Possible Roles of Periostin in the Formation of Hemodialysis Vascular Access Stenosis after Polytetrafluoroethylene Graft Implantation in Dogs.

Periostin, a recently found matricellular protein, has been implicated in neointima formation after balloon injury. However, the relationship between periostin and hyperplastic intima formation after PTFE graft implantation is unclear. Under mixed anesthesia, PTFE grafts were implanted between the canine carotid artery and jugular vein, and PTFE graft samples were harvested 1, 2, and 4 months after implantation. Intima formation started on the luminal surface of PTFE grafts at the venous anastomotic region 1 month after implantation. Thereafter, the increase in intimal volume was not only observed in the venous and arterial anastomotic regions, but also in the middle region of the PTFE grafts. In accordance with the increased intimal formation, time-dependent increases in mRNA expressions of periostin and transforming growth factor beta 1 (TGF-ß1), as well as a strong positive correlation between periostin and TGF-ß1, were observed. These findings suggest that periostin may play a very important role in the pathogenesis of hemodialysis vascular access stenosis through the acceleration of intimal formation. Thus, periostin may be a very important therapeutic target for the treatment of vascular access graft dysfunction in hemodialysis patients.

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 Japan's 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.

Effects of raloxifene on bone metabolism in postmenopausal women on chronic hemodialysis.

BACKGROUND: Postmenopausal women with end-stage renal failure are at an increased risk of fracture because of the effects of secondary hyperparathyroidism and postmenopausal osteoporosis. In the present study, we investigated the feasibility of using raloxifene to prevent fractures in postmenopausal women with end-stage renal failure on hemodialysis. METHODS: This study was conducted using a multicenter, single-arm, prospective design. Raloxifene was administered to postmenopausal women aged ≥50 years who were on maintenance hemodialysis and met any of the following criteria after a 24-week run-in period: an alkaline phosphatase level (bone formation marker) of ≥6.18 µkat/L (≥370 U/L), a bone-specific alkaline phosphatase (BAP; bone formation marker) level of ≥0.59 µkat/L (≥35.4 U/L), or a bone-derived tartrate-resistant acid phosphatase (TRACP-5b; bone resorption marker) level of ≥4.2 U/L. RESULTS: A total of 48 individuals were eligible for study inclusion. Of them, 30 individuals participated in this study. The BAP levels were significantly decreased at week 4, but returned to the baseline levels at week 24. Similarly, the TRACP-5b levels were significantly decreased at week 4, but returned to the baseline levels at week 24. The serum calcium value decreased consistently after the start of raloxifene therapy. The intact parathyroid hormone (iPTH) levels were likely increased at week 4. The ratio of BAP to iPTH levels and the ratio of TRACP-5b to iPTH levels both showed significant decreases over time. During the raloxifene therapy, no thrombosis or other drug-related adverse events developed. CONCLUSION: The study results indicated that raloxifene can transiently reduce the levels of bone metabolism markers and might be useful for preventing fractures in postmenopausal women with end-stage renal failure, although raloxifene use over the long term may not have adequate efficacy in the absence of appropriate concomitant active vitamin D therapy.

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.

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.

A case report of interferon beta monotherapy for high hepatitis C viral load in dialysis patients.

A 42-year-old male dialysis patient was infected with hepatitis C virus (HCV), and treated with interferon beta (IFN-beta) for a rapid increase in viral load. After dialysis three times a week, 3 million units of IFN-beta were intravenously infused for 1 h. The treatment was markedly effective, and the virus was eliminated in the sixth week. Therapy was continued for 24 weeks, and HCV negativity has been maintained for more than 6 months after the completion of administration. The blood IFN level slowly decreased immediately after administration. The mean trough level was 37 U/mL, and the half-life was 65 min. No adverse event requiring discontinuation of the treatment occurred, showing that IFN alone may safely eliminate the virus in dialysis patients with high hepatitis C viral load. Many dialysis patients are latently infected with HCV, and the infection affects the prognosis. Therefore, establishment of a therapeutic method is urgently needed.

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

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 x 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 x phosphate product of <55 mg(2)/dL(2) 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 x 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.

Preoperative administration of FTY720 prolonged renal allograft survival.

