Effect of oral iron on the ability of roxadustat to ameliorate anemia in peritoneal dialysis patients: A real-world 24-week study

Effect of oral iron on the ability of roxadustat to ameliorate anemia in peritoneal dialysis patients: A real-world 24-week study | Research Square window.SnipcartSettings = { analytics: { enabled: false } }; (function() { var accessVector = localStorage.getItem('access_vector') || ''; window.dataLayer = window.dataLayer || []; if (accessVector) { window.dataLayer.push({ user: { profile: { profileInfo: { snid: accessVector } } } }); } })(); (function(w,d,s,l,i){w[l]=w[l]||[];w[l].push({'gtm.start':new Date().getTime(),event:'gtm.js'});var f=d.getElementsByTagName(s)[0],j=d.createElement(s),dl=l!='dataLayer'?'&l='+l:'';j.async=true;j.src='https://www.googletagmanager.com/gtm.js?id='+i+dl;f.parentNode.insertBefore(j,f);})(window,document,'script','dataLayer','GTM-K279D39R'); Browse Preprints In Review Journals COVID-19 Preprints AJE Video Bytes Research Tools Research Promotion AJE Professional Editing AJE Rubriq About Preprint Platform In Review Editorial Policies Our Team Advisory Board Help Center Sign In Submit a Preprint Cite Share Download PDF Research Article Effect of oral iron on the ability of roxadustat to ameliorate anemia in peritoneal dialysis patients: A real-world 24-week study Xuejie Zhang This is a preprint; it has not been peer reviewed by a journal. https://doi.org/ 10.21203/rs.3.rs-8336397/v1 This work is licensed under a CC BY 4.0 License Status: Posted Version 1 posted You are reading this latest preprint version Abstract Background Roxadustat is an orally bioavailable hypoxia-inducible factor prolyl hydroxylase inhibitor (HIF-PHI) that regulates iron metabolism in patients with chronic kidney disease (CKD) primarily by reducing hepcidin levels and mobilizing internal iron stores. With increased iron utilization, iron deficiency may occur in some patients, and more data are needed to evaluate the exogenous iron requirements of peritoneal dialysis (PD) patients receiving roxadustat to treat anemia. Methods We performed a prospective cohort study of anemic (Hb ≤ 100.0 g/L) patients undergoing PD. One hundred six patients received no iron or oral iron while they were treated with roxadustat for 24 weeks. The primary endpoints included Hb compliance rates, changes in iron biomarker levels and the proportion of patients with absolute iron deficiency and functional iron deficiency. Results Compared with no iron supplementation, oral iron supplementation significantly increased Hb levels (difference, 10.20 g/L; 95% CI, 1.93 to 18.48) and Hb compliance rates (oral iron, 70.97%; no iron, 51.28%); attenuated the increase in serum soluble transferrin receptor (sTFR) levels (difference, -5.66 nmol/L; 95% CI, -10.30 to -1.02) and sTFR/logsFt levels (difference, -0.32; 95% CI, -0.54 to -0.11); and reduced the proportion of patients with absolute iron deficiency (oral iron, 16.13%; no iron, 28.21%). Hepcidin levels decreased significantly from baseline in both groups, by 23.94% in PD patients receiving no iron (n = 39) and by 23.33% in PD patients receiving oral iron (n = 31). Conclusions Compared with no iron supplementation, oral iron supplementation can significantly reduce the incidence of absolute iron deficiency and significantly improve the efficacy of roxadustat in the treatment of anemia in PD patients. These results suggest that adequate iron supplementation is necessary during roxadustat therapy. Trial registration : This study was registered on the Chinese Clinical Trial Registry on March 4, 2022 (registration number: