Biomedical subjects

Tadao Akizawa

Publications and source records attributed to Tadao Akizawa.

At least 19 recordsLinked to original sources

PubMed2005

Mineral metabolism and haemoglobin concentration among haemodialysis patients in the Dialysis Outcomes and Practice Patterns Study (DOPPS).

BACKGROUND: Bone and mineral metabolism is abnormal in most chronic haemodialysis patients and is associated with a high mortality risk. Because of possible pathogenic links between anaemia and intact parathyroid hormone (iPTH), the present study evaluated associations of mineral metabolism indicators with haemoglobin (Hb). METHODS: Data were collected from 317 facilities (12 089 haemodialysis patients) in Australia, Belgium, Canada, France, Germany, Italy, Japan, New Zealand, Spain, Sweden, the United Kingdom and the United States by the Dialysis Outcomes and Practice Patterns Study (DOPPS). The major outcome studied was probability of haemodialysis patients having a target Hb, per guidelines, of >/=11 g/dl at baseline. Major predictor variables were patient characteristics and laboratory markers of mineral metabolism: albumin-corrected serum calcium (calcium(Alb)), serum phosphorus (PO(4)) and iPTH. Analyses were adjusted for demographics, 15 comorbidity classes, baseline laboratory values, body mass index, years on dialysis, erythropoietin dose, vitamin D and catheter use, cause of end-stage renal disease and country. RESULTS: The adjusted odds ratio (AOR) of having Hb >/=11 g/dl was significantly higher (P<0.0001) in patients with higher calcium(Alb) (AOR = 1.32 per 1 mg/dl), higher PO(4) (AOR = 1.08 per 1 mg/dl) and lower iPTH (AOR = 0.96 per 100 pg/ml). Furthermore, 4 month intrapatient changes in Hb concentration were significantly (P<0.0001) related to 4 month changes in calcium(Alb) (0.17 g/dl Hb rise per 1 mg/dl higher calcium(Alb)) and PO(4) (0.11 g/dl Hb rise per 1 mg/dl higher PO(4)). Mean weekly recombinant human erythropoietin (rHuEpo) doses were higher for patients with high PO(4) or iPTH levels, but lower for patients with calcium(Alb) >9.5 mg/dl, after patient mix and Hb concentration adjustments. CONCLUSIONS: The results of this study indicate that higher serum calcium(Alb) and PO(4) levels are each independently associated with better anaemia control. This relationship is independent of vitamin D use, PTH levels and prescribed rHuEpo dose. Despite this benefit of better anaemia control at higher serum calcium(Alb) and PO(4) concentrations, lower calcium and PO(4) levels, as recommended by the K/DOQI guidelines, should still serve as the long-term goal for HD patients in order to minimize tissue calcification and mortality risk.

Adult↗

PubMed2005

HMG-coenzyme a reductase inhibitor use is associated with mortality reduction in hemodialysis patients.

BACKGROUND: Cardiovascular disease is the most common cause of mortality in patients with end-stage renal disease. Cardiovascular benefits of 3-hydroxy-3-methylglutaryl coenzyme A reductase inhibitors (statins) have been clearly established in the general population, but not in dialysis patients. This study examined statin prescription patterns and assessed the relationship between statin prescription and clinical outcomes in hemodialysis (HD) patients. METHODS: Data were analyzed from the Dialysis Outcomes and Practice Patterns Study, a prospective observational study of HD patients randomly selected from representative dialysis facilities in France, Germany, Italy, Spain, the United Kingdom, Japan, and the United States. Predictors of statin prescription were investigated by means of logistic regression. Cox regression models tested the association between statin prescription and risk for mortality and cardiac events, with adjustments for common demographic factors and comorbid conditions. RESULTS: Statins were prescribed for 11.8% of HD patients overall. Most facilities (81.2%) prescribed statins to less than 20% of their patients. Patients prescribed statins had a 31% lower relative risk for death compared with those not prescribed statins (P < 0.0001). Statins were associated with a 23% lower cardiac mortality risk (P = 0.03) and a 44% lower noncardiac mortality risk (P < 0.0001). At a facility level, prescribing statins was associated with lower overall mortality rate, with a 5% lower risk for every 10% increase in number of patients prescribed statins within the facility (P = 0.02). CONCLUSION: Statin prescription is associated with reduced mortality in HD patients, providing additional support for the value of statin therapy in this patient group.

