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Biomedical subjects

Yoshiharu Tsubakihara

Publications and source records attributed to Yoshiharu Tsubakihara.

15 recordsLinked to original sources
PubMed2006

Prospective randomized study evaluating the efficacy of the spherical adsorptive carbon AST-120 in chronic kidney disease patients with moderate decrease in renal function.

AIMS: We studied whether adding the spherical adsorptive carbon AST-120 to conventional treatments is effective in inhibiting progression of chronic kidney disease (CKD) at the stage of moderate decrease in renal function. METHODS: 43 CKD patients with moderately impaired renal function indicated by glomerular filtration rate (GFR) of 20-70 ml/min as measured by non-radiolabeled iothalamate clearance method were enrolled in the study. 26 patients showing a decrease of GFR by 5 ml/min during a 1-year observation period were randomized to receive ongoing treatments only (control group, 12 cases) or with AST-120 co-administered with ongoing treatment (AST-120 group, 14 cases). The intervention period was 1 year and the change in GFR was the primary evaluation variable. RESULTS: The mean changes of GFR per month (DeltaGFR) in the intervention period were not significantly different between both groups. However, when comparing the DeltaGFR in the observation and intervention periods for each group, the rate of decline in GFR was significantly retarded (p < 0.001) in the AST-120 group while no significant difference was observed in the control group. CONCLUSION: These results suggest that co-administration of AST-120 with conventional treatments retards decline in renal function in CKD patients with moderate decrease in renal function.

Administration, Oral↗
PubMed2006

Deoxyspergualin, an immunosuppressant, in patients suffering from nephropathies with crescent formation: an open-label trial to evaluate safety and efficacy.

BACKGROUND: Crescent formation in glomeruli means an acute active lesion that develops a rapidly progressive course. Therapies using pulse methylprednisolone, oral corticosteroids, and cyclophosphamide are recommended, but no agreement has been reached on the optimal therapy. There have been no controlled trials, because of the severity of this condition and because withholding treatment would become an ethical issue. METHODS: We evaluated the safety and efficacy of deoxyspergualin (DSG), an immunosuppressant, in a multicenter, prospective trial of 44 patients with crescent formation in over 10% of glomeruli, who were randomly placed into groups that received daily doses of 0.1 mg/kg (n = 21) and 0.2 mg/kg (n = 23) of DSG, given by a 1-h infusion for 4 weeks, and who were then monitored for 3 months. All patients received DSG in this open-label prospective study. We evaluated the levels of urinary protein and hematuria, and examined renal function after the DSG treatment. RESULTS: Urinary protein significantly decreased with each dose after starting the DSG administration and this efficacy was sustained for 2 months after the discontinuation of DSG. In the groups receiving 0.1 mg/kg and 0.2 mg/kg, mean urinary protein levels were 2.1 g/day and 2.3 g/day at the initiation of the DSG administration, 1.4 g/day and 1.6 g/day at week 4, and 1.5 g/day and 1.3 g/day at week 12, respectively. Hematuria was markedly improved by a dose of 0.2 mg/kg and was not exacerbated following the termination of DSG. Exacerbation of renal dysfunction, as measured by creatinine clearance, serum creatinine, and blood urea nitrogen was prevented by both doses of DSG. The most common adverse reaction was reversible neutropenia. CONCLUSIONS: Short-term treatment with DSG may be effective and tolerated in patients suffering from nephropathies with crescent formation.

Creatinine↗
PubMed2005

Prevalence of human polyoma virus (BK virus and JC virus) infection in patients with chronic renal disease.

