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Tadao Akizawa

Publications and source records attributed to Tadao Akizawa.

At least 19 recordsLinked to original sources
PubMed2004

Platelet-derived growth factor induces tissue factor expression in vascular smooth muscle cells via activation of Egr-1.

Activation of vascular smooth muscle cells (SMCs) by platelet-derived growth factor (PDGF) is a seminal event in the initiation and progression of the atherosclerotic lesion and may contribute to atherosclerotic plaque instability with plaque rupture and thrombus formation. Tissue factor (TF), a prothrombotic molecule expressed by various cell types within atherosclerotic plaques, is thought to play a major role in thrombus formation after plaque rupture. This study examined intracellular signaling pathways leading to TF expression and Egr-1 activation, a key element in tissue factor transcription, by PDGF-BB in rat SMCs. PDGF-BB induced TF mRNA and protein expression in a time-dependent manner. Early growth response factor-1 (Egr-1) binding activity was also induced by PDGF-BB, as well as phosphorylation of extracellular signal-regulated kinase. PDGF-BB-induced Egr-1 activation was suppressed by inhibitors of 2 upstream activators of Egr-1, extracellular signal-regulated kinase (ERK) and Src family kinases, whereas antioxidants, phosphatidylinositol 3-phosphate kinase, and p38 MAPK inhibitors had no effect. PDGF-BB-stimulated expression of the transcriptional co-repressor NAB2 was time-dependent. Furthermore, transient transfections of SMCs with wild-type and mutated TF promoter constructs showed that the Egr-1 binding region is an important transcriptional regulator of PDGF-BB-induced TF expression. Taken together, the results suggest that PDGF-BB induces TF expression and activity in SMC by a Src family kinases/ERK/Egr-1 signaling pathway and may therefore contribute to thrombus formation in advanced atherosclerosis and restenosis.

Animals↗
PubMed2004

[Renal osteodystrophy].

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Chronic Kidney Disease-Mineral and Bone Disorder↗
PubMed2004

Timing of first cannulation and vascular access failure in haemodialysis: an analysis of practice patterns at dialysis facilities in the DOPPS.

BACKGROUND: Optimal waiting time before first use of vascular access is not known. METHODS: Two practices-first cannulation time for fistulae and grafts, and blood flow rate-were examined as potential predictors of vascular access failure in the Dialysis Outcomes and Practice Patterns Study (DOPPS). Access failure (defined as time to first failure or first salvage intervention) was modelled using Cox regression. RESULTS: Among 309 haemodialysis facilities, 2730 grafts and 2154 fistulae were studied. For grafts, first cannulation typically occurred within 2-4 weeks at 62% of US, 61% of European and 42% of Japanese facilities. For fistulae, first cannulation occurred <2 months after placement in 36% of US, 79% of European and 98% of Japanese facilities. Overall, the relative risk (RR) of graft failure in Europe was lower compared with the USA (RR = 0.69, P = 0.04). The RR of graft failure (reference group = first cannulation at 2-3 weeks) was 0.84 with first cannulation at <2 weeks (P = 0.11), 0.94 with first cannulation at 3-4 weeks (P = 0.48) and 0.93 with first cannulation at >4 weeks (P = 0.48). The RR of fistula failure was 0.72 with first cannulation at <4 weeks (P = 0.08), 0.91 at 2-3 months (P = 0.43) and 0.87 at >3 months (P = 0.31) (reference group = first cannulation at 1-2 months). Facility median blood flow rate was not a significant predictor of access failure. CONCLUSIONS: Earlier cannulation of a newly placed vascular access at the haemodialysis facility level was not associated with increased risk of vascular access failure. Potential for confounding due to selection bias cannot be excluded, implying the importance of clinical judgement in determining time to first use of vascular access.

Arteriovenous Shunt, Surgical↗
PubMed2004

Anemia management and outcomes from 12 countries in the Dialysis Outcomes and Practice Patterns Study (DOPPS).

