Peritoneal Dialysis Registry With 2013 Survey Report.

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).

Retinal orientation and interactions in rhodopsin reveal a two-stage trigger mechanism for activation.

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 ß-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.

Free backbone carbonyls mediate rhodopsin activation.

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.

[Roles of and Team Medical Care Involving Clinical Engineers in Blood Purification Therapy].

Progress in medical care strongly depends on the development of pharmaceutical and medical technologies. Multi-disciplinary care by a medical team is required for the diversity of medical care. "Clinical engineering technician (CET) " is one of the national medical licenses in Japan. Many CETs are engaged in blood purification therapies. Team medical care, involving medical doctors, nurses, CETs, etc., in the hemodialysis field is useful for the early detection of complications in dialysis patients and provision of appropriate treatments. In some medical facilities, for example, progressive approaches such as appropriate nutritional guidance by a dietitian or exercise therapy by a physical therapist are practiced in advance. Clinical laboratory technologists (CLTs), furthermore, play an important role in team medical care for dial- ysis therapy. They can use ultrasonic equipment for vascular access management. Based on the results of the ABI and SPP measurements by CLTs, medical doctors can diagnose PAD in dialysis patients. [Review].

Differences in the Characteristics of Dialysis Patients in Japan Compared with Those in Other Countries.

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.

Uncovering the triggers for GPCR activation using solid-state NMR spectroscopy.

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.

Sequential structural changes in rhodopsin occurring upon photoactivation.

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.

Peritoneal Dialysis Registry With 2012 Survey Report.

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.

An Overview of Regular Dialysis Treatment in Japan (As of 31 December 2013).

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).

An overview of regular dialysis treatment in Japan (as of 31 December 2012).

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).

Associations among epoetin therapy, inflammation, nutritional status, and mortality in patients on hemodialysis.

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.

Pruritus in hemodialysis patients: Results from the Japanese Dialysis Outcomes and Practice Patterns Study (JDOPPS).

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.

Gender, low Kt/V, and mortality in Japanese hemodialysis patients: opportunities for improvement through modifiable practices.

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.

Overview of regular dialysis treatment in Japan (as of 31 December 2011).

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.

Effects of the ankle-brachial blood pressure index and skin perfusion pressure on mortality in hemodialysis patients.

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.

Study of discrepancies between recorded and actual blood flow in hemodialysis patients.

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.

Membrane peroxidation and methemoglobin formation are both necessary for band 3 clustering: mechanistic insights into human erythrocyte senescence.

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.

Patient selection and prescription of on-line HDF in Japan.

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.

An overview of regular dialysis treatment in Japan (as of 31 December 2010).

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.

The C-terminus of the G protein α subunit controls the affinity of nucleotides.

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.