Epoetin beta pegol (a continuous erythropoietin receptor activator; CERA) is usually administered once in 4 weeks or once monthly. However, the optimal dosing interval remains unknown. We, therefore, compared the effect of CERA administration between dosing intervals of 2 weeks (TWICE group) and 4 weeks (ONCE group) on erythropoiesis and iron metabolism in 20 hemodialysis patients. CERA was administered intravenously at weeks 0 and 2 for the TWICE group, and at week 0 for the ONCE group. Levels of hemoglobin (Hb), reticulocyte count, ferritin, transferrin saturation, content of Hb in reticulocytes and hepcidin-25 were monitored weekly for 4 weeks. Hemoglobin levels were significantly increased at weeks 3 and 4 in the TWICE group, while a gradual decrease after a significant increase at week 1 was observed in the ONCE group. Ferritin levels remained significantly low from week 1 to week 4 in the TWICE group. On the other hand, ferritin levels increased beyond baseline levels at week 4 in the ONCE group. Although hepcidin-25 did not significantly increase in the TWICE group, significant increases beyond baseline levels at weeks 3 and 4 were found in the ONCE group. These results indicate that continuous erythropoiesis was achieved with biweekly administration of CERA. Moreover, CERA at a 2-week interval led to a sustained suppression of ferritin and hepcidin-25 levels, suggesting a favorable influence on iron metabolism.

Epoetin beta pegol is a continuous erythropoietin receptor activator (CERA) with a long half-life. Although CERA has been shown to maintain adequate hemoglobin (Hb) levels at prolonged dosing intervals, the optimal dosing schedule remains unclear. We therefore compared the efficacy of maintaining hemoglobin levels with administration of twice-monthly CERA (TWICE) versus once-monthly CERA (ONCE). Twenty hemodialysis patients receiving epoetin beta (EPO) were enrolled in this crossover study. Patients were assigned to either the TWICE or the ONCE group based on matching Hb levels and EPO doses. After 6 months of treatment, the CERA dosage was interchanged between the groups and the study was continued for an additional 6 months. The effect of the different regimens on iron metabolism was also assessed during the first 6 months of the study. Hb levels significantly increased in the TWICE group, allowing for a reduction in CERA dosage, while the dose of CERA required to maintain Hb levels in the ONCE group remained unchanged. After the interchange, a decrease in Hb levels with incremental increase in CERA dosage was observed in the TWICE→ONCE group, with the opposite effect observed in the ONCE→TWICE group. Although increases in ferritin and hepcidin-25 levels in the ONCE group were noted at one month, they disappeared at 6 months. Although Hb levels were maintained in both the ONCE and TWICE groups, a twice-monthly administration was advantageous, as it required a lower dose of CERA.

Background/Aim: Bone loss in patients with osteoporosis may be predicted by the elevation of biochemical markers of bone turnover. Therefore, we studied the relationship between biochemical markers, including parathyroid hormone (PTH), and the 2-year change in radial cortical bone in patients under chronic hemodialysis. Methods: Tartrate-resistant acid phosphatase-5b (TRACP-5b), bone-specific alkaline phosphatase, whole PTH, and total intact PTH were measured in 53 patients under maintenance hemodialysis. Additionally, radial cortical bone mineral density (BMD) and relative cortical area (RCA) were measured by peripheral quantitative computed tomography 2 years apart. Results: In all patients, BMD decreased by 2.5% and RCA decreased by 5.8% during 2 years. TRACP-5b levels significantly correlated with decreased RCA in all and female patients, but not with decreased BMD. Bone-specific alkaline phosphatase correlated with decreased BMD in all patients and with decreased RCA in all and female patients. Whole PTH did not correlate with decreased RCA or BMD. Total intact PTH significantly correlated with decreased BMD in all and male patients and with decreased RCA in all and female patients. In stepwise multiple regression analysis, TRACP-5b and total intact PTH were selected as explanatory variables for decreased RCA and decreased BMD, respectively. Conclusion: These results suggest that TRACP-5b and total intact PTH are powerful markers to predict radial cortical bone loss in hemodialysis patients.

Calcification of the thoracic aorta determined by three-dimensional computed tomography predicts cardiovascular complications in patients on hemodialysis.

A 51-year-old Japanese woman who had been suffering from a rapid cycling affective disorder (RCAD) for 24 years responded to combined clonazepam and carbamazepine therapy. Before remission, she showed neuroendocrinological and neuroimaging abnormalities such as subclinical hypothyroidism with exaggerated response to thyrotropin releasing hormone (TRH) injection, non-suppression on the dexamethasone suppression test (DST) and hypofrontality in cerebral blood flow. Her symptoms improved remarkably soon after adjunctive clonazepam treatment. After remission, her biological markers gradually returned to normal.First, subclinical hypothyroidism improved 2 months after remission. Next, hypofrontality disappeared 18 months later. Furthermore, non-suppression on the DST normalized 24 months later. The normalization of biologcal markers with apparent recovery from R C A D suggests a decreased risk of relapse into mood disorder. These findings reiterate the importance of following-up on the biological markers in R C A D for years after remission.