[The efficacy and safety of continuous erythropoietin receptor activator in dialytic patients with chronic renal anemia: an open, randomized, controlled, multi-center trial].

OBJECTIVE: To evaluate the efficacy and safety of continuous erythropoietin receptor activator (C.E.R.A.) once every 4 weeks by subcutaneous administration on hemoglobin (Hb) maintenance in dialytic patients with chronic renal anemia who had been treated with stable dose of erythropoietin (EPO). METHODS: This was an open, randomized, controlled, multi-center trial. All the hemodialysis or peritoneal dialytic patients in EPO maintenance treatment received subcutaneous EPO-ß during the 6-week pre-treatment period to maintain Hb level between 100 g/L and 120 g/L. Eligible patients were randomized (2:1) to accept either C.E.R.A. once every 4 weeks by subcutaneous administration (C.E.R.A. group, n = 187) or subcutaneous EPO-ß 1-3 times weekly (EPO group, n = 94) for 28 weeks (including 20-week dose titration period and 8-week efficacy evaluation period). The starting dose of C.E.R.A. was converted according to the dose of EPO-ß administered in the week preceding the first study drug administration. The primary outcome was the change of Hb level between the baseline and that in the efficacy evaluation period. RESULTS: Totally 253 patients completed the whole 28-week treatment. The change of baseline-adjusted mean Hb was +2.57 g/L for C.E.R.A. group and +1.23 g/L for EPO group, resulting in a treatment difference of 1.34 g/L (95%CI -1.11 - 3.78 g/L). Since the lower limit of 95%CI was greater than the pre-defined non-inferiority margin -7.5 g/L (P < 0.0001), C.E.R.A. once every 4 weeks by subcutaneous administration was clinically non-inferior to EPO regarding the maintenance of stable Hb level. The proportion of patients maintaining Hb level within the range of 100-120 g/L through efficacy evaluation period was similar between the two groups (69.0% for C.E.R.A. group vs 68.9% for EPO group, P > 0.05). The overall incidence of adverse events was similar between the C.E.R.A.(41.7%) and EPO (46.2%) groups (P > 0.05). The safety findings were in accordance with the patients' primary diseases rather than the administration. CONCLUSIONS: Conversion from EPO to C.E.R.A. once every 4 weeks by subcutaneous injection could maintain the Hb in target level in dialytic patients with renal anemia, and it was non-inferior to EPO. In general, subcutaneous administration of C.E.R.A. is well tolerated in dialytic patients with chronic renal anemia.

[The protective effects to the function of kidney and long by clearing of cytokines in patients with open-heart surgery].

OBJECTIVE: To observe the effect of cytokines absorption on renal and respiratory function in patients with open-heart surgery. METHODS: 30 patients undergoing valve replacement with cardiopulmonary bypass (CPB) were randomly divided into two groups. A sulfonated polyacrylonitrile hemofilter (AN69) that has been used to absorb cytokines was connected into the efferent limb of CPB in Group A (n = 15), and a cellulose triacetate hemofilter (CT 190G) instead of AN69 was used as controls (Group B, n = 15). The levels of plasma pro-inflammatory (TNF-alpha, IL-6, IL-8) anti-inflammatory cytokines (IL-10, IL-1ra), C-reactive protein (CRP) levels, and post-operation renal and respiratory function were compared between the two groups. Blood samples were analysed for TNF-alpha and IL-6 and IL-8 and C-reactive protein (CRP). The changes in renal, respiratory function were also observed. RESULTS: (1) At the end of CPB, TNF-alpha 10 ng/L +/- 3 ng/L and IL-6 115 ng/L +/- 22 ng/L levels in Group A were significantly lower than that in Group B 13 ng/L +/- 3 ng/L, 134 ng/L +/- 29 ng/L) respectively (P < 0.05 in all). There is no statistical differences in plasma IL-10 and IL-1ra levels between the two groups. (2) After 24 hours of CPB, the magnitude of increased body temperature, heart rate, white blood cell and plasma CRP in Group A [1.6 degrees C +/- 0.2 degrees C, 15/min +/- 4/min, (17 +/- 3) x 10(9)/L, 56 mg/L +/- 13 mg/L], were significantly lower than that in Group B [2.1 degrees C +/- 0.2 degrees C, 23/min +/- 6/min, (22 +/- 3) x 10(9)/L, 69 mg/L +/- 15 mg/L] respectively (P < 0.05 in all). (3) After 24 hours of CPB, the levels of 24h urinary protein excretion and urinary N-acetyl-beta-D-glucosaminidase (NAG) were significantly lower in Group A when compared to that in Controls (0.20 g/d +/- 0.08 g/d vs 0.30 g/d +/- 0.14 g/d, 28 U/L +/- 11 U/L vs 38 U/L +/- 13 U/L respectively), P < 0.05 in all. The level of creatinine clearance (Ccr) in Group A (68 +/- 7) ml.min(-1).1.73 m(-2) was significantly elevated than that in Group B (57 +/- 11) ml.min(-1).1.73 m(-2) (P < 0.05). (4) One hour after the end of CPB, the magnitude of increased plateau airway pressure (P(Plateau)) and peak airway pressure (P(Peak)) in Group A were significantly lower than that in Controls (P < 0.01 in all). The duration that need mechanical ventilation after operation in Group A (4.9 h +/- 0.6 h) was much shorter than that in Group B (5.8 h +/- 0.8 h, P < 0.05). CONCLUSIONS: Lowering the plasma levels of cytokines by extracorporeal absorption may attenuate systemic inflammatory response and protect lung and kidney function in patients with open-heart surgery.

[Ultrafiltration with different membranes and respiratory function after cardiopulmonary bypass].

OBJECTIVE: To investigate the protective effect of ultrafiltration on pulmonary function after cardiopulmonary bypass (CPB) by comparing two different membranes used in the ultrafiltration. METHODS: Thirty patients undergoing cardiac surgery with CPB were randomly divided into adsorption group (n=15) and control group (n=15), and in the former group, AN69 membrane was used for ultra-infiltration, with polysulfone (PS) membrane adopted in the control group during CPB. Plateau airway pressure (P(Plateau)), peak airway pressure (P(Peak)), static pulmonary compliance (Cst), dynamic pulmonary compliance (Cdyn) and respiratory index (RI) were measured or calculated before and 5, 60, 120, and 240 min after CPB in each group respectively. RESULTS: During the period of 5 to 240 min after CPB, the increase in P(Plateau), P(Peak), RI and decrease in Cst and Cdyn were much more obvious and lasted for longer time in the adsorption group than in the control group (P<0.05). No operative death or hemoglobinuria occurred in these cases. CONCLUSION: Ultrafiltration with AN69 membrane more effectively reduces CPB-induced lung injury and improves the postoperative respiratory function than with PS membrane.