Correlation between Renal Artery Anatomy and Hypertension: A Retrospective Analysis of 3000 Patients

Objective. To assess the correlation between renal artery anatomy and blood pressure in Undiagnosed Hypertension and Diagnosed Hypertension. Methods. The renal artery CT scanning imaging data and laboratory data of 3000 inpatients and outpatients were collected retrospectively in 4 centers of China. Morphometric parameters were assessed using the quantitative vascular analysis (unit: mM). Results. 687 cases (23.2%) had accessory renal arteries unilaterally, and 216 cases (7.3%) had bilateral accessory renal arteries, including left kidney 825 (27.9%) and right kidney 798 (27.0%). The presence of accessory renal arteries and renal artery branches was higher in the diagnosed hypertension group as compared with the undiagnosed hypertension group (MARB, p p < 0.001; ARA, p < 0.001; others, p < 0.001). Consequently, multivariate regression analysis showed that age (OR = 2.519 (95% CI: 0.990–6.411, p < 0.001)), dyslipidemia (OR = 1.187 (95% CI: 0.960–1.454, p = 0.007)), renal hilum Outside the main renal artery branch (MRAB) (OR = 2.069 (95% CI: 1.614–2.524, p = 0.002)), and accessory renal artery (ARA) (OR = 2.071 (95% CI: 1.614–2.634, p = 0.001)) were risk factors of hypertension. In addition, higher renin activity was associated with ARA patients (2.19 ± 2.91 vs. 1.75 ± 2.85, p < 0.001). Conclusions. When comparing renal arteries side by side, the anatomical length of the renal arteries is significantly different. In addition, the prevalence of accessory renal arteries and renal artery branches is higher in the hypertension group. The auxiliary renal artery and the main renal artery branch outside the renal portal are independent factors of hypertension. Renal sympathetic nerve activity is affected by renin activity and is related to the accessory renal artery.

In Vivo Renin Activity Imaging in the Kidney of Progeroid Ercc1 Mutant Mice

Changes in the renin–angiotensin system, known for its critical role in the regulation of blood pressure and sodium homeostasis, may contribute to aging and age-related diseases. While the renin–angiotensin system is suppressed during aging, little is known about its regulation and activity within tissues. However, this knowledge is required to successively treat or prevent renal disease in the elderly. Ercc1 is involved in important DNA repair pathways, and when mutated causes accelerated aging phenotypes in humans and mice. In this study, we hypothesized that unrepaired DNA damage contributes to accelerated kidney failure. We tested the use of the renin-activatable near-infrared fluorescent probe ReninSense680™ in progeroid Ercc1d/− mice and compared renin activity levels in vivo to wild-type mice. First, we validated the specificity of the probe by detecting increased intrarenal activity after losartan treatment and the virtual absence of fluorescence in renin knock-out mice. Second, age-related kidney pathology, tubular anisokaryosis, glomerulosclerosis and increased apoptosis were confirmed in the kidneys of 24-week-old Ercc1d/− mice, while initial renal development was normal. Next, we examined the in vivo renin activity in these Ercc1d/− mice. Interestingly, increased intrarenal renin activity was detected by ReninSense in Ercc1d/− compared to WT mice, while their plasma renin concentrations were lower. Hence, this study demonstrates that intrarenal RAS activity does not necessarily run in parallel with circulating renin in the aging mouse. In addition, our study supports the use of this probe for longitudinal imaging of altered RAS signaling in aging.

Serum Alpha-1-Acid Glycoprotein-1 and Urinary Extracellular Vesicle miR-21-5p as Potential Biomarkers of Primary Aldosteronism

