Saccharated ferric oxide attenuates haematopoietic response induced by epoetin beta pegol in patients undergoing haemodialysis.

BACKGROUND: Decreased erythropoietin levels and impaired iron metabolism due to excessive hepcidin levels are responsible for renal anaemia in patients undergoing haemodialysis. Recently, erythroferrone (ERFE) has been identified as a factor that regulates hepcidin. In addition, fibroblast growth factor 23 (FGF23), which has been recognized as a phosphorus-regulating hormone, appears to be involved in haematopoietic regulation. Clarification of the detailed mechanism of haematopoiesis could lead to the improvement of renal anaemia treatment. METHODS: Epoetin beta pegol (CERA) was administered to patients undergoing haemodialysis at week 0, and the same amount of CERA with saccharated ferric oxide (SFO) was administered at week 4. The changes in haematopoiesis-related biomarkers, including ERFE, intact FGF23 (iFGF23), C-terminal FGF23 (cFGF23), and inflammatory markers, were examined. RESULTS: Administration of CERA increased ERFE levels, decreased hepcidin levels, and stimulated iron usage for haematopoiesis, leading to an increase in reticulocytes (Ret) and haemoglobin (Hb). Simultaneous administration of SFO with CERA (CERA + SFO) significantly attenuated the responses of ERFE, Ret, and Hb compared with CERA alone. Although iFGF23 levels were not affected by either CERA or CERA + SFO, cFGF23 was significantly elevated from baseline after CERA. Since cFGF23 levels were not affected by CERA + SFO, cFGF23 levels after CERA + SFO were significantly lower than those after CERA alone. The ratio of iFGF23 to cFGF23 (i/cFGF23 ratio) was significantly higher after CERA + SFO than that after CERA alone. In addition, high-sensitivity C-reactive protein (hsCRP) levels were significantly higher after CERA + SFO than after CERA alone. CONCLUSION: Administration of SFO suppressed haematopoietic responses induced by CERA. Elevation of i/cFGF23 ratio and hsCRP could account for the inhibitory effects of SFO on haematopoiesis. TRIAL REGISTRATION: This study was registered with the University Hospital Medical Information Network (ID UMIN000016552 ).

Clinical Benefit of an Adsorptive Technique for Elderly Long-Term Hemodialysis Patients.

BACKGROUND: With the advancement of technology, a dialysis membrane has been developed to achieve the efficient removal of beta-2 microglobulin (ß2MG), which could not be removed with previous hemodialysis (HD) membranes. Recently, there has been an increase in the population of elderly chronic kidney disease (CKD) patients with chronic inflammation and malnutrition. The optimal extracorporeal circulation treatment for elderly CKD patients is not certain. SUMMARY: We have reported the clinical advantages, such as improvements in nutritional, inflammatory, and hemodynamic conditions, of the adsorptive HD membrane for elderly HD patients. We have also reported that the use of ß2MG adsorption columns improved the symptoms of dialysis-related amyloidosis and the number of bone cysts, which could not be improved by the high-flux hemodialyzer. Both the adsorptive HD membrane and ß2MG adsorption columns remove uremic toxins and inflammatory cytokines via adsorption without aggravating the nutritional condition of these patients. Key Messages: We should reconsider the mechanisms of adsorption, in addition to diffusion and convection, in the extracorporeal circulation treatment of elderly HD patients.

The removal of serum hepcidin by different dialysis membranes.