ChiCTR2200057231). Peritoneal dialysis (PD) Anemia Hypoxia inducible factor-prolyl hydroxylase inhibitors (HIF-PHIs) Iron metabolism Figures Figure 1 Figure 2 Figure 3 Figure 4 Figure 5 Background Renal anemia is a common and severe complication in patients with CKD, particularly those with end-stage renal disease (ESRD) [ 1 ], and is closely associated with increased cardiovascular events, cognitive dysfunction, and all-cause mortality. PD, as a critical renal replacement therapy for end-stage renal disease (ESRD), involves complex pathophysiological mechanisms underlying anemia in patients. In addition to absolute or relative erythropoietin (EPO) deficiency, iron metabolism disorders—particularly functional iron deficiency driven by microinflammatory states and characterized by elevated serum ferritin (sFt) levels and decreased transferrin saturation (TSAT) levels—are the core factors contributing to refractory anemia and EPO resistance [ 2 , 3 ]. Extensive studies have confirmed that renal anemia is prevalent among peritoneal dialysis (PD) patients [ 4 ], with treatment relying on erythropoietin-stimulating agents (ESAs), iron supplements, and in severe cases, blood transfusions [ 5 ]. However, the conventional regimen of ESA combined with iron therapy faces challenges such as iron-regulated functional iron deficiency [ 6 ], inflammatory state interference [ 7 ], and potential adverse effects of intravenous iron [ 8 , 9 ]. Therefore, there is an urgent need for safer and more effective treatment options for anemia in PD patients. To address these issues, HIF-PHI are receiving increasing attention [ 10 , 11 ]. Roxadustat improves erythropoiesis at the physiological level and iron utilization by stabilizing hypoxia-inducible factor [ 12 ], upregulating endogenous EPO expression, and downregulating hepcidin synthesis [ 13 , 14 ]. Recent randomized, multicenter, double-blind clinical studies conducted in China have shown that roxadustat significantly improves the Hb levels in patients with CKD [ 15 , 16 ]. Other studies have also demonstrated that roxadustat is effective in treating renal anemia and reduces the need for blood transfusions and intravenous iron supplementation [ 17 – 19 ].This mechanism raises a key clinical question: Is traditional oral iron supplementation still necessary under roxadustat treatment? The microinflammatory state in peritoneal dialysis patients alters the actual levels of parameters such as TSAT and sFt by influencing transferrin and hepcidin levels [ 20 ]. Therefore, the level of sTFR unaffected by inflammation can provide more information for evaluating iron metabolism in CKD patients [ 21 ]. By leveraging the relationship between these two iron-deficiency-related variables, the sTFR/logFt ratio can enhance the diagnostic efficacy of using sTFR or sFt alone [ 22 ]. Here, we report a phase 3 study in which patients were not treated with roxadustat, ESAs, or iron during the first six weeks of enrolment and were assigned to receive either no iron supplementation or oral iron supplementation depending on whether they were taking iron supplements. The aim of this study was to evaluate the effect of roxadustat treatment on iron metabolism in peritoneal dialysis patients and to evaluate the exogenous iron requirement in the treatment of anemia in PD patients. Methods Study design This study is a single-center prospective cohort study, selecting PD patients with regular follow-up. This study was approved by the Ethics Committee of the Affiliated Jintan Hospital of Jiangsu University (2025-KY-007) and completed the Chinese Clinical Trial