Exosomal and Plasma Non-Coding RNA Signature Associated with Urinary Albumin Excretion in Hypertension

Non-coding RNA (ncRNA), released into circulation or packaged into exosomes, plays important roles in many biological processes in the kidney. The purpose of the present study is to identify a common ncRNA signature associated with early renal damage and its related molecular pathways. Three individual libraries (plasma and urinary exosomes, and total plasma) were prepared from each hypertensive patient (with or without albuminuria) for ncRNA sequencing analysis. Next, an RNA-based transcriptional regulatory network was constructed. The three RNA biotypes with the greatest number of differentially expressed transcripts were long-ncRNA (lncRNA), microRNA (miRNA) and piwi-interacting RNA (piRNAs). We identified a common 24 ncRNA molecular signature related to hypertension-associated urinary albumin excretion, of which lncRNAs were the most representative. In addition, the transcriptional regulatory network showed five lncRNAs (LINC02614, BAALC-AS1, FAM230B, LOC100505824 and LINC01484) and the miR-301a-3p to play a significant role in network organization and targeting critical pathways regulating filtration barrier integrity and tubule reabsorption. Our study found an ncRNA profile associated with albuminuria, independent of biofluid origin (urine or plasma, circulating or in exosomes) that identifies a handful of potential targets, which may be utilized to study mechanisms of albuminuria and cardiovascular damage.

Effect of multicomponent therapy on left ventricular diastolic function in resistant hypertension patients

The aim – to determine prognostic factors of improving left ventricular diastolic function (LV DF) in resistant hypertension (RH) patients (pts) treated with multicomponent antihypertensive therapy during three years.Materials and methods. 102 patients with true RH were included. Patients received triple fixed combination (blocker of the renin-angiotensin-aldosterone system / calcium antagonist / diuretic), to which has been added a fourth drug (spironolactone, eplerenone, moxonidine, torasemide or nebivolol). The state of LV DF was studied at the beginning and at the end of the study. Office and 24-h ambulatory blood pressure (BP) measurements, echocardiography, clinical characteristics, neurohumoral and proinflammatory status were assessed.Results and discussion. Impairment LV DF was detected in 75.5 % of pts. The first degree of LV diastolic dysfunction (DD) was observed in 63.7 %. The patients were divided into 2 groups: the first group included persons without initial impairment of LV DF (n=25), the second – pts with LV DD (n=77). Patients with LV DD were older, had a longer duration of hypertension, higher body mass index, 24-h urinary albumin excretion, office BP and 24-h ambulatory BP, more often (in 2 times) disorders of circadian BP rhythm and concomitant diabetes mellitus (DM). Left ventricular DD in 100 % of cases was associated with severe LV hypertrophy (LVH), increased plasma concentration of inflammatory proteins (CRP, fibrinogen), cytokines (IL-6, TNF-α), increased activity of leukocyte elastase, macrophage matrix metalloproteinase-12. The concentration in the blood of aldosterone, active renin, 24-h urinary excretion of metanephrines did not differ between the groups.Conclusions. Improvement and stabilization of LV DF occurred in parallel with regression of LVH (normalization of LVMI in 35.1 % of pts and significant decrease of LVMI in 64.9 %) against the background of decrease of BP and in the proportion of pts with disturbed circadian BP rhythm. The independent factors of the E/E’ ratio were the initial plasma concentrations of aldosterone (β=0.556; р=0.0001), glucose (β=0.366; р=0.0001), active renin (β=–0.223; р=0.004), 24-h urinary albumin excretion (β=0.188; р=0.016), age (β=0,192; р=0,023). The odds of an improvement in LV DF increased by 3.7 times, if the patient with RH had no DM, LVH regression occurred.