BACKGROUND: Polyoma virus infection in renal transplant patients is sometimes critical in graft survival. But, to date, polyoma virus infection or reactivation has not been checked before renal transplantation. The prevalence of polyoma viruses (BK virus and JC virus) was investigated in 45 patients with renal disease who were future candidates as renal graft recipients. METHODS: Because these viruses are excreted in urine, the urine of these 45 patients was analyzed by polymerase chain reaction (PCR). The urine of 37 age-matched normal subjects (control group) was also investigated. RESULTS: In the control group, 13.5% of the normal subjects were positive for BK virus and 24.3% were positive for JC virus. In the patients with renal disease, 33.3% were positive for BK virus and 33.3% were positive for JC virus; the prevalence of BK virus infection was significantly higher than that in the normal subjects. Patients with renal disease with corticosteroid therapy revealed an especially high prevalence of BK virus infection (55.6%), indicating the possibility of viral reactivation by corticosteroid therapy. CONCLUSIONS: More attention should be paid to polyoma virus infection in candidates for renal transplantation with a previous therapeutic history of corticosteroid administration.

Adrenal Cortex Hormones↗
PubMed2004

Hemodialysis-associated hypotension as an independent risk factor for two-year mortality in hemodialysis patients.

BACKGROUND: The relationship between blood pressure (BP) and mortality in hemodialysis patients has remained controversial. Some studies suggested that a lower pre- or postdialysis BP was associated with excess mortality, while others showed poorer outcome in patients with uncontrolled hypertension. We conducted a multicenter prospective cohort study to evaluate the impact of hemodialysis-associated hypotension on mortality. METHODS: We recruited 1244 patients (685 males; mean age, 60 +/- 13 years) who underwent hemodialysis in 28 units during the two-year study period beginning in December 1999. Pre-, intra-, and postdialysis BP, and BP upon standing soon after hemodialysis, were measured in all patients at entry. Logistic regression analysis was used to assess the effect on mortality of pre-, intra-, and postdialysis BP, a fall in BP during hemodialysis, and a fall in BP upon standing soon after hemodialysis. RESULTS: During the study period, 149 patients died. Logistic models identified the lowest intradialysis systolic blood pressure (SBP) and degree of fall in SBP upon standing soon after hemodialysis as significant factors affecting mortality, but not pre- or postdialysis SBP and diastolic BP. The adjusted odds ratio for death was 0.79 (95% CI 0.64-0.98) when the lowest intradialysis SBP was analyzed in increments of 20 mm Hg, and was 0.82 (95% CI 0.67-0.98) when the fall in SBP upon standing soon after hemodialysis was analyzed in increments of 10 mm Hg. CONCLUSION: These results suggest that intradialysis hypotension and orthostatic hypotension after hemodialysis are significant and independent factors affecting mortality in hemodialysis patients.

Aged↗
PubMed2004

2004 Japanese Society for Dialysis Therapy guidelines for renal anemia in chronic hemodialysis patients.

The guideline committee of Japanese Society for Dialysis Therapy (JSDT), chaired by Professor F. Gejyo of Niigata University, now publishes an original Japanese guideline entitled 'Guidelines for Renal Anemia in Chronic Hemodialysis Patients'. It includes the re-evaluation of the usage of recombinant human erythropoietin (rHuEPO) with the medical and economical arguments regarding the prognosis and the quality of life of Japanese hemodialysis patients. This guideline consists of 7 sections. The first section comprises the general definition and the differential diagnosis of anemia. The hemoglobin (Hb) level of the Japanese population seemed to be low when compared with that of the European and American populations. The second section describes the target Hb level in hemodialysis patients. Multivariate analysis of the data that were collected from dialysis institutions throughout the country showed that an Hb level of 10-11 g/dL (Ht level 30-33%) at the first dialysis session in a week is the ideal range for chronic hemodialysis patients in terms of the 3-5 year survival rate. The supine position at blood sampling and the sampling timing at the first dialysis session in a week might affect the lower setting of target Hb hematocrit (Ht), compared to that of European and American guidelines. However, we particularly recommended that an Hb level of 11-12 g/dL (Ht level from 33 to 36%) at the first dialysis session in a week is desirable in relatively young patients. In the third section, the markers of iron deficiency are discussed. The Transferin saturation test (TSAT) and serum ferritin were emphasized as the standard markers. The routes of administration of rHuEPO and its dosages are written in the fourth section. The subcutaneous route was associated with the occurrence of secondary red cell aplasia due to anti-rHuEPO antibodies; however, secondary red cell aplasia was seldom observed in the venous injection. From this fact we recommend venous injection for chronic hemodialysis patients. We advocate an initial dosage of 1500 U three times per week. The fifth section deals with the factors refractory to treatment with rHuEPO. If the patient shows an inadequate response to the usage of 9000 U per week, this condition defines the inadequate response to rHuEPO in Japan. Blood transfusion must be avoided where possible. The reasons for this and the adverse effects are interpreted in section six. In the final section, the adverse effects of rHuEPO are listed. Among them, hypertension, thrombotic events and secondary red cell aplasia were emphasized as the major complications.