Registration (registration number: ChiCTR2200057231). Patients were required to meet the following inclusion criteria: (1) Age 18–75 years; (2) Regular PD for at least 6 weeks; (3) No prior treatment with ESAs, roxadustat, or iron supplements within 6 weeks before enrollment; (4) Mean Hb 60–100 g/L. Patients were excluded if they met any of the following exclusion criteria: (1) Combined with other dialysis modalities; (2) Received iron supplements, ESAs, or roxadustat within 6 weeks; (3) Severe organic dysfunction of the heart, liver, lungs, or brain; (4) Incomplete clinical data. Calculation sample size The sample sizes (N1 = 34; N2 = 34) for the no iron group and the oral iron group were based on a multicenter randomized controlled clinical trial conducted [ 23 ], with a 1:1 ratio between the two groups. The sample sizes were calculated using PASS15.0 software, with two-tailed α = 0.05 and the test efficiency was 90%. A total of 106 patients were enrolled based on actual conditions, with an estimated dropout rate of 30%. Study drug administration The initial dose of roxadustat [Enambojin (China) Pharmaceutical Technology Development Co., Ltd., Sinopharm H20180024 (50 mg), H20180023 (20 mg)] was determined based on the patient's weight: 100 mg (for weight between 45 and 60 kg) or 120 mg (for weight ≥ 60 kg) three times weekly, with dosage adjusted according to the instructions, and the maximum dose was 2.5 mg/kg. Patients in the oral iron group used ferrous succinate sustained-release tablets (Jinling Pharmaceutical Co., Ltd., Sinopharm H20010307), 0.2-0.4g daily. Intravenous iron administration was prohibited during the study. End points The primary endpoints were: the proportion of patients achieving the treatment goal (defined as a Hb concentration of 110–130 g/L), changes in iron biomarker levels from baseline to week 24, including sTFR, serum iron (SI), sFt, TSAT, and total iron binding capacity (TIBC), and the proportions of patients with absolute iron deficiency (defined as TSAT < 20% and sFt < 100 ng/mL) and functional iron deficiency (defined as TSAT < 20% and sFt ≥ 100 ng/mL). The secondary endpoints were the incidence of hyperkalemia, metabolic acidosis, and peritonitis. Statistical analysis All the data were analyzed with SPSS 25.0. Continuous variables with a normal distribution were expressed as mean ± standard deviation and analyzed using the independent samples t-test. Non-normal data were presented as median and interquartile range and analyzed using the Wilcoxon rank sum test. Categorical data were expressed as percentages and analyzed using the chi-square test. A mixed-effects repeated measures model was employed to analyze the mean changes in iron biomarker levels, Hb levels, and lipid metabolism levels at week 24 compared to week 8 and baseline. A two-tailed P value < 0.05 was considered statistically significant. Results Patient characteristics and disposition Among the 106 patients enrolled (no iron, 58; oral iron, 48), 18 (8.3%) discontinued the study within the first 8 weeks, 18 (8.3%) discontinued the study at weeks 8–24, and the remaining 70 patients completed the 24-week study (Fig. 1 ). The average daily iron dose for patients receiving oral iron therapy was 3.77 mg/kg. Demographic and baseline characteristics did not significantly differ between the cohorts (Table 1 ). The mean baseline Hb concentration among the patients enrolled was 87.84 ± 9.42 g/L. Table 1 Characteristics of the patients at baseline * Characteristic No iron (n = 58) Oral iron (n = 48) P Value Male sex, n (%) 32 (55.17) 27 (56.25) 0.911 Age, years 48.40 ± 13.04 