The Effect Of Roxadustat On Iron Metabolism In Hemodialysis Patients With Microinflammatory State

Objective:Anemia is one of the most common and serious complications in patients with chronic kidney disease(CKD).To date,the supplementation of erythropoietin(ESA)and iron is the standard treatment strategy for renal anemia in patients with CKD,but there are still many unmet clinical challenges.Micro-inflammation is one of most common features in patients with CKD.The iron and ESAs supplementation are often ineffective.As a new generation of therapeutic drug for renal anemia,Roxadostat(FG‐4592)provides a new treatment option for these patients.Increasing evidence indicated that Roxadostat could improve renal anemia with independent of micro-inflammatory state.However,the effect of Roxadustat on iron metabolism in hemodialysis patients with microinflammatory state remains unclear.Here,the effect of Roxadustat on iron metabolism in the maintenance hemodialysis patients with micro-inflammatory state is investigated,thus,providing the theoretical basis for treatment of renal anemia in clinic.Methods:A total of 68 maintenance hemodialysis patients with renal anemia and micro-inflammatory state who admitted to Lin Yi Central Hospital from May to October2020 were selected(micro-inflammatory state refers to those patients with serum CRP >4.9 mg/L and no obvious infection;anemia refers to the two recent hemoglobin levels of8.0-9.0 g/d L,which is examined with an interval of at least 1 week).They were divided into control group(n=34)and Roxadustat group(n=34)using random number table method.The clinical data of all the subjects were collected,including basic data(gender,age,and age of dialysis [years]),hemoglobin(Hb),serum iron(SI),transferrin,transferrin saturation(TSAT),serum ferritin(SF),total iron binding capacity(TIBC),C-reactive protein(CRP),serum ferritin and parathyroid hormone.The control group was treated with rhu EPO after hemodialysis(the initial dose was 100 ～ 150 U/kg/week,divided into three injections,and the dose was adjusted according to the patient’s Hb and hematocrit[HCT]),while Roxadostat group was treated with Roxadustat(the initial dose was given according to the patient’s body weight,100 mg/time for patients with 40 ～ 60 kg,120mg/time for patients with > 60 kg,3 times/week after meals.The dose was adjusted according to the Hb level).They were treated for 3 months.The hemoglobin(HB)and iron metabolism indexes [serum iron(SI),total iron binding capacity(TIBC),transferrin saturation(TSAT),transferrin,serum ferritin(SF)and hepcidin] were compared between two groups before and after 3 months of treatment.Finally,appropriate statistical methods were used for statistical analysis.Results:1.There was no significant difference in age(t=1.273,P=0.106),gender(X2=1.123,P=0.113),age of dialysis(X2=1.465,P=0.098),the levels of Hb(t=1.129,P=0.124),SI(t=1.239,P=0.108),transferrin(t=1.334,P=0.076),TSAT(t=1.330,P=0.098),TIBC(t=0.998,P=0.162),SF(t=1.235,P=0.112),CRP(Z=0.868,P=0.201),parathyroid hormone(Z=1.554,P=0.086)and hepcidin(t=1.654,P=0.099)between two groups before treatment(all P>0.05).2.After 1 month of treatment,there were no statistically significant between the levels of Hb in Roxadustat treatment group and control group(9.42±0.54 vs 9.01±0.44,t=1.687,p=0.080).After 3 months of treatment,the levels of Hb were significantly increased in group with Roxadustat treatment(2 month: 10.32±0.44 vs 9.65±0.34,t=4.245,P<0.001;3 month: 11.54±0.38 vs 10.00±0.46,t=6.433,P<0.001),and the differences were statistically significant(**P < 0.001).3.After 3 months of treatment,the levels of serum iron(2 month: 8.91±0.23 vs8.32±0.22 t=2.984,P<0.001;3 month: t=5.433,P<0.001),transferrin(2 month: 2.49±0.21 vs 1.90±0.21 t=3.254,P<0.001;3 month: 2.89±0.18 vs 1.83±0.11 t=4.329,P<0.001)and TIBC(2 month: 61.89±3.45 vs 47.73±5.76 t=3.854,P<0.001: 3 month: 70.87±5.37 vs47.63±4.87 t=5.322,P<0.001)were significantly increased in those with Roxadustat treatment,while the levels of SF(1 month: 235.87±12.31 vs 269.32±10.24 t=2.245,P=0.030;2 month: 187.62±13.22 vs 241.20±12.11 t=3.851,P<0.001;3 month:129.34±15.36 vs240.10±10.36 t=6.433 t=6.433,P<0.001),and TSAT(1 month:20.20±1.21 vs 23.27±1.62 t=2.268,P=0.032;2 month: 19.20±1.10 vs 23.58±1.13 t=3.567,P<0.001;3 month: 17.60±1.02 22.70±1.22 t=4.852,P<0.001)were significantly decreased.And the differences were statistically significant(all P < 0.05).4.After 1 month of treatment,there were no statistically significant between the levels of hepcidin in Roxadustat treatment group and control group(130.32±8.6 vs145.54±7.54,t=1.806,p=0.07).After 3 months of treatment,the levels of Hb were significantly increased in group with Roxadustat treatment(2 month: 100.40±10.2 vs143.54±8.94,t=3.445;3 month: 67.30±7.5 vs 136.43±10.24,t=7.343),and the differences were statistically significant(**P < 0.001).Conclusion:Compared with rhu EPO,Roxadustat can significantly correct anemia in maintenance hemodialysis patients with micro-inflammation condition,improve the abnormal iron metabolism,and increases the utilization of iron,providing important evidence for treatment in clinic.