BACKGROUND: Anemia is common in hemodialysis (HD) patients. METHODS: Data collected from nationally representative samples of HD patients (n = 11,041) in 2002 to 2003 were used to describe current anemia management for long-term HD patients at 309 dialysis units in 12 countries. Analyses of associations and outcomes were adjusted for demographics, 15 comorbid classes, laboratory values, country, and facility clustering. RESULTS: For patients on dialysis therapy for longer than 180 days, 23% to 77% had a hemoglobin (Hgb) concentration less than 11 g/dL (<110 g/L), depending on country; 83% to 94% were administered erythropoietin (EPO). Mean Hgb levels were 12 g/dL (120 g/L) in Sweden; 11.6 to 11.7 g/dL (116 to 117 g/L) in the United States, Spain, Belgium, and Canada; 11.1 to 11.5 g/dL (111 to 115 g/L) in Australia/New Zealand, Germany, Italy, the United Kingdom, and France; and 10.1 g/dL (101 g/L) in Japan. Hgb levels were substantially lower for new patients with end-stage renal disease, and EPO use before ESRD ranged from 27% (United States) to 65% (Sweden). By patient, EPO use significantly declined with greater Hgb concentration (adjusted odds ratio, 0.61 per 1-g/dL [10-g/L] greater Hgb level; P < 0.0001), as did EPO dosage. Case-mix-adjusted mortality and hospitalization risk declined by 5% and 6% per 1-g/dL greater patient baseline Hgb level (P < or = 0.003 each), respectively. Furthermore, patient mortality and hospitalization risks were 10% to 12% lower for every 1-g/dL greater facility mean Hgb level. Patients were significantly more likely to have Hgb levels of 11 g/dL or greater (> or =110 g/L) if they were older; were men; had polycystic kidney disease; had greater albumin, transferrin saturation, or calcium levels; were not dialyzing with a catheter; or had lower ferritin levels. Facilities with greater intravenous iron use showed significantly greater facility mean Hgb concentrations. Mean EPO dose varied from 5,297 (Japan) to 17,360 U/wk (United States). Greater country mean EPO doses were significantly associated with greater country mean Hgb concentrations. Several patient characteristics were associated with greater EPO doses. Even in some countries with high intravenous iron use, 35% to 40% of patients had a transferrin saturation less than 20% (below guidelines). CONCLUSION: These findings indicate large international variations in anemia management, with significant improvements during the last 5 years, although many patients remain below current anemia guidelines, suggesting large and specific opportunities for improvement.

Anemia↗
PubMed2004

Anemia management for hemodialysis patients: Kidney Disease Outcomes Quality Initiative (K/DOQI) guidelines and Dialysis Outcomes and Practice Patterns Study (DOPPS) findings.

BACKGROUND: After recombinant human erythropoietin was introduced into routine nephrologic practice, specific clinical guidelines were developed to optimize the quality of anemia management for patients with chronic kidney disease. METHODS: The Dialysis Outcomes and Practice Patterns Study (DOPPS), an international investigation providing patient- and facility-level data on hemodialysis practice, was developed to provide information on various aspects of current practices in hemodialysis management, including treatment of renal anemia. RESULTS: Hemoglobin concentration is strongly associated with both morbidity and mortality in hemodialysis patients. Although some improvements can be documented in anemia management practices in the years after the publication of international guidelines, wide variations in anemia management are still observed among countries. CONCLUSION: Many efforts are still needed to allow a greater proportion of patients to reach the recommended hemoglobin concentrations. Significantly improved outcomes may therefore be expected by a more widespread reaching of the recommended hemoglobin levels. The results of the DOPPS point to the difficulties in implementing clinical guidelines in the everyday management of individual patients. In specific circumstances, a well-designed observational study may offer credible information and serve as a basic instrument for monitoring the implementation of clinical guidelines in typical clinical practice.

Anemia↗
PubMed2004

Calcimimetic compound upregulates decreased calcium-sensing receptor expression level in parathyroid glands of rats with chronic renal insufficiency.