46.63 ± 14.38 0.508 BMI, kg/m 2 23.84 ± 3.80 23.27 ± 3.49 0.427 Duration of PD, weeks 86.00 (45.25,139.25) 78.00 (37.25,115.00) 0.648 Mean arterial pressure, mmHg 108.17 ± 16.86 109.53 ± 18.63 0.693 Glucose, mmol/L 5.06 ± 1.53 5.78 ± 2.35 0.063 History of hypertension, n (%) 52 (89.66) 42 (87.50) 0.727 History of diabetes mellitus, n (%) 12 (20.69) 8 (16.67) 0.598 Peritoneal transport type: High transport, n (%) 4 (6.90) 4 (8.33) High average transport, n (%) 13 (22.41) 12 (25.00) Low transport, n (%) 3 (5.17) 5 (10.42) 0.417 Low average transport, n (%) 21 (36.21) 20 (41.67) Unknown, n (%) 17 (29.31) 7 (14.58) Pathological diagnosis: Chronic glomerulonephritis, n (%) 19 (32.76) 20 (41.67) Polycystic kidney, n (%) 4 (6.90) 4 (8.33) Hypertension, n (%) 17 (29.31) 13 (27.08) Diabetes, n (%) 11 (18.97) 7 (14.58) 0.925 Nephrotic syndrome, n (%) 4 (6.90) 2 (4.17) Others, n (%) 3 (5.17) 2 (4.17) sTFR, nmol/L 36.81 ± 11.49 36.98 ± 8.11 0.931 Hepcidin, ng/ml 105.04 ± 29.00 104.28 ± 25.65 0.887 SI, µmol/L 14.53 ± 6.33 12.35 ± 6.49 0.085 sFt, ng/ml 210.35 (81.47,354.95) 200.90 (55.14,322.65) 0.356 sTFR/LogsFt 1.46 ± 0.65 1.52 ± 0.45 0.574 TSAT, % 34.57 ± 15.32 29.18 ± 14.75 0.070 TIBC, µmol/L 42.89 ± 10.39 43.86 ± 12.68 0.666 Hemoglobin, g/L 87.81 ± 9.01 87.88 ± 10.00 0.972 RBC, 10 12 /L 2.98 ± 0.37 2.90 ± 0.39 0.270 EPO, mIU/mL 6.80 (3.86,10.70) 5.82 (3.71,8.53) 0.175 Folate, ng/mL 6.22 (4.50,20.00) 13.8 (4.64,20.00) 0.211 Vitamin B 12 , pg/mL 479.50 (319.75,786.90) 436.50 (302.25,647.00) 0.351 K + , mmol/L 4.34 ± 0.80 4.20 ± 0.70 0.346 >5.5 mmol/L, n (%) 3 (5.17) 1 (0.21) 0.750 HCO 3− , mmol/L 21.54 ± 3.16 21.83 ± 3.89 0.673 <22.0 mmol/L, n (%) 32 (55.17) 19 (39.58) 0.129 P, mmol/L 2.16 ± 2.90 1.68 ± 0.52 0.254 PTH, pg/mL 230.35 (109.10,446.85) 269.30 (158.50,394.23) 0.501 Total cholesterol, mmol/L 3.89 ± 1.26 4.16 ± 1.13 0.252 Triglyceride, mmol/L 1.58 ± 0.96 1.49 ± 0.70 0.593 HDL-C, mmol/L 0.91 ± 0.37 0.92 ± 0.23 0.834 LDL-C, mmol/L 2.36 ± 1.06 2.52 ± 0.92 0.415 C-reactive protein, mg/L 1.70 (0.50,5.30) 2.30 (0.70,12.20) 0.129 > 4.9 mg/L, n (%) 16 (27.59) 14 (29.17) 0.857 eGFR, ml/min 6.21 ± 2.31 6.71 ± 2.17 0.254 Creatinine, µmol/L 820.17 ± 206.05 821.81 ± 230.67 0.969 *Measurement data with a normal distribution are expressed as the means ± standard deviations, and nonnormally distributed data are expressed as medians and interquartile ranges. Only patients who completed the 24−week study are listed (roxadustat, 70; ESA, 36). No significant between−group differences were found in baseline characteristics. sTFR denotes serum soluble transferrin receptor, Hepc denotes hepcidin, SI denotes serum iron, sFt denotes serum ferritin, TSAT denotes transferrin saturation, TIBC denotes total iron−binding capacity, UIBC denotes unsaturated iron−binding capacity, RBC denotes red blood cell count, EPO denotes erythropoietin, PTH denotes parathyroid hormone, HDL−C denotes high−density lipoprotein, LDL−C denotes low−density lipoprotein, WBC denotes white blood cell count, and eGFR denotes estimated glomerular filtration rate . Roxadustat doses administered At week 24, the mean dose of roxadustat was 94.29 ± 48.02 mg, whereas it was 112.45 ± 12.33 mg at week 1 (starting dose). At week 12 (P = 0.019), week 20 (P = 0.009) and week 24 (P < 0.001), the mean dose of roxadustat in the oral iron group was significantly lower than that in the no iron group. At week 24, the mean dose of roxadustat was 80.00 ± 47.96 mg in the oral iron group and 105.64 ± 45.53 mg in the no iron group (Fig. 2 ). Changes in iron metabolism indicators At week 8, the change in the hepcidin concentration from baseline