Liu Wen-Sheng, Chu Da-Chen, Chan Hsiang-Lin, Li Szu-Yuan, Liu Chih-Kuang, Yang Chih-Yu, Chen Yu-Wei, Lee Pui-Ching, Lai Yen-Ting, Lin Chih-Ching
Division of Nephrology, Department of Medicine, Taipei City Hospital, Zhong-Xing Branch, Taipei, Taiwan.
School of Medicine, National Yang-Ming University, Taipei, Taiwan.
Clin Exp Pharmacol Physiol. 2016 Oct;43(10):875-82. doi: 10.1111/1440-1681.12618.
Anaemia is an important issue in patients undergoing haemodialysis. We aimed to identify a better dosing schedule of a fixed monthly dose of continuous erythropoietin receptor activator (CERA) in patients with chronic kidney disease (CKD) on haemodialysis. The CERA dosing schedule included 100 μg once monthly for 2 months, 50 μg twice monthly for 2 months and then 100 μg once monthly for two months. The effectiveness was determined by comparing haematocrit, nutritional status (serum protein and albumin) and inflammatory markers (tumour necrosis factor (TNF)-α, interleukin (IL)-1, IL-6 and Hepcidin) at the beginning of the study with those at the end of the study. Forty-seven out of 67 patients completed the trial. At the end, haematocrit was significantly higher (34.51 vs 33.22%, P=.004), levels of inflammatory markers were significantly lower (TNF-α (30.71 vs 35.67 ng/mL, P=.007), IL-6 (5.12 vs 7.95 ng/mL, P=.033), hepcidin (60.39 vs 74.39 ng/mL, P=.002)), blood glucose levels were significantly lower (112.40 vs 139.02 mg/dL, P=.003) and albumin was significantly higher (4.11 vs 3.98, P=.001). Patients with a better than average response had a lower initial number of red blood cells (3.3 vs 3.6 × 10(6) /mm(3) , P=.025) and a lower IL-1 (3.8 vs 12.9 ng/mL, P=.01). They also had significantly lower blood glucose levels at the end. (91.3 vs 124.0 mg/dL, P=.03). We demonstrate that a fixed monthly dose of CERA at a twice monthly dosing schedule improves nutrition, reduces the inflammation and corrects anaemia in patients on haemodialysis. This finding may provide a new strategy for treating CKD-related anaemia.
贫血是接受血液透析患者的一个重要问题。我们旨在确定慢性肾脏病(CKD)血液透析患者每月固定剂量连续促红细胞生成素受体激活剂(CERA)的更佳给药方案。CERA给药方案包括每月100μg,共2个月;每月50μg,分两次给药,共2个月;然后每月100μg,共2个月。通过比较研究开始时和结束时的血细胞比容、营养状况(血清蛋白和白蛋白)以及炎症标志物(肿瘤坏死因子(TNF)-α、白细胞介素(IL)-1、IL-6和铁调素)来确定有效性。67例患者中有47例完成了试验。最后,血细胞比容显著升高(34.51%对33.22%,P = 0.004),炎症标志物水平显著降低(TNF-α(30.71对35.67 ng/mL,P = 0.007),IL-6(5.12对7.95 ng/mL,P = 0.033),铁调素(60.39对74.39 ng/mL,P = 0.002))血糖水平显著降低(112.40对139.02 mg/dL,P = 0.003),白蛋白显著升高(4.11对3.98,P = 0.001)。反应优于平均水平的患者初始红细胞数量较低(3.3对3.6×10⁶/mm³,P = 0.025),IL-1较低(3.8对12.9 ng/mL,P = 0.01)。他们在最后血糖水平也显著较低(91.3对124.0 mg/dL,P = 0.03)。我们证明,每月固定剂量的CERA采用每月两次给药方案可改善血液透析患者的营养状况、减轻炎症并纠正贫血。这一发现可能为治疗CKD相关贫血提供一种新策略。