Objective:To investigate the association between body mass index (BMI) trajectories in children and adolescents and subclinical renal damage (SRD) in adulthood.Methods:4 623 participants aged 6-18 years old were recruited from the ongoing cohort of Hanzhong adolescent hypertension study in 1987, and the subjects were followed up in 1989, 1992, 1995, 2005, 2013 and 2017, respectively. Group-based trajectory modeling was used to identify distinct BMI trajectories in longitudinal analysis. Generalized linear model was applied to examine the association between different BMI trajectories and SRD incidence in adulthood.Results:A total of 2 678 subjects from childhood to adulthood were enrolled in this study. All subjects were divided into three groups according to three distinct BMI trajectories: low-increasing BMI group ( n=1 017), moderate-increasing BMI group ( n=1 353), and high-increasing BMI group ( n=308). Over follow up for 30 years, a total of 248 participants (9.3%) developed SRD. Urinary albumin-to-creatinine ratio (uACR) in low to high-increasing BMI group was 0.9(0.6, 1.4), 1.0(0.7, 1.7), 1.6(0.8, 3.2), respectively ( P trend<0.001), and estimated glomerular filtration rate was 98.5(87.6, 111.6) , 96.2(86.4, 109.7), 95.3 (87.5, 125.0) ml·min -1·(1.73 m 2) -1, respectively ( P trend=0.025). The generalized linear model analysis showed that uACR was increased linearly from low to high-increasing BMI group [ β=3.16(95% CI 1.02-5.31), Ptrend=0.004]. There was no correlation or linear trend between BMI trajectory and estimated glomerular filtration rate [ β=-2.30(95% CI-5.18-0.57), Ptrend=0.117]. Compared with the low-increasing BMI group, the high-increasing BMI group had greater odds of experiencing SRD in adulthood after adjusting for multiple confounders such as age, gender, medical history and lifestyle ( OR=2.83, 95% CI 1.84-4.36, Ptrend<0.001). Conclusions:Higher BMI trajectorie is correlated with higher level of uACR and risk of SRD in middle age. Identifying long-term BMI trajectorie from early age may assist in predicting individuals′ renal function in later life.

【Objective】 To explore the effects of dietary salt intake on serum and urinary levels through the chronic salt loading intervention. 【Methods】 Eighty adults （18 to 65 years old） were screened from two villages in Liquan and Lantian counties to participate in a 2-week chronic salt intervention， including a 3-day baseline survey， a 7-day low-salt diet， and a 7-day high-salt diet. Uromodulin levels in serum and urine were determined by enzyme-linked immunosorbent assay （ELISA） kits. According to the baseline blood pressure levels， all subjects were divided into normotensive and hypertensive groups. Pearson or Spearman correlation analyzed the associations of 24 h urinary sodium excretions with serum and urinary levels of uromodulin. 【Results】 At the baseline， serum uromodulin in hypertensive subjects was significantly lower than that in normotensive subjects （26.7±9.9 vs. 57.9±9.7 ng/mL， P=0.033）. Serum uromodulin levels were significantly lower on a high-salt diet than on a baseline diet ［（54.9±8.8 vs. 28.3±4.5） ng/mL， P=0.007］. In addition， daily urinary excretions of uromodulin were lower on a high-salt diet ［（28.4±6.6） ng/mL］ than on a baseline diet ［（282.1±70.0） ng/mL］ and on a low-salt diet ［（154.1±21.3） ng/mL］. The 24 h urinary sodium excretions were inversely correlated with urinary uromodulin excretions （r=-0.40， P<0.001） on both low-salt and high-salt diets， but not correlated with serum uromodulin levels. 【Conclusion】 Variations in dietary salt intake significantly affect plasma and urine uromodulin levels.

