Association of common medical comorbidities with early renal damage in the Chinese tropics with essential hypertension.

BACKGROUND: Urine albumin/creatinine ratio (UACR) is an important marker of early renal damage (ERD) caused by hypertension. Recent studies showed that blood pressure was a significant inverse association with temperature and climate. The purposes of our study were sought to explore the association of common medical comorbidities with ERD, and find independent risk factors to ERD in Chinese tropics with essential hypertension. METHODS: From January 2018 to December 2019, we assessed UACR in a total of 599 hypertensive Chinese Hainan patients. We defined ERD as a UACR between 30 mg/g and 300 mg/g. We analysed differences between qualitative variables using the chi-squared (χ2) test. We calculated correlations between UACR and age, hypertension duration (HD), systolic blood pressure (SBP), and diastolic blood pressure (DBP) using the Spearman's rho test. To determine the odds ratio (OR), we evaluated binary logistic regression models. RESULTS: Among the 599 patients, 281 (46.9%) were found to have ERD. ERD and factors related to sex, body mass index (BMI), and SBP did not differ significantly (all, p>0.05). Our main findings showed that age, HD, and DBP were associated with ERD (p<0.01, respectively). Furthermore, age ≥ 65 years, HD ≥10 years, DBP ≥ 90 mmHg, SBP ≥ 160 mmHg, and diabetes differed significantly according to ERD status (p < 0.05, respectively). In multivariate analysis using stepwise regression, age (OR = 1.468), DBP (OR = 1.853), and diabetes (OR = 2.031) were significant independent predictors of ERD. The area under the receiver operating characteristic (ROC) curve was 0.677, and the sensitivity and specificity of the optimal cut-off value were 44.5 and 81.1%, respectively. CONCLUSIONS: Common medical comorbidities are associated with ERD; age, DBP, and diabetes are independent risk factors for ERD in patients with essential hypertension who live in the Chinese tropics. Early monitoring of the UACR, as well as control of blood glucose and DBP, can effectively delay ERD.

Correlation between classical transient receptor potential channel 1 gene polymorphism and microalbuminuria in patients with primary hypertension.

OBJECTIVE: To investigate the correlation between transient receptor potential channel 1 (TRPC1) gene polymorphism and microalbuminuria in patients with primary hypertension. Methods: A total of 468 patients with primary hypertension were admitted to the Department of Hypertension of the First Affiliated Hospital of Xinjiang Medical University from April 2015 to November 2017. According to microalbuminuria, the patients were divided into two groups: high urinary albumin group (EH+mALB group, n = 71) and normal urinary microalbuminuria group (EH group, n = 397). The Sequenom detection technology was used for genotyping the single nucleotide polymorphism (SNP) sites of the TRPC1 gene, such as rs1382688, rs3821647, rs7638459, rs953239, and rs7621642. RESULTS: (1) No significant differences were detected in gender, smoking history, drinking history, family history, course of hypertension, fasting blood glucose, urea, creatinine, triglyceride, total cholesterol, high-density lipoprotein cholesterol, low-density lipoprotein cholesterol, glycosylated hemoglobin, vitamin D, homocysteine, and cystatin C between the two groups (P > .05). However, age, body mass index (BMI), 24-h mean systolic and diastolic blood pressure, and 24-h average pulse pressure were statistically significant (P < .05). (2) No significant difference was detected in the distribution frequency of the polymorphisms of the TRPC1 gene between the two groups (P > .05), while the genotype, allele, and recessive model of rs7638459 differed significantly difference (P < .05). (3) Logistic regression analysis showed that BMI and rs7638459 CC genotype were the risk factors of increased microalbuminuria in patients with primary hypertension. CONCLUSION: TRPC1 gene polymorphism is associated with increased microalbuminuria in patients with primary hypertension. The CC genotype of rs7638459 may increase the risk of microalbuminuria in patients with essential hypertension, while BMI and rs7638459 CC genotype may be the risk factors of increased microalbuminuria in patients with primary hypertension.

Correlation among high salt intake, blood pressure variability, and target organ damage in patients with essential hypertension: Study protocol clinical trial (SPIRIT compliant).

BACKGROUND: Essential hypertension is a multifactorial disease, which is affected by genetic and environmental factors, and can cause diseases such as cerebrovascular disease, heart failure, coronary heart disease, and chronic renal failure. High salt intake is a risk factor for hypertension, stroke, and cardiovascular disease. Blood pressure variability (BPV) is a reliable independent predictor of cardiovascular events and death. At present, there are few studies about the correlation among high salt intake, BPV, and target organ damage (TOD) in patients with hypertension. OBJECTIVE: The purpose of this study is to compare 24-hour urine sodium excretion, BPV, carotid intima-media thickness, left ventricular mass index, and serum creatinine or endogenous creatinine clearance rate. To clarify the relationship between high salt load and BPV and TOD in patients with hypertension.This study is a cross-sectional study. It will recruit 600 patients with essential hypertension in the outpatient and inpatient department of cardiovascular medicine of Chengdu Fifth People's Hospital. Researchers will obtain blood and urine samples with the patient's informed consent. In addition, we will measure patient's blood pressure and target organ-related information. TRIAL REGISTRY: The study protocol was approved by the Chengdu Fifth People's Hospital. Written informed consent will be obtained from all the participants. The trial was registered in the Chinese Clinical trial registry, ChiCTR2000029243. This trial will provide for the correlation among high salt intake, BPV, and TOD in patients with essential hypertension.

