Search

BACKGROUND: Previously, the Dialysis Outcomes and Practice Patterns Study (DOPPS) has shown large international variations in vascular access practice. Greater mortality risks have been seen for hemodialysis (HD) patients dialyzing with a catheter or graft versus a native arteriovenous fistula (AVF). To further understand the relationship between vascular access practice and outcomes, we have applied practice-based analyses (using an instrumental variable approach) to decrease the treatment-by-indication bias of prior patient-level analyses. STUDY DESIGN: A prospective observational study of HD practices. SETTING & PARTICIPANTS: Data collected from 1996 to 2004 from 28,196 HD patients from more than 300 dialysis units participating in the DOPPS in 12 countries. PREDICTOR OR FACTOR: Patient-level or case-mix-adjusted facility-level vascular access use. OUTCOMES/MEASUREMENTS: Mortality and hospitalization risks. RESULTS: After adjusting for demographics, comorbid conditions, and laboratory values, greater mortality risk was seen for patients using a catheter (relative risk, 1.32; 95% confidence interval, 1.22 to 1.42; P < 0.001) or graft (relative risk, 1.15; 95% confidence interval, 1.06 to 1.25; P < 0.001) versus an AVF. Every 20% greater case-mix-adjusted catheter use within a facility was associated with 20% greater mortality risk (versus facility AVF use, P < 0.001); and every 20% greater facility graft use was associated with 9% greater mortality risk (P < 0.001). Greater facility catheter and graft use were both associated with greater all-cause and infection-related hospitalization. Catheter and graft use were greater in the United States than in Japan and many European countries. More than half the 36% to 43% greater case-mix-adjusted mortality risk for HD patients in the United States versus the 5 European countries from the DOPPS I and II was attributable to differences in vascular access practice, even after adjusting for other HD practices. Vascular access practice differences accounted for nearly 30% of the greater US mortality compared with Japan. LIMITATIONS: Possible existence of unmeasured facility- and patient-level confounders that could impact the relationship of vascular access use with outcomes. CONCLUSIONS: Facility-based analyses diminish treatment-by-indication bias and suggest that less catheter and graft use improves patient survival. Copyright © 2009 American Society for Nutrition [ABSTRACT FROM AUTHOR]

Premedication is often used to reduce the stress associated with anesthesia-related procedures. However, in some cases, patients may not cooperate with medication delivery because of significant fear and anxiety. We report a case of an uncooperative patient with severe intellectual disabilities who was successfully premedicated with the unique technique of sublingual midazolam administration using a suction toothbrush. The 38-year-old male patient was planned to receive dental treatment under deep intravenous sedation (IVS), but he refused both intravenous cannulation and mask induction. Preanesthetic medication delivery using other routes was attempted but not accepted. As the patient tolerated toothbrushing, we used repeated practice with sublingual water administration through the toothbrush's suction hole to gradually desensitize the patient. Using that same method, sublingual midazolam was administered as a successful premedication to allow placement of a face mask for inhalational induction without distress and completion of the dental treatment under IVS. For patients who refuse other premedication routes, sublingual administration during toothbrushing with a suction toothbrush may provide a successful alternative., (© 2023 by the American Dental Society of Anesthesiology.)

Since 2009, the peritoneal dialysis (PD) registry has been carried out as part of the annual nationwide survey conducted by the Statistical Survey Committee of the Japanese Society for Dialysis Therapy with the cooperation of the Japanese Society for Peritoneal Dialysis. In this study, the current status of PD patients is reported on the basis of the results of the survey conducted at the end of 2013. The subjects were PD patients who lived in Japan and participated in the 2013 survey. Descriptive analysis was performed for various items including the current status of the combined use of PD and another dialysis method such as hemodialysis (HD) or hemodiafiltration (HDF), the method of exchanging dialysate, the use of an automated peritoneal dialysis (APD) machine, and the incidences of peritonitis and catheter exit-site infection. From the results of the facility survey in 2013, the number of PD patients was 9392, a decrease of 122 from that in 2012. Among the entire dialysis patient population, 3.0% were PD patients, a decrease of 0.1%. Among the studied patients, 292 had a peritoneal catheter and underwent peritoneal lavage, 174 were started on PD in 2013 but introduced to other blood purification methods in 2013, and 1920 underwent both PD and another dialysis method such as HD or HDF. The percentage of patients who underwent PD and another dialysis method increased with the number of years on PD: <1 year, 3.5%; 1 to < 2 years, 8.4%; 2 to < 4 years, 15.3%; 4 to < 6 years, 27.1%; 6 to < 8 years, 39.3%; 8 to < 10 years, 47.1%; and ≥ 10 years, 57.5%. The percentage of PD patients for whom the dialysate was completely manually exchanged was 31.6%, whereas the percentages of PD patients who used a bag-exchange device based on ultraviolet-light irradiation and that based on thermal sterile joint systems were 52.1 and 14.9%, respectively. The mean incidence of peritonitis was 0.22 per patient per year (once per 54.5 patients per month). The mean incidence of catheter exit-site infection was 0.34 per patient per year (once per 35.3 patients per month)., (© 2016 International Society for Apheresis, Japanese Society for Apheresis, and Japanese Society for Dialysis Therapy.)

The 11-cis retinal chromophore is tightly packed within the interior of the visual receptor rhodopsin and isomerizes to the all-trans configuration following absorption of light. The mechanism by which this isomerization event drives the outward rotation of transmembrane helix H6, a hallmark of activated G protein-coupled receptors, is not well established. To address this question, we use solid-state NMR and FTIR spectroscopy to define the orientation and interactions of the retinal chromophore in the active metarhodopsin II intermediate. Here we show that isomerization of the 11-cis retinal chromophore generates strong steric interactions between its β-ionone ring and transmembrane helices H5 and H6, while deprotonation of its protonated Schiff's base triggers the rearrangement of the hydrogen-bonding network involving residues on H6 and within the second extracellular loop. We integrate these observations with previous structural and functional studies to propose a two-stage mechanism for rhodopsin activation.

This study aimed to examine the association between the non-invasive measurement of the brachial artery volume elastic modulus (V E), an index of arterial stiffness, and the presence of coronary artery stenosis in patients with suspected stable coronary artery disease (CAD). A total of 135 patients with suspected stable CAD (87 men, mean age, 64 ± 12 years) underwent oscillometric measurement of the brachial artery to obtain V E. Coronary angiography was thereafter carried out to diagnose CAD, defined as having ≥75 % stenosis in the epicardial coronary arteries. V E was significantly higher in patients with CAD (1.94 ± 0.34 mmHg/%) than in those without CAD (1.71 ± 0.35 mmHg/%, P < 0.001). In multiple logistic regression analysis, V E was an independent predictor for the presence of CAD (odds ratio 1.19 per 0.1 mmHg/% increase, 95 % CI 1.04-1.51) even after adjusting for multiple potential confounders including the Framingham risk score (FRS). The area under the curve of the receiver operating characteristic curve analysis for discriminating CAD increased significantly after the addition of V E to the FRS (from 0.75 to 0.81, P = 0.034). The category-free net reclassification improvement and the integrated discrimination improvement by adding V E to the FRS were 0.476 (95 % CI 0.146-0.806) and 0.086 (95 % CI 0.041-0.132), respectively. In conclusion, the brachial V E was significantly associated with the presence of coronary artery stenosis. The additional measurement of V E to the FRS improved the ability to identify patients with coronary artery stenosis among those with suspected stable CAD.

