Shigeki Toma

Effects of angiotensin receptor blockade (ARB) on mortality and cardiovascular outcomes in patients with long-term haemodialysis: a randomized controlled trial

BACKGROUND Hypertension is a major risk factor for death and cardiovascular disease (CVD) in patients undergoing chronic haemodialysis (HD), but there is uncertainty surrounding the effects of blood pressure (BP) lowering on this high-risk patient group. METHODS In a multicenter, prospective, randomized, open-label, blinded-endpoint trial, 469 patients with chronic HD and elevated BP (140-199/90-99 mmHg) were assigned to receive the angiotensin receptor blockade (ARB) olmesartan (at a dose of 10-40 mg daily; n = 235) or another treatment that does not include angiotensin receptor blockers and angiotensin-converting enzyme (ACE) inhibitors (n = 234). The primary outcomes were the following: (i) composite of death, nonfatal stroke, nonfatal myocardial infarction and coronary revascularization and (ii) all-cause death. RESULTS During a mean follow-up of 3.5 years, the mean BP was 0.9/0.0 mmHg lower in the olmesartan group than in the control group (not significant). A total of 68 patients (28.9%) in the olmesartan group and 67 patients (28.6%) in the control group had subsequent primary composite endpoints [hazard ratio (HR) in the olmesartan group 1.00, 95% confidence interval (CI) 0.71-1.40, P = 0.99]. All-cause deaths occurred in 38 patients (16.2%) in the olmesartan group and 39 (16.7%) in the control group (HR, 0.97; 95% CI, 0.62-1.52, P = 0.91). Olmesartan did not alter the risks of serious adverse events. CONCLUSIONS BP-lowering treatment with an ARB did not significantly lower the risks of major cardiovascular events or death among patients with hypertension on chronic HD. (Cochrane Renal Group Prospective Trial Register number CRG010600030).

Increased Risk of Cardiovascular Disease with Erythropoietin in Chronic Dialysis Patients

Recombinant human erythropoietin is widely used in chronic dialysis patients. However, the long-term effect, especially on the incidence of cardiovascular disease, has not been critically evaluated. We observed the annual incidence of stroke and acute myocardial infarction from April 1988 through March 1993 in Okinawa, Japan. Until April 1990, erythropoietin was not generally used. Therefore, we have two periods: pre-erythropoietin, April 1988 through March 1990, and post-erythropoietin, April 1990 through March 1993. Two thousand one hundred and sixteen patients (1,219 males and 897 females) were on chronic dialysis during the study period by March 31, 1993. Every case of stroke and acute myocardial infarction during the study period was registered. The odds ratio was calculated using the data of the general population in each sex and age class obtained in the same area. A total of 86 cases of stroke and 15 cases of acute myocardial infarction were registered during the study period. The annual incidence, per 1,000 patient-years, of stroke was 12.5 (1988), 10.5 (1989), 12.7 (1990), 14.0 (1991), and 17.5 (1992). The incidence of stroke was increased in the post-erythropoietin period compared to the pre-erythropoietin period, odds ratio 1.22 and 95% confidence interval (95% CI 1.06-1.41, p < 0.01). The annual incidence of acute myocardial infarction was 1.0 (1988), 1.8 (1989), 0.8 (1990), 2.9 (1991) and 4.7 (1992). The incidence of acute myocardial infarction was increased significantly in the post-erythropoietin period compared to the pre-erythropoietin period, odds ratio 1.87 (95% CI 1.66-2.10, p < 0.01). The odds ratio of stroke to the general population was 4.25 (95% CI 3.10-5.82) in the pre-erythropoietin and 4.58 (95% CI 2.14-9.80) in the post-erythropoietin period. In acute myocardial infarction, it was 2.98 (95% CI 2.84-3.12) and 3.81 (95% CI 3.18-4.56). The odds ratio of acute myocardial infarction was significantly increased (p < 0.01). The introduction of erythropoietin was associated with an increased risk of cardiovascular disease, especially acute myocardial infarction. Erythropoietin may unmask the sclerotic lesion in chronic dialysis patients.

Epidemiologic Analysis of Diabetic Patients on Chronic Dialysis

We retrospectively surveyed all of the available medical records of 404 (191 females and 213 males) chronic dialysis patients, of whom 16 (4%) had insulin-dependent diabetes mellitus (IDDM) and 388 (96%) non-insulin-dependent diabetes mellitus (NIDDM). The patients were among 2,214 dialysis patients in Okinawa, Japan, of whom 443 were diabetic. The patients entered a large population-based dialysis registry. The mean duration from the diagnosis of diabetes mellitus (DM) to dialysis was 181.6 months in the IDDM patients and 150.4 months in the NIDDM patients. The NIDDM patients were classified into four subgroups according to their status when DM was first suspected. The duration from the diagnosis of DM until the onset of dialysis treatment was significantly shorter than in any other subgroup or in the IDDM subgroup with major vascular disease (131.9 months). Otherwise, the course of renal disease in NIDDM patients was similar to that in IDDM individuals. Most of our dialysis patients with DM had NIDDM. In most of the NIDDM patients, the diagnosis had been delayed for several years for unknown reason. However, if diagnosed early, NIDDM shows a clinical time course until dialysis similar to that of IDDM. Whether NIDDM patients contract chronic renal disease at an equal incidence to that of IDDM patients and the fraction of all diabetic patients accepted for chronic dialysis remain to be determined.

