稲熊 大城

In dialysis patients, physical function is associated with mortality. However, the association between physical function at the time of dialysis initiation and subsequent mortality remains unknown. A total of 1496 patients with chronic kidney disease who initiated dialysis at 17 centers participating in the Aichi Cohort Study of the Prognosis in Patients Newly Initiated into Dialysis, a multicenter prospective cohort study, were included. The patients were divided into the high (H)-, middle (M)-, and low (L)-score groups according to Barthel index (BI) at the time of dialysis initiation, and the all-cause, cardiovascular disease (CVD)-related, and infection-related mortality rates were compared. Moreover, factors affecting all-cause mortality were investigated. The effects of BI on mortality were assessed in the patients stratified by age, sex, and history of CVD or cerebral infarction. A log-rank test for the Kaplan-Meier survival curve showed significant differences between the three groups in all-cause, CVD-related, and infection-related mortality rates (p < 0.001). Cox proportional hazard regression analysis with the step-wise method showed a significantly higher risk of all-cause mortality in the M and L groups than in the H group (M group: HR 1.612, 95 % CI 1.075-2.417; L group: HR 1.994, 95 % CI 1.468-2.709). Regardless of the age categories and the history of CVD, the risk of all-cause mortality was significantly higher in the L group than in the H group. Physical function assessed by BI at the time of dialysis initiation was found to be associated with subsequent mortality.

Chronic kidney disease (CKD) eventually progresses to end-stage renal disease (ESRD). However, risk factors associated with CKD progression have not been well characterized in Japanese patients with CKD who are less affected with coronary disease than Westerners. A large-scale, multicenter, prospective, cohort study was conducted in patients with CKD and under nephrology care, who met the eligibility criteria [Japanese; age 20-75 years; and estimated glomerular filtration rate (eGFR): 10-59 mL/min/1.73 m(2)]. The primary endpoint was a composite of time to a 50 % decline in eGFR from baseline or time to the initiation of renal replacement therapy (RRT). The secondary endpoints were the rate of decline in eGFR from baseline, time to a 50 % decline in eGFR from baseline, time to the initiation of RRT, and time to doubling of serum creatinine (Cre) concentration. 2966 patients (female, 38.9 %; age, 60. 3 +/- 11.6 years) were enrolled. The incidence of the primary endpoint increased significantly (P < 0.0001) in concert with CKD stage at baseline. The multivariate Cox proportional hazards models revealed that elevated systolic blood pressure (SBP) [hazard ratio (HR) 1.203, 95 % confidence interval (CI) 1.099-1.318)] and increased albumin-to-creatinine ratio (UACR >= 1000 mg/g Cre; HR: 4.523; 95 % CI 3.098-6.604) at baseline were significantly associated (P < 0.0001, respectively) with the primary endpoint. Elevated SBP and increased UACR were risk factors that were significantly associated with CKD progression to ESRD in Japanese patients under nephrology care. UMIN clinical trial registry number: UMIN000020038.

Over 300,000 patients receive maintenance dialysis in Japan; managing these patients is extremely important. This study aimed to report on prior management of chronic kidney diseases and prognostication after dialysis initiation. Seventeen institutions participated in the Aichi cohort study of prognosis in patients newly initiated into dialysis and recruited patients over a period of 2 years. Exclusion criteria were (1) patients under 20 years; (2) patients who died before hospital discharge; and (3) patients who could not provide consent. Here, we showed data on dialysis initiation time. Of 1524 patients with mean age of 67.5 +/- 13.0 years, 659 patients were put on dialysis following diabetic nephropathy diagnosis. At dialysis initiation time, creatinine and estimated glomerular filtration rate levels were 8.97 +/- 3.21 mg/dl and 5.45 +/- 2.22 ml/min/1.73 m(2), respectively. Medications taken were angiotensin II receptor blockers in 866; angiotensin-converting enzyme inhibitors in 135; calcium antagonist in 1202; and diuretics, alone or in combination, in 1059. Among patients with diabetic nephropathy, many had increased body weight and systolic blood pressure and were taking loop and thiazide diuretics at dialysis initiation time. Many patients with diabetic nephropathy had coronary artery disease and percutaneous coronary intervention. Many patients with diabetic nephropathy who registered for this study had coronary artery disease and problems with excess body fluid. Further analyses may clarify how underlying conditions and disease management before and after dialysis initiation affect prognosis.

