Association of uric acid in serum and urine with subclinical renal damage: Hanzhong Adolescent Hypertension Study.

BACKGROUND AND OBJECTIVES: The aim of the study was to examine the associations of uric acid (UA) in blood and urine with subclinical renal damage (SRD) and its progression in a Chinese cohort. METHODS: 1) 2342 participants from our previously established cohort who were followed up in 2017 were included. Cross-sectional analysis was used to examine the relationships between serum and urinary UA and the risk of SRD. 2) A total of 266 participants were recruited from the same cohort in 2013, and followed up in 2017. Longitudinal analysis was used to determine the relationships of serum and urinary UA with progression of SRD, which was defined as urinary albumin-to-creatinine ratio (uACR) progression or estimated glomerular filtration rate (eGFR) decline. RESULTS: In cross-sectional analysis, higher levels of uACR were associated with higher levels of serum uric acid (SUA) and urinary uric acid/creatinine ratio (uUA/Cre). Lower eGFR was associated with higher levels of SUA and fractional excretion of uric acid (FEUA) but lower uUA/Cre levels in all subjects. In addition, the multivariate-adjusted odds ratios for SRD compared with non-SRD were 3.574 (2.255-5.664) for uUA/Cre. Increasing uUA/Cre levels were associated with higher risk of SRD. In longitudinal analysis, 4-year changes of uUA/Cre and SUA were significantly associated with eGFR decline. CONCLUSIONS: This study suggested that urinary UA excretion was significantly associated with the risk of SRD in Chinese adults. Furthermore, 4-year changes of serum and urinary UA were associated with SRD progression. These findings suggest that UA, especially urinary UA, may be used as a simple, noninvasive marker for early detection of decreased renal function in otherwise healthy subjects.

Association between urinary sodium excretion and uric acid, and its interaction on the risk of prehypertension among Chinese young adults.

High uric acid (UA) level and high salt intake are reportedly associated with cardiovascular disease. This study investigated the association between UA and urinary sodium excretion, as well as its interaction on the risk of prehypertension. A total of 1869 participants without hypertension were recruited from a previously established cohort in Shaanxi Province, China. The participants were classified as normotensive or prehypertensive on the basis of their blood pressure. Increasing quartiles of sodium excretion were associated with high urinary UA/creatinine levels in prehypertensive participants. Estimated sodium excretion positively correlated with urinary UA/creatinine excretions in the prehypertensive group. In addition, the multivariate-adjusted odds ratios for prehypertension compared with normotension were 1.68 (1.27-2.22) for sodium excretion and 1.71 (1.21-2.42) for serum UA. Increasing sodium excretion and serum UA were associated with higher risk of prehypertension. Compared with the lowest quartiles, the highest sodium excretion and serum UA quartiles entailed 3.48 times greater risk of prehypertension. Sodium excretion is associated with urinary UA excretion in prehypertensive participants. The present study shows that high levels of salt intake and serum UA simultaneously are associated with a higher risk of prehypertension.

The Relationships of the Fractional Excretion of Uric Acid with Brachial-Ankle Pulse Wave Velocity and Ankle Brachial Index in Chinese Young Adults.

BACKGROUND/AIMS: Elevated serum uric acid (UA) was intimately correlated with vascular stiffness and abnormal ankle brachial index (ABI) in various populations. These correlations lost significance after adjustment for estimated glomerular filtration rate (eGFR), indicating that the association of UA and brachial-ankle pulse wave velocity (baPWV) or ABI might be driven by kidney function. UA is predominantly eliminated through the kidneys, and metabolic disorders can influence the clearance of UA. In this study, we aimed to explore the putative correlation between FEUA and baPWV or ABI to determine to what extent the associations with UA were affected by renal function. METHODS: This cross-sectional study enrolled 2351 participants, who underwent general health screening in Hanzhong people's hospital from March to June of 2017. BaPWV and ABI were measured using a volume-plethysmographic apparatus (BP-203RPEII; Nihon Colin, Tokyo, Japan). FEUA was divided into quartiles: Q1:FEUA≤3.07; Q2: 3.07 9.19. RESULTS: Lower FEUA predicted a higher prevalence of high baPWV and low ABI (p for trend <0.001). The respective ORs for high baPWV from the first to the third quartiles of FEUA were 1.777(1.323, 2.387); 1.561(1.158, 2.104); and 1.680 (1.250, 2.259). The prevalence of low ABI was greatly elevated with the decrement of FEUA [ORs for the first to third FEUA quartiles were 6.977(2.062, 23.610); 5.123(1.475, 17.790); and 2.685(0.709, 10.171), respectively]. The association of FEUA and ABI was independent of related confounding factors. However, the association between FEUA and baPWV was greatly influenced by corresponding confounders, especially gender. The efficacy of FEUA in the prediction of low ABI was stronger than that of serum UA. However, serum UA was more powerful in the prediction of high baPWV. CONCLUSION: Kidney function exerted a profound influence on the relationship between UA and baPWV or ABI, revealing complex interactions among cardiovascular risk factors.

