Dialysis patients not only experience disorders of social activities, but also have a variety of physical symptoms. Therefore, these patients are prone to develop anxiety/depressive state. For this reason, health professionals are encouraged to detectearly signs of depression in dialysis patients. Thus, we investigated the mental status in 61 patients receiving dialysis therapy in our department between December 2007 and March 2008, using the General Health Questionnaire-28 (GHQ-28). Subsequently, an assessment was performed by psychiatric specialists to determine whether the subjects could be classified as having major depressive disorder using the DSM-IV-TR criteria of the American Psychiatric Association. The total scores and the scores of factor A (somatic symptoms), B (anxiety and insomnia) and D (depression) in the subjects were higher than those of healthy individuals. Applicable subjects to major depressive disorder were 24.6%, showing same level as in the USA, and it greatly exceeded 1.2%, which is the prevalence in the general population in urban areas of Japan. The points for both the total scores and the scores of each factor of GHQ-28 were higher in the group with depression than in the group without depression, and appropriate cut-off values to screen for depression were 8 points for the total scores of GHQ-28 and 1 point for factor D. In conclusion, GHQ-28 would be useful to screen for major depressive disorder among dialysis patients.

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We observed circadian variations of iron metabolism markers in patients receiving hemodialysis (HD). Serum iron (sFe) levels were significantly higher at 10 o'clock than at 19 o'clock in HD patients (74±35 μg/dL vs. 54±29 μg/dL, p=0.0064). There were no significant differences in transferin iron binding capacity (TIBC) levels and srum ferritin (sFtn) levels at 19 o'clock and at 10 o'clock. Transferin saturation (TSAT) was significantly higher at 10 o'clock than at 19 o'clock (30.8±15.7% vs. 22.6±11.9%, p=0.0060). A circadian variation was observed in sFe and TSAT levels, as higher in the morning and lower in the evening in HD patients. When HD patients with sFtn level under 100 ng/mL were classified into group A (8 : 30-10 : 30), B (13 : 30-14 : 30) and C (17 : 00-19 : 00) according to the time blood was drawn, SFe of group A (70±24 μg/dL) was significantly higher than those of group B (56±20 μg/dL ; p=0.015) and group C (55±21 μg/dL ; p=0.011). TSAT was significantly higher in group A (27.1±9.5%) than group B (22.2±7.9% ; p=0.031) or group C (20.8±7.8% ; p=0.009). In cases of stored iron deficiency, existence of circadian variation in sFe levels and TSAT levels were expected. Diagnostic efficiencies of iron deficiency by TSAT were 34.2% of all HD patients, 22.9% of group A, 50.0% of group B and 27.8% of group C when the cut off level of TSAT was under 20%. All of them showed low diagnostic efficiency. Thirty-three of 90 (36.7%) HD patients with under 100 ng/mL of sFtn showed an increase of over 1.5 g/dL in Hb levels after receiving iron intravenously. In cases under 20% of TAST and under 100 ng/mL of sFtn, 19 of 36 patients (52.8%) showed the increase. Because there are circadian variations of sFe and TSAT levels, as higher in the morning and lower in the evening in HD patients, TSAT level is not an appropriate parameter for determining iron deficiency.

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Secondary hyperparathyroidism (SHPT) is known to inhibit the erythropoiesis. To determine the effect of cinacalcet treatment on renal anemia, we investigated the response to erythropoiesis-stimulating agents (ESA) in hemodialysis patients started on cinacalcet. Twenty patients on maintenance hemodialysis started on treatment with cinacalcet were enrolled in this study. Serum levels of intact parathyroid hormone (i-PTH), albumin, calcium, phosphorus, alkaline phoshatase, c-reactive protein (CRP), iron, total iron-binding capacity and hemoglobin were measured before and at 1, 4, 8 and 12 months after the start of cinacalcet therapy. Darbepoetin Alfa (DPO) was used as the ESA. We also compared the required dose of ESA. Cinacalcet therapy resulted in an immediate decrease of the serum i-PTH from the pre-treatment level of 854±293 pg/mL to 503±421 pg/mL (p<0.0001) at 1 month and a further decrease to 283±243 pg/mL (p<0.0001) at 12 months. There were no significant changes in serum albumin or CRP levels or of the transferrin saturation or hemoglobin level in the patients. The dose of DPO was gradually decreased. Compared with the pre-treatment dose (24.0±16.7 μg/week), the dose of DPO was significantly lower at 8 months (15.0±20.1 μg/week, p<0.05) and at 12 months (14.0±16.4 μg/week, p<0.05). Addition of cinacalcet to conventional SHPT therapy may be associated with an improved response to ESA administered for the treatment of renal anemia.