Background: Death in dialysis patients results mainly from cardiovascular and cerebrovascular diseases. To our knowledge, no prospective study has compared the rates of mortality or cardiovascular events between patients with and without atrial fibrillation (AF) at the time of dialysis initiation. Methods: This study included 1,516 patients who were initiated into dialysis between October 2011 and August 2013. Rates of mortality and cardiovascular events were compared between patients with and without AF, and between AF patients with and without warfarin (WF) treatment. Results: The study comprised 1,025 men and 491 women with a mean age of 67.5 +/- 13.1. Of these patients, 93 had AF, while 1,423 did not; 22.6% of the former group and 9.7% of the latter group died by March 2014 (p < 0.01). Cardiovascular events occurred in 34.4% of patients with AF and 15.1% of patients without (p < 0.01). Even after adjustments for various factors, AF remained an independent risk factor for mortality (hazard ratio (HR) 1.873, 95% CI 1.168-3.002, p < 0.01). It was also an independent risk factor for cardiovascular events (HR 1.872, 95% CI 1.262-2.778, p < 0.01). No difference in any parameter was noted between the groups that did and did not receive WF treatment. Conclusion: Patients with AF at the time of dialysis initiation show a poor prognosis and are at high risk of cardiovascular events. Therefore, AF should be taken into consideration in dialysis patients. (C) 2016 S. Karger AG, Basel

Background: Recently, sleep apnea syndrome (SAS) has been associated with hypertension, cardiovascular disease and death. Patients with chronic kidney disease (CKD) have higher rates of SAS, atherosclerotic complications and death than do patients without CKD. Although the relationship between SAS and atherosclerosis is well known, few papers have described this relationship in humans, especially in CKD patients. Patients and Methods: This was a cross-sectional study of 110 clinically stable, non-dialysis patients with CKD who attended a CKD educational program from April 2014 to September 2015. The diagnosis of SAS and its severity were assessed using a type 3 portable monitor. Other atherosclerosis-related data were obtained from the patients' medical records in order to determine the factors associated with the severity of SAS. Results: 95 men and 15 women with a mean age of 71.4 +/- 9.9 years were included in the study. The patients' mean body mass index was 24.0 +/- 3.9, their mean blood pressure 134.3 +/- 21.2/73.6 +/- 13.4 mm Hg and their mean estimated glomerular filtration rate 19.8 +/- 9.5 ml/min/1.7 m(2). Adjusted plaque score was a significant predictor of severe SAS (odds ratio = 1.13, p = 0.0182). Mixed plaque was significantly associated with severe SAS (correlation ratio = 0.48, p < 0.0001). Conclusions: Many patients with CKD also have SAS. Our findings demonstrate the relationship between plaque score and the severity of SAS. (C) 2016 S. Karger AG, Basel

Background: Vitamin D receptor activator (VDRA) administration has been linked with a reduced incidence of cardiovascular disease (CVD). However, it is unclear whether VDRA administration during the predialysis stage is associated with CVD incidence after dialysis initiation in patients with chronic kidney disease. Therefore, we examined the association between VDRA use and CVD events. Methods: This multicenter observational study included 1,516 patients; they were divided into 2 groups: those who did and did not receive oral VDRA for at least 3 months before dialysis initiation. The CVD incidence was compared between these groups. Factors that impacted CVD incidence were extracted through a multivariate analysis. Subgroups were created based on prior CVD history and serum CRP levels. Results: The incidence of CVD was significantly lower in the VDRA group (log-rank test, p = 0.014). Stepwise multivariate analyses identified age, gender, diabetes, CVD history, calcium channel blockers, beta-blockers, loop diuretics, anti-platelet agents, phosphate binders, VDRA, erythropoiesis stimulating agents, and cardiothoracic ratio as factors affecting CVD incidence. In the group with no CVD history, VDRA use was associated with a low incidence of CVD (HR 0.35). In the group with serum CRP levels <1.0 mg/dl, VDRA use was associated with a low incidence of CVD (HR 0.47). Conclusion: Administration of VDRA during predialysis was associated with a low incidence of CVD onset after dialysis initiation. (C) 2016 S. Karger AG, Basel.