Effect of Salt Intake on Plasma and Urinary Uric Acid Levels in Chinese Adults: An Interventional Trial.

Uric acid (UA) has been proposed as an important risk factor for cardiovascular and renal morbidity. We conducted an interventional trial to assess effects of altered salt intake on plasma and urine UA levels and the relationship between UA levels and salt sensitivity in humans. Ninety subjects (18-65 years old) were sequentially maintained on a normal diet for 3 days at baseline, a low-salt diet for 7 days (3.0 g/day, NaCl), and a high-salt diet for an additional 7 days (18.0 g/day of NaCl). Plasma UA levels significantly increased from baseline to low-salt diet and decreased from low-salt to high-salt diet. By contrast, daily urinary levels of UA significantly decreased from baseline to low-salt diet and increased from low-salt to high-salt diet. The 24 h urinary sodium excretions showed inverse correlation with plasma UA and positive correlation with urinary UA excretions. Additionally, salt-sensitive subjects presented significantly higher plasma UA changes in comparison to salt-resistant subjects, and a negative correlation was observed between degree of salt sensitivity and plasma UA difference. The present study indicates that variations in dietary salt intake affect plasma and urine UA levels, and plasma UA may be involved in pathophysiological process of salt sensitivity.

Effect of Salt Intake on Serum Glucagon-Like Peptide-1 Levels in Normotensive Salt-Sensitive Subjects.

BACKGROUND/AIMS: Excess dietary salt is a critical risk factor of salt-sensitive hypertension. Glucagon-like peptide-1 (GLP-1) , a gut incretin hormone, conferring benefits for blood pressure by natriuresis and diuresis. We implemented a randomized trial to verify the effect of altered salt intake on serum GLP-1 level in human beings. METHODS: The 38 subjects were recruited from a rural community of Northern China. All subjects were sequentially maintained a baseline diet period for 3 days, a low-salt diet period for 7 days (3.0g/day of NaCl) , and a high-salt diet period for additional 7 days (18.0g/day of NaCl). RESULTS: Serum GLP-1 level increased significantly with the change from the baseline period to the low-salt diet period and decreased with the change from the low-salt to high-salt diet in normotensive salt-sensitive (SS) but not salt-resistant (SR) individuals. There was a significant inverse correlation between the serum GLP-1 level and the MAP in SS subjects. Inverse correlation between the serum GLP-1 level and 24-h urinary sodium excretion was also found among different dietary interventions in SS subjects. CONCLUSIONS: Our study indicates that variations in dietary salt intake affect the serum GLP-1 level in normotensive salt-sensitive Chinese adults.

The Role of Uric Acid in Hypertension of Adolescents, Prehypertension and Salt Sensitivity of Blood Pressure.

Uric acid is the end product of purine metabolism. Metabolic disorders of uric acid are associated with many disease states. Substantial evidence suggests the possible role of uric acid as a mediator of high blood pressure. Elevated uric acid is closely associated with new onset essential hypertension in adolescents and prehypertension; and urate-lowering agents can significantly improve these early stages of hypertension. Uric acid also influences salt sensitivity of blood pressure through two phases. Local renin-angiotensin-aldosterone system activation initiates renal damage, arteriolopathy, and endothelium dysfunction, which is followed by the dysregulation of sodium homeostasis, thereby leading to increased salt sensitivity. In this review we summarize the available evidence to contribute to a better understanding of the casual relationship between uric acid and early or intermediate stages of hypertension. We hope our review can contribute to the prevention of hypertension or provide new insights into a treatment that would slow the progression of hypertension.

Plasma Renalase is Not Associated with Blood Pressure and Brachial-Ankle Pulse Wave Velocity in Chinese Adults With Normal Renal Function.

