A state of metabolic acidosis in hemodialysis patients is linked to a frequency of hospitalization and worsening of their survival prognosis, and it has also been reported to have a negative impact on their bone metabolism. We performed a prospective observational study using phosphorus (P) adsorbing agents sevelamer hydrochloride (SH) and lanthanum carbonate (LC) during hemodialysis with a citric acid dialysate (Carbostar^®), which contains a large amount of bicarbonic acid. Then we assessed the effect of SH on metabolic acidosis and the P-adsorbing efficacy of both SH and LC. Methods : Forty patients who orally ingested large doses of SH (≥5,250 mg/day) despite diet therapy were randomly assigned to one of 2 groups of 20 patients each, an SH group and an LC group. The groups took their respective P-adsorbing agent orally for 5 weeks, and then both groups took SH orally for 4 weeks. Results : Severe metabolic acidosis (HCO₃^-≤20 mEq/L), was observed in both groups at baseline despite the use of citric acid dialysate. When the study began, however, there was a gradual tendency for metabolic acidosis to improve in the LC group, and the difference between the two groups was significant from the second week onward (LC group : HCO₃^- concentration before dialysis after 4 weeks 22.3±2.5 mEq/L ; HCO₃^- concentration after 5 weeks 23.0±2.0 mEq/L). However, as a result of the change from LC to SH from the 6th week onward, in the 7th week there was rapid deterioration to the baseline metabolic acidosis level. After 5 weeks, 1,500 mg of LC corresponded to approximately 6,500 mg of SH in the LC group. Discussion : We think that it is necessary to bear in mind the progression of metabolic acidosis by SH when treating hyperphosphatemia and to select an appropriate P-absorbing agent.

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An increased serum undercarboxylated osteocalcin (ucOC) level is evidence of vitamin K (VK) deficiency. In patients with osteoporosis, the ucOC cut-off value for VK treatment has been clarified. However, in hemodialysis patients, the serum ucOC level is extremely high, and the cut-off value has not yet been determined. Therefore, the ucOC cut-off value for VK treatment was examined in hemodialysis patients. Serum VK, ucOC, osteocalcin (OC), and intact parathyroid hormone (iPTH) levels were examined before VK treatment, and the effects of VK treatment for 3 months on serum ucOC, OC, and iPTH levels were evaluated in 54 hemodialysis patients. These patients were stratified into groups demonstrating serum VK levels <2.36 ng/mL (VK deficiency) and ≥2.36 ng/mL (VK sufficiency). Using receiver operating characteristic (ROC) curve analysis, the optimal ucOC cut-off level that was able to detect a serum VK level 2.36 ng/mL was 35.9 ng/mL. In 32 patients with VK deficiency, the serum ucOC level decreased significantly from a baseline value of 57.7±54.4 ng/mL to 39.3±29.8 ng/mL after 1 month of VK treatment and 40.9±35.30 ng/mL after 3 months (p<0.01), but serum OC and iPTH values did not show any significant changes throughout this period. Therefore, we considered that decrease of the ucOC level after VK treatment indicated VK recovery. Moreover, since the ucOC level showed no significant change between, VK was considered repleted in 1 month after VK treatment. In 32 patients with VK deficiency, using ROC curve analysis to compare ucOC levels before and after 1 month of VK treatment, the optimal cut-off ucOC level to judge VK repletion after VK treatment was 36.2 ng/mL. In patients with baseline ucOC levels ≥35 ng/mL, the ucOC level decreased significantly from a baseline value of 73.5±49.7 ng/mL to 50.9±26.1 ng/mL (p<0.01) after 1 month. Almost the same ucOC cut-off values were derived from examinations of serum VK values before VK treatment and from the ucOC level changes after VK treatment. Hemodialysis patients with serum ucOC levels ≥35 ng/mL appear to be suitable candidates for VK treatment.

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In patients with dialysis therapy, cardiovascular diseases have a great impact on morbidity and mortality. Because physicians have recently been encountering more patients with diabetes mellitus as well as more elderly patients, the importance of evaluating atherosclerosis has continuously increased. It has been reported that ischemic heart diseases or cerebrovascular diseases can be estimated using non-invasive ultrasonography. In addition, we can also diagnose coronary stenosis using computed tomography more easily than before. In this study, we in vestigated the efficacy of carotid ultrasonography in estimating coronary artery stenosis in patients with hemodialysis. One hundred and eight patients (58 men and 50 women with a mean age of 69±12 years, and a mean dialysis duration of 6.7±6.2 years) were enrolled in this study. We measured the maximum intima-media thickness (max-IMT), the distribution and the properties of plaque and plaque scores at carotid arteries using ultrasonography, and examined the degree of stenosis and the number of stenotic coronary arteries using computed tomography. As the max-IMT or plaque scores increased, the degree of stenosis became significantly more severe and multi-vessel disease was observed with significantly greater frequency. End stage renal disease is one of most significant cardiovascular risk factors. However, it is difficult to diagnose ischemic heart disease correctly in these patients because they sometimes have few symptoms due to diabetes and often show atypical electrocardiograms due to ventricular hypertrophy or electrolyte disorders. In this study, we clearly showed the correlation between atherosclerosis in the carotid arteries and stenosis in the coronary arteries. It is suggested that carotid ultrasonography is useful to estimate coronary artery stenosis, and effective for evaluating the risk of ischemic heart diseases non-invasively in patients with hemodialysis.