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We investigated hemoglobin (Hb) variability in 124 hemodialysis patients treated with erythropoiesis stimulating agent (ESA). In these patients, recombinant human erythropoietin (rHuEPO) was replaced with Darbepoietin α (DA). We compared the results obtained between the EPO, DA1 and DA2 stages. The EPO stage represents the 24-week period before rHuEPO was replaced with DA ; the DA1 stage, the 24-week period after replacement ; the DA2 stage, the 24-week period after the DA1 stage. In order to characterize Hb variability, we examined Hb cycling, calculated the standard deviation (SD) and residual standard deviation (RSD) and defined 6 patients groups based on the patterns of Hb level fluctuation. The percentage of cases in which the target Hb level (10 g/dL≤Hb≤12 g/dL) was achieved was as follows. Pre replacement ; 55%, 24 weeks after replacement ; 69%, 48 weeks after replacement ; 60%. The percentage of cases in which excursion was observed was as follows. EPO stage ; 56%, DA1 stage ; 67%, DA2 stage ; 57%. SD and RSD were 0.581±0.227 g/dL and 0.445±0.183 g/dL respectively at the EPO stage, and 0.681±0.293 g/dL and 0.517±0.202 g/dL respectively, at the DA1 stage. Thus, the fluctuations showed a significant increase from the EPO to DA1 stage. In contrast, fluctuations at the DA2 stage were not significantly different from those at the EPO stage. We found a significant increase in the high amplitude group from 2.4% at the EPO stage to 23.4% at the DA1 stage. It was 14.5% at the DA2 stage. In brief, Hb variability was significantly greater when DA was administered than when EPO was administered. The increase in variability, however, had a tendency to decrease as DA administration was continued. The strong erythropoietic effect of DA probably increased the number of cases that achieved the target Hb level, and led to an increase in Hb variability at the DA1 stage. Under continued administration, the effects of EPO and DA on Hb variability were almost identical.

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Background : Hemodialysis (HD) patients are likely to perceive difficulties in performing lower-limb-related activities of daily living (ADL) due to decreased motor function and the presence of comorbidities. In our previous study, a novel questionnaire evaluating perceived difficulty in performing ADL related to lower limb function (HD-PDADL) was developed for patients undergoing HD therapy and its reliability and validity were assessed. Purpose : The present study assessed the responsiveness of the HD-PDADL to exercise training. Methods : After a 6-month observation period, 11 ambulatory HD patients (mean age, 63±9 years) without dementia completed a 3-month home-based exercise training program. We serially measured clinical characteristics, motor function and lower-limb-related ADL at the start of the observation period, and immedately before and after the 3-month exercise training. Motor function measures included leg strength, functional reach and maximal walking speed. Lower-limb-related ADL was evaluated using the functional independence measure (FIM) and the HD-PDADL. For HD-PDADL, patients were asked to grade the perceived difficulty of 12 items on a scale of 1 (inability) to 5 (no difficulty). Changes in leg strength, functional reach, maximal walking speed and FIM and HD-PDADL scores during the observation period and exercise training were analyzed successively using analysis of variance, and standardized response means (SRMs) were calculated to examine the responsiveness of FIM and HD-PDADL. Results : Following exercise training, leg strength and HD-PDADL score significantly increased (p<0.05, respectively), but other motor function measures and FIM score did not show any significant changes. Moreover, there was a correlation between changes in HD-PDADL score and leg strength during exercise training (p<0.05). SRMs of FIM and HD-PDADL during exercise training were 0.45 and 1.17, respectively. Conclusion : These findings suggest that HD-PDADL is highly responsive to exercise training in HD patients.

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Darbepoetin is an analogue of recombinant human erythropoietin showing an increased terminal half-life. However, there are few reports discussing hematological change after discontinuing administration of erythropoiesis stimulating agent (ESA) except for reports describing progression of anemia. We here report 2 cases of thrombocytopenia after discontinuation of darbepoetin. Then, the effects of ESA on thrombocytes were examined. One patient was a 59-year-old woman with a 7-year history of hemodialysis due to polycystic kidney. She demonstrated thrombocytopenia (platelet pre;12.4→post;6.5×10 ⁴/μL) 6 weeks after 20 μg/week of darbepoetin was discontinued. The second patient was an 80-year-old man with a 2-year history of hemodialysis due to ANCA-related nephritis. He had thrombocytopenia (pre;10.9→post;5.0×10 ⁴/μL) after 2 weeks of stopping 30 μg/week of darbepoetin. There had not been any changes in the dialysis method or other medications in either case. The platelet counts recovered to their former levels after darbepoetin administration was reinitiated. Next, we retrospectively examined the frequency of thrombocytopenia after human ESA discontinuation in 72 hemodialysis patients during a 2-year observational study. Thenty-eight patients (total of 37 episodes) underwent ESA discontinuation. Epoetin was involved 17 times and darbepoetin 20 times. The proportion of patients showing thrombocytopenia decreasing below 80% compared to the pre-administration level did not significantly differ between darbepoetin and epoetin. Thrombocytopenia preceded the progression of anemia, and there was a positive correlation among decreases in hemoglobin (Hb), hemotocrit (Ht) and platelet counts in patients with thrombocytopenia. In conclusion, some hemodialysis patients may develop thrombocytopenia preceding the progression of anemia when ESA therapy is discontinued. This study indicates that we must pay attention to platelet count in addition to Hb and Ht levels when discontinuing ESA administration in hemodialysis patients.

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