Nobuhisa Shibahara

AST-120 Treatment in Pre-Dialysis Period Affects the Prognosis in Patients on Hemodialysis

Background/Aims. An oral adsorbent, AST-120, has been shown to retard the deterioration of renal function in patients with chronic kidney disease (CKD) by decreasing serum nephrotoxic substances such as indoxyl sulfate. Recent studies have suggested that a high level of serum indoxyl sulfate may be one of the mechanisms underlying the progression of atherosclerotic lesion, which is the leading cause of cardiovascular event or death in dialysis patients. In this study, we examined retrospectively whether AST-120 given to patients in the pre-dialysis period influences the prognosis after the initiation of dialysis. Methods. One hundred and ninety-two CKD patients on dialysis were studied. The survival and causes of death after the initiation of dialysis were compared between patients who were administrated AST-120 (AST-120 group, n = 101) and those not administrated AST-120 (non-AST-120 group, n = 91) prior to the initiation of dialysis. Results. The five-year survival rate was 72.6% in the AST-120 group and 52.6% in the non-AST-120 group, and was significantly higher in the AST-120 group (p = 0.018). The risk of death was increased 1.91-fold in the non-AST-120 group. However, no difference in the causes of death was observed between two groups. Conclusion. This study suggests that AST-120 given prior to the initiation of dialysis improves the prognosis of CKD patients under dialysis, although there is no association between AST-120 treatment and death caused by cardiovascular diseases such as heart failure, myocardial infarction, and cerebral hemorrhage. Further studies are needed to elucidate the effect of AST-120 on cardiovascular events and the prognosis in dialysis patients.

AST-120, an oral adsorbent, delays the initiation of dialysis in patients with chronic kidney diseases.

Abstract:  The effects of an oral adsorbent, AST‐120, in chronic kidney disease (CKD) patients was evaluated by the 24‐month dialysis‐free rate and 50% dialysis‐free period. This study retrospectively analyzed 193 patients admitted to the Osaka Medical College Hospital between January 1994 and December 2001 because of CKD and who later started dialysis. The propensity score on multiple factors was used to match two groups of patients (AST‐120 group, n = 78; non‐AST‐120 group, n = 78). Then, the proportion of patients remaining dialysis‐free and the 50% dialysis‐free period during the 24 months after starting treatment with or without AST‐120 were analyzed. The impact of AST‐120 on the risk of dialysis initiation was also determined by multivariate analysis. There were no significant differences in the clinical background and laboratory values after matching the two groups using the propensity score. The 50% dialysis‐free period was significantly prolonged in the AST‐120 group compared to the non‐AST‐120 group for all patients analyzed, as well as for the subgroup with diabetic or non‐diabetic renal disease. When AST‐120 treatment was started at a serum creatinine level below 3 mg/dL, the dialysis‐free period was longer than 24 months in the AST‐120 group, compared with 16.2 months in the non‐AST‐120 group. The 24‐month dialysis‐free rate was higher in the AST‐120 group in every patient category. The risk of dialysis initiation was increased 3.48‐fold in patients who were not administered AST‐120. These results show that AST‐120 delays the initiation of dialysis in CKD patients. Thus, AST‐120 is an effective supplementary therapy to prevent the initiation of dialysis in CKD patients.

Effect of Chymase Inhibition on the Arteriovenous Fistula Stenosis in Dogs

It was hypothesized that chymase may participate in hemodialysis vascular access dysfunction, as chymase has been known to be an effective enzyme in the conversion of angiotensin I (Ang I) to Ang II and in the latent TGF-beta1 to the active form. An arteriovenous (AV) fistula was created between the brachial artery and vein in dogs. In the AV anastomosis, when the walls of the venous and arterial sides were compared, the eccentric neointimal formation was most evident in the venous wall. Compared with the venous side downstream of the AV anastomosis, a severe neointimal hyperplasia was found in the venous side upstream of the AV anastomosis (intima/media, 153 +/- 25%). The chymase- and TGF-beta-positive mast cells were markedly accumulated in the proliferous neointima and media. In association with the reduction of chymase expression, a marked decrease in Ang II-, AT(1) receptor-, and TGF-beta-positive areas was achieved by NK3201 (a chymase inhibitor) treatment, and the neointima formation (intima/media: region A, 53 +/- 9%, P < 0.001; region B, 54 +/- 14%, P < 0.001) was also significantly suppressed in this group. Although lisinopril treatment also provided some beneficial effects with regard to the prevention of neointimal formation, the degree was less than that seen with chymase inhibition. These findings indicate that mast cell-derived chymase plays an essential role in the pathogenesis of the AV fistula access failure and that chymase inhibition may be a therapeutic target for the treatment of hemodialysis vascular access dysfunction in clinic settings.

