Tatsuyori Morita

Decreased plasma level of vitamin C in chronic kidney disease: comparison between diabetic and non-diabetic patients

BACKGROUND A decreased plasma level of vitamin C has been reported to be associated with an increased risk of cardiovascular morbidity and mortality. Here, we sought to determine the vitamin C status of patients with chronic kidney disease and the pathophysiological role of vitamin C in these patients. METHODS We studied 58 patients and evaluated the relationship between renal function and plasma vitamin C concentration, as well as the effect of diabetes on this relationship. Endothelium-dependent flow-mediated dilation of brachial artery was measured to assess the endothelial function. Serum malondialdehyde low-density lipoprotein was measured as a marker for oxidative stress. RESULTS Plasma vitamin C concentration had a positive linear relationship with eGFR in both diabetic and non-diabetic patients (P = 0.006 and P = 0.004, respectively). When vitamin C concentration and eGFR relationships were compared in the two groups, vitamin C concentration was significantly lower in diabetic patients at every eGFR (P = 0.006). Flow-mediated vasodilatation of the brachial artery was positively correlated with vitamin C concentration in non-diabetic patients (P = 0.047) but not in diabetic patients. There was a negative correlation between serum malondialdehyde low-density lipoprotein and vitamin C concentration in non-diabetic patients (P = 0.044) but not in diabetic patients. CONCLUSIONS Renal dysfunction was associated with a decrease in plasma vitamin C level. Moreover, decreased vitamin C may cause endothelial dysfunction via an increase in oxidative stress in non-diabetic chronic kidney disease patients.

Risk Factors of Normal Ankle–Brachial Index and Low Toe–Brachial Index in Hemodialysis Patients

The prevalence of peripheral arterial occlusive disease is high in patients with terminal renal failure, and it is a major problem in those on dialysis. A low ankle–brachial index (ABI) suggests the presence of arterial stenotic lesions between the aorta and the ankle joint, while a low toe–brachial index (TBI) suggests stenotic lesions between the aorta and the toes. Therefore, a normal ABI (≥0.9) and a low TBI (<0.6) may indicate the presence of stenotic lesions located only on the peripheral side of the ankle joint. In the present study, risk factors of normal ABI/low TBI were investigated. In 115 patients on maintenance dialysis, the ABI and TBI were simultaneously measured, and the background factors and laboratory data of patients with normal ABI/low TBI (L group) and those with normal ABI/normal TBI (≥0.6) (N group) were compared. Low ankle–brachial and toe–brachial indices were detected in 13% and 22% of the patients, respectively. Comparison of the background factors and laboratory data between the N and L groups showed that the ratio of diabetes mellitus, interdialytic body weight gain, and HbA1c values were significantly higher in the L group than in the N group. It was clarified that diabetes and excess body weight gain are involved as risk factors in dialysis patients with normal ABI/low TBI.

Efficacy of an L- and N-type calcium channel blocker in hypertensive patients with neurovascular compression of the rostral ventrolateral medulla

The rostral ventrolateral medulla is an important regulation center of sympathetic nerve activity. Several clinical studies have indicated a possible association between essential hypertension and neurovascular compression of the rostral ventrolateral medulla. We have found that patients with essential hypertension and neurovascular compression of the rostral ventrolateral medulla by adjacent arteries have increased sympathetic nerve activity and that microvascular decompression of the rostral ventrolateral medulla normalizes blood pressure and sympathetic nerve activity. Although sympatholytic agents are expected to lower blood pressure in these patients, this remains to be clarified. In this study, we evaluated the effect of cilnidipine, a calcium channel blocker that blocks both vascular L-type and sympathetic N-type Ca2+ channels in hypertensive patients with neurovascular compression. Using high-resolution magnetic resonance imaging, 46 patients with untreated essential hypertension were distributed into those with and without neurovascular compression of the rostral ventrolateral medulla. All patients were prescribed 10 mg of cilnidipine for 16 weeks. Office and home blood pressure, plasma norepinephrine and left ventricular mass index were measured by echocardiography before and after cilnidipine treatment, and changes were compared between the two groups. At baseline, plasma norepinephrine was significantly higher in patients with neurovascular compression. Decreases in office and home blood pressure, plasma norepinephrine and left ventricular mass index were significantly greater in patients with neurovascular compression. These results suggest that cilnidipine lowers blood pressure by inhibiting enhanced sympathetic nerve activity and reduces left ventricular mass in hypertensive patients with neurovascular compression of the rostral ventrolateral medulla.