The reduced expression level of the calcium-sensing receptor (CaR) is attributed to the hyposensitivity of parathyroid cells to extracellular calcium concentration [Ca2+]o, which plays a crucial role in the pathogenesis of secondary hyperparathyroidism (SHPT) in patients and rats with chronic renal insufficiency (CRI). Calcimimetic compounds have been demonstrated to improve the decreased sensitivity of CaR to extracellular calcium concentration and to suppress both parathyroid hormone (PTH) oversecretion and parathyroid cell proliferation. However, the effect of calcimimetics on the reduced CaR expression level in parathyroid cells in CRI remains unclarified. The aim of this investigation was to examine the effect of the calcimimetic compound NSP R-568 (R-568) on the CaR expression in the parathyroid cells of rats with experimental CRI. Subtotally nephrectomized rats were fed a high-phosphorus diet for 8 (n = 12; Nx-8 group) or 9 wk (n = 11; Nx-9 group) to induce severe SHPT. Another group of uremic rats were fed a high-phosphorus diet for 8 wk and then orally administered R-568 (100 micromol/kg body wt) once a day for 7 d (n = 11; Nx+R-568 group). Sham-operated rats that were fed a standard diet for 9 wk were used as controls (n = 8). R-568 treatment induced a significant reduction in plasma PTH level with significant decrease in serum calcium and without change in serum phosphorus concentration. Serum 1,25(OH)2D3 level was not affected by R-568 administration. CaR mRNA and protein levels in the Nx-8 and Nx-9 groups significantly decreased compared with those in the controls; however, no significant difference in these parameters was observed between the Nx-8 and Nx-9 groups. In the Nx+R-568 group, CaR mRNA and protein levels significantly increased compared with those in either the Nx-8 or Nx-9 group. R-568 was effective in reducing the number of proliferating cell nuclear antigen-positive cells along with parathyroid gland growth suppression in the Nx+R-568 group compared with that in the Nx-9 group. The results suggest that the calcimimetic compound R-568 upregulates decreased CaR expression, and the upregulation possibly has an enhancement effect on PTH secretion and parathyroid cell hyperplasia through the improved sensitivity of CaR to [Ca2+]o.

Analysis of Variance↗
PubMed2004

The calcimimetic agent KRN 1493 lowers plasma parathyroid hormone and ionized calcium concentrations in patients with chronic renal failure on haemodialysis both on the day of haemodialysis and on the day without haemodialysis.

AIMS: Treatment with vitamin D sterols can lower plasma parathyroid hormone (PTH) in patients with secondary hyperparathyroidism; however, hypercalcaemia, hyperphosphataemia, or both, often develop. Calcimimetic agents, employed in alternative therapeutic approaches, directly inhibit PTH secretion by activating the calcium-sensing receptor in the parathyroid glands. METHODS: In this study, patients were given orally 25, 50, and 100 mg doses of the calcimimetic agent KRN 1493 each on two occasions, on the day of haemodialysis and on the day without haemodialysis. RESULTS: In the pharmacokinetic results, because the clearance of KRN 1493 by haemodialysis was much smaller than the systemic clearance, the influence of haemodialysis was not remarkable. In the pharmacodynamic study, on both the days with or without haemodialysis, plasma PTH concentrations decreased in a dose-dependent manner. Serum calcium concentrations decreased in association with the decrease in plasma PTH concentrations. Mild dose-dependent adverse effects (mainly nausea) were seen after the administration of KRN 1493 on both the day of haemodialysis and the day without haemodialysis. CONCLUSIONS: We conclude that the pharmacokinetics of KRN 1493 after a single administration were similar on the day of haemodialysis and the day without haemodialysis. KRN 1493 is safe and effective in suppressing PTH secretion and serum calcium concentrations on the day of haemodialysis and on the day without haemodialysis in patients with secondary hyperparathyroidism.

Administration, Oral↗
PubMed2004

Protective effect of an oral adsorbent on renal function in chronic renal failure: determinants of its efficacy in diabetic nephropathy.

