Blood pressure control and satisfaction of hypertensive patients following a switch to combined drugs of an angiotensin receptor blocker and a calcium channel blocker in clinical practice of nephrology.

BACKGROUND: Combination drugs containing an angiotensin receptor blocker and a calcium channel blocker have been widely commercialized in recent years, and their advantages, such as improvements in adherence, and reductions in medication costs, have been greatly emphasized. However, the actual situations and the impact of switching to combination drugs in clinical practice of nephrology are not fully understood. METHODS: This study was conducted in outpatients of nephrology who received antihypertensive medicines, and who switched to combination drugs. Changes in the potency of the antihypertensive drugs, and blood pressure were examined retrospectively before and after changing treatments. In addition, the study also involved patients' questionnaire, which examined changes in blood pressure at home, the presence or absence of missed doses, the impact on medication-related expenses, and the level of patients' satisfaction with regard to combination drugs. RESULTS: Survey results from 90 participants revealed that changing to combination drugs resulted in a reduction of missed doses, a decrease in blood pressure measured in an outpatient setting, and a reduction in medication-related expenses in total patients, non-chronic kidney disease (CKD) patients, and CKD patients. CONCLUSION: Our study shows that switching to combination antihypertensive drugs resulted in an improvement in adherence and a reduction in medication-related expenses, and revealed that patient satisfaction was high. Combination drugs for hypertensive patients may be beneficial in both medical and economical viewpoints.

Sonographic detection of a radiolucent object in dialysis vascular access.

Percutaneous endovascular angioplasty is a valuable tool to salvage dialysis vascular access failure, but is accident-prone if performed by unskilled operators. We report a case of vascular access failure caused by the plastic protective tube of a balloon catheter, which had been mistakenly left in the vasculature and was undetectable on radiography but was detected by ultrasonography.

Intestinal absorption of fucoidan extracted from the brown seaweed, Cladosiphon okamuranus.

The aim of this study was to examine the absorption of fucoidan through the intestinal tract. Fucoidan (0.1, 0.5, 1.0, 1.5 and 2.0 mg/mL) was added to Transwell inserts containing Caco-2 cells. The transport of fucoidan across Caco-2 cells increased in a dose-dependent manner up to 1.0 mg/mL. It reached a maximum after 1 h and then rapidly decreased. In another experiment, rats were fed standard chow containing 2% fucoidan for one or two weeks. Immunohistochemical staining revealed that fucoidan accumulated in jejunal epithelial cells, mononuclear cells in the jejunal lamina propria and sinusoidal non-parenchymal cells in the liver. Since we previously speculated that nitrosamine may enhance the intestinal absorption of fucoidan, its absorption was estimated in rats administered N-butyl-N-(4-hydroxybutyl) nitrosamine (BBN) in their drinking water. Rats were fed 0.2% fucoidan chow (BBN + 0.2% fucoidan rats), 2% fucoidan chow (BBN + 2% fucoidan rats) and standard chow for eight weeks. The uptake of fucoidan through the intestinal tract seemed to be low, but was measurable by our ELISA method. Fucoidan-positive cells were abundant in the small intestinal mucosa of BBN + 2% fucoidan rats. Most fucoidan-positive cells also stained positive for ED1, suggesting that fucoidan was incorporated into intestinal macrophages. The uptake of fucoidan by Kupffer cells was observed in the livers of BBN + 2% fucoidan rats. In conclusion, the absorption of fucoidan through the small intestine was demonstrated both in vivo and in vitro.

Induction of anti-carbonic-anhydrase-II antibody causes renal tubular acidosis in a mouse model of Sjogren's syndrome.

