Chikao Yamazaki

Infection with hepatitis GB virus C in patients on maintenance hemodialysis.

BACKGROUND A recently discovered non-A-E hepatitis virus has been designated hepatitis GB virus C (HGBV-C), but little is known about its mode of transmission and its clinical manifestations. We studied 519 patients on maintenance hemodialysis to determine whether they were infected with HGBV-C. METHODS HGBV-C RNA was identified in serum by a reverse-transcription-polymerase-chain-reaction assay with nested primers deduced from a non-structural region. A nucleotide sequence of 100 bp in the nonstructural region was determined on HGBV-C clones. RESULTS HGBV-C RNA was detected on 3.1 percent of the patients on hemodialysis (16 of 519), as compared with 0.9 percent of healthy blood donors (4 of 448, P<0.03). None of the 16 patients had evidence of active liver disease, although 7 were also infected with hepatitis C virus. Eight patients with HGBV-C infection were followed for 7 to 16 years. In two patients the virus was present at the start of hemodialysis. One had a history of transfusion, and HGBV-C persisted over a period of 16 years; the other became free of HGBV-C after 10 years. In five patients, HGBV-C RNA was first detected 3 to 20 weeks after blood transfusion and persisted for up to 13 years. One patient with no history of transfusion was infected with an HGBV-C variant with the same sequence as in two of the patients with post-transfusion HGBV-C infections. CONCLUSIONS Patients on maintenance hemodialysis are at increased risk for HGBV-C infection. This virus produces persistent infections, which may be transmitted by transfusions but may also be transmitted by other means.

An Overview of Regular Dialysis Treatment in Japan (as of 31 December 2004)

Abstract:  A statistical survey of 3932 nationwide hemodialysis (hereafter, dialysis) facilities was carried out at the end of 2004, and 3882 facilities (98.73%) responded. The population undergoing dialysis at the end of 2004 was 248 166, an increase of 10 456 patients (4.4%) from that at the end of 2003. The number of dialysis patients per million people was 1943.5. The crude death rate of dialysis patients from the end of 2003 to the end of 2004 was 9.4%. The mean age of patients who underwent dialysis in 2004 was 65.8 years, and that of the total dialysis population was 63.3 years. The percentage distribution of patients who underwent dialysis according to a newly underlying disease showed that 41.3% of patients had diabetic nephropathy and 28.1% had chronic glomerulonephritis. The frequency of calcium carbonate use for dialysis patients was 75.1% and that of sevelamer hydrochloride use was 26.2%. The frequency of sevelamer hydrochloride use does not necessarily have a strong correlation with the dose of calcium carbonate. Patients who received high doses of sevelamer hydrochloride tended to have a low concentration of arterial blood HCO3–. Approximately 15% of dialysis patients used an intravenous vitamin D preparation, generally maxacalcitol. The longer the patients had been on dialysis, the higher the frequency of use of an intravenous vitamin D preparation. When the concentration of serum intact parathyroid hormone (PTH) was more than 200 pg/mL, the frequency of use of an orally administered vitamin D preparation decreased; but that of intravenous vitamin D preparation increased. The percentage of dialysis patients who received percutaneous ethanol injection therapy (PEIT) was 1.4%. The percentage was more than 50% in the patients who had been on dialysis for more than 10 years. The percentage of patients who received PEIT again was 35.0%. The percentage of patients who had been on hemodialysis for more than 10 years and received PEIT again was more than 50%. 

The organization and financing of end-stage renal disease treatment in Japan

End-stage renal disease (ESRD) affects 230,000 Japanese, with about 36,000 cases diagnosed each year. Recent increases in ESRD incidence are attributed mainly to increases in diabetes and a rapidly aging population. Renal transplantation is rare in Japan. In private dialysis clinics, the majority of treatment costs are paid as fixed fees per session and the rest are fee for service. Payments for hospital-based dialysis are either fee-for-service or diagnosis-related. Dialysis is widely available, but reimbursement rates have recently been reduced. Clinical outcomes of dialysis are better in Japan than in other countries, but this may change given recent ESRD cost containment policies.