Conserved prolines in the transmembrane helices of G-protein-coupled receptors (GPCRs) are often considered to function as hinges that divide the helix into two segments capable of independent motion. Depending on their potential to hydrogen-bond, the free C=O groups associated with these prolines can facilitate conformational flexibility, conformational switching or stabilization of the receptor structure. To address the role of conserved prolines in family A GPCRs through solid-state NMR spectroscopy, we focus on bovine rhodopsin, a GPCR in the visual receptor subfamily. The free backbone C=O groups on helices H5 and H7 stabilize the inactive rhodopsin structure through hydrogen-bonds to residues on adjacent helices. In response to light-induced isomerization of the retinal chromophore, hydrogen-bonding interactions involving these C=O groups are released, thus facilitating repacking of H5 and H7 onto the transmembrane core of the receptor. These results provide insights into the multiple structural and functional roles of prolines in membrane proteins.

Sleep-disordered breathing (SDB) is known as a cardiovascular risk factor and has high prevalence in hypertension, which is a major risk factor of aortic dissection (AD). However, the impact of SDB on AD has not been fully clarified. The aim of this study is to elucidate the impact of SDB on AD, especially on the type of false lumen in AD. We enrolled twenty-three consecutive patients with acute AD (mean age: 66 ± 13 years). All subjects were evaluated by an ambulatory polygraphic sleep monitoring within 1 month from the onset. AD was evaluated by axial images of computed tomography. We comparatively analyzed SDB and AD. 35 % of the subjects presented severe OSA (apnea-hypopnea index: AHI ≥30). The patent false lumen group showed significantly higher systolic and diastolic blood pressure (BP) on arrival and AHI, and lower percutaneous oxygen saturation (SaO2) compared with those in the thrombosed false lumen group. The prevalence of severe SDB was higher in the patent false lumen group (60 vs 15 %, p = 0.039). Systolic BP on arrival was significantly correlated with AHI (r = 0.457, p = 0.033) and the minimum SaO2 (r = -0.537, p = 0.010). The present study revealed close linkage between SDB and AD, and a high prevalence of SDB among AD patients. Severe SDB was related to the development of AD, especially for the patent false lumen type through highly elevated BP which might be easily evoked in the presence of severe SDB. Repetitive occurrence of intrathoracic negative pressure also might influence the repair or closure of false lumen of AD, although the present analysis did not reach statistical significance.

A nationwide survey of 4325 dialysis facilities was conducted at the end of 2013, among which 4268 (98.7%) responded. The number of new dialysis patients was 38,095 in 2013. Since 2008, the number of new dialysis patients has remained almost the same without any marked increase or decrease. The number of dialysis patients who died in 2013 was 30,751. The dialysis patient population has been growing every year in Japan; it was 314,438 at the end of 2013. The number of dialysis patients per million at the end of 2013 was 2470. The crude death rate of dialysis patients in 2013 was 9.8%. The mean age of new dialysis patients was 68.7 years and the mean age of the entire dialysis patient population was 67.2 years. The most common primary cause of renal failure among new dialysis patients was diabetic nephropathy (43.8%). The actual number of new dialysis patients with diabetic nephropathy has almost been unchanged for the last few years. Diabetic nephropathy was also the most common primary disease among the entire dialysis patient population (37.6%), followed by chronic glomerulonephritis (32.4%). The percentage of dialysis patients with diabetic nephropathy has been increasing continuously, whereas the percentage of dialysis patients with chronic glomerulonephritis has been decreasing. The number of patients who underwent hemodiafiltration (HDF) at the end of 2013 was 31,371, a marked increase from that in 2012. This number is more than twice that at the end of 2011 and approximately 1.5 times the number at the end of 2012. In particular, the number of patients who underwent online HDF increased approximately fivefold over the last 2 years. Among 151,426 dialysis patients with primary causes of renal failure other than diabetic nephropathy, 10.8% had a history of diabetes. Among those with a history of diabetes, 26.8% used glycoalbumin as an indicator of blood glucose level; and 33.0 and 27.6% were administered insulin and dipeptidyl peptidase (DPP)-4 inhibitor, respectively, as a medication of diabetes. The facility survey showed that 9392 patients underwent peritoneal dialysis (PD). The patient survey revealed that 1920 of these PD patients also underwent another dialysis method using extracorporeal circulation, such as hemodialysis (HD) or HDF. The number of patients who underwent HD at home at the end of 2013 was 461, a marked increase from that at the end of 2012 (393)., (© 2015 Japanese Society for Dialysis Therapy Reproduced with permission.)

Since 2009, the peritoneal dialysis (PD) registry survey has been carried out as part of the annual nationwide survey conducted by the Statistical Survey Committee of the Japanese Society for Dialysis Therapy with the cooperation of the Japanese Society for Peritoneal Dialysis. In this report, the current status of PD patients is presented on the basis of the results of the survey conducted at the end of 2012. The subjects were PD patients who lived in Japan and participated in the 2012 survey. Descriptive analysis of various items was performed, which included the current status of the combined use of PD and another dialysis method such as hemodialysis (HD) or hemodiafiltration (HDF), the method of exchanging dialysate, the use of an automated peritoneal dialysis (APD) machine, and the rates of peritonitis and catheter exit-site infection. From the results of the facility survey in 2012, the number of PD patients was 9514, a decrease of 128 from 2011. Among the entire dialysis patient population, 3.1% were PD patients, a decrease of 0.1%. Among the studied patients, 347 had a peritoneal catheter and underwent peritoneal lavage, 175 were started on PD in 2012 but introduced to other blood purification methods in the same year, and 1932 underwent both PD and another dialysis method such as HD or HDF. The percentage of patients who underwent PD and another dialysis method increased with PD vintage: <1 year, 4.8%; 1 to <2 years, 9.2%; 2 to <4 years, 16.3%; 4 to <8 years, 32.0%; and ≥8 years, 47.5%. The percentage of PD patients who completely manually exchanged the dialysate was 29.8%. The percentages of PD patients who used a double-bag exchange system with ultraviolet-light irradiation and those who used the same system but with a sterile connecting device were 54.7 and 13.9%, respectively. The percentage of patients on PD for <1 year using an APD machine was 43.4%, and it decreased with a PD vintage of ≥2 years. The mean rate of peritonitis was 0.22 per patient per year. The mean rate of catheter exit-site infections was 0.36 per patient per year., (© 2015 Japanese Society for Dialysis Therapy Reproduced with permission.)