Prevalence of Helicobacter pylori antibodies in long‐term dialysis patients

Background:  Helicobacter pylori has been reported to play an important role in the development of gastritis and gastric ulcer.

Effect of combined therapy using balloon-occluded arterial infusion of cisplatin and hemodialysis with concurrent radiation for locally invasive bladder cancer.

Objective:We tested the usefulness of combined therapy using balloon-occluded arterial infusion (BOAI) of cisplatin and hemodialysis, which delivers an extremely high concentration of cisplatin to the site of a tumor without systemic adverse effects, with concurrent radiation in patients with locally advanced bladder cancer. Methods:Patients underwent transurethral resection of the bladder tumor followed by BOAI of cisplatin (100, 200, or 300 mg) concurrent with hemodialysis, via both common iliac veins, for 2 hours after initiation of BOAI. A total of 60.4 Gy of radiation was delivered, starting from the day of BOAI. Results:Forty-one patients (30 males and 11 females, aged 55–98 years) were enrolled and assessable for toxicity and response. None of the patients suffered grade II or more severe toxicities; some experienced grade I blood/bone marrow toxicity, gastrointestinal toxicity, or neuropathy. All patients with histologically confirmed transitional cell carcinoma stage T2 or T3 (29 patients) achieved a complete response and were able to retain their bladder with no evidence of recurrent disease or distant metastasis at a mean follow-up of 132 weeks (range 8–648 weeks) after therapy. Patients with stage T4 tumors, besides transitional cell carcinoma, or lymph node involvement had stable or progressive disease. Conclusion:This therapy is a new strategy for patients with locally advanced bladder cancer. It can be a curative treatment not only in patients for whom total cystectomy is indicated, but also in patients whose condition is not amenable to curative treatment and for whom merely palliative treatment would otherwise seem the only option.

A functional and quantitative mutational analysis of p53 mutations in yeast indicates strand biases and different roles of mutations in DMBA- and BBN-induced tumors in rats

In order to analyze the mutational events and to understand the biological significance of the p53 gene in chemical carcinogenesis, we applied a new yeast‐based p53 functional assay to ovarian tumors induced by 7, 12‐dimethylbenz[a]anthracene (DMBA), as well as to transitional cell carcinomas of the urinary bladder induced by N‐butyl‐N‐(4‐hydroxybutyl) nitrosamine (BBN) in rats. The assay demonstrated that 15 of 19 DMBA induced tumors harbored clonal p53 mutations, which is consistent with the expectations of the “clonal expansion” hypothesis. The majority of the mutations were purine (AG) to pyrimidine (CT) transversions (12/19) on the non‐transcribed (sense) strand (NTS), which is likely to be due to depurination created by DMBA adduct formation on the NTS. In contrast, we found no purine to pyrimidine transversion on the NTS. After cessation of BBN treatment, BBN‐induced multifocal lesions in the bladder contained heterogeneous p53 mutations at an early stage. In the later stage, however, clonal p53 mutations were identified in 4 out of 7 bladders analyzed, conforming with the concept of “field cancerization”. The observed base substitutions were G→A (1/6) or C →T transitions (2/6), and mutations at T (3/6) on the NTS in clonal mutations, together with non‐clonal mutations, showing a preference of C→T to G→A (17 vs. 0). Thus, preferential repair was found in the transcribed strand of the p53 gene, whether modified by DMBA or by BBN carcinogens. Very similar mutation patterns were observed between clonal and non‐clonal mutations in the DMBA‐ and BBN‐induced tumors, indicating that the rat yeast p53 functional assay can be a potential tool for the characterization of in vivo mutation patterns of p53, when modified by chemical carcinogens. Int. J. Cancer 83:700‐705, 1999.