Effect of high fiber density ratio polysulfone dialyzer on protein removal.

Background/Aims: A dialyzer (APS-EX) with a higher hollow fiber density ratio was manufactured using the highest performance polysulfone hollow fiber from Asahi-Kasei Medical. Methods: We compared the performance of this device in comparison with hemodialysis (HD; APS-S) and hemodiafiltration (HDF) conditions (APS-S, 10 l post-HDF) to evaluate its merit as an internal filtration-enhanced dialyzer. Results: With low molecular weight proteins, APS-EX had a reduction ratio of 74.3% for β2-microglobulin (β2-MG), and 31.0% for α1-MG. APS-EX had a significant higher removal amount of α1-MG compared to APS-S (HDF). Significant differences were seen in albumin loss, 4.0 g for APS-EX, 3.0 g for APS-S (HDF), and 0.9 g for APS-S (HD). Using HD mode, APS-EX demonstrated a performance which was more than equivalent to approximately 10 l post-HDF. Conclusions: The results suggested the possibility that HD equivalent to HDF can be performed safely with the ultrapure dialysate when using APS-EX with internal filtration.

Deformity of Buttonhole Entry Site Causes Higher Frequency of Vascular Access-Related Infection.

BACKGROUND Vascular access-related infection is more frequent in patients using the buttonhole method for cannulation of the arteriovenous access for hemodialysis. Deformity of buttonhole entry sites is frequently observed among patients on the buttonhole method for extended periods of time. With deformed buttonhole entry sites, moreover, scabs are often incompletely removed at the time of buttonhole cannulation. METHOD In 166 patients using the buttonhole method at Hino Clinic in Osaka, Japan as of June 30, 2014, the shapes of buttonhole entry sites were categorized into the following 3 types: flat, depressive deformity, and bulging deformity. A multivariate logistic regression method was used to analyze associations between various data including shapes of buttonhole entry sites and occurrence of access-related infection. We also examined microscopic features of the buttonhole entry site tissue that was removed from a patient who died after 3 years of buttonhole cannulation. RESULTS For the flat buttonhole entry sites, frequency of access-related infection was 0.12 events/1,000 arteriovenous fistulas as compared to 0.47 events/1,000 arteriovenous fistulas for the entry sites with bulging deformity. Such infection did not occur for the entry sites with depressive deformity. The multivariate logistic regression analysis revealed a significant association between an entry site with bulging deformity and occurrence of access-related infection (odds ratio = 5.369, p = 0.0085). Furthermore, the microscopic section showed granulations beneath the skin at the buttonhole entry site and around the buttonhole tract. CONCLUSION A significant association was shown between an entry site with bulging deformity and occurrence of access-related infection. The microscopic features of the buttonhole entry site of the patient on the buttonhole method for 3 years suggest that the entity of bulging deformity at the entry site is hypertrophic granulation.

A New Method That Enables Complete Removal of Scabs at Buttonhole Entry Sites

BACKGROUND Scab removal is a time-consuming process and often injures the skin at a buttonhole entry site. Incomplete removal of scabs may cause access-related infection. METHODS In a new procedure, buttonhole entry sites were treated with a moist healing step after hemodialysis, and then a formed scab was wiped off with a microfiber towel during bathing on the night prior to hemodialysis, which was performed on the following day. In the moist healing step, the entry site was disinfected with a diluted povidone-iodine solution (0.1% povidone-iodine solution). RESULTS When the buttonhole entry sites of the patients were treated with the new procedure, the scabs had already been removed at the buttonhole entry sites, and the sites were covered with a thin transparent membrane. Histological examination showed the thin membrane was stratum corneum, in which nuclei are still seen in keratinocytes. CONCLUSION By treating the buttonhole entry sites of patients with the wound moist healing method and then rubbing the sites with a microfiber towel during bathing, scabs can be removed without injuring the skin at the sites in advance.

Access-Related Infections Involving the Buttonhole Technique

Purpose: In this study, we discuss a mechanism of development of access-related Staphylococcus aureus infections in patients on buttonhole (BH) method and logically construct a measure to prevent such infections on the basis of the mechanism. Summary:S. aureus can colonize a BH track. Once S. aureus colonizes a BH track, access-related infections may develop when the equilibrium is upset between the factors of host resistance and a level of bacterial growth in a BH track. Thus, the logically constructed measure to prevent access-related infections are as follows: (1) decolonization of S. aureus from a BH track by applying mupirocin ointment to a BH entry site when a patient has been proven to be a carrier of S. aureus in the track, (2) prevention of bacterial invasion of the BH track by a new method to remove a scab completely, and (3) control of bacterial growth in the BH track by disinfecting the site with diluted povidone-iodine solution (0.1% povidone-iodine solution) before access vessel cannulation.

Contents Vol. 41, 2016

Annual Congress of the 293 Chinese Blood Purification Center Administration Commitee August 20–22, 2015, Tianjin, China Guest Editor: Tao Wei (Beijing) (available online only