Senescent Kidney Cells in Hypertensive Patients Release Urinary Extracellular Vesicles.

Background Hypertension may be associated with renal cellular injury. Cells in distress release extracellular vesicles (EVs), and their numbers in urine may reflect renal injury. Cellular senescence, an irreversible growth arrest in response to a noxious milieu, is characterized by release of proinflammatory cytokines. We hypothesized that EVs released by senescent nephron cells can be identified in urine of patients with hypertension. Methods and Results We recruited patients with essential hypertension (EH) or renovascular hypertension and healthy volunteers (n=14 each). Renal oxygenation was assessed using magnetic resonance imaging and blood samples collected from both renal veins for cytokine-level measurements. EVs isolated from urine samples were characterized by imaging flow cytometry based on specific markers, including p16 (senescence marker), calyxin (podocytes), urate transporter 1 (proximal tubules), uromodulin (ascending limb of Henle's loop), and prominin-2 (distal tubules). Overall percentage of urinary p16+ EVs was elevated in EH and renovascular hypertension patients compared with healthy volunteers and correlated inversely with renal function and directly with renal vein cytokine levels. Urinary levels of p16+/urate transporter 1+ were elevated in all hypertensive subjects compared with healthy volunteers, whereas p16+/prominin-2+ levels were elevated only in EH versus healthy volunteers and p16+/uromodulin+ in renovascular hypertension versus EH. Conclusions Levels of p16+ EVs are elevated in urine of hypertensive patients and may reflect increased proximal tubular cellular senescence. In EH, EVs originate also from distal tubules and in renovascular hypertension from Henle's loop. Hence, urinary EVs levels may be useful to identify intrarenal sites of cellular senescence.

Urinary Metabolic Signature of Primary Aldosteronism: Gender and Subtype-Specific Alterations.

PURPOSE: The current clinical investigation for primary aldosteronism (PA) diagnosis requires complex expensive tests from the initial suspicion to the final subtype classification, including invasive approaches; therefore, appropriate markers for subtype definition are greatly desirable. The present study performs a metabolomics analysis to further examine specific molecular signatures of PA urines EXPERIMENTAL DESIGN: The study considered PA subtype and gender-related differences using two orthogonal advanced UHPLC-MS metabolomics approaches. Patients with essential hypertension (n = 36) and PA (n = 50) who were referred to the outpatient hypertension clinic and matched healthy subjects (n = 10) are investigated. RESULTS: Statistically significant changes (p < 0.05 ANOVA, Fc > 1.5) of metabolites involved in central carbon, energy, and nitrogen metabolism are identified, especially purine and pyrimidine nucleosides and precursors, and free amino acids. PLS-DA interpretation provides strong evidence of a disease-specific metabolic pattern with dAMP, diiodothyronine, and 5-methoxytryptophan as leading factors, and a sex-specific metabolic pattern associated with orotidine 5-phosphate, N-acetylalanine, hydroxyproline, and cysteine. The results are verified using an independent sample set, which confirms the identification of specific signatures. CONCLUSIONS AND CLINICAL RELEVANCE: Metabolomics is used to identify low molecular weight molecular markers of PA, which paves the way for follow-up validation studies in larger cohorts.

The association of miR-29a with proteinuria in essential hypertension.

Recently, miRNAs have emerged as new indirect markers of inflammation that are associated with adverse outcomes in cardiovascular disease. The aim of the study was to evaluate the relationship between miR29a and proteinuria in hypertension. Fifty patients with normal albuminuria, fifty patients with micro-albuminuria, and fifty patients with macro-albuminuria were enrolled. The highest levels of miR-29a and transforming growth factor-ß1 (TGF-ß1) were observed in the macro-albuminuria group, followed by the micro-albuminuria and the normal albuminuria groups. The level of miR-29a was negatively correlated with the glomerular filtration rate, but was positively correlated with C-reactive protein, TGF-ß1, and the urinary albumin to creatinine ratio (UACR). Circulating miR-29a was found to be significantly and independently associated with proteinuria. Our findings showed that miR-29a reflects the pathogenesis of hypertensive nephropathy and may serve as a potential non-invasive marker for detecting early stages of hypertensive nephropathy.