Primary aldosteronism (PA) is the most common cause of secondary hypertension and reaches a prevalence of 6-10%. PA is an endocrine disorder, currently identified as a broad-spectrum phenotype, spanning from normotension to hypertension. In this regard, several studies have made advances in the identification of mediators and novel biomarkers of PA as specific proteins, miRNAs, and lately, extracellular vesicles (EVs) and their cargo.AimTo evaluate lipocalins LCN2 and AGP1, and specific urinary EV miR-21-5p and Let-7i-5p as novel biomarkers for PA.Subjects and MethodsA cross-sectional study was performed in 41 adult subjects classified as normotensive controls (CTL), essential hypertensives (EH), and primary aldosteronism (PA) subjects, who were similar in gender, age, and BMI. Systolic (SBP) and diastolic (DBP) blood pressure, aldosterone, plasma renin activity (PRA), and aldosterone to renin ratio (ARR) were determined. Inflammatory parameters were defined as hs-C-reactive protein (hs-CRP), PAI-1, MMP9, IL6, LCN2, LCN2-MMP9, and AGP1. We isolated urinary EVs (uEVs) and measured two miRNA cargo miR-21-5p and Let-7i-5p by Taqman-qPCR. Statistical analyses as group comparisons were performed by Kruskall-Wallis, and discriminatory analyses by ROC curves were performed with SPSS v21 and Graphpad-Prism v9.ResultsPA and EH subjects have significantly higher SBP and DBP (p &lt;0.05) than the control group. PA subjects have similar hs-CRP, PAI-1, IL-6, MMP9, LCN2, and LCN2-MMP9 but have higher levels of AGP1 (p &lt;0.05) than the CTL&amp;EH group. The concentration and size of uEVs and miRNA Let-7i-5p did not show any difference between groups. In PA, we found significantly lower levels of miR-21-5p than controls (p &lt;0.05). AGP1 was associated with aldosterone, PRA, and ARR. ROC curves detected AUC for AGP1 of 0.90 (IC 95 [0.79 – 1.00], p &lt;0.001), and combination of AGP1 and EV-miR-21-5p showed an AUC of 0.94 (IC 95 [0.85 – 1.00], p&lt;0.001) to discriminate the PA condition from EH and controls.ConclusionSerum AGP1 protein was found to be increased, and miR-21-5p in uEVs was decreased in subjects classified as PA. Association of AGP1 with aldosterone, renin activity, and ARR, besides the high discriminatory capacity of AGP1 and uEV-miR-21-5p to identify the PA condition, place both as potential biomarkers of PA.

Metabolomics Signature of Plasma Renin Activity and Linkage with Blood Pressure Response to Beta Blockers and Thiazide Diuretics in Hypertensive European American Patients

Plasma renin activity (PRA) is a predictive biomarker of blood pressure (BP) response to antihypertensives in European–American hypertensive patients. We aimed to identify the metabolic signatures of baseline PRA and the linkages with BP response to β-blockers and thiazides. Using data from the Pharmacogenomic Evaluation of Antihypertensive Responses-2 (PEAR-2) trial, multivariable linear regression adjusting for age, sex and baseline systolic-BP (SBP) was performed on European–American individuals treated with metoprolol (n = 198) and chlorthalidone (n = 181), to test associations between 856 metabolites and baseline PRA. Metabolites with a false discovery rate (FDR) < 0.05 or p < 0.01 were tested for replication in 463 European–American individuals treated with atenolol or hydrochlorothiazide. Replicated metabolites were then tested for validation based on the directionality of association with BP response. Sixty-three metabolites were associated with baseline PRA, of which nine, including six lipids, were replicated. Of those replicated, two metabolites associated with higher baseline PRA were validated: caprate was associated with greater metoprolol SBP response (β = −1.7 ± 0.6, p = 0.006) and sphingosine-1-phosphate was associated with reduced hydrochlorothiazide SBP response (β = 7.6 ± 2.8, p = 0.007). These metabolites are clustered with metabolites involved in sphingolipid, phospholipid, and purine metabolic pathways. The identified metabolic signatures provide insights into the mechanisms underlying BP response.

Global REACH 2018: Volume regulation in high-altitude Andeans with and without chronic mountain sickness