Transient Receptor Potential Cation Channel 6 (TRPC6) Contributes to Kidney Injury Induced by Diabetes and Hypertension

Diabetes (DM) and hypertension (HTN) are major risk factors for chronic kidney injury, together accounting for >70% of end-stage renal disease. In this study, we assessed whether DM and HTN interact synergistically to promote kidney dysfunction and if Transient Receptor Potential Cation Channel 6 (TRPC6) contributes to this synergism. In wild type (WT; B6/129s background) and TRPC6 knockout (KO) mice, DM was induced by streptozotocin injection to increase fasting glucose levels to 250-350 mg/dL. HTN was induced by aorta constriction (AC) between the renal arteries. AC increased blood pressure (BP) by ~25 mmHg in the right kidney (above AC) while BP in the left kidney (below AC) returned to near normal after 8 weeks, with both kidneys exposed to the same levels of blood glucose, circulating hormones, and neural influences. Kidneys of WT mice exposed to DM or HTN alone had only mild glomerular injury and urinary albumin excretion. In contrast, kidneys exposed to DM plus HTN (WT-DM+AC mice) for 8 weeks had much greater increases in albumin excretion and histological injury. Marked increased apoptosis was also observed in the right kidneys of WT-DM+AC mice. In contrast, in TRPC6 KO-DM+AC mice, the right kidneys exposed to the same levels of high BP and high glucose had lower albumin excretion, less glomerular damage and apoptotic cell injury compared to right kidneys of WT-DM+AC mice. Our results suggest that TRPC6 may contribute to the interaction of DM and HTN to promote kidney dysfunction and apoptotic cell injury.

Increased Dosage of MRA Improves BP and Urinary Albumin Excretion in Primary Aldosteronism With Suppressed Plasma Renin

Purpose Excessive aldosterone secretion causes a high risk of cardio-cerebrovascular events. Mineralocorticoid receptor antagonist (MRA) is 1 of the treatment strategies for primary aldosteronism (PA). However, current MRA treatment is insufficient because MRA-treated patients with suppressed plasma renin activity (PRA) < 1 ng/mL/h still had a higher risk of cardiovascular disease than those with unsuppressed PRA. This is a prospective interventional study to determine the effects of an increase in MRA dosage on blood pressure (BP) control and urinary albumin excretion (UAE) in MRA-treated PA patients. Methods Thirty-four PA patients were recruited, and 24 patients (6 male, 18 female) completed this study. Serum potassium concentration was assessed every two months to adjust the dosage of MRA safely for 6 months. The primary outcomes were the changes in BP and UAE between baseline and 6 months. Results Systolic BP (SBP) and log10UAE decreased significantly as the daily dose of MRA increased. Diastolic BP (DBP) tended to decrease. We divided the PA patients into two groups (baseline PRA < 1 ng/mL/h and baseline PRA ≥ 1 ng/mL/h) according to PRA. In the group with baseline PRA < 1 ng/mL/h but not that with baseline PRA ≥ 1 ng/mL/h, SBP, DBP and log10UAE after 6 months were significantly lower than those at baseline. Conclusions The increase in MRA dosage improved BP and UAE in PA patients with suppressed PRA.

Choroidal thickness in relation to urinary albumin excretion rate in type 2 diabetes mellitus without retinopathy

Background To evaluate choroidal thickness (CT) in diabetic patients without diabetic retinopathy (DR) in relation to the urinary albumin excretion rate (UAER). Methods This is a prospective case-control study that included a consecutive sample of 120 patients with type 2 diabetes without clinically evident DR and a group of 60 matched healthy controls. Diabetic patients were included in two groups according to their UAER (normoalbuminuria and microalbuminuria). Complete ophthalmological examination was performed followed by optical coherence tomography (SD-OCT) for retinal and choroidal assessment. Twenty-four-hour urine samples were collected for UAER and blood samples for HbA1c and serum creatinine were obtained. Results The study included 180 eyes from 180 subjects in three groups. Patients with higher levels of albuminuria had a thinner choroid than normal controls, with decremental thinning as albuminuria progressed. Diabetics with normoalbuminuria showed no significant differences from controls. Choroidal thickness showed a significant moderate negative correlation with UAER (r = − 0.58, p < 0.001). Multiple regression analyses for diabetic patients with microalbuminuria demonstrated that UAER is the most important determinant of subfoveal choroidal thickness (SFCT) (p < 0.001). Conclusions Decreased CT was significantly correlated with UAER in diabetic patients without retinopathy and otherwise normal kidney functions. This decrease in thickness might be a predictor of DR.