G protein-coupled receptors (GPCRs) span cell membranes with seven transmembrane helices and respond to a diverse array of extracellular signals. Crystal structures of GPCRs have provided key insights into the architecture of these receptors and the role of conserved residues. However, the question of how ligand binding induces the conformational changes that are essential for activation remains largely unanswered. Since the extracellular sequences and structures of GPCRs are not conserved between receptor subfamilies, it is likely that the initial molecular triggers for activation vary depending on the specific type of ligand and receptor. In this article, we describe NMR studies on the rhodopsin subfamily of GPCRs and propose a mechanism for how retinal isomerization switches the receptor to the active conformation. These results suggest a general approach for determining the triggers for activation in other GPCR subfamilies using NMR spectroscopy., (Copyright © 2015 Elsevier Inc. All rights reserved.)

Background: Japanese patients undergoing dialysis have an extremely low mortality rate compared with those in the United States and Europe. As shown in the Dialysis Outcomes 38; Practice Patterns Study (DOPPS), certain features of dialysis treatment, such as single treatment time and amount of blood flow, are unique to Japan, but factors contributing to the low mortality risk are unclear. Although DOPPS is a multi-country prospective cohort study, the study results may not entirely reflect the real trend in Japan because the number of Japanese institutions participating in the study is small., Summary: In this article, we review the data reported for Japan and other countries and reveal country-specific differences, particularly in patient age distribution and duration of dialysis., Key Messages: The mean age of prevalent dialysis patients is rising every year in Japan, and the proportion of patients undergoing dialysis for long periods of time is also increasing. In addition, the proportion of dialysis patients with diabetes, one of the primary diseases, has increased to a level similar to that observed in Western countries. However, no significant decline in the crude death rate among prevalent dialysis patients has been observed in Japan, presumably because of technological advances in dialysis treatment, but further studies are needed to elucidate the contributing factors., (© 2015 S. Karger AG, Basel.)

We describe the use of solid-state magic angle spinning NMR spectroscopy for characterizing the structure and dynamics of dark, inactive rhodopsin and the active metarhodopsin II intermediate. Solid-state NMR spectroscopy is well suited for structural measurements in both detergent micelles and membrane bilayer environments. We first outline the methods for large-scale production of stable, functional rhodopsin containing (13)C- and (15)N-labeled amino acids. The expression methods make use of eukaryotic HEK293S cell lines that produce correctly folded, fully functional receptors. We subsequently describe the basic methods used for solid-state magic angle spinning NMR measurements of chemical shifts and dipolar couplings, which provide information on rhodopsin structure and dynamics, and describe the use of low-temperature methods to trap the active metarhodopsin II intermediate.

A nationwide statistical survey of 4279 dialysis facilities was conducted at the end of 2012, among which 4238 responded (99.0%). The number of new dialysis patients was 38055 in 2012. Since 2008, the number of new dialysis patients has remained almost the same without any marked increase or decrease. The number of dialysis patients who died in 2012 was 30710; a slight decrease from 2011 (30743). The dialysis patient population has been growing every year in Japan; it was 310007 at the end of 2012, which exceeded 310000 for the first time. The number of dialysis patients per million at the end of 2012 was 2431.2. The crude death rate of dialysis patients in 2012 was 10.0%, a slight decrease from that in 2011 (10.2%). The mean age of new dialysis patients was 68.5 years and the mean age of the entire dialysis patient population was 66.9 years. The most common primary cause of renal failure among new dialysis patients was diabetic nephropathy (44.2%). The actual number of new dialysis patients with diabetic nephropathy has been approximately 16000 for the last few years. Diabetic nephropathy was also the most common primary disease among the entire dialysis patient population (37.1%), followed by chronic glomerulonephritis (33.6%). The percentage of dialysis patients with diabetic nephropathy has been continuously increasing, whereas not only the percentage but also the actual number of dialysis patients with chronic glomerulonephritis has decreased. The number of patients who underwent hemodiafiltration (HDF) at the end of 2012 was 21725, a marked increase from that in 2011 (14115). In particular, the number of patients who underwent on-line HDF increased threefold from 4890 in 2011 to 14069 in 2012. From the results of the facility survey, the number of patients who underwent peritoneal dialysis (PD) was 9514 and that of patients who did not undergo PD despite having a PD catheter in the abdominal cavity was 347. From the results of the patient survey, among the PD patients, 1932 also underwent another dialysis method using extracorporeal circulation, such as hemodialysis (HD) and HDF. The number of patients who underwent HD at home in 2012 was 393, a marked increase from that in 2011 (327)., (© 2014 Japanese Society for Dialysis Therapy. Reproduced with permission.)

Objective: Inflammation contributes to hemopoiesis by lowering responses to epoetin (EPO) and to an increase in the mortality of patients on hemodialysis. However, nutritional status might alter associations among inflammation, EPO responsiveness, and the risk of mortality. We assessed the effect of inflammation on mortality according to nutritional status among EPO responses in a cohort of prevalent hemodialysis patients., Design and Methods: The observational cohort study analyzed data from the Japanese Dialysis Registry (2005-2006; n = 36,956; mean follow-up 11.5 months). Patients were categorized into tertiles of the EPO responsiveness index (ERI; the weekly weight-adjusted EPO dose [IU/kg/week] divided by hemoglobin [g/dL]) and an EPO-free group. Body mass index (BMI) and C-reactive protein (CRP) levels were measured., Results: Bimodal peaks indicated associations between CRP and BMI in each group. Hazard ratio (HR) curves of CRP for mortality according to BMI in the upper ERI tertile, particularly among those with diabetes mellitus (DM), were reverse J-shaped. However, HR curves in the other groups were increased below a threshold BMI of 21 kg/m(2). These associations were confirmed in propensity score-matched populations., Conclusion: Risk of CRP for death is apparently changed by BMI in hemodialysis patients with a lower EPO response, especially in those with DM., (Copyright © 2014 National Kidney Foundation, Inc. Published by Elsevier Inc. All rights reserved.)

Guidelines have recommended single pool Kt/V > 1.2 as the minimum dose for chronic hemodialysis (HD) patients on thrice weekly HD. The Dialysis Outcomes and Practice Patterns Study (DOPPS) has shown that "low Kt/V" (<1.2) is more prevalent in Japan than many other countries, though survival is longer in Japan. We examined trends in low Kt/V, dialysis practices associated with low Kt/V, and associations between Kt/V and mortality overall and by gender in Japanese dialysis patients. We analyzed 5784 HD patients from Japan DOPPS (1999-2011), restricted to patients dialyzing for >1 year and receiving thrice weekly dialysis. Logistic regression models estimated the relationships of patient characteristics with Kt/V. Logistic models also were used to estimate the proportion of low Kt/V cases attributable to various treatment practices. Multivariable Cox regression was used to estimate the associations of low Kt/V, blood flow rate (BFR), and treatment time (TT), with all-cause mortality. From 1999 to 2009, the prevalence of low Kt/V declined in men (37-27%) and women (15-10%). BFR <200 mL/min, TT <240 minutes, and dialyzate flow rate (DFR) < 500 mL/min were common (35, 13, and 19% of patients, respectively) and strongly associated with low Kt/V. Fifteen percent of low Kt/V cases were attributable to BFR <200 and 13% to TT <240, compared to only 3% for DFR <500. Lower Kt/V was associated with elevated mortality, more so among women (hazard ratio [HR] = 1.13 per 0.1 lower Kt/V, 95% CI: 1.07-1.20) than among men (HR = 1.06 per 0.1 lower Kt/V, 95% CI: 1.00-1.12). The relatively large proportion of low Kt/V cases in Japanese facilities may potentially be reduced 30% by increasing BFR to 200 mL/min and TT to 4 hours thrice weekly in HD patients. Associations of low Kt/V with elevated mortality suggest that modification of these practices may further improve survival for Japanese HD patients., (© 2014 International Society for Hemodialysis.)

