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.

Impact of Obesity in Kidney Diseases

The clinical consequences of obesity on the kidneys, with or without metabolic abnormalities, involve both renal function and structures. The mechanisms linking obesity and renal damage are well understood, including several effector mechanisms with interconnected pathways. Higher prevalence of urinary albumin excretion, sub-nephrotic syndrome, nephrolithiasis, increased risk of developing CKD, and progression to ESKD have been identified as being associated with obesity and having a relevant clinical impact. Moreover, renal replacement therapy and kidney transplantation are also influenced by obesity. Losing weight is key in limiting the impact that obesity produces on the kidneys by reducing albuminuria/proteinuria, declining rate of eGFR deterioration, delaying the development of CKD and ESKD, and improving the outcome of a renal transplant. Weight reduction may also contribute to appropriate control of cardiometabolic risk factors such as hypertension, metabolic syndrome, diabetes, and dyslipidemia which may be protective not only in renal damage but also cardiovascular disease. Lifestyle changes, some drugs, and bariatric surgery have demonstrated the benefits.

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.

Insulin Resistance Associated with Clinical Manifestations of Diabetic Kidney Disease (Glomerular Hyperfiltration, Albuminuria, and Kidney Function Decline)

: Clinical features of diabetic kidney disease include glomerular hyperfiltration, albuminuria, and kidney function decline towards End-Stage Kidney Disease (ESKD). There are presently neither specific markers of kidney involvement in patients with diabetes nor strong predictors of rapid progression to ESKD. Serum-creatinine-based equations used to estimate glomerular filtration rate are notoriously unreliable in patients with diabetes. Early kidney function decline, reduced glomerular filtration rate, and proteinuria contribute to identifying diabetic patients at higher risk for rapid kidney function decline. Unlike proteinuria, the elevation of urinary albumin excretion in the range of microalbuminuria is frequently transient in patients with diabetes and does not always predict progression towards ESKD. Although the rate of progression of kidney function decline is usually accelerated in the presence of proteinuria, histological lesions of diabetes and ESKD may occur with normal urinary albumin excretion. No substantial reduction in the rate of ESKD associated with diabetes has been observed during the last decades despite intensified glycemic control and reno-protective strategies, indicating that existing therapies do not target underlying pathogenic mechanisms of kidney function decline. Very long-term effects of sodium-glucose transporters-2 inhibitors and glucagon-like peptide-1 analogs remain to be defined. In patients with diabetes, glucagon secretion is typically elevated and induces insulin resistance. Insulin resistance is consistently and strongly associated with clinical manifestations of diabetic kidney disease, suggesting that reduced insulin sensitivity participates in the pathogenesis of the disease and may represent a therapeutic objective. Amelioration of insulin sensitivity in patients with diabetes is associated with cardioprotective and kidney-protective effects.

Fibrosis biomarkers and echocardiographic parameters in patients with type 2 diabetes depending on the degree of albuminuria

Background. Diabetic nephropathy (DN) in patients with type 2 diabetes mellitus (T2DM) is associated with a risk of developing chronic heart failure (CHF). The degree of albuminuria is a marker of DN and is associated with an increased risk of chronic heart failure (CHF).Aim. To evaluate fibrosis biomarkers and echocardiographic parameters in patients with T2DM without CHF, depending on urinary albumin excretion.Materials and methods. The study included 42 patients with T2DM without verified CHF. The patients were divided into two groups: 1) a group with normoalbuminuria and 2) a group with a moderate increase in albuminuria (albumin / creatinine ratio of 30–300 mg / g). Echocardiography was performed and galectin-3, ST-2, PIСP, MMP-9, and TIMP-1 concentrations were measured.Results. The groups did not differ by age, sex, body mass index (BMI), glycated hemoglobin (HbA1c), and glomerular filtration rate (GFR). Galectin-3 concentrations were significantly higher in the group with a moderate increase in albuminuria than in the group of patients without albuminuria – 13.6 (11.2; 15.1) ng / ml and 7.4 (6.7; 7.9) ng / ml, respectively, p = 0.002. The groups also did not differ in the values of biomarkers, such as P1CP, TIMP-1, and MMP-9. Besides, the group with normoalbuminuria had lower E/e’ values than the group with a moderate increase in albuminuria – 8 (7; 9) and 10 (9; 12.5), p = 0.02.Conclusion. The patients with type 2 diabetes and a moderate increase in albuminuria have higher values of galectin-3 and a more pronounced diastolic dysfunction. The identified changes may reflect a higher risk of chronic heart failure in this group of patients.

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.

A randomized, prospective, open label comparative study of the efficacy of azilsartan and ramipril in the management of hypertension in patients with type-2 diabetes mellitus

Background: Patients with diabetes are prone to have hypertension. Hypertension is risk factors for complications of the vascular system, cardiovascular diseases and leads to atherosclerosis. It has been estimated that the diabetics tend to have about two times more risk of having hypertension than the general population. Objective of current study is to study and compare the efficacy of azilsartan and ramipril in the management of Hypertensive patients with type 2 diabetes mellitusMethods: randomized, prospective, open label comparative study was carried out among 60 known cases of diabetes mellitus type-2 with hypertension. Patients were randomly allocated into two groups: group-A (N=30) taking ACE Inhibitor tablet ramipril 5 mg Once daily orally. Group-B (N=30) taking angiotensin II receptor antagonist tablet azilsartan 40 mg once daily orally. At the commencement of the trial, patients were subjected to thorough clinical examination with necessary investigations and base line values were recorded.Results: Both the groups were comparable for age, sex and treatment taken. There was a significant reduction in the mean arterial pressure (17.43 for azilsartan group vs. 14.5 for ramipril group) (mmHg), creatinine clearance (mean reduction of 18.8 for azilsartan group vs. 13.94 for ramipril group), and urinary albumin excretion (mean reduction of 29.74 in azilsartan group vs. 17.25 for ramipril group). In azilsartan group the reduction was more in all parameters compared to ramipril group without effecting renal parameters.Conclusions: Azilsartan was more effective in reducing the mean arterial pressure (mmHg), creatinine clearance as well as urinary albumin excretion in Hypertensive patients with Type 2 diabetes mellitus without effecting renal parameters.

STUDY OF CORRELATION OF RETINOPATHY AND MICROALBUMINURIA IN PATIENT OF ESSENTIAL HYPERTENSION

Background: Hypertension is one of the leading causes of global burden of disease. Essential hypertension produces clinical proteinuria and microalbuminuria and is an early sign of kidney disease. Microalbuminuria has been shown to be a marker for end organ damage and results in retinopathy in the eye. Aims: The aim of the study was to determine the correlation between microalbuminuria and hypertensive retinopathy in patients of essential hypertension. Methods:This cross-sectional study was performed in 100 patients with essential hypertension of a tertiary care teaching hospital in eastern India, conducted between July 2020 to June 2021. Urinary albumin excretion was assessed by turbidimetry method and fundus was examined for grading of hypertensive retinopathy Result: Microalbuminuria was found to be present in 36 % patients of whom 65 % were males and 35% were females. Hypertensive retinopathy was observed in 66.7 % (24) patients, out of which 36 % patients had associated microalbuminuria. (p=0.001871) Conclusion: Investigation must be initiated for evidence of early renal disease in hypertensive patients to prevent MA and the resultant end organ damage. Furthermore, MA had a signicant correlation with retinopathy therefore fundus examination should be undertaken to predict the presence of ongoing vascular damage which can prevent atherosclerotic processes in the entire vascular system