Clinical effects of L-threo-3,4-dihydroxyphenylserine on orthostatic hypotension in hemodialysis patients

Orthostatic hypotension is one of the major factors interfering with everyday activities in hemodialysis patients, but there has been no effective agent for treating it. In order to clarify the clinical effects of L-threo-3,4-dihydroxyphenylserine (L-DOPS) on orthostatic hypotension of hemodialysis patients, we conducted a randomized, double-blind comparative trial. 149 regular hemodialysis patients with orthostatic hypotension were randomly allocated to three groups and L-DOPS at doses of 400 mg, 200 mg or placebo was orally administrated to each group 30 min before starting every hemodialysis for 4 weeks. Changes of blood pressure (BP) in orthostatic hypotension immediately after completion of hemodialysis and symptoms related to orthostatic hypotension were compared between the three groups. In the 400-mg group, systolic and diastolic BP after standing increased significantly and the drop of mean BP after standing was also reduced compared with pretreatment levels. No such changes were observed in the placebo group. Fatiguability, malaise/weakness, dizziness and light-headed feeling, the interdialytic symptoms commonly observed in hemodialysis patients who developed orthostatic hypotension, were improved to a significant extent in the L-DOPS group compared with the placebo group. In particular, the improvement was more remarkable for the L-DOPS 400-mg group than the placebo group in patients with diabetic nephropathy, lower systolic BP after standing, and the long duration type of orthostatic hypotension. The incidence of adverse events was comparable between the three groups, and all recovered after discontinuation of L-DOPS or concomitantly administered drugs, or without any treatment. These findings indicate that L-DOPS taken before hemodialysis prevents orthostatic hypotension in patients undergoing hemodialysis, and is also effective for the interdialytic symptoms related to orthostatic hypotension.

Effects of L-threo-3,4-dihydroxyphenylserine on orthostatic hypotension in hemodialysis patients.

Background: Orthostatic hypotension (OH) is a serious complication observed in hemodialysis (HD) patients after HD as well as during the interdialytic period. L-Threo-3,4-dihydroxyphenylserine (L-DOPS) is a nonphysiological neutral amino acid that is directly converted to the neurotransmitter norepinephrine by aromatic L-amino acid decarboxylase. Methods: A placebo-controlled double-blind study for 4 consecutive weeks and a long-term study (24–52 weeks) were conducted to evaluate the efficacy of L-DOPS for OH after HD. The drug was administered orally 30 min before the start of each HD period in both studies. Doses of 400 mg of L-DOPS or placebo were given to HD patients with OH (45 and 41 patients, respectively) in the double-blind study, and doses of 200 or 400 mg of L-DOPS were given to 74 HD patients in the long-term study. Results: In the double-blind study, L-DOPS significantly ameliorated subjective symptoms related to OH, including dizziness/light-headed feeling, and malaise, throughout the interdialytic period. For 19 patients with delayed-type OH, hypotension with the lowest blood pressure recorded 10 min after standing, the decrease in blood pressure was suppressed significantly after L-DOPS treatment (10 patients) as compared with the placebo-treated group (9 patients). In the long-term study, the efficacy of L-DOPS was not attenuated, and the marked fluctuations in the plasma L-DOPS and norepinephrine levels were not noted after long-term use, without increases in incidence or severity of adverse reactions. Conclusions: These results indicate that L-DOPS is effective for improving OH-related interdialytic subjective symptoms in HD patients after short-term as well as after long-term administration.

Multicenter Study of Pegylated Interferon α-2a Monotherapy for Hepatitis C Virus-Infected Patients on Hemodialysis: REACH Study

Many studies have reported poor vital prognosis in hepatitis C virus (HCV)‐infected dialysis patients. The rate of HCV‐infected dialysis patients in Japan is as high as 9.8%, and antiviral therapy is believed to be important for improving vital prognosis. We conducted a multicenter study to examine the administration method for pegylated interferon α‐2a (PEG‐IFNα‐2a) monotherapy in HCV‐infected dialysis. We studied 56 patients: 14 with low viral loads (HCV RNA < 5.0 log IU/mL) were treated with 90 μg PEG‐IFNα‐2a weekly, 42 with high viral loads (HCV RNA ≥ 5.0 log IU/mL) were treated with 135 μg PEG‐IFNα‐2a weekly. We examined the sustained virological response (SVR), factors affecting the SVR, and treatment safety. The overall SVR rate was 39% (22/56); that for genotype 1, genotype 2, low viral loads, and high viral loads was 29%, 67%, 93%, and 21%, respectively. From receiver operating characteristic (ROC) analysis, the HCV RNA cutoff values likely to achieve SVR for genotypes 1 and 2 were <5.7 log IU/mL (SVR rate: 64% 9/14) and <6.5 log IU/mL (SVR rate: 88% 7/8), respectively. If there was HCV RNA negativation at 4 weeks (rapid virological response), the SVR rate was 94% (16/17), whereas it was 6% (1/16) if there was HCV RNA positivity at 24 weeks. The rate of treatment discontinuation from adverse events or aggravated complications was 25% (14/56). High SVR rates can potentially be achieved with PEG‐IFN monotherapy by identifying the target patients, based on virus type and viral load before initiating treatment and by modifying therapy during treatment according to responsiveness.