Large-scale clinical trials have shown that the oral adsorbent AST-120 improves renal function and delays the initiation of dialysis in chronic renal failure (CRF) secondary to chronic glomerulonephritis. If renal failure progresses via common mechanisms, then the same effects can be expected in diabetic nephropathy. However, no study on diabetic nephropathy has been reported. Thus, we enrolled patients with statistically significant progression of CRF secondary to diabetic nephropathy, and analyzed the changes in renal function after AST-120 therapy, and the clinical factors associated with response to therapy. We enrolled 276 patients with diabetic nephropathy, whose serum creatinine (Scr) had increased from 3.4 to 4.5 mg/dL during the 4.5 +/- 3.7 months prior to the study. These patients took AST-120 at a dose of 5.0 +/- 1.4 g/day for 6 months. The clinical data were analyzed by dividing the patients into three groups based on the changes in Scr after AST-120 therapy, with responders showing a decrease (N = 82), partial responders showing <1.5-fold increase (N = 144), and non-responders showing >/=1.5-fold increase (N = 50). AST-120 significantly lowered the slope of 1/Scr-time line, suggesting that AST-120 suppressed the progression of renal impairment. No responders required dialysis, whereas 24.3% of the partial responders and 36.0% of the non-responders started dialysis therapy. In responders, the 1/Scr-time slope showed a negative-to-positive shift and serum urea nitrogen decreased significantly, whereas the improvement was moderate in partial responders and minimal in non-responders. Among responders, AST-120 therapy significantly improved renal function despite the presence of hypoproteinemia, hyperlipidemia, anemia or hypertension in many patients. The beneficial effect of AST-120 was significantly more marked in patients with blood pressure controlled within the normal ranges and hematocrit maintained at 30% or above. AST-120 reversed renal dysfunction or delayed the initiation of dialysis therapy in patients with progressive aggravation of CRF secondary to diabetic nephropathy, independent of hypoproteinemia, hyperlipidemia, anemia and hypertension. Active use of AST-120 may be recommended in patients with good control of blood pressure and hematocrit above 30%.

Aged↗
PubMed2004

Extracorporeal albumin dialysis.

Previous studies reported that dialysis with albumin dialysate (AD) was effective in removing albumin-binding toxins (ABT), and the Molecular Adsorption Recycling System (MARS) and Continuous Albumin Purification System (CAPS) have been developed. These blood purification therapies were categorized into the concept of extracorporeal albumin dialysis (ECAD). ECAD is defined as extracorporeal therapies using AD for the removal of not only water-soluble but also ABT. It was reported that symmetric as well as asymmetric membrane dialyzers had the effect of the removal of bilirubin by AD. The larger pore size membrane can remove more bilirubin. In the greater albumin concentration in AD, the removal capacity for bilirubin by AD increased. Bilirubin in AD could be removed by a charcoal and a bilirubin adsorption column, and its concentration in AD remained approximately constant. In clinical performance of CAPS, cellulose triacetate membrane, 5% AD, bilirubin adsorber columns, and charcoal adsorber columns were used. This system was applied continuously for 24 h for treatment. CAPS could control not only renal but also liver function during the 24 h, without any adverse effect. MARS removes many toxic substances including ABT, and has beneficial effect on brain, liver, renal, and cardiovascular functions, and improvement of 30-day survival were reported. ECAD may become a possible therapeutic tool in patients with the disease state of ABT accumulation as an artificial kidney and liver. However, several attempts such as the application of recombinant human albumin and acetate free dialysate, should be required.

Albumins↗
PubMed2004

[Biocompatibility].

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Biocompatible Materials↗
PubMed2004

[Hemoperfusion].

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Acute Kidney Injury↗
PubMed2003

Management of secondary hyperparathyroidism of dialysis patients.

Hyperphosphatemia, vitamin D deficiency, and resulted hypocalcemia have been regarded as classical pathogeneses of secondary hyperparathyroidism. These factors have been treated by the administration of phosphorus binder and vitamin D derivatives. However, these therapies have not brought about a successful result for the prevention and treatment of secondary hyperparathyroidism. The reason could be mainly attributed to the hypercalcemia that results from the administration of calcium salts as a phosphorus binder and the calcemic action of vitamin D. To prevent hypercalcemia, non-calcium containing phosphorus binder (sevelamer hydrochloride) and vitamin D analogues, which suppress PTH secretion with minimum calcemic action, have been developed. These new vitamin D analogues include 19-nor-1-alpha, 25-dihydroxyvitamin D2 (paricalcitol), 1-alpha-hydroxyvitamin D2 (doxercalciferol), 22oxa-calcitriol (maxacalcitol) and F6-calcitriol (falecalcitriol). Furthermore, calcimimetics that stimulate calcium-sensing receptor of parathyroid cells as calcium and suppress PTH secretion are now under clinical trial. Percutaneous direct injection therapy of vitamin D, vitamin D analogue or calcimimetics into parathyroid gland has also been reported. The combination of these new strategies is expected to effectively and safely suppresses secondary hyperparathyroidism that has been resistant to conventional medical treatments.