【Objective】 To investigate the relationship of miRNA gene polymorphisms with blood pressure (BP) responses to the sodium and potassium diet intervention. 【Methods】 In 2004, we recruited 514 participants from 124 families in seven villages of Baoji, Shaanxi Province, China. All subjects were given a three-day normal diet, followed by a seven-day low-salt diet, a seven-day high-salt diet, and finally a seven-day high-salt and potassium supplementation. A total of 19 miRNA single nucleotide polymorphisms (SNPs) were selected for analysis. 【Results】 Throughout the sodium-potassium dietary intervention, the BP of the subjects fluctuated across all phases, showing a decrease during the low-salt period and an increase during the high-salt period, followed by a reduction in BP subsequent to potassium supplementation during the high-salt diet. MiR-210-3p SNP rs12364149 was significantly associated with systolic BP (SBP), diastolic BP (DBP) and mean arterial pressure (MAP) responses to low-salt diet. MiR-4638-3p SNP rs6601178 was significantly associated with SBP while miR-26b-3p SNP rs115254818 was significantly associated with MAP responses to low-salt intervention. In addition, miR-26b-3p SNP rs115254818 was significantly correlated with SBP, DBP and MAP responses to high-salt intervention. MiR-1307-5p SNPs rs11191676 and rs2292807 were associated with SBP and MAP responses to high-salt diet. MiR-4638-3p SNP rs6601178, miR-210-3p SNP rs12364149, miR-382-5p SNP rs4906032 and rs4143957 were significantly associated with SBP response to high-salt diet. In addition, miR-26b-3p SNP rs115254818 was significantly associated with SBP, DBP and MAP responses to potassium supplementation. MiR-1307-5p SNPs rs11191676, rs2292807, and miR-19a-3p SNP rs4284505 were significantly associated with SBP responses to high-salt and potassium supplementation. 【Conclusion】 miRNA gene polymorphisms are associated with BP response to sodium and potassium, suggesting that miRNA genes may be involved in the pathophysiological process of salt sensitivity and potassium sensitivity.

【Objective】 To investigate the association between genetic variations in the glucagon-like peptide-1 receptor (GLP-1R) gene and BP responses to sodium and potassium intake. 【Methods】 A total of 514 subjects from 124 families were recruited in Meixian County, Shaanxi Province, in 2004, resulting in the establishment of a "salt-sensitive hypertension study cohort" . The subjects followed a dietary regimen which involved a normal diet for 3 days, a low-salt diet for 7 days, a high-salt diet for 7 days, and a high-salt potassium-supplemented diet for 7 days. BP measurement was conducted at different intervention periods, and peripheral blood samples were collected. Additionally, eight single nucleotide polymorphisms (SNPs) of the GLP-1R gene were genotyped using the MassARRAY detection platform. 【Results】 The GLP-1R gene SNP rs9462472 exhibited a significant association with systolic BP, diastolic BP, and mean arterial pressure response to high-salt intervention. Similarly, SNP rs2268637 showed a significant association with systolic BP response to high-salt intervention. Furthermore, SNP rs2268637 was significantly associated with systolic BP and mean arterial pressure responses to high-salt plus potassium supplementation intervention. 【Conclusion】 Our findings indicate a significant association of genetic variations in the GLP-1R gene with BP responses to sodium and potassium intake. This suggests that the GLP-1R gene plays a role in the regulation of BP salt sensitivity and potassium sensitivity.

【Objective】 Based on our previously established salt-sensitive hypertension cohort, we conducted chronic salt loading and potassium supplementation interventions, aiming to examine the association between genetic variants in renalase and blood pressure (BP) responses to dietary interventions of salt and potassium intake. 【Methods】 In 2004, 514 subjects from 126 families were recruited in Shaanxi Province to establish the salt-sensitive hypertension study cohort. Among them, 334 non-parent subjects were selected and sequentially maintained on a low-salt diet for 7 days, then a high-salt diet for 7 days and a high-salt diet with potassium supplementation for another 7 days. Ten single nucleotide polymorphisms (SNPs) in the renalase gene were genotyped on the MassARRAY platform. 【Results】 SNP rs2576178 of the renalasegene was significantly associated with systolic BP (SBP) and mean arterial pressure (MAP) responses to low-salt intervention (SBP: β=-2.730, P<0.05; MAP: β=-1.718, P<0.05). In addition, SNP rs12356177 was significantly associated with diastolic BP response to low-salt diet (β=-1.608, P<0.05). However, we did not find any association for the renalase SNPs with BP response to high-salt diet with potassium supplementation reached nominal statistical significance. 【Conclusion】 Genetic variants in renalase gene are significantly associated with BP response to low-salt diet, suggesting that renalase may be mechanistically involved in BP salt-sensitivity.