BACKGROUND/AIM: We recently reported that renal tubular acidosis (RTA) in Sjogren's syndrome (SjS) is associated with high titers of an autoantibody against carbonic anhydrase (CA) II, an important enzyme in renal acid-base regulation. The purpose of this study was to determine whether a CA-II antibody could cause RTA in a mouse model of SjS. METHODS: PL/J mice were immunized with human CA II to induce CA II antibody formation, whereas controls were injected with phosphate-buffered saline and adjuvant. After 6 weeks, anti-CA-II antibody titers were measured, then ammonium chloride was administered orally for 1 week to detect any acidification defect. RESULTS: CA-II-immunized mice showed higher anti-CA-II antibody titers than control mice. Pathologically, lymphocytic and plasma cell infiltration was seen in the salivary glands and kidneys of CA-II-immunized mice, but not in controls. On acid loading, blood pH and urine pH decreased in both groups of mice, but the slope of urine pH versus blood pH was less steep in the CA-II-immunized mice, suggesting that these mice had an impaired ability to reduce their urine pH in the face of metabolic acidosis. CONCLUSION: CA-II-immunized mice had a urinary acidification defect, which may be similar to that seen in patients with SjS.

Determination of the serum metallothionein (MT)1/2 concentration in patients with Wilson's disease and Menkes disease.

We have developed an easy and specific enzyme-linked immunoassay (ELISA) for the simultaneous determination of serum metallothinein-1 (MT-1) and 2 (MT-2) in both humans and experimental animals. A competitive ELISA was established using a specific polyclonal antibody against rat MT-2. The antibody used for this ELISA had exhibited the same cross-reactivity with MT in humans and experimental animals. The NH2 terminal peptide of MT containing acetylated methionine was shown to be the epitope of this antibody. The reactivity of this ELISA system with the liver, kidney and brain in MT1/2 knock-out mice was significantly low, but was normal in an MT-3 knock-out mouse. The lowest detection limit of this ELISA was 0.6ng/ml and the spiked MT-1was fully recovered from the plasma. We investigated the normal range of MT1/2 (25-75%tile) in 200 healthy human serum and found it to be 27-48ng/ml, and this was compared with the serum levels in various liver diseases. The serum MT1/2 levels in chronic hepatitis C (HCV) patients were significantly lower than healthy controls and also other liver diseases. In the chronic hepatitis cases, the MT1/I2 levels increased gradually, followed by the progression of the disease to liver cirrhosis and hepatocellular carcinoma. In particular, we found significantly elevated MT1/2 plasma levels in Wilson's disease patients, levels which were very similar to those in the Long-Evans Cinnamon (LEC) rat (model animal of Wilson's disease). Furthermore, a significantly elevated MT1/2 level was found in patients with Menkes disease, an inborn error of copper metabolism such as Wilson's disease.

Renoprotective effects of angiotensin II receptor blocker, candesartan cilexetil, in patients with stage 4-5 chronic kidney disease.

BACKGROUND: To investigate the renoprotective effects and safety of angiotensin II receptor blocker (ARB) for patients with stage 4-5 chronic kidney disease. METHODS: An ARB, candesartan cilexetil, was administered to 13 patients (ARB group, n = 7; control group, n = 6) with a serum creatinine level of 2.52-5.95 mg/dl whose blood pressure had been maintained below 140/90 mmHg by the use of drugs other than ARBs. Routine measurements were conducted for 48 weeks, and renal survival analysis was observed for up to 3 years with the endpoints being doubling of the serum creatinine level, entry to hemodialysis, or death. The results were compared with those of the control group that was not treated with ARB. RESULTS: No significant changes were observed in the blood pressure in either group. Proteinuria significantly decreased from 0.95 +/- 0.51 to 0.39 +/- 0.12 g/day (paired t test, P = 0.033) in the ARB group, but did not change in the control group. Creatinine clearance in the control group decreased significantly from 16.2 +/- 5.7 to 10.4 +/- 4.8 ml/min per 1.73 m2 (paired t test, P = 0.011), but did not change in the other group. Thus, the slopes of the reciprocal serum creatinine values became less steep in the ARB group as compared with the control (-0.002 +/- 0.015 vs. -0.025 +/- 0.015 dl/mg per month; unpaired t test, P = 0.019). Kaplan-Meier analysis revealed that ARB exhibited more favorable renal outcome at 3 years (log-rank, P = 0.025). No serious adverse events were noted in the study. CONCLUSION: These results show that ARB reduces proteinuria and protects renal function even in the advanced renal failure.