Infrainguinal arterial reconstruction in end-stage renal disease.

A total of 14 infrainguinal revascularizations in 11 patients with end-stage renal disease resulting from diabetes mellitus were reviewed. Indications for surgery comprised gangrene or non-healing ulcerations in eight patients (11 limbs), ischaemic rest pain in two (two limbs) and disabling claudication in one (one limb). No graft failures occurred during the period of observation. There were two immediate postoperative deaths, one amputation, and four persistent non-healing foot ulcers. The remaining four patients showed improvement. Six deaths occurred, including two perioperative deaths. Four patients with non-healing ulcers died within 1 year and 10 months after revascularization, but their deaths were not associated with the foot ulcers. The cumulative patient survival rate was 42% at 1 year. Infrainguinal revascularization in patients with end-stage renal disease caused by diabetes mellitus is feasible when meticulous preoperative assessment and careful perioperative management are employed to minimize operative risk.

Utility of Venography in Shunt Surgery on Hemodialyzed Patients

Fifty-eight examples of upper extremity venography in 40 patients undergoing or about to undergo hemodialysis and 18 normal subjects were evaluated. In the normal subjects, tools and conditions of venography were investigated. It was considered necessary to maintain 30 degrees flexion of the cubital joint and supination of the antebrachium and use a 35 x 43 cm film to facilitate upper extremity venous system interpretation. In the patient group, standard venography was compared with shunt-delineating venography (called shuntgraphy) as to advantages and drawbacks. Venography proved to be of excellent use in shunt constructive and reconstructive surgeries in that it provided information supplementary to that obtained in shuntgraphy, or even more valuable information.

A study on low-dialysate flow rates

透析液の低流量化に関して, 以下の検討を行った.1.24症例を対象に, QD300ml/minとした透析を長期間 (最長38週) 施行した.結果は, 大面積ダイアライザー使用群において, 透析前BUNが低減後2カ月以降に有意な上昇を示し, 透析前クレアチニンは, 低減後上昇傾向にあるが, 有意な上昇は3カ月目のみであった.標準および小面積ダイアライザー使用群では, 透析前BUNやクレアチニンの上昇は認められなかった.カリウム, カルシウム, リンは, 変更後も変化なく, 貧血の亢進も認められなかった.2.QD500ml/minおよび300ml/minでの溶質除去量を測定したところ, 溶質除去量は透析前血中濃度と有意な正の一次相関をもつこと, 溶質除去能 (M/C0), QD 500ml/minの時の方が高いことがわかった. 3.4種類のダイアライザーを用い, QD500ml/min, 400ml/min, 300ml/minのときのクリアランスを脈動流および平滑流にて測定した.QDやダイアライザーの違いにかかわらず, 脈動流と平滑流とではクリアランスに差はなかった.以上の検討により, 脈動流, 平滑流のいずれにおいても, QD300ml/minでの低流量透析は可能と考えられる.

Hepatic injury in hemodialysis center of Japan (with special referance to Tokai districts)

過去6年間にわたり人工透析施設の肝障害の実態とその特徴を計5回のアンケート調査により追跡した.また,中規模透析2施設においては詳細なHB virus関連抗原,抗体の検索を行なった.6年間で透析患者数は548名より2,433名と増加,各年度における肝障害を有する比率は,12.2%～15.0%で,HBs抗原陽性率は全透析患者中では6.5%～9.8%,肝障害者中では12.9%～26.9%の範囲にありいずれもきわめて高率で減少傾向がみられなかった.1974年度に肝障害を有し5年後まで追跡できた53例の検討より,25例(47%)が5年後においても比較的軽いTransaminaseの異常が認められ遷延傾向が窺われた. HB virus関連抗原,抗体の検索では透析患者190例中20例(10.5%)にHBs抗原陽性,77例(40.5%)がHBs抗体陽性であった. HBs抗原陽性者20例中,e抗原14例(70%), e抗体3例(15.0%)が陽性で,e抗原陽性率が高かった.