Pruritus affects many patients undergoing hemodialysis (HD). In this study, pruritus and its relationship to morbidity, quality of life (QoL), sleep quality, and patient laboratory measures were analyzed in a large sample of Japanese patients undergoing HD. Severity of patient-reported pruritus symptoms experienced during a 4-week period was collected from 6480 Japanese patients undergoing HD in three phases of the Dialysis Outcomes and Practice Patterns Study (DOPPS; 1996-2008; 60-65 study facilities/phase). Adjusted linear and logistic regressions were used to identify associations of pruritus with treatment parameters and QoL outcomes. Adjusted Cox regressions examined the influence of pruritus severity on mortality. Moderate to extreme pruritus was experienced by 44% of prevalent patients undergoing HD in the Japanese Dialysis Outcomes and Practice Patterns Study. Many patient characteristics were significantly associated with pruritus, but this did not explain the large differences in pruritus among facilities (20-70%). Pruritus was slightly less common in patients starting HD than in patients on dialysis >1 year. Patients with moderate to extreme pruritus were more likely to feel drained (adjusted odds ratio = 2.2-5.8, P < 0.0001), have poor sleep quality (adjusted odds ratio = 1.9-3.7, P < 0.0001), and have QoL mental and physical composite scores 2.3-6.7 points lower (P < 0.0001) than patients with no/mild pruritus. Pruritus in patients undergoing HD was associated with a 23% higher mortality risk (P = 0.09). The many poor outcomes associated with pruritus underscore the need for better therapeutic agents to provide relief for the 40-50% of prevalent patients undergoing HD substantially affected by pruritus. Pruritus in new patients with end-stage renal disease likely results from uremia or pre-existing conditions (not HD per se), indicating the need to understand development of pruritus before end-stage renal disease., (© 2014 International Society for Hemodialysis.)

A nationwide statistical survey of 4255 dialysis facilities was conducted at the end of 2011. Responses were submitted by 4213 facilities (99.0%). The number of new patients started on dialysis was 38,613 in 2011. Although the number of new patients decreased in 2009 and 2010, it increased in 2011. The number of patients who died each year has been increasing; it was 30,743 in 2011, which exceeded 30,000 for the first time. The number of patients undergoing dialysis has also been increasing every year; it was 304,856 at the end of 2011, which exceeded 300,000 for the first time. The number of dialysis patients per million at the end of 2011 was 2385.4. The crude death rate of dialysis patients in 2011 was 10.2%, which exceeded 10% for the first time in the last 20 years. The mean age of new dialysis patients was 67.84 years and the mean age of the entire dialysis patient population was 66.55 years. The most common primary cause of renal failure among new dialysis patients was diabetic nephropathy (44.3%). Diabetic nephropathy was also the most common primary disease among the entire dialysis patient population (36.7%), exceeding chronic glomerulonephritis (34.8%) which had been the highest until last year. The survey included questions related to the Great East Japan Earthquake, which occurred on 11 March 2011. The results on items associated with the Great East Japan Earthquake were reported separately from this report. The mean uric acid levels of the male and female patients were 7.30 and 7.19 mg/dL, respectively. Certain drugs for hyperuricemia were prescribed for approximately 17% of patients. From the results of the facility survey, the number of patients who underwent peritoneal dialysis (PD) was 9642 and the number of patients who did not undergo PD despite having a peritoneal dialysis catheter was 369. A basic summary of the results on the survey items associated with PD is included in this report and the details were reported separately., (© 2013 The Authors. Therapeutic Apheresis and Dialysis © 2013 International Society for Apheresis.)

Adequate blood flow (Qb) is necessary for effective hemodialysis (HD). Aim of the study was to examine relationship between the actually delivered Qb (dQb) and reported Qb (rQb) with dialysis machine. One hundred HD patients with arteriovenous fistula were enrolled. Delivered Qb was measured at the beginning and end of each HD session. dQb/rQb < 1 indicated a discrepancy between actual dQb and rQb reported using a dialysis machine. In addition, dQb/rQb was examined in HD patients using needles of different gauges during treatment. The average levels of dQb/rQb at start and end of HD session were 1.01 ± 0.04 and 0.98 ± 0.05, respectively. In the 16 gauge and 17 gauge needle groups, the percentage of patients with dQb/rQb < 1 increased in accordance with the increase in rQb or as the HD session progressed. In the 15 gauge needle group, the percentage of patients with dQb/rQb < 1 was <50% at any level of rQb. Selection of needle gauge is important factors for determining actual dQb in HD patients.

Oxidative damage and clustering of band 3 in the membrane have been implicated in the removal of senescent human erythrocytes from the circulation at the end of their 120 day life span. However, the biochemical and mechanistic events leading to band 3 cluster formation have yet to be fully defined. Here we show that while neither membrane peroxidation nor methemoglobin (MetHb) formation on their own can induce band 3 clustering in the human erythrocytes, they can do so when acting in combination. We further show that binding of MetHb to the cytoplasmic domain of band 3 in peroxidized, but not in untreated, erythrocyte membranes induces cluster formation. Age-fractionated populations of erythrocytes from normal human blood, obtained by a density gradient procedure, have allowed us to examine a subpopulation, highly enriched in senescent cells. We have found that band 3 clustering is a feature of only this small fraction, amounting to ∼0.1% of total circulating erythrocytes. These senescent cells are characterized by an increased proportion of MetHb as a result of reduced nicotinamide adenine dinucleotide-dependent reductase activity and accumulated oxidative membrane damage. These findings have allowed us to establish that the combined effects of membrane peroxidation and MetHb formation are necessary for band 3 clustering, and this is a very late event in erythrocyte life. A plausible mechanism for the combined effects of membrane peroxidation and MetHb is proposed, involving high-affinity cooperative binding of MetHb to the cytoplasmic domain of oxidized band 3, probably because of its carbonylation, rather than other forms of oxidative damage. This modification leads to dissociation of ankyrin from band 3, allowing the tetrameric MetHb to cross-link the resulting freely diffusible band 3 dimers, with formation of clusters.