【Objective】 Dyslipidemia has shown to be associated with cardiovascular, metabolic and renal diseases. This study aimed to investigate the association between residual cholesterol and the risk of subclinical renal damage (SRD). 【Methods】 A total of 2 342 participants were recruited from the previously established Hanzhong Adolescent Hypertension Study cohort. According to estimated glomerular filtration rate(eGFR) and urinary albumin-to-creatine ratio(uACR), the subjects were divided into SRD group and non-SRD group. The associations of residual cholesterol with eGFR, uACR, and the risk of SRD were analyzed by multiple linear and Logistic regression analyses. 【Results】 Residual cholesterol was positively correlated with uACR(r=0.081, P<0.001) but negatively correlated with eGFR (r=-0.091, P<0.001). Multiple linear regression analysis revealed that residual cholesterol was an influencing factor of uACR (β=0.075, P<0.001) and eGFR (β=-0.027, P<0.001) after adjustment for gender, age, smoke, alcohol, exercise, BMI, hypertension, diabetes and serum uric acid. In addition, Logistic regression analysis revealed that residual cholesterol was significantly associated with the risk of SRD independently of potential confounders [OR(95% CI)=1.387 (1.113-1.728), P<0.001]. Further subgroup analysis showed that residual cholesterol was significantly associated with the risk of SRD in women but not in men. 【Conclusion】 Residual cholesterol is a contributing factor in the risk of subclinical renal damage with gender-specific association.

【Objective】 Corin, a transmembrane serine protease that can cleave atrial natriuretic peptide precursor (pro-ANP) into atrial natriuretic peptide with smaller bioactive molecules, participates in the pathophysiological process of hypertension and cardiac hypertrophy. The purpose of this study was to explore the relationship of Corin gene variation with blood pressure responses to sodium and potassium dietary interventions. 【Methods】 In 2004, we recruited 514 participants from 124 families in 7 villages of Baoji, Shaanxi Province, China. All the subjects received a 3-day normal diet, a 7-day low-salt diet, a 7-day high-salt diet, and finally a 7-day high-salt and potassium supplementation. Fifteen single nucleotide polymorphisms (SNPs) of Corin gene were selected for final analysis. 【Results】 SNPs rs12509275 were significantly associated with diastolic blood pressure (DBP) response to low-salt diet, while rs3749584 was associated with pulse pressure (PP) response to low-salt diet.SNP rs3749584 and rs10517195 were significantly associated with PP response to high-salt diet. In addition,rs17654278 were significantly associated with systolic blood pressure (SBP) response to high-salt and potassium supplementation, rs2271037 was significantly correlated with DBP responses to high-salt and potassium supplementation, and rs4695253, rs12509275, rs2351783, rs36090894 were significantly associated with PP response to high-salt and potassium supplementation. 【Conclusion】 Corin gene polymorphisms were associated with blood pressure response to sodium and potassium, suggesting that Corin gene may be involved in pathophysiological process of salt sensitivity and potassium sensitivity.