The high-altitude maladaptation syndrome known as chronic mountain sickness (CMS) is characterized by polycythemia and is associated with proteinuria despite unaltered glomerular filtration rate. However, it remains unclear if indigenous highlanders with CMS have altered volume regulatory hormones. We assessed N-terminal pro-B-type natriuretic peptide (NT pro-BNP), plasma aldosterone concentration, plasma renin activity, kidney function (urinary microalbumin, glomerular filtration rate), blood volume, and estimated pulmonary artery systolic pressure (ePASP), in Andean males without (n=14; age=39±11) and with (n=10; age=40±12) CMS at 4330 meters (Cerro de Pasco, Peru). Plasma renin activity (non-CMS: 15.8±7.9 vs. CMS: 8.7±5.4 ng/ml; p=0.025) and plasma aldosterone concentration (non-CMS: 77.5±35.5 vs. CMS: 54.2±28.9 pg/ml; p=0.018) were lower in highlanders with CMS compared to non-CMS, while NT pro-BNP was not different between groups (non-CMS: 1394.9±214.3 vs. CMS: 1451.1±327.8 pg/ml; p=0.15). Highlanders had similar total blood volume (non-CMS: 90±15 vs. CMS: 103±18 ml • kg-1; p=0.071), but Andeans with CMS had greater total red blood cell volume (non-CMS: 46±10 vs. CMS 66±14 ml • kg-1; p<0.01) and smaller plasma volume (non-CMS 43±7 vs. CMS 35±5 ml • kg-1; p=0.03) compared to non-CMS. There were no differences in ePASP between groups (non-CMS 32±9 vs. CMS 31±8 mmHg; p=0.6). A negative correlation was found between plasma renin activity and glomerular filtration rate in both groups (group: r=-0.66; p<0.01; non-CMS: r=-0.60; p=0.022; CMS: r=-0.63; p=0.049). A smaller plasma volume in Andeans with CMS may indicate an additional CMS maladaptation to high-altitude, causing potentially greater polycythemia and clinical symptoms.

High plasma renin activity associates with obesity-related diabetes and arterial hypertension, and predicts persistent hypertension after bariatric surgery

Background Information about the renin–angiotensin–aldosterone system (RAAS) in obese individuals before and after bariatric surgery is scarce. Aim of this study was to analyze the RAAS in severely obese subjects, in relation to anthropometric and metabolic variables, with special reference to glucose tolerance. Methods 239 subjects were evaluated at baseline, and 181 one year after bariatric surgery [laparoscopic gastric banding (LAGB)]. Results At baseline, renin (plasma renin activity, PRA) was increased from normal to glucose tolerance and more in diabetes, also correlating with ferritin. After LAGB, the decrease of PRA and aldosterone was significant in hypertensive, but not in normotensive subjects, and correlatied with decrease of ferritin. PRA and glucose levels were predictive of persistent hypertension 1 year after LAGB. Conclusions These data support the role of RAAS in the pathophysiology of glucose homeostasis, and in the regulation of blood pressure in obesity. Ferritin, as a proxy of subclinical inflammation, could be another factor contributing to the cross-talk between RAAS and glucose metabolism.

Plasma Renin Activity after Diuretic Treatment in Patients with Stable Heart Failure: With Special Reference to its Association with Electrolyte Chloride

A recent study reported an intimate association between urinary chloride (Cl) and plasma renin activity (PRA) in acute heart failure (HF) status, reflecting normal functioning of the ‘tubulo-glomerular feedback’ mechanism. Whether the ‘tubuloglomerular feedback’ mechanism functions normally in stable HF status, however, is unclear. This study examined whether the ‘tubulo-glomerular feedback’ mechanism functions normally under resolution of worsening HF after decongestive therapy. Data from 26 patients with acute HF and its recovery after decongestive therapy were analyzed. Clinical tests included measurement of peripheral blood tests, serum and spot urinary electrolytes, plasma neurohormones, and fractional urinary excretions of electrolytes. In a total of 26 patients, PRA increased after acute HF treatment (from 1.64±2.0 to 5.48±6.1 ng/ mL/h, p=0.002). Changes in the serum logPRA and urinary Cl concentration from worsening to its recovery tended to be inversely correlated (R2 =0.12, p=0.085) and logPRA and the serum Cl concentration at recovery were inversely correlated (R2 =0.23, p=0.01). When divided into 2 groups (n=13 in each) according to the median PRA, the group with greater PRA changes showed a larger decrease in the urinary Cl concentration (from 110±44 to 72.8±38, p=0.03). The group with higher PRA at recovery showed a lower serum Cl concentration than the group with lower PRA at recovery (102±6.5 vs 107±4.2 mEq/L, p=0.04). In conclusion, the association between PRA and the serum/urinary Cl concentration is blunted in stable HF under-decongestive therapy, possibly due to the physiologic status under full cardiovascular medication compared with that in acute HF status.