Background: Although several clinical trials have shown the superior efficacy and safety of second-generation everolimus-eluting stents (EES) in comparison with first-generation paclitaxel-eluting stents (PES), the differences in the vascular healing process between EES and PES in a human coronary artery during an early stage are unknown., Methods: A prospective optical coherence tomography (OCT) observation was performed for 25 EES in 21 patients and 27 PES in 21 patients at 6 months after implantation. Cross-sections within single-stent segments were analyzed at intervals of 1mm. The neointimal (NI) thickness on each strut was measured. Uncovered struts (NI thickness=0 μm), malapposed struts, NI area (%), uncovered strut ratio >0.3 (UCSR; number of uncovered struts/number of total struts) per cross-section, and in-stent thrombus were evaluated., Results: A total of 5198 EES struts in 514 cross-sections and 4243 PES struts in 469 cross-sections were identified. NI thickness and its area were smaller for EES than PES (80.0 ± 84.8 μm vs. 117.9 ± 140.0 μm and 19.1 ± 8.9% vs. 23.7 ± 11.5%, respectively; P<0.001). The frequencies of uncovered struts and malapposed struts were lower in EES compared to PES (2.3% vs. 5.2% and 2.1% vs. 5.7%, respectively; P<0.001). Patients who had cross-sections of UCSR >0.3 and thrombi were identified less frequently in EES than in PES group (5% vs. 57%; P<0.001, and 19% vs. 48%; P=0.05, respectively)., Conclusions: Six-month OCT examination showed a favorable vessel healing response after the implantation of EES, demonstrating less in-stent late loss as well as fewer uncovered struts and better stent apposition to the vessel wall in comparison with PES., (Copyright © 2011 Elsevier Ireland Ltd. All rights reserved.)

Objective: To determine if prediabetes is associated with atherosclerosis of coronary arteries, we evaluated the degree of coronary atherosclerosis in nondiabetic, prediabetic, and diabetic patients by using coronary angioscopy to identify plaque vulnerability based on yellow color intensity., Research Design and Methods: Sixty-seven patients with coronary artery disease (CAD) underwent angioscopic observation of multiple main-trunk coronary arteries. According to the American Diabetes Association guidelines, patients were divided into nondiabetic (n = 16), prediabetic (n = 28), and diabetic (n = 23) groups. Plaque color grade was defined as 1 (light yellow), 2 (yellow), or 3 (intense yellow) based on angioscopic findings. The number of yellow plaques (NYPs) per vessel and maximum yellow grade (MYG) were compared among the groups., Results: Mean NYP and MYG differed significantly between the groups (P = 0.01 and P = 0.047, respectively). These indexes were higher in prediabetic than in nondiabetic patients (P = 0.02 and P = 0.04, respectively), but similar in prediabetic and diabetic patients (P = 0.44 and P = 0.21, respectively). Diabetes and prediabetes were independent predictors of multiple yellow plaques (NYPs ≥2) in multivariate logistic regression analysis (odds ratio [OR] 10.8 [95% CI 2.09-55.6], P = 0.005; and OR 4.13 [95% CI 1.01-17.0], P = 0.049, respectively)., Conclusions: Coronary atherosclerosis and plaque vulnerability were more advanced in prediabetic than in nondiabetic patients and comparable between prediabetic and diabetic patients. Slight or mild disorders in glucose metabolism, such as prediabetes, could be a risk factor for CAD, as is diabetes itself.

Objective: Clinically, the ankle-brachial blood pressure index (ABI) and skin perfusion pressure (SPP) are used to screen for subclinical peripheral artery disease. However, the association between the SPP and mortality in hemodialysis patients has not been previously reported. We investigated these factors and compared the ABI and SPP in patients receiving hemodialysis., Methods: A total of 102 patients receiving maintenance hemodialysis were enrolled in this study. The ABI was determined using an ABI-form (Colin, Japan). The SPP was measured using a SensiLase(TM) PAD3000 (Kaneka, Osaka, Japan)., Results: The mean follow-up period was 3.2 ± 1.4 years. A multivariate Cox analysis identified a low ABI (p=0.019) and a low SPP (p=0.047) as being independent predictors of mortality. A receiver operating characteristic (ROC) analysis of the ABI revealed a cutoff point of 1.1 and an area under the curve (AUC) of 0.79, with a sensitivity of 90% and a specificity of 62%. A ROC analysis of the SPP revealed a cutoff point of 54.0 mmHg and an AUC of 0.71, with a sensitivity of 55% and a specificity of 84%., Conclusion: Both low ABI and SPP values were found to be independent risk factors for mortality among hemodialysis patients. The cutoff point for ABI as a predictor of mortality was 1.1, while that for SPP was 54.0 mmHg.

A 17-year-old girl with multiple areas of skin hemangiomas that had been present since birth was referred to our institution complaining of sudden onset of dyspnea. Enhanced CT demonstrated a pulmonary thromboembolism and transthoracic echocardiogram showed a thrombus-like echo in the right ventricle. CT further revealed thrombi in the inferior vena cava (IVC) and peripheral vein. The thrombi, especially those in the RV, were highly life-threatening; therefore, immediate thrombectomy was performed and an IVC filter was placed. Because no major complications occurred, the patient was discharged 34 days after admission. In such young women, carefully using anticoagulation therapy and planning pregnancy are recommended.

The heart failure guideline in Japan has stated the necessity of investigating the role of oral inotropic agents in patients with chronic heart failure (CHF), which are clinically available only in Japan. A total of 1,846 consecutive patients with heart failure (mean: 69.5 years old, 1,279 males) treated at our institute from November 2009 to August 2010 were investigated retrospectively. Thirty-one patients (1.84%) who had taken oral inotropic agents (pimobendan 27, docarpamine 6, and denopamine 4) were extracted for this study, and the efficacy and limitations of the treatments were analyzed. Following the oral inotropic treatment, the NYHA functional class (P = 0.017), cardiothoracic ratio (P = 0.002) and B-type natriuretic peptide levels (P = 0.011) were significantly improved, and the number of emergency room (ER) visits (P < 0.001) and hospitalizations (P < 0.001) were significantly reduced. The nonsurviving patients (n = 7/31, 22.6%) were significantly older (P = 0.02) and tended to have a larger cardiothoracic ratio (P = 0.084) compared with the survivors. An absence of concomitant beta-blocker therapy was significantly associated with a worse prognosis (oneyear mortality 2/21 versus 5/10, log rank, P = 0.011). Oral inotropic agents brought about improvements in the clinical parameters of CHF and a reduction in ER visits and hospitalizations. However, concomitant beta-blocker therapy should be considered for patients receiving oral inotropic treatment.