BACKGROUND/AIMS: This study aimed to investigate the association of renalase with blood pressure (BP) and brachial-ankle pulse wave velocity (baPWV) in order to better understand the role of renalase in the pathogenesis of hypertension and atherosclerosis. METHODS: A total of 344 subjects with normal kidney function were recruited from our previously established cohort in Shaanxi Province, China. They were divided into the normotensive (NT) and hypertensive (HT) groups or high baPWV and normal baPWV on the basis of BP levels or baPWV measured with an automatic waveform analyzer. Plasma renalase was determined through an enzyme-linked immunosorbent assay. RESULTS: Plasma renalase did not significantly differ between HT and NT groups (3.71 ± 0.69 µg/mL vs. 3.72 ± 0.73 µg/mL, P = 0.905) and between subjects with and without high baPWV (3.67 ± 0.66 µg/mL vs. 3.73 ± 0.74 µg/mL, P = 0.505). However, baPWV was significantly higher in the HT group than in the NT group (1460.4 ± 236.7 vs. 1240.7 ± 174.5 cm/s, P < 0.001). Plasma renalase was not correlated with BP levels and baPWV in the entire group. Linear and logistic regression analysis revealed that plasma renalase was not significantly associated with hypertension and high baPWV. CONCLUSION: Plasma renalase may not be associated with BP and baPWV in Chinese subjects with normal renal function.

Association of Renalase SNPs rs2296545 and rs2576178 with the Risk of Hypertension: A Meta-Analysis.

BACKGROUND/AIMS: Two renalase single nucleotide polymorphisms (SNPs) rs2296545 and rs2576178 have been reported to be associated with the susceptibility to hypertension (HT). Given the inconsistent results, we conducted a meta-analysis to assess the association between these two SNPs and the risk of HT. METHODS: Electronic databases were systematically searched to find relevant studies. Subgroup analysis was conducted according to the different concomitant diseases and ethnicities in the study population. Pooled odds ratios (OR) and 95% confidence intervals (CI) were calculated using fixed-effect or random-effect models. RESULTS: A total of six case-control studies on rs2296545 and six studies on rs2576178 were included. In the combined analysis, results showed a significant association between SNP rs2296545 and risk of HT in all genetic models (dominant model CG+CC/GG: OR = 1.43, 95% CI = 1.24-1.65; recessive model CC/CG+GG: OR = 1.36, 95% CI = 1.09-1.69; codominant model CC/GG: OR = 1.63, 95% CI = 1.20-2.20, CG/GG: OR = 1.30, 95% CI = 1.12-1.52; allelic model C/G: OR = 1.29, 95% CI = 1.10-1.51). In subgroup analysis, we observed a significant association between rs2296545 and risk of essential HT. Although we did not observe an association between rs2576178 polymorphism and HT in the combined analysis, an increased risk was observed in the essential HT patients versus healthy controls (subgroup 1) analysis under the dominant, recessive, and codominant genetic models. CONCLUSIONS: Renalase gene rs2296545 polymorphism is significantly associated with increased risk of HT, whereas rs2576178 polymorphism may not be associated with the susceptibility to HT.

Effects of Renin-Angiotensin System Inhibitors on Renal Expression of Renalase in Sprague-Dawley Rats Fed With High Salt Diet.

BACKGROUND/AIMS: The aim of our study was to investigate the effect of high-salt diet on the renal expression of renalase and the potential role of the local renin-angiotensin system in this process. METHODS: Sprague-Dawley (SD) rats were divided into groups according to salt content in diet and drug treatment as follows: normal-salt diet (NS), high-salt diet (HS), high-salt intake with hydralazine (HS+H), high-salt diet with enalapril (HS+E), and high-salt diet with valsartan (HS+V). The dietary intervention and drugs were given for four weeks. Renin activity and angiotensin II type 1 receptor (AT1R) levels were detected by real-time PCR. Renalase mRNA and protein were also measured. RESULTS: After four weeks, systolic blood pressure and proteinuria were significantly increased in the HS group with respect to the NS group. Dietary salt intake caused a dramatic decrease in renalase expression in the rat kidneys. Renal cortex renin and AT1R increased significantly in the HS and HS+H groups. Urinary protein was positively correlated with renal renin and AT1R levels. However, in the HS+E and HS+V groups, enalapril and valsartan failed to influence renal renalase expression but abolished the increase in proteinuria, renal cortex renin, and AT1R levels with respect to the HS group. CONCLUSION: This study indicates that high salt intake reduces renal expression, and renal RAS may be not involved in the regulation of renalase in SD rats fed with high-salt diet.