In recent times, therapy for renal anemia has changed dramatically in that iron administration has increased and doses of erythropoiesis-stimulating agents (ESAs) have decreased. Here we used a prospective, observational, multicenter design and measured the serum ferritin and hemoglobin levels every 3 months for 2 years in 1086 patients on maintenance hemodialysis therapy. The associations of adverse events with fluctuations in ferritin and hemoglobin levels and ESA and iron doses were measured using a Cox proportional hazards model for time-dependent variables. The risks of cerebrovascular and cardiovascular disease (CCVD), infection, and hospitalization were higher among patients who failed to maintain a target-range hemoglobin level and who exhibited high-amplitude fluctuations in hemoglobin compared with patients who maintained a target-range hemoglobin level. Patients with a higher compared with a lower ferritin level had an elevated risk of CCVD and infectious disease. Moreover, the risk of death was significantly higher among patients with high-amplitude ferritin fluctuations compared with those with a low ferritin level. The risks of CCVD, infection, and hospitalization were significantly higher among patients who were treated with high weekly doses of intravenous iron compared with no intravenous iron. Thus, there is a high risk of death and/or adverse events in patients with hemoglobin levels outside the target range, in those with high-amplitude hemoglobin fluctuations, in those with consistently high serum ferritin levels, and in those with high-amplitude ferritin fluctuations.

To determine whether the onset of coronary artery disease may precede the initiation of dialysis in patients with end-stage renal disease, we performed coronary angiography within 1 month of initiation of maintenance haemodialysis in 24 patients (age range 42-78 years; mean 63.7 +/- 11). Coronary angiography was performed regardless of the absence or presence of angina. Fifteen patients had diabetic nephropathy, and nine had non-diabetic nephropathy. Significant coronary stenosis was defined as at least 75% narrowing of the reference segment. Fifteen patients (62.5%) with a total of 49 lesions were classified as the coronary artery disease present group. Eleven of those 15 (73.3%) had multivessel disease. The average number of stenotic lesions was 3.3 per patient. The most common patterns of stenosis were complex (23 lesions; 47%), and diffuse lesions over 20 mm long (14 lesions; 29%). None of the clinical or haematological factors evaluated differed significantly between the groups with and without coronary artery disease. The prevalence of coronary artery disease was 72.7% in the symptomatic patients and 53.8% in the asymptomatic patients. The diagnosis of coronary artery disease at the start of maintenance haemodialysis based only on chest symptoms and clinical factors proved to be difficult. Coronary angiography is thus essential for evaluating coronary artery disease in uraemic patients. Many patients with end-stage renal disease had coronary artery disease prior to the start of haemodialysis.

The annual survey of the Japanese Society for Dialysis Therapy Renal Data Registry (JRDR) was sent to 4458 dialysis facilities at the end of 2018; among these facilities, 4402 facilities (98.7%) responded to the facility questionnaire, and 4222 (94.7%) responded to the patient questionnaire. The number of chronic dialysis patients in Japan continues to increase every year; as of the end of 2018, it had reached 339,841 patients, representing 2688 patients per million population. Among the prevalent dialysis patients, the mean age was 68.75 years, and diabetic nephropathy was the most common primary disease among the prevalent dialysis patients (39.0%), followed by chronic glomerulonephritis (26.8%) and nephrosclerosis (10.8%). The number of incident dialysis patients was 40, 468, and a reduction by 491 from 2017. The mean age of the incident dialysis patients was 69.99 years old. Diabetic nephropathy was also the most common primary disease (42.3%), representing a 0.2 percent point reduction from 2017. The distribution of diabetic nephropathy appears to have reached a plateau. The number of deceased patients during 2018 was 33,863, and the crude annual death rate was 10.0%. Heart failure was the most common cause of death (23.5%), followed by infection (21.3%) and malignant tumor (8.4%); these causes were similar to