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Aim : We evaluated the impact of cinacalcet on achieving the targets listed in the guidelines of the Japanese Society for Dialysis Therapy (JSDT) [phosphate (P) 3.5～6.0 mg/dL, corrected calcium (Ca) 8.4～10.0 mg/dL and intact parathyroid hormone (iPTH) 60～180 pg/mL]. Patients and methods : We examined the medical records of 52 hemodialyzed Japanese patients who were treated with cinacalcet between January and December 2008. Cinacalcet was discontinued in 5 patients due to adverse effects and iPTH levels were not followed in 1 patient. Therefore, we analyzed data from 46 patients. Results : During the follow-up periods, 24 patients achieved iPTH levels within the target range and 19 patients achieved the target ranges for P, Ca and iPTH (group A). Baseline iPTH levels were significantly different between group A and patients who did not achieve the target levels of P, Ca or iPTH (group NA) (353±124 pg/mL vs. 668±383 pg/mL, p<0.01). The baseline Ca level was also significantly lower in group A than in group NA. Of patients with baseline intact PTH level≤500 pg/mL, 78% achieved the target iPTH level and 63% were classified into group A. Of patients with baseline iPTH>500 pg/mL, 16% achieved the target iPTH level and 11% were classified into group A. Parathyroid gland size, which was measured by ultrasonography in 5 patients, was significantly reduced from the baseline to week 24 (580±349 mm³ vs. 357±254 mm³, p=0.03). Conclusion : The presence of a low iPTH level (180～500 pg/mL) without elevated Ca level predicts a good response to cinacalcet. Cinacalcet may also be effective in patients with enlarged parathyroid glands.

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Treatment of renal anemia in patients with renal failure includes administration of recombinant human erythropoietin (rHuEPO). At present, 2 types of rHuEPO-epoetin α and epoetin β-are available, but these agents both cause pain after being injected subcutaneously. The pain is considered due to inactive ingredients or the pH of the preparations. In 2009, epoetin β preparations were improved so that the pH ranges between 6.8 and 7.2. This improvement is expected to reduce pain. Therefore, in the present study, we compared the degree of pain produced by these 2 types of preparations in 38 patients with predialysis chronic kidney disease (CKD) who received subcutaneous injection of rHuEPO preparations for renal anemia on an outpatient basis. The study was conducted in a crossover design, and the patients were classified into 2 groups according to age and sex. The A group first received an epoetin α preparation (epoetin α), then they received an epoetin β preparation (epoetin β), followed by an injection of epoetin α. The B group was first administered epoetin β, then epoetin α, followed by epoetin β. After each injection, patients assessed the degree of pain they had experienced using a visual analogue scale (VAS) in a questionnaire survey. We compared the VAS scores between epoetin α and β groups and found that epoetin β caused significantly less pain, with a VAS score of 0.46±2.75 cm in the epoetin α group and -1.04±3.50 cm in the epoetin β group (p=0.032). We also compared the degree of pain experienced by predialysis chronic kidney disease (CKD) patients who were subcutaneously injected with rHuEPO and found that the pain produced by epoetin β was less than that produced by epoetin α.

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Few published reports have investigated the factors leading to errors in the measurement of the solute concentration in pooled dialysis effluent (hereafter referred to as “effluent”). In our recent study, we compared full-volume pooling (pooling the entire effluent) with partial pooling (pooling a portion of the effluent). The study demonstrated that the use of the former method facilitated the removal of significantly higher levels of 2 proteins-β₂-microlgobulin (β₂M) and albumin (Alb) -although there was no significant difference between the 2 methods in the level of low-molecular-weight solutes such as urea. Between the 2 pooling methods, there was a difference in the area of contact per milliliter of the effluent with the surface of the plastic container being used for pooling. That is, the contact area per unit volume of the effluent was several times greater with the partial pooling method, which has a lower effluent protein level, than with the full volume pooling method. This difference may be explained by nonspecific adsorption of proteins due to interactions between the hydrophobic group on the plastic surface and the hydrophobic group of proteins such as β₂M and Alb. To verify this, we examined whether or not the use of a surfactant with both a hydrophilic group and a hydrophobic group reduces the nonspecific adsorption of proteins. The following nonionic surfactants polyoxyethylene (20) sorbitan monolaurate (Tween 20) were investigated in this study. Our findings showed that the use of these surfactants reduced the extent of nonspecific adsorption of proteins, resulting in the elimination of significant differences in the effluent protein level between the full-volume pooling method and the partial pooling method. Thus, the addition of surfactants to the dialysis effluent allows more accurate measurement of the solute level in the dialysis effluent.

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A 55-year-old female who had been on hemodialysis was admitted with cerebellar ataxia. She had been undergoing chemotherapy for myeloproliferative disease, and had started hemodialysis 10 months prior to admission. T2-weighted imagings on brain MRI showed demyelination in the cerebellum. Although it was not typical that the demyelinated region was limited to the cerebellum and the brain stem, progressive multifocal leukoencephalopathy (PML) was highly suspected because of the positive PCR finding of JC virus in her cerebrospinal fluid. The demyelinated region increased, and her symptoms worsened. Involuntary movement, dysarthria and dysphagia appeared. She died 10 months after onset due to repeated aspiration pneumonia. Autopsy demonstrated demyelination in the cerebellum and brain stem with JC viral protein in the same region. Thus, she was diagnosed with the cerebellar form of PML. Retrospective review of renal biopsy demonstrated an abundance of JC viral protein in the atrophic tubular epithelial cells. There have been some case reports of the cerebellar form of PML in hemodialysis patients in Japan. Although the cerebellar form has been reported to be rare, there is a possibility that the cerebellar form is not rare among hemodialysis patients. In this case, JC virus infection in the tubular cells may have been related to renal dysfunction. Although the relationship between JC viral infection and renal dysfunction is currently unclear, the pathological significance of JC viral infection in kidney needs to be elucidated.

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[in Japanese]

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