【Objective】 4-like protein with down-regulated expression and development in neural precursor cells (NEDD4L) plays an important role in blood pressure (BP) regulation and sodium homeostasis by regulating epithelial sodium channel protein. In this study, we aimed to explore the relationship of NEDD4L gene polymorphisms with BP responses to sodium and potassium intake. 【Methods】 In 2004, 514 subjects from 124 families in Meixian County, Shaanxi Province, were recruited to establish a salt-sensitive hypertension study cohort. All the subjects received a 3-day baseline survey, a 7-day low-salt diet, a 7-day high-salt diet, and finally a 7-day high-salt and potassium supplementation. Their BP was measured and peripheral blood samples were collected at different intervention periods. The 14 gene polymorphisms of NEDD4L gene were genotyped and analyzed by MassARRAY platform. 【Results】 BP decreased on a low-salt diet, and significantly increased on a high-salt diet, and decreased again after potassium supplementation. NEDD4L SNPs rs74408486 were significantly associated with systolic BP, diastolic BP and mean arterial pressure responses to the low-salt diet. SNPs rs292449 and rs2288775 were significantly associated with pulse pressure response to the high-salt diet. In addition, SNPs rs563283 and rs292449 were significantly associated with diastolic BP, mean arterial pressure, and pulse pressure responses to high-salt and potassium supplementation diet. 【Conclusion】 NEDD4L gene polymorphisms were significantly associated with BP responses to sodium and potassium intake, suggesting that NEDD4L gene may be involved in the development of salt sensitivity and potassium sensitivity.

【Objective】 Based on our previously established salt-sensitive hypertension cohort, we aimed to examine the association of genetic variants in uromodulin with blood pressure(BP) responses to dietary interventions of sodium and potassium intake. 【Methods】 In 2004, 514 subjects from 124 families in Mei County, Shaanxi Province, were recruited to establish the salt-sensitive hypertension study cohort. Among them, 333 non-parent subjects were selected and sequentially maintained on a normal-diet for 3 days, low-salt diet for 7 days, then a high-salt diet for 7 days and a high-salt diet with potassium supplementation for another 7 days. Thirteen single nucleotide polymorphisms(SNPs) in the uromodulin gene were genotyped on the MassARRAY platform. 【Results】 BP levels decreased from the baseline to low-salt diet, increased from low-salt to high-salt diet, and decreased again from the high-salt diet to the high-salt plus potassium supplementation intervention. SNPs rs77875418 and rs4997081 of the uromodulin gene were significantly associated with diastolic BP(DBP) and mean arterial pressure(MAP) responses to high-salt diet. In addition, SNPs rs77875418, rs79245268, rs4293393, rs6497476, rs4997081, rs13333226, and rs12917707 were significantly associated with systolic BP(SBP), DBP, and MAP responses to high-salt diet with potassium supplementation. 【Conclusion】 Genetic variants in uromodulin gene are significantly associated with BP responses to sodium and potassium supplementation, suggesting that uromodulin may be mechanistically involved in BP sodium-sensitivity and potassium-sensitivity.

【Objective】 M3 muscarinic acetylcholine receptor(M3 receptor), encoded by CHRM3 gene, is widely distributed in the cardiovascular system and plays an important role in cardiac regulation. The aim of this study was to assess the association of genetic variants in M3 receptor with blood pressure(BP) responses to controlled dietary sodium and potassium interventions. 【Methods】 A total of 333 subjects from 124 families were recruited from the rural areas of northern China. After a three-day baseline observation, they were sequentially on a seven-day low-salt diet, a seven-day high-salt diet, and a seven-day high-salt diet plus potassium supplementation. Thirteen CHRM3 single nucleotide polymorphisms(SNPs) were selected for analysis. 【Results】 SNP rs10802811 of the CHRM3 was significantly associated with diastolic BP(DBP) and mean arterial pressure(MAP) responses to both low-salt and high-salt diets while SNPs rs6429147, rs373288072, rs114677844 and rs663148 showed significant associations with systolic BP(SBP) and MAP responses to high-salt diet. In addition, SNP rs6692904 was significantly associated with SBP, DBP and MAP responses to high-salt diet with potassium supplementation. 【Conclusion】 Genetic variants in M3 receptor are significantly associated with BP responses to sodium and potassium intervention, suggesting that M3 receptor may be mechanistically involved in BP salt and potassium sensitivity.