Primary aldosteronism

Primary aldosteronism (PA) is the most common cause of secondary hypertension, accounting for 10% of all hypertension. Far from being benign, hypertension due to PA is associated with high cardiovascular morbidity and mortality. However, PA is still underdiagnosed in general practice. Recent reports strongly recommend that identifying patients with PA is cost-beneficial based on improved cardiovascular outcomes afforded by specific surgical and medical treatment. This review provides an update of PA including controversial aspects of diagnosis and treatment.     

The redox state of albumin and serious cardiovascular incidence in hemodialysis patients

Human serum albumin is composed of human mercaptoalbumin (HMA) with cysteine residues having reducing powers and oxidized human non-mercaptoalbumin. The aim of this study is to clarify whether such redox state of albumin (HSA-redox) influences the incidence of cardiovascular disease (CVD) in chronic kidney disease patients on regular hemodialysis (HD). We measured HSA-redox using high-performance liquid chromatography in 86 anuric HD patients. The association between HSA-redox and incidental CVD events was evaluated. Twenty patients experienced symptomatic CVD events (16 patients died) at the 2-year follow-up. The fraction of HMA (f(HMA)) showed a significantly lower value in patients with CVD than that without CVD, in both pre-HD (36.5 ± 5.8% and 44.6 ± 9.8%, respectively) and post-HD (57.2 ± 6.2% and 67.2 ± 7.4%, respectively). The adjusted odds ratio (OR) for the incidental CVD event in patients with pre-HD f(HMA) < 40% was 5.0 (95% CI; 1.2 to 21.3), and that in patients with post-HD f(HMA) < 60% was 20.6 (3.2 to 134.7). Likewise, the adjusted OR for the CVD death in patients with pre-HD f(HMA) < 40% was 2.5 (0.6 to 12.5), and that in patients with post-HD f(HMA) < 60% was 25.6 (2.5 to 262.8). In conclusion, HSA-redox is closely related to serious CVD incidence and mortality among HD patients.     

ARB affects nicotine-induced gene expression profile in human coronary artery endothelial cells

AIM: To investigate the effects of nicotine and nicotine plus angiotensin II receptor blocker (ARB) on the gene expression profile of human coronary artery endothelial cells (HCAECs). METHODS: The changes in gene expression profiles in HCAECs treated with nicotine and nicotine plus ARB olmesartan were analyzed by DNA microarray. In nicotine-treated HCAECs, 432 genes selected by P < 0.01 were greater than 1.5-fold compared with the untreated cells. Data were analyzed using IPA (Ingenuity^® Systems, www.ingenuity.com). RESULTS: The gene expression levels of tumor necrosis factor-α, collagen type 1, matrix metalloproteinase-10, and disintegrin and metalloprotease domain 8, which are related to “cardiovascular function and disease”, were significantly increased. In canonical pathway analyses using IPA, “atherosclerosis signaling” was strongly affected by nicotine treatment and this effect was reduced by co-incubation with ARB olmesartan. These data indicate that the deleterious cardiovascular consequences of cigarette smoking may, at least in part, be due to the nicotine-induced gene expression profile related to “atherosclerosis signaling”. CONCLUSION: The inhibitory effect of ARB against the nicotine-induced gene expression profile may possibly induce anti-atherosclerotic effects that are independent of those from lowering the blood pressure.     

Reduction in the magnitude of serum potassium elevation in combination therapy with esaxerenone (CS‐3150) and sodium–glucose cotransporter 2 inhibitor in patients with diabetic kidney disease: Subanalysis of two phase III studies

Aims/IntroductionWe evaluated the effect of co‐administration of esaxerenone and a sodium–glucose cotransporter 2 (SGLT2) inhibitor on the magnitude of serum potassium elevation in Japanese patients with diabetic kidney disease.Materials and MethodsWe carried out a prespecified subanalysis of data from two phase III studies: a multicenter, randomized, double‐blind, placebo‐controlled trial in patients with type 2 diabetes and microalbuminuria (J308); and a multicenter, single‐arm, open‐label trial in patients with type 2 diabetes and macroalbuminuria (J309). Changes in serum potassium levels during the studies and other measures were evaluated according to SGLT2 inhibitor use.ResultsIn both studies, time‐course changes in serum potassium levels, and incidence rates of serum potassium elevation were lower in patients with co‐administration of SGLT2 inhibitor in both the placebo and esaxerenone groups than those without the inhibitor. In contrast, time‐course changes and mean percentage changes from baseline in urinary albumin‐to‐creatinine ratio, the proportion of patients with albuminuria remission and time‐course changes in blood pressure did not change with or without SGLT2 inhibitor, whereas the albumin‐to‐creatinine ratio and blood pressure were reduced with esaxerenone. The blood glucose‐lowering effect of SGLT2 inhibitor was not affected by esaxerenone.ConclusionsIn Japanese patients with type 2 diabetes and albuminuria treated with esaxerenone, concomitant use of SGLT2 inhibitor reduced the magnitude of serum potassium elevation without any change of its antihypertensive and albuminuria‐suppressing effects. Co‐administration of esaxerenone and SGLT2 inhibitor might be a beneficial treatment option for patients with diabetic kidney disease.     