Renal replacement therapy for end-stage kidney disease can be achieved by several interventions including hemodialysis (HD), hemodiafiltration (HDF), peritoneal dialysis (PD) and kidney transplantation, and others. The December 31, 2011 prevalent population included 270,072 patients on HD, 9,094 on PD and 14,051 on HDF; the total treated ESRD population thus rose above 300,000. In contrast, the number of HDF patients decreased after 2007, one of the reasons for Japan's health insurance system. On-line HDF patients were preferentially selected because of their younger age, longer vintage and their lower clinical comorbidity conditions than HD or off-line HDF patients. However, on-line HDF was approved by Japan's health insurance system in 2012. Owing to this approval the number of on-line HDFs may increase in the future., (Copyright © 2013 S. Karger AG, Basel.)

Background: The aim of this study is to determine the prevalence of minute myocardial damage (MMD) in already statin-treated dyslipidemic patients with a low high-density lipoprotein-cholesterol (HDL-C) level, and to evaluate whether pitavastatin could affect the lipid profiles and biomarkers reflecting myocardial stress and injury., Methods: Twenty patients (15 men; age 66 ± 8) being treated with any statin but who had HDL-C < 40 mg/dL, were switched to pitavastatin (2 mg/day) treatment. The patient lipid profiles and the levels of N-terminal pro-brain natriuretic peptide (NT-proBNP), high-sensitive troponin T (hsTnT), and high-sensitive C-reactive protein (hs-CRP) were evaluated for six months., Results: At three months after the statin replacement, the HDL-C significantly increased from 37 ± 3 mg/dL to 40 ± 5 mg/dL (P < 0.05), and the low-density lipoprotein-cholesterol (LDL-C) and LDL-C/HDL-C ratio significantly reduced (100 ± 28 mg/dL to 86 ± 22 mg/dL, P < 0.05; 2.68 ± 0.67 to 2.17 ± 0.64, P < 0.05, respectively), and these changes were sustained for six months. In the whole study population, no significant changes were observed in the NT-proBNP, hsTnT, or hsCRP for six months. However, in 11 cases who showed a positive (> 0.003 ng/mL) hsTnT at baseline, a significant reduction in the hsTnT was observed (0.016 ± 0.020 ng/mL to 0.014 ± 0.020 ng/mL, P < 0.05), and its percent reduction significantly correlated with the percent increase in HDL-C (r = -0.68, P < 0.05)., Conclusions: MMD (positive hsTnT) was observed in more than half of patients with low HDL-C despite the administration of any statin, and the replacement of their previous statin with pitavastatin further improved their lipid profiles and led to better myocardial protection, possibly mediated via the elevation of the HDL-C level.

A nationwide statistical survey of 4226 dialysis facilities was conducted at the end of 2010, and 4166 facilities (98.6%) responded. The number of new patients introduced into dialysis was 37,512 in 2010. This number has decreased for two consecutive years since it peaked in 2008. The number of patients who died in 2010 was 28,882, which has been increasing every year. The number of patients undergoing dialysis at the end of 2010 was 298,252, which is an increase of 7591 (2.6%) compared with that at the end of 2009. The number of dialysis patients per million at the end of 2010 was 2329.1. The crude death rate of dialysis patients in 2010 was 9.8%, and has been gradually increasing. The mean age of the new patients introduced into dialysis was 67.8 years and the mean age of the entire dialysis patient population was 66.2 years. Regarding the primary disease of the new patients introduced into dialysis, the percentage of patients with diabetic nephropathy was 43.6%, which is a slight decrease from that in the previous year (44.5%). Patients with diabetic nephropathy as the primary disease accounted for 35.9% of the entire dialysis patient population, which approaches the percentage of patients with chronic glomerulonephritis as the primary disease (36.2%). The percentage of patients who had undergone carpal tunnel release surgery (CTx) was 4.3%, which is a slight decrease from that at the end of 1999 (5.5%). The decrease in the percentage of patients who had undergone CTx was significant among the patients with dialysis durations of 20-24 years (1999, 48.0%; 2010, 23.2%). A total weekly Kt/V attributable to peritoneal dialysis and their residual functional kidney was 1.7 or higher for 59.4% of patients who underwent peritoneal dialysis., (© 2012 The Authors. Therapeutic Apheresis and Dialysis © 2012 International Society for Apheresis.)

Background: Sleep disordered breathing (SDB) is highly prevalent in patients with cardiovascular disease, although it is not clear whether SDB has any link to coronary atherosclerotic burden in patients with stable coronary artery disease (CAD). This study sought to analyze the links between SDB, coronary atherosclerotic burden, and cardiac biomarkers in stable CAD patients., Methods and Results: We studied 83 consecutive patients who underwent coronary angiography or scheduled percutaneous coronary intervention. SDB was evaluated by an ambulatory polysomnographic monitoring device. Coronary atherosclerotic burden was evaluated by the Gensini score, and myocardial stress/injury were assessed by measuring plasma levels of N-terminal pro-B-type natriuretic peptide (NT-proBNP) and high sensitivity troponin T (hs-TnT). Patients with an apnea hypopnea index (AHI)≧15 events/h (n=32) showed significantly higher Gensini score (35.7±38.0 vs 20.1±19.7, p=0.033) than those with AHI<15. The higher AHI group showed significantly higher NT-proBNP (275.8±402.6 pg/ml vs 131.9±146.3 pg/ml, p=0.047) and hs-TnT levels (0.011±0.005 ng/ml vs 0.008±0.003 ng/ml, p=0.015). Furthermore it was revealed that AHI significantly correlated with the Gensini score (r=0.253, p=0.036), NT-proBNP (r=0.266, p=0.027), and hs-TnT (r=0.274, p=0.023), and multiple stepwise linear regression analysis revealed that AHI (β=0.257, p=0.029) and history of smoking (β=0.244, p=0.038) were independently correlated with Gensini score among clinical and SDB-related parameters., Conclusions: Severity of SDB has a significant link to the severity of coronary atherosclerotic burden, which also reflected elevated NT-proBNP and hs-TnT as silent myocardial ischemia and minute myocardial injury even in stable CAD patients., (Copyright © 2012 Japanese College of Cardiology. Published by Elsevier Ltd. All rights reserved.)

In Japan, a revised Food Recycling Law went into effect in 2007 to promote a "recycling loop" that requires food industries to purchase farm products that are grown using food waste-derived compost/animal feed. To realize and expand food recycling, it is necessary to evaluate how the recycling facilities work in the recycling loop. The purpose of this study is to assess the environmental and economic efficiency of the food recycling facilities that are involved in the recycling loop, which are also known as looped facilities. The global warming potential and running cost of five looped facilities were evaluated by LCA (life cycle assessment) and LCC (life cycle cost) approaches: machine integrated compost, windrow compost, liquid feed, dry feed, and bio-gasification. The LCA results showed low total GHG (greenhouse gas) emissions of -126 and -49 kg-CO(2)/t-waste, respectively, for dry feed and bio-gasification facilities, due to a high substitution effect. The LCC study showed a low running cost for composting facilities of -15,648 and -18,955 yen/t-waste, respectively, due to high revenue from the food waste collection. It was found that the mandatory reporting of food waste emitters to the government increased collection fees; however, the collection fee in animal feed facilities was relatively low because food waste was collected at a low price or nutritious food waste was purchased to produce quality feed. In the characterisation survey of various treatment methods, the composting facilities showed a relatively low environmental impact and a high economic efficiency. Animal feed facilities had a wide distribution of the total GHG emissions, depending on both the energy usage during the drying process and the substitution effect, which were related to the water content of the food waste and the number of recycled products. In comparison with incineration, the majority of the food recycling facilities showed low GHG emissions and economic effectiveness. This paper also reported on the effects of recycling loops by comparing looped and non-looped animal feed facilities, and confirmed that the looped facilities were economically effective, due to an increased amount of food waste collection., (Copyright © 2012 Elsevier B.V. All rights reserved.)