Association of Sodium, Potassium and Sodium-to-Potassium Ratio with Urine Albumin Excretion among the General Chinese Population

Mixed evidence was published regarding the association of sodium, potassium and sodium-to-potassium ratio (Na/K ratio) with renal function impairment. This study was conducted to further explore the relationship between sodium, potassium, NA/K ratio and kidney function in the general adult Chinese population. We performed a cross-sectional analysis using the baseline data from the Action on Salt China (ASC) study. 5185 eligible general adult participants from the baseline investigation of the ASC study were included in this analysis. Sodium, potassium and albumin excretion were examined from 24-h urine collection. Albuminuria was defined as albumin excretion rate (AER) greater than or equal to 30 mg/24-h. Mixed linear regression models, adjusted for confounders, were fitted to analyze the association between sodium, potassium and Na/K ratio, and natural log transformed AER. Mixed effects logistic regression models were performed to analyze the odds ratio of albuminuria at each quintile of sodium, potassium and Na/K ratio. The mean age of the participants was 49.5 ± 12.8 years, and 48.2% were male. The proportion of albuminuria was 7.5%.The adjusted mixed linear models indicated that sodium and Na/K ratio was positively associated with natural log transformed AER (Sodium: β = 0.069, 95%CI [0.050, 0.087], p < 0.001; Na/K ratio: β = 0.026, 95%CI [0.012, 0.040], p < 0.001). Mixed effects logistic regression models showed that the odds of albuminuria significantly increased with the quintiles of sodium (p < 0.001) and Na/K ratio (p = 0.001). No significant association was found between potassium and the outcome indicators. Higher sodium intake and higher Na/K ratio are associated with early renal function impairment, while potassium intake was not associated with kidney function measured by albumin excretion.

Cardio Vascular Autonomic Dysfunction in Type 2 Diabetes Patients with Microalbuminuria

Objective: Main objective of this study is to determine the prevalence of cardiovascular autonomic dysfunction in type-2 diabetes patients with microalbuminuria. Study Design: Descriptive/ observational study Place and Duration: Study was conducted at Diabetes Hospital Hayatabad Peshawar and Mukhtar A Sheikh Hospital Multan for duration of six months from September, 2019 to February, 2020. Methods: Total 70 patients of both genders diagnosed diabetes 2 mellitus were presented in this study. Patients were aged between 20-80 years. Patients’ details demographics were recorded after taking written consent. Prevalence of cardiovascular autonomic dysfunction with microalbuminuria was assessed by statistical analysis. Microalbuminuria was diagnosed among patients if urinary albumin excretion was >30-300mg/g and graded into mild, moderate and severe according to value of urinary albumin excretion was (20–50 mg/24 hr, 50–100 mg/24 hr, 100–300 mg/24 hr). Complete data was analyzed by SPSS 20.0 version. Results: Out of 70, 38 (54.3%) were males and 32 (45.7%) were females. Mean age of the patients were 49.71±17.8 years with mean BMI 28.41±9.42 kg/m2. Mean ACR of microalbuminuria was 166.7±47.8 mg/gm. Among 70 cases, mild microalbuminuria was found in 28 (40%) cases, moderate microalbuminuria was among 31 (44.3%) and 11 (15.7%) was severe microalbuminuria. Lethargy was the most common symptom found in 25 (35.7%) followed by anorexia 20 (28.6%). Frequency of Cardiac autonomic neuropathy was 58 (82.86%), Parasympathetic dysfunction found in 59 (84.3%) and sympathetic dysfunction was among 62 (88.6%). Conclusion: We concluded in this study that the cardiovascular autonomic dysfunction in type-2 diabetes patients highly associated with microalbuminuria with increased systolic diastolic pressure and heart rate. Keywords: Microalbuminuria, Type 2 Diabetes, Cardio autonomic dysfunction