Ethanol↗
PubMed2003

Percutaneous maxacalcitol injection therapy regresses hyperplasia of parathyroid and induces apoptosis in uremia.

BACKGROUND: A high level of parathyroid hormone (PTH) is considered to be an indicator of poor prognosis and a poor quality of life of dialysis patients; therefore, an effective and safe therapy for secondary hyperparathyroidism (SHPT) has been developed. METHODS: In 20 patients with SHPT resistant to maxacalcitol (OCT) intravenously administered, all detectably enlarged parathyroid glands were treated by percutaneous maxacalcitol injection therapy (PMIT) under ultrasonographic guidance consecutively 6 times, which was followed by OCT that was intravenously administered. The clinical effects of PMIT were evaluated based on the changes in the serum intact-PTH, adjusted Ca, phosphorus, and bone marker levels, and the parathyroid gland volume determined by ultrasonography. Morphologic examination, apoptosis analysis, and PTH mRNA expression level determination by reverse transcription-polymerase chain reaction (RT-PCR) using parathyroid tissues obtained by a biopsy technique were performed. RESULTS: PMIT and subsequent intravenous OCT administrations significantly decreased the serum intact-PTH level and parathyroid gland volume for at least 12 weeks after PMIT without major complications. Parathyroid tissues obtained after PMIT exhibited some partial defects of parathyroid cells, a marked increase in the number of the terminal deoxynucleotidyl transferase-mediated dUTP nick end-labeling (TUNEL)-positive cells, the ladder formation determined by DNA electrophoresis, and the decrease in the PTH mRNA expression level. CONCLUSION: PMIT is effective and safe for the treatment of refractory SHPT, and a locally high level of OCT suppresses PTH secretion and regresses parathyroid hyperplasia, which is involved in the induction of apoptosis of parathyroid cells.

Administration, Cutaneous↗
PubMed2003

Effect of beta(2)-microglobulin adsorption column on dialysis-related amyloidosis.

BACKGROUND: beta2-microglobulin (beta2-m) is considered a major pathogenic factor in dialysis-related amyloidosis (DRA), often seen in long-term dialysis patients. No effective therapy for this severely debilitating disease is currently available. Lixelle, an adsorption column, has been developed for the elimination of beta2-m; the efficacy of this column has been evaluated in this study. METHODS: Seventeen hemodialysis patients with DRA were first treated with high-flux dialysis for a minimum of 1 year. This was followed by 1-year treatment with Lixelle column connected in series to the high-flux dialyzer. Treatments were used three times a week for both phases of this study. During the study period, beta2-m, pinch strength, motor terminal latency, and activities of daily living were evaluated. RESULTS: After 1-year treatment with high-flux dialysis the beta2-m level remained unchanged; however, after 1-year treatment with the addition of the Lixelle column, beta2-m level decreased significantly from 34.5 +/- 8.4 mg/L to 28.8 +/- 7.3 mg/L (P < 0.05). After 1 year of Lixelle column use, the pinch strength increased from 6.8 +/- 4.7 pounds to 9.1 +/- 5.5 pounds (P < 0.01), and the median motor terminal latency was significantly reduced from 5.1 +/- 1.0 mseconds to 4.5 +/- 1.1 mseconds. A significant improvement was also observed in the activities of daily living score of the upper extremities. CONCLUSION: These results suggest that the addition of Lixelle to the high-flux dialyzer is associated with a significant clinical improvement in DRA patients.

Adsorption↗
PubMed2003

Health-related quality of life among dialysis patients on three continents: the Dialysis Outcomes and Practice Patterns Study.