was − 11.23 ± 24.14 ng/ml in the oral iron group and − 13.47 ± 24.98 ng/ml in the no iron group (Fig. 3 ). At week 24, the difference in the hepcidin concentration between the two groups was 0.061 ± 20.35 ng/ml, and the changes in the hepcidin concentration from baseline were − 24.33 ± 20.35 ng/ml and − 25.15 ± 24.80 ng/ml, respectively (Fig. 3 ). At week 8, the sTFR levels in the oral iron group and the no iron group increased by 1.49 ± 9.87 nmol/L and 4.25 ± 10.31 nmol/L, respectively, from baseline (Fig. 4 a). The intergroup difference was − 2.76 nmol/L (95% CI, − 7.08 to 1.56). By week 24, the change from baseline in the oral iron group was 5.49 ± 8.82 nmol/L, and in the no iron group, it was 11.15 ± 10.29 nmol/L, with an intergroup difference of -5.66 nmol/L (95% CI, -10.30 to -1.02) (Fig. 4 b). In the oral iron group, the LogsFt level remained clinically stable, with a change from baseline of 0.02 ± 0.42% (95% CI, -7.04 to 0.53), and the TIBC and SI levels increased, with changes from baseline of 4.74 ± 9.31 µmol/L (95% CI, 0.54–10.01) and 3.30 ± 5.910 µmol/L (95% CI, 0.41–6.17), respectively. In the no iron group, the SI level remained clinically stable, with a change from baseline of -1.81 ± 7.78 µmol/L (95% CI, -4.66 to 1.05); the LogsFt level decreased from baseline by 0.21 ± 0.38 (95% CI, -0.36 to -0.02), and the TIBC level increased from baseline by 8.35 ± 10.15 µmol/L (95% CI, 4.89–13.22). The sTFR/LogsFt ratio remained stable in the oral iron group and significantly increased in the no iron group (Fig. 4 c): at week 24 of the study, the proportion of patients with a sTFR/LogsFt ratio > 2 was 51.28% in the no iron group and 19.35% in the oral iron group (Fig. 4 d). At week 8, the change in the TSAT level from baseline in the oral iron group was 1.79 ± 13.69%, whereas it was − 6.50 ± 14.24% in the no iron group. At week 24, the difference in TSAT levels between the two groups was 8.29 nmol/L (95% CI, 0.87 to 15.70), and the changes in TSAT levels from baseline were 4.31 ± 15.05 nmol/L and − 9.37 ± 15.74 nmol/L, respectively (Table 2 ). Table 2 Iron biomarker levels* No iron Oral iron Baseline ( n = 58) Week 8 ( n = 49) Week 24 ( n = 39) Baseline ( n = 48) Week 8 ( n = 39) Week 24 ( n = 31) SI, µmol/L 14.53 ± 6.33 14.28 ± 8.22 12.72 ± 7.78 12.35 ± 6.49 14.86 ± 6.34 15.65 ± 5.91 a LogsFt, µg/ml 2.23 ± 0.43 2.04 ± 0.42 a 2.04 ± 0.38 a 2.16 ± 0.45 2.02 ± 0.40 2.18 ± 0.42 <2 µg/l− n (%) 15 (25.86) 22 (44.88) a 19 (48.72) a 17 (35.42) 18 (46.15) 11 (35.48) TSAT, % 34.57 ± 15.32 29.43 ± 15.28 a 25.20 ± 15.74 C 29.18 ± 14.75 31.65 ± 12.73 33.49 ± 15.05 b <20%, n (%) 10 (17.24) 16 (32.65) a 19 (48.72) a 15 (31.25) 6 (15.38) 9 (29.03) TIBC, µmol/L 42.89 ± 10.39 48.71 ± 10.62 a 51.94 ± 9.73 a 43.86 ± 12.68 46.93 ± 7.61 48.59 ± 9.31 a *Measurement data with a normal distribution are expressed as the means ± standard deviations, and nonnormally distributed data are expressed as medians and interquartile ranges. SI denotes serum iron, sFt denotes serum ferritin, TSAT denotes transferrin saturation, and TIBC denotes total iron-binding capacity. a: Significant difference from baseline ( P < 0.05); b: Significant difference between the groups ( P < 0.05); C: Significant difference from baseline (P < 0.05) and between the groups (P < 0.05). At week 24, 7.69% of the patients in the no iron group and 16.13% of the patients in the oral iron group had functional iron deficiency, with no significant difference between the groups (P = 0.270). Moreover, we observed that the percentage of patients with absolute iron deficiency remained stable in the oral iron group (P = 0.852) and