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Background This study aimed to determine associations among short- and long-acting erythropoiesis stimulating agents (ESAs), changes in serum fibroblast growth factor 23 (FGF23) and biomarkers of iron metabolism. Methods Among 108 patients on hemodialysis (HD), 44 received every 2 weeks or monthly doses of continuous erythropoiesis receptor activator (CERA), 31 received weekly doses of darbepoetin-α, 24 received three doses per week of epoetin-β and 9 were not treated with an ESA. Intact and C-terminal FGF23 and transferrin saturation (TSAT), ferritin, erythroferrone and hepcidin 25 were measured in blood samples collected before the HD session at the end of the dialysis week (baseline, Day 0) and on Days 3, 5, 7 and 14 thereafter. Results Levels of ferritin, hepcidin 25 and erythroferrone as well as TSAT were significantly decreased or elevated in patients treated with CERA compared with other types of ESAs. Levels of C-terminal FGF23 increased in all groups during the observation period. Levels of intact FGF23 and ratios of intact FGF23 to C-terminal FGF23 gradually decreased between Days 3 and 7 in the CERA but not in the other groups. Multivariate models associated changes in hepcidin 25 and phosphate with those of intact FGF23. Conclusion The long-acting ESA CERA might influence levels of intact FGF23 by increasing FGF23 cleavage in patients on HD in association with prolonged hepcidin 25 suppression.

The risk factors for intradialytic systolic blood pressure decline remain poorly understood. We aimed to identify clinical and laboratory predictors of the intradialytic systolic blood pressure decline, considering its seasonal variation. In a retrospective cohort of 47,219 hemodialysis sessions of 307 patients undergoing hemodialysis over one year in three dialysis clinics, the seasonal variation and the predictors of intradialytic systolic blood pressure decline (predialysis systolic blood pressure--nadir intradialytic systolic blood pressure) were assessed using cosinor analysis and linear mixed models adjusted for baseline or monthly hemodialysis-related variables, respectively. The intradialytic systolic blood pressure decline was greatest and least in the winter and summer, respectively, showing a clear seasonal pattern. In both models adjusted for baseline and monthly hemodialysis-related parameters, calcium channel blocker use was associated with a smaller decline (-4.58 [95% confidence interval (CI), -5.84 to -3.33], P < 0.001; -3.66 [95% CI, -5.69 to -1.64], P < 0.001) and α blocker use, with a greater decline (3.25 [95% CI, 1.53-4.97], P < 0.001; 3.57 [95% CI, 1.08-6.06], P = 0.005). Baseline and monthly serum phosphorus levels were positively correlated with the decline (1.55 [95% CI, 0.30-2.80], P = 0.02; 0.59 [95% CI, 0.16-1.00], P = 0.007), and baseline and monthly normalized protein catabolic rates were inversely correlated (respectively, -22.41 [95% CI, -33.53 to -11.28], P < 0.001; 9.65 [95% CI, 4.60-14.70], P < 0.001). In conclusion, calcium channel blocker use, α blocker avoidance, and serum phosphorus-lowering therapy may attenuate the intradialytic systolic blood pressure decline and should be investigated in prospective trials.

Aims: This study assessed the impact of iron administration on serum fibroblast growth factor 23 (FGF23) levels. Methods: Of 123 hemodialysis (HD) patients treated with erythropoiesis-stimulating agents, 22 received once-weekly intravenous iron and 17 received daily oral iron with iron-containing phosphate binders. Intact FGF23 and biomarkers of iron metabolism were measured from blood samples drawn before each HD session, at baseline and on days 3, 5, 7, and 14. Results: Phosphate levels did not differ among the 3 groups during the 14-day period. Ferritin levels were significantly increased in both iron treatment groups compared with the non-iron treatment group, but changes in transferrin saturation levels were similar in the intravenous iron and non-iron groups. However, intact FGF23 levels were continuously higher in the intravenous iron group than those in the other groups. Conclusion: Intravenous iron administration may influence intact FGF23 levels in HD patients independently of phosphate and iron metabolism.

Continuous erythropoietin receptor activator (CERA) and darbepoetin-α (DA) might differently affect iron metabolism and erythropoiesis in patients on hemodialysis (HD). This prospective study examined a cohort of patients on HD who had received either intravenous CERA every 2 or 4 weeks (N = 25) or DA once each week (N = 47). Blood was sampled before HD sessions on days 0, 2, 4, 7 and 14, and on days 0, 3, 5, 7 and 14 from patients who were injected with ESA at the beginning and end of the dialysis week, respectively. Changes in factors indicating erythropoiesis and biomarkers of iron metabolism were examined. Hemoglobin levels were maintained in the target range between 10.0 and 11.0 g/dL and ferritin levels at baseline and during the study period were similar between the DA and CERA groups. Levels of hepcidin 25 decreased from days 2-3 to day 5 and returned to the baseline at day 7 in the DA group, whereas those and transferrin saturation were serially suppressed from days 2-3 to day 14 in the CERA group. Levels of soluble transferrin receptor and reticulocyte counts were significantly elevated from days 4-5 to day 14 by CERA. Both DA and CERA stabilized erythropoiesis, but CERA might mobilize iron from body stores more effectively than DA in patients on HD.