Anemia↗
PubMed2004

[K/DOQI clinical practice guidelines for management of renal osteodystrophy in predialysis patients].

Blood levels of PTH (parathyroid hormone) begin to rise when GFR falls below 60 mL/min/1.73 m2, and evidence of bone disease due to hyperparathyroidism may be present at Stage 3 of chronic kidney disease (CKD). IntactPTH(i-PTH) is a useful test in detecting high turnover bone disorder and low turnover bone disorder. The Work Group taken target range of serum i-PTH in predialysis patients by their opinion. Dietary phosphorus should be restricted when the serum levels of i-PTH are elevated above target range of CKD stage. If phosphorus and i-PTH levels can not be controlled within the target range, despite dietary phosphorus restriction, phosphate binders should be prescribed. Only calcium based phosphate binders are available in predialysis patients in Japan. To avoid soft tissue calcification, total elemental calcium intake should not exceed 2,000 mg/day. If vitamin D deficiency are present, vitamin D2 should be supplied. But we can't measure serum 25(OH) D and prescribe vitamin D2 in Japan. Low dose of active vitamin D sterols are effective on renal osteodystrophy in predialysis patient. Active vitamin D sterols should be prescribed from low doses and serum calcium levels and renal function should be checked frequently. It is necessary to evaluate this K/DOQI (Kidney disease outcomes quality initiative) guideline and to establish guideline in Japan.

Biomarkers↗
PubMed2003

Carbonic adsorbent AST-120 retards progression of renal failure by additive effect with ACEI and protein restriction diet.

BACKGROUND: In order to slow the progression of chronic renal failure (CRF), a multimodal approach should be applied if the efficacy is proved. Although compelling evidence of a beneficial effect exists for the use of angiotensin-converting enzyme inhibitors (ACEIs) and low-protein diets, there is little evidence on whether carbon adsorbent has an effect on retardation of the progression of CRF. METHODS: In experiment 1, we examined whether the oral carbon adsorbent, AST-120, conferred an additive effect with captopril and an 80% restriction diet on the survival rate of 3/4 nephrectomized rats (3/4 NX). The 3/4 NX rats were divided into three groups (C, control, n = 7; AD, captopril (an ACEI) +80% restriction diet (RD), n = 8; and ADK, ACEI + RD + AST-120, n = 8) and survival was observed for 72 weeks. In experiment 2, 3/4 NX rats were divided into four groups (C, control, n = 4; D, 80% restriction diet, n = 4; AD, temocapril + RD, n = 9; and ADK, temocapril + RD + AST-120, n = 9) for the examination of renal function, blood pressure, hematocrit (Ht), serum albumin, and proteinuria every month. We analyzed morphological changes in the kidney at 48 weeks. RESULTS: In experiment 1, ADK did not improve the survival rate compared with AD, although ADK prolonged the survival significantly compared with C (C vs AD, P = 0.24; C vs ADK, P = 0.0007; AD vs ADK, P = 0.073). In experiment 2, renal function and proteinuria were significantly ameliorated in the ADK group compared with AD at 48 weeks. Concomitantly with the preservation of renal function, pathological indices, including the glomerular sclerosis index and the interstitial fibrosis index, were significantly improved in ADK compared with AD. In the ADK group, Ht and serum albumin did not change over the 48 weeks. CONCLUSIONS: Administration of AST-120 in addition to an ACEI and a restriction diet preserves renal function independently of blood pressure control, angiotensin II inhibition, and protein restriction in 3/4 NX rats at 48 weeks, but does not improve the survival significantly.