Urinary exosome miR-146a is a potential marker of albuminuria in essential hypertension.

BACKGROUND: There is increasing interest in using extracellular vesicle-derived microRNAs (miRNAs) as biomarkers in renal dysfunction and injury. Preliminary evidence indicates that miRNAs regulate the progression of glomerular disease. Indeed, exosomes from the renal system have provided novel evidence in the clinical setting of albuminuria. Thus, the aim of this study was to quantify the urinary miRNAs present in exosome and microvesicles (MVs), and to assess their association with the presence of increased urinary albumin excretion in essential hypertension. METHODS: Exosomes were collected from urine specimens from a cohort of hypertensive patients with (n = 24) or without albuminuria (n = 28), and from 20 healthy volunteers as a control group. Urinary exosomes were phenotyped by Western blot, tunable resistive pulse sensing, and electronic microscopy. Expression of miR-146a and miR-335* was analysed by qRT-PCR and any associations between albuminuria and exosomal miRNAs were analysed. RESULTS: Urinary miRNAs are highly enriched in exosome subpopulations compared to MVs, both in patients with or without increased albuminuria (p < 0.001), but not in the control group. High albuminuria was associated with 2.5-fold less miR-146a in exosomes (p = 0.017), whereas miR-146a levels in MV did not change. In addition, exosome miR-146a levels were inversely associated with albuminuria (r = 0.65, p < 0.0001), and discriminated the presence of urinary albumin excretion presence [area under the curve = 0.80, 95% confidence interval: 0.66-0.95; p = 0.0013]. CONCLUSIONS: Our results indicate that miRNAs were enriched in the urinary exosome subpopulation in hypertensive patients and that low miR-146a expression in exosomes was associated with the presence of albuminuria. Thus, urinary exosome miR-146a may be a potentially useful tool for studying early renal injury in hypertension.

Identification of essential hypertension biomarkers in human urine by non-targeted metabolomics based on UPLC-Q-TOF/MS.

BACKGROUND: In recent years, using metabolomics technology to study hypertension has made some progress. However, in actual clinical studies, there are few studies on hypertension related metabonomics with human urine as samples. In this study, the urine samples of patients with essential hypertension (EH) were studied by comparing with healthy people to explore the changes of urine metabolites between hypertensive patients and healthy people in order to find potential biomarkers and metabolic pathways. METHODS: An ultra performance liquid chromatography coupled with quadrupole time-of-flight mass spectrometry (UPLC-Q-TOF/MS) technology was used to analyze the urine metabolites of 75 cases of essential hypertension group (EH) and 75 cases of healthy control group (HC). RESULTS: According to the PLS-DA pattern recognition analysis, substances with significant differences (P < .05) between the EH group and the HC group were screened out, including 10 potential biomarkers such as L-methionine. The metabolic pathways involved were amino acid metabolism, fatty acid metabolism steroid hormone, biosynthesis and oxidative stress. CONCLUSION: The non-targeted metabolomics based on UPLC-Q-TOF/MS technology can effectively identify the differential metabolites of potential biomarkers in the urine of essential hypertensive patients and provide a theoretical basis for the treatment of clinical hypertension.

Salt and essential hypertension: pathophysiology and implications for treatment.

Essential hypertension is common and is associated with significant morbidity and mortality. However, questions remain as to the exact physiological mechanisms underlying this disease. First, we discuss how essential hypertension may be largely a result of a maladaptation to a high-salt diet and that high blood pressure, rather than being an inactive side effect of high salt intake, may be an adaptive mechanism to improve salt secretion. Next, we explain how any physiological state that reduces urinary sodium concentrating ability may increase an individual's risk for salt-induced hypertension. Finally, we conclude that natriuresis is a crucial criterion for effective long-term pharmacologic treatment of essential hypertension.

Usefulness of the renal resistive index to predict an increase in urinary albumin excretion in patients with essential hypertension.

Microalbuminuria is a risk factor for cardiovascular events and death in hypertensive patients. Patients who are expected to increase albuminuria need strict blood pressure control. In the present study, we assessed the association between the renal resistive index (RI) and future increases in albuminuria in patients with essential hypertension. Sixty-six patients with essential hypertension were included in the study. Univariate and multivariate logistic regression analyses were used to identify the factors, including renal RI, that were significant independent determinants of increased in urinary albumin excretion (UAE), defined as an increase of >50% in the urinary albumin-to-creatinine ratio over 2 years. Receiver operator characteristics curve analysis was used to select the optimal cut-off point that predicted an increase in UAE. RI was the only significant variable that predicted the increase in UAE, with the optimal cut-off value of renal RI that predicted this increase being 0.71 (sensitivity 52.4% and specificity 84.4%). Renal RI is associated with the future increase in albuminuria in patients with essential hypertension.