BACKGROUND: FTY729 is an immunomodulator obtained by chemical modification of Myriocin(ISI-1) which exists in the culture filtrate of an ascomycete, Isaria sinclairii. It has been reported that postoperative administration of FTY720 prolonged survival of various kinds of transplanted organs. In the present study, we evaluated the effect of 2-day preoperative administration of FTY 720 on graft survival. MATERIALS AND METHODS: We used a rat renal transplantation model in which Wistar King Aptekman Hokkaido (WKAH, RT1K) served as the organ donor and Lewis (LEW, RTl) as the recipient. FTY720 was given to the recipients consecutively 2 days (day-2, day-1) before transplantation at the doses of 1, 3 or 5 mg/kg/day. Renal allograft survivals, hematological parameters of recipient blood and phenotypic analysis of recipient splenic cells and graft infiltrate were evaluated. RESULTS: Consecutive 2-day preoperative oral administration of FTY 720 at the doses of 1, 3 or 5 mg/kg/day significantly prolonged WKAH allograft survivals compared with those of the untreated recipients. The number of peripheral blood lymphocytes was markedly decreased in the recipients treated with FTY720 at the doses of 3 mg/kg/day or 5 mg/kg/day on the 5th postoperative day. Preoperative FTY 720 administration significantly decreased the number of CD4 positive cells and the percentage of interleukin 2 receptor (IL-2 R) positive cells infiltrating both spleen and allograft at the dose of 3 mg/kg/day or 5 mg/kg/day. CONCLUSION: FTY 720 could act as a safe and potent immunomodulator by decreasing the number of peripheral lymphocytes, especially CD4 positive cells and IL-2R positive cells when it is given to the recipient preoperatively.

Ultrasound evaluation of the effects of leukocytapheresis on rheumatoid arthritis.

Leukocytapheresis (LCAP) is effective in treating rheumatoid arthritis (RA). Ultrasound (US) examination of joints is useful for evaluating disease activity and therapeutic effects in RA, but the clinical assessment of LCAP therapy with US has been little reported. We investigated the usefulness of US for evaluating the effects of LCAP in patients with RA. US examination was performed in six patients (total of seven cases) who underwent LCAP. Twenty-eight joints (bilateral shoulders, elbows, wrists, 1st to 5th metacarpophalangeal joints, 1st to 5th proximal interphalangeal joints, and knee joints) were evaluated by a systematic multiplanar grey-scale and power Doppler (PD) examination. Disease activity of RA was evaluated using the 28-joint Disease Activity Score with erythrocyte sedimentation rate (DAS28-ESR). Moderate or good responses to LCAP based on the DAS28-ESR were observed in four of the seven cases although C-reactive protein (CRP) and ESR did not decrease. LCAP significantly reduced the mean total PD score 17.3 ± 11.6 to 13.0 ± 10.5 (P = 0.0469). The total PD score decreased in six of the seven cases, and the number of joints with PD score ≥ 2 decreased in five of the seven cases. The rate of decrease in the number of joints with PD score ≥ 2 correlated strongly with the DAS28-ESR and its components, especially swollen joint counts and evaluator's global assessment, but not with the rate of decrease in CRP and ESR. US imaging of joints may be useful for evaluating the therapeutic effects of LCAP on RA compared to other inflammatory parameters.

Dialysis and quality of dialysate in southeast asian developing countries.

BACKGROUND: The number of dialysis patients has been increasing in Southeast Asia, but statistical data about these patients and on the quality of dialysates in Southeast Asian dialysis facilities are still imprecise. For this study, dialysis-related statistical data were collected in Southeast Asia. METHODS: A survey of the quality of dialysates was carried out at 4 dialysis facilities in Vietnam and Cambodia. The dialysis patient survey included the numbers of dialysis facilities and patients receiving dialysis, a ranking of underlying diseases causing the initiation of dialysis, the number of patients receiving hemodialysis (HD)/on-line hemodiafiltration/continuous ambulatory peritoneal dialysis, the number of HD monitoring devices installed, the cost of each session of dialysis (in USD), the percentage of out-of-pocket payments, and the 1-year survival rates of the dialysis patients (in percent). The dialysate survey covered the endotoxin (ET) level and bacterial count in tap water, in water filtered through a reverse osmosis system and in dialysate. RESULTS: In each of the countries, the most frequent reason for the initiation of dialysis is diabetes mellitus. HD is usually carried out according to the 'reuse' principle. The 1-year survival rates are 70% in Myanmar and about 90% in the Philippines and Malaysia. The ET levels in standard dialysates were satisfactory at 2 facilities. The bacterial counts in dialysates were not acceptable at any of the facilities investigated. CONCLUSION: There is an urgent need to teach medical workers involved in dialysis how to prepare sterile and ET-free dialysates.

A case report of successful treatment with plasma exchange for hemophagocytic syndrome associated with severe systemic juvenile idiopathic arthritis in an infant girl.