Background: Preventive medications for dialysis-requiring congestive heart failure (CHF) in non-dialysis Japanese patients with Stage 5 chronic kidney disease (CKD) are unknown. Our aim was to explore which CKD medication was associated with a reduced prevalence of dialysis-requiring CHF in non-dialysis Japanese patients with Stage 5 CKD. Methods: The present multicenter, retrospective, cross-sectional study examined the association between CKD medications and the prevalence of dialysis-requiring CHF in non-dialysis Japanese patients with Stage 5 CKD. Results: There were 1536 Japanese Stage 5 CKD patients who satisfied our inclusion criteria. We had 309 (20.1%) patients whom had developed dialysis-requiring CHF and 940 patients (60.8%) whom had been using angiotensin-II receptor blockers (ARBs) before initiating dialysis. In our multivariate analysis, only ARB use was significantly associated with a lower risk of CHF (Odds ratio (OR): 0.680, 95% confidence interval (CI): 0.516-0.897; p = 0.0064), of the CKD treatments examined in this study. Conclusions: We found that ARB use during the pre-dialysis period is associated with a lower prevalence of CHF in the non-dialysis Japanese patients with Stage 5 CKD, suggesting a possible prevention of dialysis-requiring CHF by ARBs, in non-dialysis Japanese patients with Stage 5 CKD.

Vitamin D deficiency is common among patients with chronic kidney disease (CKD). However, the benefits of vitamin D supplementation versus vitamin D receptor activator (VDRA) administration have yet to be established. Recently, an association between activated vitamin D and cardiovascular factors was reported. To evaluate the benefits of VDRA in advanced CKD, we analyzed the association between VDRA administration and the prevalence of pulmonary congestion. This retrospective, cross-sectional analysis included patients initiated on dialysis between October 2011 and September 2013 at 17 Japanese institutions. Data from 952 participants were analyzed using a multivariate logistic regression model and a linear regression model. We also analyzed subgroup data for groups classified by selection of peritoneal dialysis or hemodialysis. Of the 952 participants, 303 patients received VDRA. VDRA administration was associated with a low prevalence of pulmonary congestion in the multivariate logistic regression model (odds ratio [OR], 0.64; 95 % confidence interval [CI], 0.44-0.94; P = 0.02). There was no significant association between VDRA administration and systolic blood pressure, diastolic blood pressure, or pulse pressure. Subgroup analysis revealed a tendency that VDRA administration was associated with low prevalence of pulmonary congestion in both groups. In this study, VDRA administration was associated with a low prevalence of pulmonary congestion in patients initiated on dialysis. Appropriate VDRA administration may prevent pulmonary congestion.

Recently, preemptive kidney transplantation (PKT) has increased in Japan; however, the effects of PKT on calcium (Ca) and phosphorus (Pi) metabolism are poorly understood. Thirty-two consecutive patients were enrolled in this study at Nagoya Daini Red Cross Hospital. Fifteen patients were in the PKT group and 17 patients were in the non-PKT group. Parameters of Ca and Pi metabolism, including fibroblast growth factor (FGF) 23 and intact parathyroid hormone, were measured before transplantation and 1, 3, and 24 weeks after transplantation. FGF 23 decreased dramatically in both groups after transplantation; however, FGF 23 before transplantation and at 1 and 3 weeks after transplantation was significantly lower in the PKT group than in the non-PKT group (p < 0.05). Although iPTH levels were higher in the PKT group than in the non-PKT group before transplantation, these levels were lower in the PKT group at 24 weeks after transplantation (p < 0.05). Corrected Ca was lower at 24 weeks in the PKT group (p < 0.05), whereas Pi was lower in the non-PKT group at 1 and 3 weeks (p < 0.05), but not significantly different at 24 weeks. Multivariate linear regression analysis revealed that FGF 23 before transplantation was the strongest predictor of Ca and Pi disorders in early post-transplant recipients. This study suggests that PKT has beneficial effects on Ca and Pi metabolism and pre-transplant FGF 23 levels are a good marker of post-transplant Ca and Pi metabolism disorders.

Context: PTH is a critical factor in mineral homeostasis, and chronic kidney disease mineral and bone metabolism disorder is a very important problem in patients with renal failure. Abnormal levels of PTH, serum phosphate, and calcium influence chronic kidney disease mineral and bone metabolism disorder, but there is little information about the influence of magnesium (Mg) on PTH. Objective: The aim of this study was to elucidate the correlation between magnesium and PTH levels in uremic patients just prior to beginning hemodialysis (HD) for the first time. Patients: We enrolled 1231 patients in nine Japanese facilities who had begun HD for end-stage renal disease. We investigated their serum Mg levels and the correlation between intact PTH (iPTH) and the serum Mg levels and other clinical parameters and medications. Results: The mean serum Mg was 2.2 +/- 0.5 mg/dL, and hypermagnesemia was found in 663 patients (53.9%). Divided into two groups according to median iPTH level, the serum Mg levels were significantly higher in patients with low iPTH (2.3 +/- 0.5 vs 2.1 +/- 0.5, P <.01). Furthermore, divided into two groups according to the Mg level, iPTH levels were lower in patients with high Mg than in patients with normal serum Mg levels (277.9 +/- 195.9 pg/mL vs 321.9 +/- 203.7 pg/mL, P <.01). In the multiple regression analysis according to the effect of iPTH level, the serum Mg level was an independent variable after adjustment for other factors. Conclusions: A high serum level of Mg is frequent in uremic patients with end-stage renal disease just prior to beginning HD. In the present set of patients, there was a significant correlation between the serum Mg and iPTH levels. Furthermore, the serum Mg level was an independent factor apart from the other factors regulating iPTH. These results suggest that serum Mg may be one of the factors regulating the serum PTH level in uremic patients.