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Increased glomerular hydraulic pressure has been suggested as a major causative factor in the development of glomerular sclerosis. The elevation of glomerular pressure increases the magnitude of stretch to mesangial cells. The study was, therefore, designed to investigate the effect of mechanical stretch on expression of TGF-beta and extracellular matrix components in cultured rat mesangial cells. The results showed that mechanical stretch stimulated mRNA expression for TGF-beta1 and TGF-beta3 in a time dependent manner, and that mesangial cells secreted substantial amounts of TGF-beta proteins in response to stretch. Stretch was also shown to stimulate mRNA expression for collagen types I and IV, and fibronectin, major components of mesangial extracellular matrix. The stretch-induced mRNA expression for extracellular matrix components was inhibited by neutralizing antibody to TGF-beta. Moreover, stretch-induced mRNA expression of TGF-beta was inhibited by tyrosine kinase inhibitors, genistein or herbimycin A, whereas Ca channel blockers nitrendipine or Gd3+, and inhibitors for protein kinase A or C had no effect. These findings indicate that stretch induced TGF-beta mRNA primarily through tyrosine kinase-dependent mechanisms in cultured rat mesangial cells, and the secreted TGF-beta may play a significant role for the stretch-induced expression of extracellular matrix proteins. Our results suggest that stretch-induced TGF-beta of mesangial cells might be a mediator in the progression of glomerular sclerosis as an autocrine/paracrine factor.

The annual survey of the Japanese Society for Dialysis Therapy Renal Data Registry (JRDR) was conducted for 4413 dialysis facilities at the end of 2017; among which 4360 facilities (98.8%) responded to the facility questionnaire, and 4188 (94.9%) responded to the patient questionnaire. The response rate of the 2017 survey was comparable with the past, even though it was the third year after the new anonymization method. The number of chronic dialysis patients in Japan continues to increase every year; it has reached 334,505 at the end of 2017. The mean age was 68.43 years. The prevalence rate was 2640 patients per million population. Diabetic nephropathy was the most common primary disease among the prevalent dialysis patients (39.0%), followed by chronic glomerulonephritis (27.8%) and nephrosclerosis (10.3%). The rate of diabetic nephropathy and nephrosclerosis has been increasing year by year, whereas that of chronic glomerulonephritis was declining. The number of incident dialysis patients during 2017 was 40,959; it has remained stable since 2008. The average age was 69.68 years and diabetic nephropathy (42.5%) was the most common cause in the incident dialysis patients. These patients caused by diabetes did not change in number for recent several years. Further, 32,532 patients died in 2017; the crude mortality rate was 9.8%. The patients treated by hemodiafiltration (HDF) have been increasing rapidly from the revision of medical reimbursement for HDF therapy in 2012. It has attained 95,140 patients at the end of 2017, which were 18,304 greater than that in 2016. The number of peritoneal dialysis (PD) patients was 9090 in 2017, which had been slightly decreasing since 2014. Further, 19.4% of PD patients treated in the combination of hemodialysis (HD) or HDF therapy (hybrid therapy). And 984 patients were treated by home HD therapy at the end of 2017; it increased by 49 from 2016. Trial registration: JRDR was approved by the ethical committee of JSDT (approval number 1-3) and has been registered in "University hospital Medical Information Network (UMIN) Clinical Trials Registry" as a clinical trial ID of UMIN000018641 at 8th August 2015. https://upload.umin.ac.jp/cgi-bin/ctr/ctr_view_reg.cgi?recptno=R000021578 (Accessed 31 July 2019).

The fluid volume balance between intracellular water (ICW) and extracellular water (ECW) gradually changes with age and various medical conditions. Comprehension of these physiological changes would aid in clinical decision-making related to body fluid assessments. A total of 1,992 individuals (753 men and 1,239 women) aged ≥15 yr included in this study had their body composition measurements performed at training gyms in 2014. We developed a regression formula to assess the association of age with the ratio of ECW to ICW in these subjects. The mean ages of male and female subjects were 51.2 ± 15.2 and 57.4 ± 15.2 yr, and their mean body mass indexes were 23.4 ± 3.3 and 21.1 ± 2.8 kg/m, respectively. The total fluid volumes of male and female subjects were 39.6 ± 4.9 and 27.7 ± 3.0 liters, whereas the percent body fat mass per kilogram of body weight were 19 and 26%, respectively. The ECW-to-ICW ratio increased with age because of the steeper decrease in the ICW content than in the ECW content, especially after the age of 70 yr. The regression formulas used for calculating the age-adjusted ECW/ICW ratio were as follows: 0.5857 + 7.4334 × 10 × (age) in men and 0.6062 + 5.5775 × 10 × (age) in women. In conclusion, the fluid imbalance between ICW and ECW contents is driven by decreased cell volume associated with aging and muscle attenuation. Therefore, our proposed formula may serve as a useful assessment tool for the calculation of body fluid composition.