e., at least of 7100 steps/day), should be encouraged to decrease central arterial stiffness in middle-aged and older adults.

Ascending aortic impedance in young endurance athletes: a time-resolved phase-contrast MRI study.

Ventricular-vascular coupling in endurance athletes remains incompletely understood. The purpose of this study was to determine the ascending aortic impedance in endurance athletes and explore its associations with traditional cardiovascular measurements. In 15 young male endurance runners and 19 young healthy men, time-resolved (CINE) two-dimensional (2-D) phase-contrast MRI quantified the ascending aortic flow while the pressure waveform was simultaneously collected via a generalized transfer function. The aortic impedance modulus and phase were calculated in the frequency domain while characteristic impedance (ZcF) was calculated by averaging moduli between the 4th and 8th heart rate (HR) harmonics. Stroke volume (SV), left ventricular (LV) morphometry, double product, aortic compliance, and total peripheral resistance (TPR) were also measured. Endurance athletes had higher SV, slower HR, greater LV end-diastolic volume and mass, and lower double product than sedentary participants (all P < 0.05). ZcF was significantly lower in athletes than in sedentary participants (73.3 ± 19.2 vs. 93.4 ± 19.0 dyn·s/cm5, P = 0.005). Furthermore, ZcF was negatively correlated with SV (r = -0.691) and aortic compliance (r = -0.601) but was positively correlated with double product (r = 0.445) and TPR (r = 0.458; all P < 0.05). Multivariate analysis revealed that ZcF was the strongest predictor of SV followed by TPR and HR (adjusted R2 = 0.788, P < 0.001). Therefore, our findings collectively suggest that LV afterload quantified by aortic ZcF is significantly lower in endurance athletes than in sedentary adults. The lower pulsatile LV afterload may contribute to greater SV in endurance athletes.NEW & NOTEWORTHY This is the first study to investigate aortic impedance with the noninvasive, simultaneous recordings of aortic pressure using SphygmoCor XCEL and flow using phase-contrast MRI. We found that the characteristic impedance (Zc) is significantly lower in endurance athletes than sedentary adults, is the strongest predictor of stroke volume (SV), and is inversely associated with aortic compliance. These findings suggest that aortic impedance is a key determinant of the ventricular-vascular coupling adapted to long-term training in endurance athletes.

Effects of plant- and animal-based-protein meals for a day on serum nitric oxide and peroxynitrite levels in healthy young men.

Plant-based diets that replace animal-based proteins with plant-based proteins have received increased attention for cardiovascular protection. Nitric oxide (NO) plays an essential role in the maintenance of endothelial function. However, under higher oxidative stress, NO generation produces peroxynitrite, a powerful oxidant and vasoconstrictor. Diet-replaced protein sources has been reported to decrease oxidative stress. However, the effects of plant-based protein on NO and peroxynitrite have not yet been clarified. Therefore, this study aimed to compare the effects of plant- and animal-based-protein meals for a day on NO, peroxynitrite, and NO/peroxynitrite balance. A crossover trial of two meal conditions involving nine healthy men was performed. Participants ate standard meals during day 1. On day 2, baseline measurements were performed and the participants were provided with plant-based-protein meals or animal-based-protein meals. The standard and test meals consisted of breakfast, lunch, and dinner and were designed to be isocaloric. Plant-based-protein meals contained no animal protein. Blood samples were collected in the morning after overnight fasting before and after the test meals consumption. In the plant-based-protein meal condition, serum NOx levels (the sum of serum nitrite and nitrate) significantly increased, while serum peroxynitrite levels did not change significantly. Animal-based-protein meals significantly increased serum peroxynitrite levels but showed a trend of reduction in the serum NOx levels. Furthermore, serum NO/peroxynitrite balance significantly increased after plant-based-protein meals consumption, but significantly decreased after animal-based-protein meals consumption. These results suggest that, compared with animal-based-protein meals, plant-based-protein meals increase NO levels and NO/peroxynitrite balance, which reflects increased endothelial function.

Association of Lower Extremity Muscle Strength and Function with Renal Resistive Index in Individuals with and without Chronic Kidney Disease.

Age-related loss of lower extremity muscle strength is pronounced in individuals with chronic kidney disease (CKD). In contrast, an increase in intrarenal flow pulsatility results in initial age-related changes in renal hemodynamics, leading to the development of CKD. To date, it remains unclear whether lower extremity muscle strength determines elevated renal flow pulsatility. This study aimed to determine the association of lower extremity muscle strength and function with intrarenal hemodynamics in individuals with and without CKD. One hundred seventy-six individuals without CKD (aged 63 ± 9 years) and 101 individuals with CKD (aged 66 ± 8 years) were included in this study. Using Doppler ultrasound, the renal resistive index (RI) was measured as a parameter of renal hemodynamics. Knee extensor muscle strength (KES), gait speed (GS), and the 30 s chair stand test (30s-CST) were used to measure lower extremity muscle strength and function. Multivariate analyses showed that GS and 30s-CST scores were independent determinants of renal RI, whereas the KES score was not associated with renal RI in individuals with and without CKD. In the two-way analysis of covariance, renal RI was the highest in individuals with CKD who had lower KES, GS, and 30s-CST scores. Reduced lower extremity muscle strength and function are independent determinants of elevated renal flow pulsatility in individuals with and without CKD.