With the recent increase in renal transplantations in Japan, accurate assessment of renal function is required. This study included 73 patients who had undergone renal transplantation at Nagoya Daini Red Cross Hospital at least 6 months previously and had stable renal function for > 3 months. Glomerular filtration rates (GFRs) were measured by inulin clearance (mGFR) and compared with estimated cystatin C-based GFRs (eGFRcys), estimated creatinine-based GFRs (eGFRcre) and their average values (eGFRave). mGFR was 43.3 +/- A 14.1 mL/min/1.73 m(2), eGFRcre was 39.6 +/- A 11.7, eGFRcys was 56.0 +/- A 17.1, and eGFRave was 47.8 +/- A 13.7 mL/min/1.73 m(2). Serum cystatin C was 1.39 +/- A 0.37 mg/L and serum creatinine was 1.58 +/- A 0.51 mg/dL. The correlation coefficients between mGFR and eGFRcre, eGFRcys, and eGFRave were 0.768, 0.831, and 0.841, respectively (P < 0.001, for all).The intraclass correlation coefficients were 0.754, 0.816, and 0.840, respectively (P < 0.001, for all).The mean differences between measured and estimated GFR values were 3.74 mL/min/1.73 m(2) with a root-mean square error (RMSE) of 9.06 for eGFRcre, +12.64 with RMSE of 9.48 for eGFRcys, and +4.45 with RMSE of 7.86 for eGFRave. Bland-Altman plots showed that eGFRcys overestimated GFR values compared with mGFR values in most cases and that eGFRave overestimated GFR values in 53 of 73 cases, whereas eGFRcre underestimated the values in 53 of 73 cases. eGFRave may be the best marker to estimate kidney function in Japanese renal transplant recipients with mildly reduced or normal kidney function.

Background/Aim: The present study explores associations between hemoglobin (Hb) levels and patients with cardiac enlargement in end-stage kidney disease (ESKD) to help prevent cardiac remodeling during the predialysis phase of chronic kidney disease (CKD). Methods: This cross-sectional study included 2,249 patients with ESKD (age, 67 +/- 13 years; male, 67%; diabetic kidney disease, 41%) who started hemodialysis (HD) between January 2006 and October 2013 at eight participating hospitals. We examined associations between Hb levels immediately before the first HD session and cardiothoracic ratios (CTRs). Clinical factors associated with the CTR were also assessed. Results: The mean Hb level was 8.7 +/- 1.6 g/dl, and the mean and median CTRs were 55.0 and 54.7%, respectively. The correlation between the Hb level and the CTR was linear and negative (r = -0.129, p < 0.001). The mean CTR and the prevalence of patients with a CTR >50% obviously decreased with increasing Hb levels (both p < 0.001 for trend). Univariate logistic regression analysis revealed an approximately 20% reduction in the odds ratio for complicating CTRs >50% per 1 g/dl increase in Hb. Hb levels of <9 g/dl were significantly associated with CTRs >50%. Numerical and categorical Hb remained significantly associated with CTRs >50% after adjusting for confounding variables. Conclusions: Lower Hb levels participate in progressive CTR enlargement in patients with ESKD, and maintaining Hb levels of >9 g/dl might help prevent cardiac remodeling during the predialysis phase of CKD. (C) 2014 S. Karger AG, Basel

The C4d staining as a special tissue marker for humoral immunity has served criteria of pathological diagnosis for antibody-mediated rejection (ABMR) in Banff classification since 2003. However, the sensitivity and specificity of C4d staining have been questioned, and recently, C4d-negative ABMR has been more focused in renal allograft pathology. The aim of this study was to make certain of C4d staining for ABMR that was diagnosed by clinical and morphological findings. C4d staining was employed by immunofluorescence. This study included 14 patients with acute ABMR and 16 with chronic active ABMR. Eight of acute ABMR were ABO-blood-type-incompatible renal transplantation (ABOinRTx) pre-treated by DFPP and splenectomy or rituximub. In acute ABMR after ABOinRTx, C4d staining along peritubular capillary (PTC) was positive in five of them (62.5%). Only one graft biopsy of five acute ABMR with donor-specific antibody (DSA) showed C4d positive. We assembled 16 graft biopsies showing typical transplant glomerulopathy and thickened PTC basement membrane with peritubular capillaritis as a suspicious pathological chronic active ABMR. Four of eight DSA-positive patients were C4d negative in PTC; however, three of four DSA-positive and C4d-negative patients in PTC chronic active ABMR were C4d positive in only glomerular capillaries. C4d positivity could not come to a specific marker of ABMR diagnosing based on clinically and ordinary morphological findings.