Comorbidity↗

PubMed2005

Effect of MCI-196 (colestilan) as a phosphate binder on hyperphosphataemia in aemodialysis patients: a double-blind, placebo-controlled, short-term trial.

BACKGROUND: MCI-196 (colestilan), an anion exchange resin, is widely used as an anti-hypercholesterolaemic drug in Japan. To evaluate the efficacy and safety of MCI-196 as a phosphate binder, a double-blind, randomized, placebo-controlled prospective trial was conducted in Japanese end-stage renal disease patients with hyperphosphataemia on intermittent haemodialysis treatment. METHODS: Phosphate binders were discontinued during a 2-week washout period. Subsequently, patients whose serum phosphorus levels were > or =6.5 mg/dl, but <10 mg/dl were eligible to enter the treatment protocol. Patients were randomized to either MCI-196 6 g/day or placebo for 2 weeks. The efficacy and safety of MCI-196 were assessed in 33 and 46 patients, respectively. RESULTS: Serum phosphorus in the placebo group increased by 0.84+/-0.95 mg/dl (mean+/-SD), while serum phosphorus in the MCI-196 group decreased by 0.55+/-1.23 mg/dl. The difference between the two groups was statistically significant (P = 0.002). A reduction of > or =1 mg/dl in serum phosphorus was observed in 43% in the MCI-196 group and 0% of patients in the placebo group (P = 0.0122). Calcium-phosphorus (Ca x P) product, intact parathyroid hormone (iPTH) and low-density lipoprotein (LDL)-cholesterol in the MCI-196 group also decreased significantly compared with the placebo group, while serum calcium was unchanged. Adverse reactions were observed in 51.7% of the MCI-196 group and 29.4% of the placebo group (P = 0.2186). The most frequent adverse reactions in the MCI-196 group were gastrointestinal symptoms and signs, including constipation. CONCLUSIONS: The present findings suggest that the short-term administration of MCI-196 is effective in decreasing serum phosphorus in haemodialysis patients. Its long-term efficacy needs to be evaluated.

Bile Acids and Salts↗

PubMed2005

Predictors and consequences of altered mineral metabolism: the Dialysis Outcomes and Practice Patterns Study.

BACKGROUND: Altered mineral metabolism contributes to bone disease, cardiovascular disease, and other clinical problems in patients with end-stage renal disease. METHODS: This study describes the recent status, significant predictors, and potential consequences of abnormal mineral metabolism in representative groups of hemodialysis facilities (N= 307) and patients (N= 17,236) participating in the Dialysis Outcomes and Practice Patterns Study (DOPPS) in the United States, Europe, and Japan from 1996 to 2001. RESULTS: Many patients fell out of the recommended guideline range for serum concentrations of phosphorus (8% of patients below lower target range, 52% of patients above upper target range), albumin-corrected calcium (9% below, 50% above), calcium-phosphorus product (44% above), and intact PTH (51% below, 27% above). All-cause mortality was significantly and independently associated with serum concentrations of phosphorus (RR 1.04 per 1 mg/dL, P= 0.0003), calcium (RR 1.10 per 1 mg/dL, P < 0.0001), calcium-phosphorus product (RR 1.02 per 5 mg(2)/dL(2), P= 0.0001), PTH (1.01 per 100 pg/dL, P= 0.04), and dialysate calcium (RR 1.13 per 1 mEq/L, P= 0.01). Cardiovascular mortality was significantly associated with the serum concentrations of phosphorus (RR 1.09, P < 0.0001), calcium (RR 1.14, P < 0.0001), calcium-phosphorus product (RR 1.05, P < 0.0001), and PTH (RR 1.02, P= 0.03). The adjusted rate of parathyroidectomy varied 4-fold across the DOPPS countries, and was significantly associated with baseline concentrations of phosphorus (RR 1.17, P < 0.0001), calcium (RR 1.58, P < 0.0001), calcium-phosphorus product (RR 1.11, P < 0.0001), PTH (RR 1.07, P < 0.0001), and dialysate calcium concentration (RR 0.57, P= 0.03). Overall, 52% of patients received some form of vitamin D therapy, with parenteral forms almost exclusively restricted to the United States. Vitamin D was potentially underused in up to 34% of patients with high PTH, and overused in up to 46% of patients with low PTH. Phosphorus binders (mostly calcium salts during the study period) were used by 81% of patients, with potential overuse in up to 77% patients with low serum phosphorus concentration, and potential underuse in up to 18% of patients with a high serum phosphorus concentration. CONCLUSION: This study expands our understanding of the relationship between altered mineral metabolism and outcomes and identifies several potential opportunities for improved practice in this area.