PURPOSE: Hepcidin has been suspected to be associated with anemia of chronic disease, which is commonly observed in patients with maintenance hemodialysis (MHD). As almost of hepcidin is bounded to protein, it is essential to clarify which kind of dialysis membrane can remove it efficiently. METHODS: Ex vivo study: 50 mL of whole blood from healthy volunteers were circulated for 2 h in a microcircuit with mini-dialyzers (acrylonitrile-co-methallyl sulfonate (AN69) or polysulfone (PS)) without ultrafiltration. We measured hepcidin-25 levels at 0, 60, and 120 min in the blood samples. In vivo study: Blood samples were taken from 28 MHD patients at the start and end of HD sessions with PS or AN69. We measured serum levels of hepcidin 20, 22, and 25 by liquid chromatography tandem mass spectrometry, and also measured serum levels of urea nitrogen (UN), ß2microglobulin (MG). RESULTS: Ex vivo study: Although serum hepcidin 25 levels increased after the ex vivo session with PS, they significantly decreased with AN69. In vivo study: The reduction ratio of ß2MG by PS was significantly higher than that of AN69. On the other hand, there was no significant difference in the reduction ratio of hepcidin 20, 22, and 25 between PS and AN69. CONCLUSIONS: Both super-flux PS and AN69 similarly removed hepcidin 20 22, and 25. HD with PS might achieve a high removal ratio of hepcidin by enhanced diffusion performance and an increased clearance of small molecule solutes. On the other hand, AN69 might remove hepcidin by adsorption.

A crossover study of the acrylonitrile-co-methallyl sulfonate and polysulfone membranes for elderly hemodialysis patients: the effect on hemodynamic, nutritional, and inflammatory conditions.

Many maintenance hemodialysis (MHD) patients have recently been treated with high flux (HF) dialysis membranes such as polysulfone (PSu) membranes. However, the appropriateness of HF for elderly MHD remains to be elucidated. In order to estimate hemodialysis (HD) efficiency, the hemodynamic condition during HD, and the nutritional status, 28 elderly MHD patients were treated with PSu for 3 months. After this, the patients were switched to acrylonitrile-co-methallyl sulfonate (AN69) membranes for the next 3 months and then returned to PSu for another 3 months. Reduction ratio of inflammatory cytokines (interleukin [IL]-6) by AN69 was significantly higher than the reduction ratio by PSu. After 3 months with AN69, the serum total protein, albumin, and cholesterol levels significantly increased, and after switching back to PSu, the levels returned to baseline. Furthermore, the frequency of saline used to treat episodes of hypotension during HD significantly decreased in the AN69 period. In elderly MHD patients, it was possible to achieve improvements in both malnutrition and chronic inflammatory conditions with AN69. This suggests that AN69 may be the preferred membrane for elderly MHD, because it stabilizes the hemodynamic condition and demonstrates a higher removal of inflammatory cytokines during HD.

Comparison of the effects of cellulose triacetate and polysulfone membrane on GPIIb/IIIa and platelet activation.

BACKGROUND: During hemodialysis session, several adverse reactions can occur on platelets, which are attributable to bioincompatibility of the dialysis membrane. Glycoprotein IIb/IIIa (GPIIb/IIIa) is the receptor for fibrinogen, which mediates platelet aggregation and adhesion. Accordingly, we compared the influence of a cellulose triacetate (CTA) and polysulfone (PS) membrane on GPIIb/IIIa and platelet activation. METHODS: Blood samples from 5 patients on hemodialysis were taken at 0 time, 15 min, 30 min, 60 min and 240 min, during a single hemodialysis session, by a crossover design using CTA or PS. Platelet count and plasma concentration of GPIIb/IIIa, beta-thromboglobulin (beta-TG) and platelet factor 4 (PF-4) were measured. GPIIb/IIIa was measured by flow cytometry. beta-TG and PF-4 were measured by ELISA. RESULTS: There was no significant change in the total amount of GPIIb/IIIa during dialysis session between the CTA and PS. However, the level of bound GPIIb/IIIa was significantly (p < 0.0002) increased from 1,426 +/- 435 to 40,446 +/- 2,777 mol/PLT with PS. In contrast, there was no significant change with CTA (3,258 +/- 1,469 to 4,301 +/- 1,422 mol/PLT). The platelet counts and beta-TG and PF-4 behavior during the dialysis session did not show significant change between the PS and CTA. CONCLUSION: The characterization of changes in platelet membrane receptor (GPIIb/IIIa) may be a useful marker for studying the biocompatibility of dialysis membranes. On platelet aggregation, CTA might be more biocompatible membrane than PS.