Background: Intracranial artery calcification has been reported to be an independent risk factor for ischemic stroke. Also, existence of a positive correlation has been reported between the presence of arterial calcification and that of ischemic changes in the area supplied by such arteries. While intracranial artery calcification has frequently been observed on computed tomographic (CT) images of the brain in hemodialysis patients, its prevalence has not been reported previously. We investigated our hemodialysis outpatients to determine the prevalence of intracranial artery calcification in these patients in comparison with that in healthy controls., Methods: Brain CT examinations were performed in 107 patients under maintenance hemodialysis therapy. For comparison, 43 representatives of the general population who underwent a brain CT examination as part of a health checkup were also studied as control subjects., Results: Intracranial calcifications were more frequently found among hemodialysis patients (87.9%) than among control subjects (53.5%, P = 0.0003), and the prevalences of calcification in each of the intracranial arteries in the two groups were as follows: vertebral artery (65.5% vs. 25.6%, P = 0.0002), internal carotid artery (62.1% vs. 18.6%, P < 0.0001), basilar artery (34.5% vs. 34.9%, ns), anterior cerebral artery (0 vs. 2.3%, ns), middle cerebral artery (24.1% vs. 20.9%, ns), and posterior cerebral artery (5.2% vs. 4.7%, ns)., Conclusions: A much higher rate of intracranial artery calcification was observed in hemodialysis patients than in the general population, and the most frequently involved sites of calcification in these patients were the relatively large intracranial arteries.

The C-terminus of the G protein α subunit has a well-known role in determining the selective coupling with the cognate G protein-coupled receptor (GPCR). In fact, rhodopsin, a prototypical GPCR, exhibits active state [metarhodopsin II (MII)] stabilization by interacting with G protein [extra formation of MII (eMII)], and the extent of stabilization is affected by the C-terminal sequence of Gα. Here we examine the relationship between the amount of eMII and the activation efficiency of Gi mutants whose Giα forms have different lengths of the C-terminal sequence of Goα. The results show that both the activation efficiencies of Gi and the amounts of eMII were affected by mutations; however, there was no correlation between them. This finding suggested that the C-terminal region of Gα not only stabilizes MII (active state) but also affects the nucleotide-binding site of Gα. Therefore, we measured the activation efficiency of these mutants by MII at several concentrations of GDP and GTP and calculated the rate constants of GDP release, GDP uptake, and GTP uptake. These rate constants of the Gi mutants were substantially different from those of the wild type, indicating that the replacement of the amino acid residues in the C-terminus alters the affinity of nucleotides. The rate constants of GDP uptake and GTP uptake showed a strong correlation, suggesting that the C-terminus of Giα controls the accessibility of the nucleotide-binding site. Therefore, our results strongly suggest that there is a long-range interlink between the C-terminus of Giα and its nucleotide-binding site.

Background: Peripheral artery disease (PAD) is a common complication in hemodialysis patients. The ankle-brachial blood pressure index (ABI) has been widely used to screen for subclinical PAD. In the present study, we investigated the association between ABI and long-term (up to 8.8 years) mortality among hemodialysis patients., Methods: A total of 86 consecutive patients receiving maintenance hemodialysis who underwent an ABI examination between 2001 and 2003 were retrospectively enrolled in this study. Patients with an ABI of less than 0.9 were considered as having PAD; those with an ABI of more than 0.9 in both legs were considered as being free from PAD. We examined the relationship between mortality and several risk factors., Results: During the follow-up period, 43 deaths were recorded. In the univariate regression analysis, the mortality hazard ratio (HR) of patients with PAD was 1.67 (95% confidence interval [CI], 1.18-2.28). Other predictive variables for mortality included male gender, age, and diabetes mellitus (P = 0.006, P = 0.024, and P = 0.023, respectively). A multivariate Cox analysis identified PAD and male gender as independent predictors of mortality (P = 0.033 and P = 0.028, respectively). The impact of age and diabetes mellitus on mortality was no longer significant in the multivariate analysis., Conclusion: After a relatively long-term observation period, a multivariate analysis indicated that PAD acted independently of other risk factors, including advanced age and the presence of diabetes mellitus. ABI measurements can be used to identify high-risk hemodialysis patients requiring intensive follow-up care.

A nationwide statistical survey of 4196 dialysis facilities was conducted at the end of 2009, and 4133 facilities (98.5%) responded. The number of patients undergoing dialysis at the end of 2009 was determined to be 290 661, an increase of 7240 patients (2.6%) compared with that of 2008. The number of dialysis patients per million at the end of 2009 was 2279.5. The crude death rate of dialysis patients from the end of 2008 to the end of 2009 was 9.6%. The mean age of the new patients introduced into dialysis was 67.3 years old and the mean age of the entire dialysis patient population was 65.8 years old. Primary diseases such as diabetic nephropathy and chronic glomerulonephritis for new dialysis patients, showed a percentage of 44.5% and 21.9%, respectively. Based on the facilities surveyed, 84.2% of the facilities that responded to the questionnaire satisfied the microbiological quality standard for dialysis fluids for the Japanese Society for Dialysis Therapy (JSDT), with an endotoxin concentration of less than 0.05 EU/mL in the dialysis fluid. Similarly, 98.2% of the facilities surveyed satisfied another standard of the society of a bacterial count of less than 100 cfu/mL in the dialysis fluid. The facility survey indicated that the number of patients who were treated by blood purification by both peritoneal dialysis and extracorporeal circulation, such as hemodialysis, was 1720. Among the total number of patients, 24.8% were satisfied with the management target recommended in the treatment guidelines for secondary hyperparathyroidism. These standards are set by the JSDT, based on the three parameters, i.e. serum calcium concentration, serum phosphorus concentration, and serum intact parathyroid hormone concentration. According to the questionnaire, 9.8% of the patients were considered to have a complication of dementia., (© 2012 The Authors. Therapeutic Apheresis and Dialysis © 2012 International Society for Apheresis.)