CONTRACTILE PROPERTIES OF AFFERENT AND EFFERENT ARTERIOLES

1. The balance of vascular tone of the afferent and efferent arteriole is a crucial determinant of glomerular haemodynamics. Despite their intimate anatomical relationship in the juxtaglomerular apparatus, the mechanisms that regulate afferent and efferent arteriolar tone are different. 2. In the afferent arteriole, two intrinsic mechanisms, the myogenic response and macula densa-mediated tubuloglo-merular feedback (TGF) play a dominant role, maintaining the glomerular filtration rate (GFR) at a constant level over a wide range of renal perfusion pressure. Studies have shown that these two mechanisms are modulated by nitric oxide (NO). In addition, an interaction between TGF and angiotensin II (AngII) seems to be essential to maintaining GFR despite large variations in daily intake of salt and water. 3. In the efferent arteriole, neither myogenic response nor TGF seems to be important, while AngII is one major factor involved in the control of vascular resistance. In addition, recent studies have provided evidence that NO and prostaglandins produced by the glomerulus may control resistance of the downstream efferent arteriole. 4. As the early segment of the efferent arteriole resides within the glomerulus, various autacoid hormones produced by the glomerulus may reach and directly act on this segment, thereby controlling the glomerular capillary pressure. Thus, it would be important to understand the differences in the mechanisms operating at the afferent and efferent arteriole, as well as their alterations in various physiological and pathological conditions.     

The correlation between human plasma melatonin levels and urinary 6-hydroxymelatonin excretion

A significant correlation (0.76) has been found between nighttime peak plasma melatonin levels and the 24-h urinary excretion totals for conjugated 6-hydroxy-melatonin for a group of 22 women. This study validates the comparison of plasma levels of the hormone or urinary levels of its metabolite to assess pineal gland production of melatonin in humans.     

Antibody Response Determined with Antibody-Dependent Cell-Mediated Cytotoxicity (ADCC), Neutralizing Antibody, and Varicella Skin Test in Children with Natural Varicella and After Varicella Immunization

Humoral and cellular immune responses were examined in 115 children with varicella and in 21 children who had been immunized with live varicella vaccine. Antibody determined with antibody-dependent cell-mediated cytotoxicity (ADCC) was detected earlier than neutralizing antibody (NT) in both groups. While humoral and cellular immunity were detected simultaneously in the natural varicella group, cellular immunity was detected earlier than humoral immunity in the immunized group. This suggests that ADCC, rather than NT, is involved in the early stages of recovery from varicella-zoster virus (VZV) infection.     

Kidney dysfunction as a risk factor for first symptomatic stroke events in a general Japanese population--the Ohasama study.

BACKGROUND: Chronic Kidney Disease (CKD) has been shown to be a risk factor for mortality as well as for morbidity such as cardiovascular disease (CVD) in the general population. However, in the context of CVD events, there is a difference in the incidence of cardiac and stroke events between Western and Asian populations. Although a high prevalence of stroke is a characteristic feature in Japanese populations, it is unclear whether CKD constitutes a risk for stroke events. METHODS: To clarify this issue, we estimated creatinine clearance and obtained dipstick tests from spot-urine samples in 1977 subjects (mean 62.9-years-old, men/women: 731/1246) from a general Japanese population. First symptomatic stroke events and all-cause mortality were analysed according to stratification of kidney function and by positive tests for macroalbuminuria using a Cox proportional hazards regression model adjusted for possible confounding factors. RESULTS: During the observation period (mean 7.76 years), we recorded 112 events of first symptomatic stroke and 187 deaths (58 cases due to CVD). After adjustment for all variables, we found that increases in relative hazard (RH) for the first symptomatic stroke events were associated with decreasing kidney function (RH, 3.1; 95% CI, 1.24-7.84 in Ccr<40 ml/min, 1.9; 95% CI, 1.06-3.75 in Ccr 40-70 ml/min, ref in Ccr>70 ml/min) and with the presence of macroalbuminuria (RH, 1.4; 95% CI, 0.80-2.41). CONCLUSION: Decreased kidney function increased the risk of first symptomatic stroke events in a general Japanese population. The high prevalence of stroke in this population prompts the need for greater public awareness about risks for CKD.