An infantile case of hemophagocytic syndrome (HPS) with systemic juvenile idiopathic arthritis (s-JIA), refractory to methylprednisolone pulse therapy and cyclosporine A administration, was successfully treated by plasma exchange. The patient was a one-year-old Japanese girl who had developed recurrent steroid-dependent signs, including fever, skin eruption, and hepatopathy, while in France, where she had been diagnosed as having s-JIA at eight months of age. As a high fever and rheumatoid rash were evident on arrival at our hospital, she was admitted and given intravenous methylprednisolone pulse therapy and cyclosporine A. She developed pancytopenia with a generalized clonic seizure, high fever, and liver dysfunction after her cytomegalovirus (CMV) titer became positive during the course of treatment; therefore, she was treated with ganciclovir. She was subsequently diagnosed as having HPS complicating s-JIA from the findings of a bone marrow aspirate. At this time, her blood examination data including a high level of C-reactive protein and hyperferritinemia, suggested that her s-JIA was very active, and the pancytopenia continued after her CMV titer became negative. Therefore, CMV infection against a background of active s-JIA could have triggered the HPS in this case. Because the HPS was resistant to an immunosuppressive regime of methylprednisolone pulse therapy and cyclosporine A, plasma exchange therapy was started. After three sessions of this therapy, the patient's symptoms and laboratory data were markedly improved. Our experience suggests that plasma exchange should be considered as a therapeutic tool for HPS refractory to conventional therapy.

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.

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.

Helicobacter pylori in patients receiving long-term dialysis.

BACKGROUND: Helicobacter pylori (H. pylori) is considered to cause gastritis and gastric ulcer. In dialysis patients, digestive tract hemorrhage is sometimes fatal. However, in regard to H. pylori infection in patients with end-stage renal disease (ESRD), many issues remain to be clarified. METHODS: This study included 76 symptom-free patients with ESRD. The subjects consisted of 25 patients with chronic renal failure who had not received dialysis and 51 patients receiving dialysis. On upper digestive tract endoscopy, specimens were taken for analysis of H. pylori. Urease test, culture, and microscopy were performed. RESULTS: In non-dialysed patients, the prevalence of H. pylori-positive patients was 56.0%. In dialysed patients, the percentage was significantly lower (27.5%). In dialysed patients, the mean duration of dialysis was 8.1 +/- 7.5 months (mean +/- SD) in H. pylori-positive patients and 56.2 +/- 60.9 months (mean +/- SD) in H. pylori-negative patients (p < 0.001). 11 of 13 non-dialysed patients with chronic gastritis were positive for H. pylori. However, only 5 of 24 dialysed patients were positive for H. pylori infection. CONCLUSIONS: Long-term dialysis decreased the prevalence of H. pylori. The reduction of gastric acid secretion related to chronic gastritis may be involved.

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. METHODS: This study included 168 patients with end-stage renal disease (ESRD; 30 non-dialysis patients, 138 patients receiving dialysis; mean duration of dialysis: 57.3 +/- 61.7 months) and 138 control volunteers. We investigated the prevalence of H. pylori infection by measuring H. pylori antibody (IgG) levels. RESULTS: The prevalence of H. pylori infection was 62.3% in the control group, 53.3% in the non-dialysis patients, and 36.9% in the dialysis patients. The percentage decreased with a reduction of renal function. In addition, the proportion of H. pylori-positive patients decreased with the duration of dialysis, and the antibody titre was also significantly decreased. There was no association between long-term oral administration of H2RA (H2 receptor antagonist) and the incidence of H. pylori infection. CONCLUSION: Among dialysis patients, the proportion of H. pylori-positive patients was low. An aetiological factor other than H2RA agents was suggested. Renal failure or dialysis treatment may influence H. pylori infection.

Dialyzability of the antiepileptic drug zonisamide in patients undergoing hemodialysis.

PURPOSE: The influence of hemodialysis on plasma zonisamide (ZNS) concentration has not been clarified. In this study, the dialyzability of ZNS during hemodialysis was investigated in four ZNS-treated women with systemic lupus erythematosus complicated by seizures. METHODS: The total and unbound plasma concentrations of ZNS were measured before and after hemodialysis. The concentration of ZNS in the spent dialysate also was determined. RESULTS: The reduction in plasma ZNS concentration after a 4.5-h hemodialysis was 52.0 +/- 7.6%, and the dialyzer (BLF-16GW) clearance of ZNS was 55.1 +/- 7.0 ml/min. Dosage was gradually increased up to 200 to 500 mg/day, and the seizures were controlled satisfactorily. CONCLUSIONS: The plasma concentration of ZNS was reduced by approximately 50% during one session of dialysis. For patients undergoing daytime hemodialysis sessions every 2 or 3 days, the usual dosage of ZNS (4-8 mg/kg/day) may be prescribed once a day in the evening. If seizures occur after hemodialysis, a supplemental daily dose may be prescribed in the morning.