Background: New bone metabolic markers have become available clinically for evaluating chronic kidney disease mineral and bone disorders (CKD-MBD). The aim of this study was to correlate these new bone metabolic markers with conventional markers in regular hemodialysis (HD) patients., Methods: One hundred forty three HD patients underwent cross-sectional assessment. Two bone formation markers, bone-specific alkaline phosphatase (BAP) and osteocalcin (OC), and one bone resorption marker, amino-terminal telopeptides of type 1 collagen (NTx), were selected for study., Results: Both circulating OC and NTx levels showed positive correlations with serum intact parathyroid hormone (iPTH) levels. The levels of NTx and OC showed a strongly positive correlation, although they are known to be markers of different aspects of bone metabolism: bone formation and resorption. Patients with high iPTH (≥300pg/mL) had significantly higher levels of all the three bone markers compared with patients with low or normal iPTH ., Conclusion: Serum OC and NTx levels may be useful markers of serum iPTH levels for evaluating bone turnover in HD patients and may eventually prove useful in the management of patients with CKD-MBD.

The standard measurement of parathyroid hormone (PTH) is the intact PTH (iPTH) assay, which is used for approximately 90% of Japanese dialysis patients. The iPTH assay reacts not only with 1-84 PTH, but also with large truncated fragments of non-1-84 PTH, including 7-84 PTH. On the other hand, the whole PTH assay is specific for 1-84 PTH. The aim of the current study was to define the validity of both whole and intact PTH assays. A total of 738 hemodialysis patients were enrolled from twelve dialysis services. The serum PTH level was evaluated by both intact and whole PTH assays simultaneously. Non-1-84 PTH was determined by subtracting the whole PTH value from that of the intact PTH assay. The median level of whole PTH was 121 pg/mL, and that of iPTH was 210 pg/mL. The whole PTH assay had a very high correlation with the iPTH assay (r = 0.870, P < 0.001). For 43 out of 738 patients (5.8%) the value for intact PTH-whole PTH was <0. Both assays significantly correlated with non-1-84 PTH (P < 0.001), while the iPTH assay, particularly, had a very high correlation with non-1-84 PTH (r = 0.791). As a whole, 18% of the total population was misclassified into a different Japanese guideline category. Stratified by Japanese guideline classifications, 28% of patients within an iPTH target range were misclassified. Using Bland-Altman plot analysis, as the serum PTH level increased, there was a large difference between two assays. Both PTH assays correlate strongly, although the whole PTH assay may be more useful for precise evaluation of PTH function than the iPTH assay., (© 2011 The Authors. Therapeutic Apheresis and Dialysis © 2011 International Society for Apheresis.)

Objective: We investigated the safety and feasibility of sorafenib in patients with end-stage renal disease undergoing hemodialysis by examining the influence of pharmacokinetic parameters to their benefit and also the occurrence of drug-related adverse events of sorafenib., Methods: Ten patients with metastatic renal cell carcinoma undergoing hemodialysis received sorafenib. Initial dose was 200 mg once daily, and the dose was increased up to the maintenance dose of 200 mg twice daily. The pharmacokinetic study was performed after a steady state was reached with 200 mg twice daily in six patients., Results: Complete response occurred in one patient, partial response in three, stable disease in four and progressive disease in two. Median progression-free survival was 6.3 months. Serious adverse events were found in nine patients, including a Grade 5 subarachnoid hemorrhage and a Grade 4 cerebellar hemorrhage. In the pharmacokinetic study, the geometric mean of maximum concentration and area under the curve from 0 to 10 h of plasma concentration were similar on the day of hemodialysis and the day off hemodialysis. These data were lower than those from Japanese people with healthy kidneys and normal kidney function. There was no association between objective response or the occurrence of serious adverse events and pharmacokinetic parameters., Conclusions: Treatment with sorafenib of patients with metastatic renal cell carcinoma undergoing hemodialysis appears to be feasible, but we express some concern about the higher incidence of serious adverse events even with the reduced dose. However, clinical efficacy was not compromised.

Frequently, focal segmental glomerulosclerosis (FSGS) recurs after renal transplantation, resulting in poor graft survival. Pathological mechanisms of the recurrence are still unknown, but both B and T cell disorders are suspected based on much evidence. This supports theoretical benefits using plasma exchange (PE) and lymphocytapheresis (LCAP). A renal transplant was performed for a 35-year-old woman, who suffered steroid-resistant FSGS and developed to chronic kidney disease stage 5D at 31 years old. We treated the patient with recurrent FSGS by LACP and examined whether peripheral neutrophils were dynamically changed after the therapy. Further, we performed flowcytometric analysis to examine lymphocyte fractions before and after LCAP. The decrease of helper (CD4 positive) and memory (CD4 and CD45RO positive) T cells was prominent after LCAP. Although B cells were at the nadir because of rituximab treatment, LCAP also decreased peripheral B cells. These suggest that LCAP has the potential to suppress the activities of recurrent FSGS after renal transplant.

A nationwide statistical survey of 4124 dialysis facilities was conducted at the end of 2008 and 4081 facilities (99.0%) responded. The number of patients undergoing dialysis at the end of 2008 was determined to be 283,421, an increase of 8179 patients (3.0%) compared with that at the end of 2007. The number of dialysis patients per million at the end of 2008 was 2220. The crude death rate of dialysis patients from the end of 2007 to the end of 2008 was 9.8%. The mean age of the new patients begun on dialysis was 67.2 years and the mean age of the entire dialysis patient population was 65.3 years. For the primary diseases of the new patients begun on dialysis, the percentages of patients with diabetic nephropathy and chronic glomerulonephritis were 43.3% and 22.8%, respectively. Among the facilities that measured bacterial count in the dialysate solution in 2008, 52.0% of facilities ensured that a minimum dialysate solution volume of 10 mL was sampled. Among the patients treated by facility dialysis, 95.4% of patients were treated three times a week, and the average time required for one treatment was 3.92 ± 0.53 (SD) h. The average amounts of blood flow and dialysate solution flow were 197 ± 31 and 487 ± 33 mL/min, respectively. The number of patients using a polysulfone membrane dialyzer was the largest (50.7%) and the average membrane area was 1.63 ± 0.35 m(2). According to the classification of dialyzers by function, the number of patients using a type IV dialyzer was the largest (80.3%). The average concentrations of each electrolyte before treatment in patients treated with blood purification by extracorporeal circulation were 138.8 ± 3.3 mEq/L for serum sodium, 4.96 ± 0.81 mEq/L for serum potassium, 102.1 ± 3.1 mEq/L for serum chloride, and 20.7 ± 3.0 mEq/L for HCO(3) (-) ; the average serum pH was 7.35 ± 0.05. Regarding the type of vascular access in patients treated by facility dialysis, in 89.7% of patients an arteriovenous fistula was used and in 7.1% an arteriovenous graft was used. The percentage of hepatitis C virus (HCV)-positive patients who were HCV-negative in 2007 was 1.04%; the percentage is particularly high in patients with a period of dialysis of 20 years or longer. The risk of becoming HCV-positive was high in patients with low serum creatinine, serum albumin, and serum total cholesterol levels, and/or a low body mass index before beginning dialysis., (© 2010 The Authors. Journal compilation © 2010 International Society for Apheresis.)