Background: The goal of the present study was to explore the effect of medications that are commonly prescribed for CKD patients on uremic state. Methods: This was a cross-sectional study. From January 2006 to October 2009, 1,623 patients with end-stage kidney disease (ESKD) commenced hemodialysis (HD) at the 9 participating hospitals. The criteria for exclusion from the database were 1) serum C-reactive protein (CRP)> 3 mg/dL, 2) WBC count > 9,000/mm(3) or < 4,000/mm(3), and 3) patients with cancer, immune complex disease, or vasculitis. A total of 900 patients were entered into the final database. We explored the association of serum CRP just before the first HD session with clinical characteristics, laboratory data, and medications for CKD in the predialysis period. Results: On univariate analysis, age, CTR, eGFR, and WBC were significantly correlated with CRP. Systolic and diastolic blood pressure, serum albumin, LDL-C, HDL-C, Hb, Cr, and Ca were inversely associated with CRP. Use of erythropoietin-stimulating agents (ESA) using (r = -0.111, p = 0.0015), renin-angiotensin-aldosterone system inhibitors (r = -0.083, p = 0.0154), and calcium channel blockers (r = -0.1, p = 0.0039) was also negatively correlated with CRP. However, only use of ESA showed a significant negative correlation with CRP that was independent of other clinical factors and CKD medications on multiple regression analysis. Conclusion: ESA may strongly reduce uremic inflammation in addition to improving anemia. To confirm this potential effect, a large-scale longitudinal study would be required.

The aim of this study was to investigate the factors influencing serum parathyroid (PTH) levels, including medications for treating chronic kidney disease-mineral and bone metabolism disorder (CKD-MBD) in patients with end-stage renal disease. We enrolled 1,076 patients in nine Japanese facilities who had begun hemodialysis (HD) due to ESRD. We investigated the relationships between intact PTH (iPTH) levels and clinical parameters and medications just prior to beginning HD. Significant decreases in serum iPTH levels were seen in males, in the presence of diabetes mellitus (DM), and with administration of renin-angiotensin system inhibitors (RASIs). Significant correlations were found between serum calcium and iPTH levels. In the patients administered RASIs, there was a significant decrease in serum iPTH levels with DM, male gender, and administration of active vitamin D sterols (VDs) compared with those not administered RASIs, although serum-corrected calcium levels were not different. Multiple regression analysis found gender, age, presence of DM, and serum calcium and phosphate levels to be significant contributing factors. In addition, administration of angiotensin II receptor blockers (ARBs) may also be a contributing factor to iPTH levels at the beginning HD (p = 0.050). In this study, serum iPTH levels were related to administration of ARBs besides gender, age, the presence of DM and serum calcium levels. Our study suggests that the RA system involve serum iPTH levels in uremic patients.

Acute glomerulonephritis (AGN) is one of the most common renal diseases. They are often associated with infections and can result in diffuse proliferative glomerulonephritis (GN). This case report reviews an interesting case in which renal endarteritis coexisted in AGN with diffuse endocapillary proliferation. The discussion highlights important pathological findings and clinical aspects in acute endocapillary proliferative GN with renal endarteritis. Coexisting endarteritis should be in the differential diagnosis of AGN in patients with persistent clinical courses.