Characteristics of 20-Year Survivors Undergoing Maintenance Hemodialysis

Hemodialysis techniques have improved remarkably in recent decades and the number of long‐term survivors among patients with end‐stage renal disease has increased. The mortality rate of hemodialysis patients has been reported to be low in Japan. However, the long‐term survival rate of dialysis patients is still low: 23.6% for 15 years and 17.4% for 20 years, even in Japan, and background information on patients undergoing hemodialysis therapy for more than 20 years is scarce in this country. In the present study, we investigated the characteristics of 20‐year survivors undergoing maintenance hemodialysis at our medical center. We compared the characteristics of hemodialysis patients who had survived for more than 20 years after the initiation of hemodialysis with those of patients who started hemodialysis at the same time and had already died. No patient among those who were still alive had diabetes mellitus while 15% of patients who had died had diabetes mellitus at the time of initiation of hemodialysis. Age, cardiothoracic ratio, and serum levels of total cholesterol and triglyceride 6 months after the initiation of hemodialysis, as well as decreases in body weight per year were significantly lower in those who had survived than in those who had died. These results suggest that long‐term hemodialysis survivors are characterized by (i) initiation of hemodialysis at a young age (ii) being free of diabetes mellitus (iii) a well‐controlled cardiothoracic ratio (iv) small successive change in body weight, and (v) being free of hypercholesterolemia and hypertriglyceridemia.

Olmesartan Induces Renoprotective Effects by Stimulating Angiotensin Type 2 Receptors and Reducing Oxidative Stress in Diabetic Nephropathy

Background: Angiotensin receptor blockers reduce the progression of diabetic nephropathy primarily by inhibiting angiotensin type 1 (AT1) receptors. In the present study, we investigated the role of angiotensin type 2 (AT2) receptors on the renoprotective effects of olmesartan in diabetic nephropathy. Methods: Six-week-old mice were treated with streptozotocin and divided into four groups: the OLM group (mice treated with olmesartan), the OLM+Ang II group (mice treated with olmesartan and angiotensin II), the OLM+PD group (mice treated with olmesartan and the AT2 antagonist PD 123319), and the vehicle group. Nondiabetic mice were used as controls. We measured blood glucose levels and urinary excretions of albumin and 8-hydroxy-2’-deoxyguanosine (8-OHdG), which is a marker for oxidative stress. Results: Although urinary albumin excretion in the OLM and OLM+Ang II groups showed a tendency to be reduced compared to the vehicle group, it was significantly lower compared to the OLM+PD group. Urinary excretion of 8-OHdG was also significantly lower in the OLM and OLM+Ang II groups compared to the OLM+PD group. Conclusions: In diabetic nephropathy, the renoprotective effects of olmesartan are due not only to the blockade of AT1 receptors, but also to a reduction in oxidative stress via stimulation of AT2 receptors.

Critical appraisal and pooled analysis of telmisartan alone or in combination with hydrochlorothiazide for achieving blood pressure goals

Rigid control of blood pressure (BP) is essential to prevent cardiovascular disease. However, only about 40% of hypertensive patients undergoing pharmacological intervention with a single agent achieve their BP goals in contemporary clinical practice. Combined therapy using currently available agents is effective in maximizing treatment outcome, although it raises medical costs and decreases the drug compliance rate. To overcome such negative consequences, a combination tablet containing an angiotensin II receptor blocker (ARB) with a small dose of hydrochlorothiazide (HCTZ) is now available on the international market, including Japan. This article briefly describes the unique properties of telmisartan, a highly selective ARB for the angiotensin II type 1 receptor, including its long-acting characteristics and recent prospective multicenter randomized clinical trials, followed by a description of a newly-introduced combination tablet in Japan, which contains telmisartan and HCTZ. This article also reviews its safety and efficacy based on currently available evidence. Finally, evidence comparing telmisartan/HCTZ with other combination therapies is presented.

Czech Society News

Nephrology has a long tradition in the Czech Republic. The first acute dialysis was performed in 1955, a chronic dialysis programme started in the early 60ies, and a transplantation programme in 1966. This was reflected by many important international meetings held in Prague: The 2nd Congress of the International Society of Nephrology (1963), 17th Congress of the European Dialysis and Transplantation Association (1980) and the 15th Congress of the European Society of Artificial Organs (1988). More recently, the 17th and 25th meetings of the International Society of Blood Purification (1999 and 2007), 11th ANCA and Vasculitis Workshop (2003), 7th European Peritoneal Dialysis Meeting (2005), 13th Congress of the European Society of Organ Transplantation (2007) and finally, this year, the 48th Congress of ERA-EDTA.