BACKGROUND: Assessing health-related quality of life (HRQOL) can provide information on the types and degrees of burdens that afflict patients with chronic medical conditions, including end-stage renal disease (ESRD). Several studies have shown important international differences among ESRD patients treated with hemodialysis, but no studies have compared these patients' HRQOL. Our goal was to document international differences in HRQOL among dialysis patients and to identify possible explanations of those differences. METHODS: We examined data from the Dialysis Outcomes and Practice Patterns Study (DOPPS), a prospective, observational, international study of hemodialysis patients. We performed a cross-sectional analysis of DOPPS data from the United States, five countries in Europe (France, Germany, Italy, Spain, and the United Kingdom), and Japan. Linear mixed models were used to analyze differences in HRQOL, using the KDQOL-SFTM. Norm-based scores were used to minimize cultural response bias. Linear regression analysis was used to adjust for confounding factors. Other variables included demographic variables, comorbidities, primary cause of ESRD, complications of ESRD and treatment, and socioeconomic status. RESULTS: In all generic HRQOL subscales, patients on all three continents had much lower scores than their respective population norm values. Patients in the United States had the highest scores on the mental health subscale and the highest mental component summary scores. Japanese patients reported better physical functioning than did patients in the United States or Europe, but they also reported the greatest burden of kidney disease. Overall, these differences remained even after adjusting for possible confounders. CONCLUSION: On all three continents, ESRD and hemodialysis profoundly affect HRQOL. In the United States, the effects on mental health are smaller than in other countries. Japanese hemodialysis patients perceived that their kidney disease imposes a greater burden, but their physical functioning was significantly higher. Different distributions of socioeconomic factors and major comorbid conditions could explain little of this difference in physical functioning. Other possible factors, such as quality of dialysis and related health care, deserve careful study.

Cost of Illness↗
PubMed2003

Creation, cannulation and survival of arteriovenous fistulae: data from the Dialysis Outcomes and Practice Patterns Study.

BACKGROUND: An arteriovenous (A-V) fistula is the optimal vascular access for hemodialysis. The National Kidney Foundation Dialysis Outcomes Quality Initiative (DOQI) recommends that fistulae should mature for at least one month before cannulation, but this recommendation is not evidence-based. If fistulae are created prior to ESRD and cannulation is possible earlier without compromising fistula survival, the need for temporary catheters would be reduced. METHODS: Prospective observational data were analyzed for a random sample (N = 3674) of incident patients at the time of initiating hemodialysis, hemofiltration or hemodiafiltration in 309 facilities in France, Germany, Italy, Japan, Spain, the United Kingdom, and the United States, taking part in the Dialysis Outcomes and Practice Patterns Study (DOPPS). RESULTS: Although the proportion of patients who had pre-dialysis care by a nephrologist differed little between countries, there were large variations in the proportion of patients who commenced hemodialysis via an A-V fistula, A-V graft or central venous catheter. The usual time interval between referral and creation of A-V fistulae also differed greatly between countries. For new hemodialysis (HD) patients initiating HD with an A-V fistula (N = 894) the following results were observed: (1). median time to first cannulation varied greatly between countries: Japan and Italy (25 and 27 days), Germany (42 days), Spain and France (80 and 86 days), UK and US (96 and 98 days). (2). No association was found between cannulation 28 days for patient characteristics of age, gender, and fifteen different classes of patient co-morbid factors. (3). Risk of A-V fistula failure was increased for incident patients who had a prior temporary access [relative risk (RR) = 1.81, P = 0.01] or who were female (RR = 1.52, P = 0.02). (4). Cannulation 14 days. (5) No significant difference in A-V fistula failure was seen for fistulae cannulated in 15 to 28 days compared with 43 to 84 days. CONCLUSION: Significant differences in clinical practice currently exist between countries regarding the creation of A-V fistulae prior to starting hemodialysis and the timing of initial cannulation. Cannulation within 14 days of creation is associated with reduced long-term fistula survival. Fistulae ideally should be left to mature for at least 14 days before first cannulation.

Adolescent↗