Background In Japan, the population of patients on peritoneal dialysis (PD) is <4% of the total number of patients with end-stage renal disease. Few systemic analyses have examined why the number of PD patients has not increased in Japan. We organized a registry to analyze PD patients and retrospectively investigated 561 PD patients (about 5% of all Japanese PD patients) from 13 hospitals in the Tokai area for 3 years from 2005. Methods We investigated background, physical status, laboratory data, status of PD therapy, and the occurrence of PD-related complications, and analyzed reasons for withdrawal from PD. Results Nutrition did not change significantly during our observation. Urinary volume showed continued decreases after the introduction period. In contrast, PD fluid demand and ultrafiltration volume were significantly increased. For calcium metabolism, multiple phosphate binders were required after the second year of PD therapy. Early dropout within 3 years after starting PD therapy comprised 50.9% of total withdrawals, with PD-related peritonitis as the most common reason, mainly caused by Gram-positive organisms. Incidence of peritonitis was 42.8 months/patient. Culture-negative results were obtained for 32% of peritonitis cultures. Diabetes affects the prognosis of PD therapy, but not the incidence of peritonitis. Conclusion We examined clinical status over 3 years in the Tokai area. The results suggest that the incidence of peritonitis needs to be decreased to prevent early withdrawal of PD patients. Education systems to decrease the incidence of peritonitis and techniques to decrease culture-negative results might be important for improving the prognosis of peritonitis.

The Banff 2007 classification allows chronic rejection to be differentiated based on clinicopathological characteristics evidenced by two independent immunologic mechanisms; chronic active antibody-mediated rejection and chronic active T-lymphocyte mediated rejection. However, several incompletely understood issues concerning chronic active antibody-mediated rejection remain. Chronic active antibody-mediated rejection is characterized by C4d deposition in the capillary basement membrane(PTC), the presence of circulating anti-donor antibodies(DSA), and morphologic evidence of chronic tissue injury such as glomerular double contours compatible with transplant glomerulopathy (TPG), PTC basement membrane multilayering, interstitial fibrosis/tubular atrophy, and fibrous arterial intimal thickening. PTC basement membrane multilayering correlates highly with TPG, and most of TPG have evidence of either C4d-positive staining or DSA. However, the proposed criteria do not apply to all situations of chronic active antibody-mediated rejection. C4d is not a magic marker for antibody-mediated rejection. C4d staining is not always highly sensitive for detecting antibody-mediated rejection. Multi-institutional studies should be conducted to better understand the clinicopathological context of chronic antibody-mediated rejection. These studies should include well-designed serial protocol biopsies with evaluation by electron microscopy, C4d staining performed on frozen sections, and assessment using sensitive DSA detection methods.

Darbepoetin alfa, which has a much longer half-life than recombinant human erythropoietin, is used to treat renal anemia. However, there are few reports investigating the efficacy of darbepoetin alfa administered every 2 weeks (Q2W). We performed the single-center, prospective, and randomized study in chronic hemodialysis patients. Clinically stable patients on hemodialysis were recruited, and darbepoetin alfa 15-40 mu g/week was administered intravenously once a week (QW) to achieve a hemoglobin (Hb) level of 10.5-12.0 g/dl for 8 weeks prior to randomization. The patients were randomly assigned to 2 different dosing frequency groups: once a week (QW) or every 2 weeks (Q2W). We switched to a double dose in the Q2W group. We measured Hb level every 2 weeks and administered darbepoetin alfa to achieve an Hb level of 10.5-11.5 g/dl. The primary endpoints were the weekly dose of darbepoetin alfa administered at week 24. We assigned 19 and 20 patients into QW and Q2W, respectively. There were no significant differences between the groups in Hb, transferrin saturation, ferritin, and weekly dose of darbepoetin alfa at end of the baseline period. There was no significant difference in Hb level at week 24, at which time the weekly dose requirement and dose per dry body weight were much higher in the Q2W than in the QW group. Administration of darbepoetin alfa Q2W could maintain Hb level similarly to to that obtained QW, but we did not confirm efficiency at a higher dose requirement or blood pressure elevation.

Anemia is common among patients with chronic kidney disease (CKD). The introduction of erythropoietin treatment has changed anemia management, but the therapeutic hemoglobin (Hb) target is still under debate, and clinical evidence for its effect on cardiac functions and QOL is sparse. A 16-week dose-response study and a 32-week follow-Up study were combined. After correcting anemia of less than 10 g/dl in pre-dialysis Japanese CKD patients, a higher Hb target (12-13 g/dl) by darbepoetin alfa (DPO) was compared with the conventional Hb target by epoetin alfa (EPO). Outcomes were anemia correction, management of the left ventricular mass index (LVMI) and QOL scores. No significant difference was seen in Hb at baseline and week 16, but a significant difference was recorded at week 34 (12.34 +/- A 0.93 g/dl for DPO and 10.43 +/- A 0.90 g/dl for EPO). In both groups, LVMI decreased similarly until week 16, but the decrease of EPO was retarded, and a significant difference between LVMI was seen only in DPO at week 34 (100.7 +/- A 16.6 g/m(2) for DPO and 110.9 +/- A 25.2 g/m(2) for EPO). Relationships between Hb and LVMI change at week 34 were examined by stratifying Hb into four groups (Hb < 10 g/dl, 10 g/dl a parts per thousand currency sign Hb < 11 g/dl, 11 g/dl a parts per thousand currency sign Hb < 12 g/dl and 12 g/dl a parts per thousand currency sign Hb), and a decrease of LVMI was prominent in the 12 g/dl a parts per thousand currency sign Hb group. Correction of anemia to 11 g/dl or more led to improved QOL scores. No safety difference was observed among the treatments. Targeting a higher Hb around 12 g/dl was more beneficial than targeting conventional Hb in terms of reduction of LVMI and QOL. Further studies to determine the appropriate Hb target are necessary.