Ruptured cerebral aneurysm not detected by magnetic resonance angiography in juvenile autosomal dominant polycystic kidney

Recently, it has been reported that magnetic resonance angiography (MRA) is useful for screening and following up cerebral aneurysms in patients with autosomal dominant polycystic kidney disease (ADPKD). However, a patient was encountered with a ruptured cerebral aneurysm that was not detected by routine MRA. The patient, a 29‐year‐old man with ADPKD, was followed up at our hospital for more than 5 years. Ten months after an MRA examination, he suddenly developed severe headache. Brain computed tomography revealed subarachnoid hemorrhage. Digital subtraction angiography detected an aneurysm with a diameter of approximately 2 mm in the anterior communicating artery. Clipping of the aneurysm was immediately performed and he recovered without sequela after operation. Magnetic resonance angiography is useful to detect cerebral aneurysms, but it can not detect aneurysms measuring less than 4 mm.

Influence of sevelamer on mineral metabolism and hyperparathyroidism in Japanese hemodialysis patients.

Abstract:  In June 2003, sevelamer hydrochloride became widely available in Japan and was expected to control hyperphosphatemia in hemodialysis patients without inducing hypercalcemia. To evaluate the impact of sevelamer therapy on mineral metabolism, we recruited 954 hemodialysis patients from 21 renal units just before the general release of sevelamer in Japan. The serum calcium, phosphate, and parathyroid hormone levels determined on enrollment were compared with those later measured in June 2004. Sevelamer was prescribed for 169 of the 859 patients for whom data were available in 2004. The mean calcium level, phosphate level, and calcium × phosphate product were all significantly reduced during the 12‐month study period, but the intact parathyroid hormone (iPTH) level did not change. As a result, the percentage of patients who achieved a calcium × phosphate product of <55 mg2/dL2 was significantly increased, but there were no changes in that of patients who achieved the target ranges for phosphate (3.5–5.5 mg/dL) or iPTH (150–300 pg/mL). Among sevelamer‐treated patients, iPTH significantly increased, and this change was more marked in the patients with an initial iPTH level <150 pg/mL. Sevelamer was useful for reducing the serum calcium level and calcium × phosphate product, but hyperphosphatemia and hyperparathyroidism were not improved in our study population at 12 months after the release of sevelamer. A decrease in the calcium load might result in the exacerbation of hyperparathyroidism. However, among patients with relative hypoparathyroidism, sevelamer therapy may be beneficial for the prevention of adynamic bone disease.

Support for Dialysis Therapy in Vietnam, Cambodia, and Myanmar by Japanese Societies in the Field of Blood Purification

With recent economic development in Southeast Asia, there have been improvements in medical services and healthcare provision. This has led to increased numbers of dialysis patients and increased numbers of dialysis facilities in the region. To assist economically developing countries in managing this change, support projects from Japan have been conducted in the region since around 2007. This article summarizes and discusses Japans support activities, in which some of the authors were directly involved, in Vietnam, Cambodia, and Myanmar. Initial support was mainly organized by the non-governmental organization Ubiquitous Blood Purification International (NGO UBPI), and currently several organizations in the field of blood purification work together to offer ongoing support in the region. Many positive changes have resulted from these activities in Southeast Asia, but challenges remaining for the future are to establish an educational system for each dialysis specialty and develop dialysis techniques ensuring high treatment quality and safety.

The Lack of the Knowledge about the Postprandial Blood Glucose by the Education using the Single Absolute Tool for the Diabetic Dietary Therapy in Japan

Energy counting based on diabetic food exchange lists, in which 1 exchange unit is equivalent to 80 kcal, has been used as the single absolute tool in dietary education in Japan for patients with diabetes for 1993 to 2013 by Japan Diabetes Society. And the 5th and 6th editions of this material had put emphasis on only energy intake and made light of the fact that the postprandial blood glucose levels depend on carbohydrate intake. This approach may have created a misunderstanding among Japanese people that postprandial blood glucose levels are dependent on energy intake.