Adsorption↗
PubMed2003

Effects of the oral adsorbent AST-120 on tryptophan metabolism in uremic patients.

BACKGROUND: Tryptophan (TRP), an essential amino acid, is bound mostly to albumin in plasma. However, it is reported that binding is inhibited by indoles that accumulate in uremic plasma. This may be responsible for the malnutrition observed in uremic patients. AST-120, an oral adsorbent of uremic toxins, can reduce concentrations of indoxyl sulfate (IS), the most abundant indolic metabolite in uremic plasma. We therefore investigated whether AST-120 recovers TRP binding to plasma proteins and improves the nutritional state of uremic patients. METHODS: The in vitro binding ratio of TRP to bovine serum albumin (BSA) was measured in the presence of IS by the equilibrium dialysis technique. In addition, five predialysis patients with chronic renal failure (CRF) were administered AST-120 for 2 months. Plasma concentrations of total TRP, IS, and free TRP were measured in five healthy volunteers (normal [N] group) and five patients with CRF before and after 2 weeks of AST-120 therapy (6 g/d). Their nutritional statuses also were compared before and after 2 months of AST-120 administration. RESULTS: IS inhibited in vitro binding of TRP to BSA in a dose-dependent manner. Total TRP concentrations and protein-binding ratios in patients with CRF (0.90 +/- 0.08 mg/dL and 68.7% +/- 6.8%, respectively) were significantly lower than those in the N group (2.45 +/- 0.45 mg/dL and 92.0% +/- 1.4%, respectively). However, a 2-week administration of AST-120 significantly reduced IS levels from 1.79 +/- 1.01 to 1.15 +/- 0.85 mg/dL (N group, 0.06 +/- 0.01 mg/dL), increased total TRP levels (1.16 +/- 0.18 mg/dL), and improved the TRP plasma protein-binding ratio to 83.1% +/- 3.8%, whereas total protein and albumin levels remained unchanged. After 2 months of AST-120 administration, serum albumin and transferrin levels increased significantly. CONCLUSION: AST-120 improves nutritional state, at least partly through correcting impaired TRP metabolism, in patients with CRF.

Administration, Oral↗
PubMed2002

[Chemotherapy for small-cell lung cancer (SCLC) patients with renal failure].

We administered chemotherapy in three cases of small-cell lung cancer (SCLC) with renal failure under different situations. Hemodialysis (HD) was used in 2 out of the 3 cases. Case 1 was complicated by acute renal failure from extensive bilateral tumor invasion. After chemotherapy (CBDCA + ETP) under HD, renal metastases regressed and renal function improved, although the final response was PD. In case 2, HD had been introduced for diabetic nephropathy. After 2 cycles of chemotherapy (CBDCA + ETP) under HD, the patient attained a PR. Case 3 is an example of paraneoplastic nephrotic syndrome with renal failure. Chemotherapy including CBDCA or CDDP was performed and the QOL of the patient improved. Pro-GRP and serum creatinine changed in parallel during the clinical course of 6 admissions. In conclusion, individualized therapy is necessary to increase survival time of SCLC patients with renal failure. Although chemotherapy is useful, further study is needed for the selection of suitable chemotherapeutic regimens, optimal dosage of each drug and the timing of HD.

Adult↗
PubMed2002

[Hyperphosphatemia and diet therapy].

Hyperphosphatemia cause not only renal bone disease but also poor prognosis in hemodialysis patients. We should control serum phosphate levels within near normal range. Although many patients are prescribed phosphate binder, they should restrict oral phosphate intake. There are poor prognosis in malnutrition patients, they should take sufficient protein. Contents of phosphate in foods increase proportionaly with protein contents. It is important that they should take foods with low phosphate contents and low phosphate/protein ratio. They should restrict preserved food, confectionary, seasoning which contain phosphate compounds as food additive. It is useful to take special low phosphate food.

English Abstract↗
PubMedDate not supplied

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.

Autonomic Nervous System Diseases↗