Besides its effect on calcium metabolism, vitamin D may play a part in preventing the onset and progression of cardiovascular disease (CVD) events. Only a few reports on the studies relating to whether vitamin D may reduce CVD events in patients with predialysis chronic kidney disease (CKD) are available, and many ambiguities remain. We conducted a retrospective cohort study of 665 patients with predialysis CKD. With log-rank test using the Kaplan-Meyer survival curve, comparison of incidences of CVD events, CVD-related mortality, and all-cause mortality were made between patients in the alfacalcidol treatment group (107 patients) in the predialysis stage to whom alfacalcidol 0.25-0.5 mu g/day was orally administered for at least 24 weeks, and patients in the nontreatment group (558 patients) who received no administration of alfacalcidol or other type of activated vitamin D and its analogues. Patients to whom alfacalcidol administration was discontinued within 24 weeks as well as initiation of dialysis of < 24 weeks were excluded for this study. Factors relating to CVD events were examined using Cox's proportional hazards analysis. The mean follow-up period was 55.1 +/- A 38.9 months in the alfacalcidol treatment group and 41.9 +/- A 38.4 months in the nontreatment group. CVD events occurred in 172 patients during the follow-up period, and 74 of those occurred during the predialysis period. In the alfacalcidol treatment group, the incidence of cumulative CVD events was significantly lower. In relation to all-cause deaths and CVD-related deaths, the cumulative mortality rate was significantly lower in the alfacalcidol treatment group during the follow-up period. Throughout the follow-up period, the association between CVD events and alfacalcidol use was detected when adjusted for age, sex, diabetes, hypertension, use of renin-angiotensin system inhibitors, estimated glomerular filtration rate, and albumin and parathyroid hormone. These data showed that oral administration of alfacalcidol for predialysis CKD patients was associated with reduced risk for CVD.

Background It is known that vitamin D has many functions besides involvement in calcium metabolism. It has recently been recognized that vitamin D deficiency is associated with mortality, especially in cardiovascular disease (CVD). Vitamin D deficiency is common in end-stage renal disease, but develops from the early stage of chronic kidney disease (CKD). So we investigated whether the serum level of the activated form of vitamin D (1,25-dihydroxyvitamin D) affected mortality in patients with CKD stages 3 and 4. Methods Between January 1, 1995, and June 30, 2006 we measured serum 1,25-dihydroxyvitamin D In 226 patients with CKD stages 3 and 4 and classified the results into two groups depending on whether the level was below (group I) or above (group II) 20 pg/ml. We ended the follow-up period on December 31, 2006. We compared all-cause and cardiovascular mortality between the two groups. We also examined predictors of mortality by using Cox proportional regression analysis. Results Two-hundred and twenty-six patients (67 men and 159 women, mean age 67.0) were registered in this study, and groups 1 and 2 comprised 84 and 142 patients, respectively. During the follow-up period 43 patients died. CVD was the major cause of death, followed by infectious disease. The Kaplan-Meier survival curve revealed that all-cause mortality was significantly higher in group I, but a significant difference between CVD mortality in the two groups was not demonstrated. By Cox proportional regression analysis, group I was related to all-cause mortality, but this was not proved to be an independent predictor. Conclusion The results suggested that serum level of 1,25-dihydroxyvitamin D was associated with all-cause mortality in patients with CKD stages 3 and 4.