Calcium↗

PubMed2004

Biochemical and cellular effects of direct maxacalcitol injection into parathyroid gland in uremic rats.

The most important etiological factors of resistance to medical treatments for secondary hyperparathyroidism are the decreased contents of the vitamin D receptor (VDR) and Ca-sensing receptor (CaSR) in parathyroid cells and a severely swollen parathyroid gland (PTG) as a result of hyperplasia. The effects of direct maxacalcitol (OCT) injection into PTG in terms of these factors were investigated in this study. The PTG of Sprague-Dawley rats that were 5/6 nephrectomized and fed a high-phosphate diet were treated by a direct injection of OCT (DI-OCT) or vehicle (DI-vehicle). The changes in serum intact parathyroid hormone (PTH), Ca(2+), and phosphorus levels, in VDR and CaSR expression levels in parathyroid cells, and in Ca(2+)-PTH curves were examined. Apoptosis was analyzed by the terminal deoxynucleotidyl transferase-mediated dUTP nick end-labeling method and DNA electrophoresis for PTG. DI-OCT markedly decreased serum intact PTH level, and a significant difference in this level between DI-OCT and DI-vehicle was observed. However, serum Ca(2+) and phosphorus levels did not changed markedly in both groups. The upregulations of both VDR and CaSR, the clear shift to the left downward in the Ca(2+)-PTH curve, and the induction of apoptosis after DI-OCT were observed. These findings were not observed in the DI-vehicle-treated rats. Moreover, these effects of DI-OCT were confirmed by the DI-OCT into one PTG and DI-vehicle alone into another PTG in the same rat. DI-OCT may introduce simultaneous VDR and CaSR upregulations and the regression of hyperplastic PTG, and these effects may provide a strategy for strongly suppressing PTH levels in very severe secondary hyperparathyroidism.

Animals↗

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

Dose-response study of 22-oxacalcitriol in patients with secondary hyperparathyroidism.

The dose-response relationships and the safety of administering 22-oxacalcitriol (OCT) to patients with secondary hyperparathyroidism (2HPT) under regular three-times-weekly hemodialysis (HD) were evaluated by double-blind parallel group design. A total of 203 patients with 2HPT were randomly allocated into four groups, and 5 microg (Group L), 10 microg (Group M), or 15 microg (Group H) OCT, or placebo (Group P) was administrated at the end of every HD for 12 weeks. Reductions of intact-parathyroid hormone (iPTH) concentration greater than 30% from baseline were observed in 7.7% of Group P as compared to 77.3% of the pooled OCT groups after 12 weeks of treatment (Mantel test: P < 0.001). Time-trends (slopes) of log-iPTH concentration calculated by least-squares line fitting to each patient's data during treatment differed between Group P and the pooled OCT groups (t-test: P < 0.001) and these iPTH slopes decreased dose-dependently (linear trend by t-test: P < 0.001). Slopes of serum calcium corrected for albumin (corrected-sCa) concentrations also differed between Group P and the pooled OCT groups (t-test: P < 0.001), and increased dose-dependently (linear trend by t-test: P < 0.0001). Serum phosphorus and Ca x P product increased significantly only in high dose groups. Slopes of log(iPTH) and corrected-sCa concentrations were reciprocally related. Most adverse events were hypercalcemia and dose-related, but occasionally comprised pruritus or increased serum creatinine phosphokinase. These results indicate that OCT produced a strong and dose-dependent suppression of PTH and an increase of corrected-sCa concentration in patients with 2HPT. The recommended initial dosages of OCT would appear to be 5 microg when pretreatment iPTH concentrations are less than 500 pg/mL, and 10 microg when greater than 500 pg/mL for safe and effective treatment. As in the case of PTH, calcium and phosphorus showed dose-dependent increases. It is therefore essential to take precautions as to possible increases in calcium and phosphorus.

Acid Phosphatase↗

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

[Biocompatibility].

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Biocompatible Materials↗

PubMed2004

[Hemoperfusion].

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Acute Kidney Injury↗