In conventional hemodialysis (HD) treatment, excessive water removal sometimes induces a rapid drop in blood pressure. Intermittent infusion hemodiafiltration (I-HDF) has been developed to improve patients' peripheral circulation by repeated intermittent infusion during HD treatment.A prospective, multicenter, parallel group comparative trial examined the clinical effectiveness of I-HDF compared with predilution on-line HDF (pre-HDF), the most popular on-line HDF therapy in Japan. Patients were allocated to 2 groups after matching for age (± 5 years), dry weight (± 5 kg), and presence/absence of diabetes. After informed consent was obtained, 36 patients (18 pairs) participated in the trial. The results showed no difference in clinical condition or quality of life (QOL) scores between the 2 therapy groups. The rate of reduction in systolic blood pressure initially showed no difference between the groups, but decreased slightly as the trial proceeded after changing from HD therapy. There was also no difference in the incidence rate of treatments initially, although this significantly decreased in both groups as the trial proceeded. Rates of β2-microglobulin removal were significantly higher in the pre-HDF group than in the I-HDF group. At the same time, the amount of albumin leakage during treatment was significantly greater in the pre-HDF group. Key Messages: The clinical condition and QOL of patients receiving I-HDF was not inferior to those receiving pre-HDF. Pre-HDF demonstrated a significantly higher removal rate of middle- and larger-molecular-weight solutes and higher albumin leakage compared with I-HDF.

Background: In conventional hemodialysis (HD) treatment, excessive water removal sometimes induces a rapid drop in blood pressure. Intermittent infusion hemodiafiltration (I-HDF) has been developed to improve patients' peripheral circulation by repeated intermittent infusion during HD treatment. Summary: A prospective, multicenter, parallel group comparative trial examined the clinical effectiveness of I-HDF compared with predilution on-line HDF (pre-HDF), the most popular on-line HDF therapy in Japan. Patients were allocated to 2 groups after matching for age (± 5 years), dry weight (± 5 kg), and presence/absence of diabetes. After informed consent was obtained, 36 patients (18 pairs) participated in the trial. The results showed no difference in clinical condition or quality of life (QOL) scores between the 2 therapy groups. The rate of reduction in systolic blood pressure initially showed no difference between the groups, but decreased slightly as the trial proceeded after changing from HD therapy. There was also no difference in the incidence rate of treatments initially, although this significantly decreased in both groups as the trial proceeded. Rates of β2-microglobulin removal were significantly higher in the pre-HDF group than in the I-HDF group. At the same time, the amount of albumin leakage during treatment was significantly greater in the pre-HDF group. Key Messages: The clinical condition and QOL of patients receiving I-HDF was not inferior to those receiving pre-HDF. Pre-HDF demonstrated a significantly higher removal rate of middle- and larger-molecular-weight solutes and higher albumin leakage compared with I-HDF.

Background We aimed to identify associations between erythroferrone (ERFE), a regulator of hepcidin 25, and biomarkers of erythropoiesis and iron metabolism. We also aimed to determine the effects of erythropoiesis-stimulating agents (ESA), continuous erythropoietin receptor activator (CERA) and darbepoetin-α (DA) on ERFE production in patients on hemodialysis (HD). Methods Blood samples were obtained from 59 patients before HD sessions on day 0 (baseline). Twenty patients who were injected with either CERA (N = 10) or DA (N = 10) at the end of the dialysis week (day 0), who had ferritin ≥ 100 ng/mL and/or transferrin saturation ≥ 20%, and hemoglobin > 9 g/dL were selected from among the 59 patients. Blood was sampled serially before HD sessions on days 3, 5, 7 from patients on DA and on the same days plus day 14 from those on CERA. Results Levels of ERFE correlated inversely with those of hepcidin 25 and ferritin, and positively with those of soluble transferrin receptor. The hepcidin 25: ERFE ratio and hepcidin 25 levels positively correlated with ferritin levels. Levels of ERFE significantly increased from day 3 of treatment with DA and CERA and decreased by days 7 and 14, respectively. Erythropoiesis-stimulating agents concomitantly decreased levels of hepcidin 25 as those of ERFE increased. Conclusion We identified a novel association between ESA and ERFE in patients on HD. Both DA and CERA increased levels of ERFE that regulated hepcidin 25 and led to iron mobilization from body stores during erythropoiesis.