Background. The number of patients with end-stage renal disease (ESRD) in Japan has continuously increased in the past three decades. In 2005, 36 063 patients whose average age was 66 years entered a new dialysis program. This large number of ESRD patients could be just the tip of the iceberg of an increasing number of patients with chronic kidney disease (CKD). However, to date, a nationwide epidemiological study has not been conducted yet to survey the CKD population. Methods. Data for 527 594 (male, 211 034 female, 316 560) participants were obtained from the general adult population aged over 20 years who received annual health check programs in 2000-2004, from seven different prefectures in Japan: Hokkaido, Fukushima, Ibaraki, Tokyo, Osaka, Fukuoka, and Okinawa prefectures. The glomerular filtration rate (GFR) for each participant was estimated from the serum creatinine values, using the abbreviated Modification of Diet in Renal Disease (MDRD) study equation modified by the Japanese coefficient. Results. The prevalences of CKD stage 3 in the study population, stratified by age groups of 20-29, 30-39, 40-49, 50-59, 60-69, 70-79, and 80-89 years, were 1.4%, 3.6%, 10.8%, 15.9%, 31.8%, 44.0%, and 59.1%, respectively, predicting 19.1 million patients with stage 3 CKD in the Japanese general adult population of 103.2 million in 2004. CKD stage 4 + 5 was predicted in 200 000 patients in the Japanese general adult population. Comorbidity of hypertension, diabetes, and proteinuria increased as the estimated GFR (eGFR) decreased. The prevalence of concurrent CKD was significantly higher in hypertensive and diabetic populations than in the study population overall when CKD was defined as being present with an eGFR of less than 40 ml/min per 1.73 m2 instead of less than 60 ml/min per 1.73 m2. Conclusions. About 20% of the Japanese adult population (i.e., approximately 19 million people) are predicted to have stage 3 to 5 CKD, as defined by a GFR of less than 60 ml/min per 1.73 m2. © 2007 Japanese Society of Nephrology.

Background. As hypertension and diabetes mellitus increase, the number of patients developing complications of cardiovascular disease (CVD) associated with conventional risk factors is increasing. In addition to these risk factors for CVD, chronic kidney disease (CKD) has also been reported to play an important role. We investigated the association of representative ischemic heart disease and CKD. Methods. Between July 1, 2000, and June 30, 2005, a total of 790 patients who underwent percutaneous coronary intervention (PCI) for angina pectoris or myocardial infarction in our division of cardiovascular disease were reviewed. Serum markers at the implementation of PCI were compared in patients classified according to renal function. For prognosis, in-hospital mortality, 1-year survival rate, overall mortality, and CVD death were investigated. Changes in renal function were also monitored during the follow-up period. The glomerular filtration rate (GFR) was calculated by the Modification of Diet in Renal Disease Study Group (MDRD) formula. Results. The mean estimated GFR (eGFR) at PCI implementation was 66.2 ± 21.0 ml/min/1.73 m2. Stage 2 CKD was shown in 51.5% of all the patients. During the overall follow-up period, 126 patients died. With the progression of CKD stage, all-cause, CVD, and in-hospital mortality increased, and the 1-year survival rate decreased. It was proved that a medical history of hypertension, hyperlipidemia, and diabetes, multiple vessel lesions, hypoalbuminemia, C-reactive protein (CRP), and estimated GFR were independent risk factors for all-cause death. In CVD death, in addition to the above risk factors, anemia and total cholesterol were also an independent risk factor. Renal function deteriorated significantly during the follow-up period. Conclusions. Patients with ischemic heart disease requiring PCI often develop renal dysfunction, which may considerably affect prognosis. © 2007 Japanese Society of Nephrology.

Background. The purpose of the treatment and management of chronic renal failure during the predialysis period is mainly to retard the progression of the deterioration of renal function. Optimal dialysis initiation is important to improve the patient's outcome after therapy. We investigated whether providing information through an original educational program could facilitate dialysis initiation, with the patient in a better condition, and therefore greater cost-effectiveness. Methods. One hundred and seventy-six patients who underwent dialysis initiation for chronic renal failure in our hospital between April 2002 and March 2005 were divided into two groups according to their participation or nonparticipation in an educational program. Participation in the education program was of their own free will. The instructors consisted of nephrologists, nursing staff, clinical engineering technologists, national registered dietitians, and medical social workers. We investigated whether the education program facilitated trouble-free dialysis initiation by comparing findings of blood tests at the start, the existence of heart-failure symptoms, type of blood access, percentage of scheduled initiation, and the number of days and cost of hospitalization as indices between participating and nonparticipating groups. Results. The number of patients using a double-lumen dialysis catheter, and the duration and cost of hospitalization in training the participating group, were significantly less than those in the nonparticipating group. Although there was no significant difference in renal function at the initiation of renal replacement therapy (RRT) between the two groups, serum albumin, hemoglobin, and hematocrit in the participating group were significantly higher than those of the nonparticipating group. Conclusions. This study suggests that providing sufficient information before dialysis initiation may be effective in both physical condition at dialysis initiation, and medical economic benefits through the understanding of the dialysis. © 2006 Japanese Society of Nephrology.