Continuous erythropoietin receptor activator (CERA) and darbepoetin-α (DA) might differently affect iron metabolism and erythropoiesis in patients on hemodialysis (HD). This prospective study examined a cohort of patients on HD who had received either intravenous CERA every 2 or 4 weeks (N = 25) or DA once each week (N = 47). Blood was sampled before HD sessions on days 0, 2, 4, 7 and 14, and on days 0, 3, 5, 7 and 14 from patients who were injected with ESA at the beginning and end of the dialysis week, respectively. Changes in factors indicating erythropoiesis and biomarkers of iron metabolism were examined. Hemoglobin levels were maintained in the target range between 10.0 and 11.0 g/dL and ferritin levels at baseline and during the study period were similar between the DA and CERA groups. Levels of hepcidin 25 decreased from days 2-3 to day 5 and returned to the baseline at day 7 in the DA group, whereas those and transferrin saturation were serially suppressed from days 2-3 to day 14 in the CERA group. Levels of soluble transferrin receptor and reticulocyte counts were significantly elevated from days 4-5 to day 14 by CERA. Both DA and CERA stabilized erythropoiesis, but CERA might mobilize iron from body stores more effectively than DA in patients on HD.

OBJECTIVE: Increased Na+-H+ exchanger activity (NHE) has been reported as an intermediate phenotype in hypertensive subjects, particularly those with insulin resistance. To investigate whether NHE abnormality plays a role in hypertension, Wistar fatty rat (WFR) with overt obesity, hyperglycemia and marked hyperinsulinemia was examined. METHODS: WFR and Wistar lean rats (WLR) as a control (n = 12, each) were fed either with normal (0.38%) or high sodium (4% NaCl) diet for 12 weeks and then sacrificed to examine platelets NHE activity. RESULTS: Mean arterial pressure (MAP) was higher in WFR than in WLR (113 +/- 4 versus 96 +/- 7 mmHg, P < 0.05) under a normal chow. Vmax values of NHE activity were significantly higher in WFR than in WLR. WFR fed with a high sodium diet showed higher MAP than those with a normal chow (128 +/- 3 versus 113 +/- 4 mmHg, P < 0.05). Though Km values were not different between WFR and WLR under a normal chow, both maximal transport rate (Vmax) and half maximal transport (Km) values were significantly higher in WFR with a high salt diet than those with a control diet. Vmax showed significant correlation with MAP, whereas Km values correlated with immunoreactive insulin (IRI) levels. Significant interaction between dietary sodium intake and the strain differences was observed both on blood pressure and on IRI levels by two-way analysis of variance (ANOVA). CONCLUSION: WFR presented salt-sensitive blood pressure elevation. NHE activity was enhanced in WFR in correlation with the blood pressure. These results suggest that augmented NHE activity contributes to the development of salt-sensitive blood pressure elevation in WFR.

The case report of a 53-year-old woman with abdominal pain and bloody diarrhoea is described. Prior to the onset of symptoms the patient had taken royal jelly for 25 days. Colonoscopy revealed that the mucosa was haemorrhagic and oedematous throughout the 20 cm long sigmoid colon. Histopathologically, mucosal haemorrhage, oedema, and infiltration of inflammatory cells were observed. Transmission electron microscopic examination revealed platelet aggregation in 30% of capillaries in the mucosal lesions. The drug-induced lymphocyte stimulation test was slightly positive for royal jelly (847 c.p.m., SI = 147%) compared with the control (576 c.p.m.). The patient's signs and symptoms disappeared within a few days after the initiation of conservative therapy, and the colonic lesions disappeared after 2 weeks of this therapy. This is the first reported case of haemorrhagic colitis associated with royal jelly intake.

症例は47歳アルコール依存症の女性.自宅にて意識もうろう・尿失禁状態でいたところを発見され来院した.腹部X線上ニボーを伴う大腸・小腸の拡張を認めた.イレウス管挿入・補液にて症状は一時的に改善したが再び増悪した.腹部CTにてS字結腸の狭窄が疑われたが,大腸・小腸造影,大腸鏡検査では器質的病変はなかった.その後甲状腺機能低下症と判明,ホルモン補充療法を施行したところ閉塞症状は軽快した.本例では続発性偽性腸閉塞の原因として甲状腺機能低下症,また誘因としてアルコール依存症が考えられ,興味ある稀な症例と考え報告した.

Insulin resistance is associated with chronic renal failure, which may amplify its cardiovascular pathologic manifestations. We previously showed the presence of insulin resistance in mild renal insufficiency due to chronic glomerulonephritis. These observations may be explained by a decrease in insulin sensitivity due to renal dysfunction. The aim of the present study was to evaluate the effects of unilateral and subtotal nephrectomy on insulin sensitivity.Unilateral heminephrectomy and five-sixths nephrectomy (5/6Nx) were performed in male Sprague-Dawley rats, measuring steady-state plasma glucose (SSPG) during the insulin suppression test.The glomerular filtration rate (GFR) decreased significantly from sham-operated rats, to unilateral heminephrectomy group, to 5/6Nx rats. SSPG was unexpectedly lower in the unilateral heminephrectomy group than in controls, suggesting that unilateral heminephrectomy increased the sensitivity to insulin despite a mild decrease in renal function. However, when the analysis was limited to the 5/6Nx group, SSPG was inversely correlated with GFR (r = -0.65, p0.05). When renal failure caused by 5/6Nx had reached end stage, the rats became insulin resistant, despite a profound reduction in renal mass.It is suggested that unilateral heminephrectomy reduced GFR and increased the sensitivity to insulin. When rats became uremic, insulin sensitivity decreased, even, in 5/6Nx.