increased significantly in the no iron group (P = 0.011) (Fig. 5 a). Changes in Hb levels At week 24, the logEPO levels in the oral iron group and the no iron group increased by 0.11 ± 0.08 mIU/mL and 0.15 ± 0.42 mIU/mL, respectively, from baseline, with a between-group difference of -0.04 mIU/mL (95% CI, -0.24 to 0.17). During the treatment with roxadustat, the Hb levels in both groups significantly increased from baseline. At week 24, the increase in the Hb concentration was 29.57 ± 15.59 g/L in the oral iron group and 19.37 ± 18.44 g/L in the no iron group. The between-group difference was 10.20 g/L (95% CI, 1.93 to 18.48). At week 24, 70.97% of the patients in the oral iron group had Hb concentrations ≥ 110 g/L and < 130 g/L, and the proportion was 51.28% in the no iron group (Fig. 5 b). Safety Roxadustat was well tolerated in the patients. One patient in the no iron group died during the follow-up period, and the investigators determined that it was unrelated to roxadustat. Hypertension requiring increased or altered antihypertensive medication was the most common adverse event, with 35 patients in the no iron group and 15 in the oral iron group. In the 24-week study, roxadustat did not increase the incidence of hyperkalemia in PD patients (P = 0.651). In the no iron group, 5.17% of patients had hyperkalemia (defined as serum potassium concentration > 5.50 mmol/L) at baseline, and 0.00% had hyperkalemia at week 24. In the oral iron group, this proportion was 2.08% at baseline and 3.23% at week 24. The incidence of acidosis was significantly lower in the no iron group (P < 0.001) and remained stable in the oral iron group. High-sensitivity C-reactive protein levels were evaluated, and the proportion of patients with C-reactive protein levels above the normal range remained stable throughout the study. Eleven cases of peritonitis occurred during the 24-week study (4 in the no iron group; 7 in the oral iron group). The severity of peritonitis was mild or moderate, and both types were resolved with antibiotic treatment; no patients stopped using roxadustat due to peritonitis. Discussion In this 24-week clinical study involving patients with PD, roxadustat significantly improved iron metabolism by reducing hepcidin levels and mobilizing stored iron. However, with an increase in the iron utilization rate, the proportion of patients with absolute iron deficiency in the no iron group increased significantly, suggesting that appropriate iron supplementation is necessary during roxadustat treatment. Additionally, roxadustat effectively alleviated anemia in PD patients without increasing the incidence of hyperkalemia or acidosis. Roxadustat increased the mean Hb concentration by 8 g/L within 8 weeks of treatment, independent of whether oral iron was administered. During the last 8 weeks of the treatment period, greater changes in Hb levels were observed in the oral iron group than in the no iron group. In contrast to EPO analogues, roxadustat modestly increased endogenous EPO levels. Mild supplementation with oral iron (median: 200 mg per day) resulted in a marked change in Hb levels. The mechanism of renal anemia is complex, and reduced EPO levels and iron metabolism disorders are considered the main causes [ 24 , 25 ]. PD patients often experience iron metabolism disorders due to chronic inflammation, blood loss, use of anemia medications, intestinal absorption defects, and reduced reabsorption [ 26 , 27 ]. In clinical practice, the sFt level is typically used as an indicator of iron storage status, whereas the TSAT level serves as a measure of iron utilization [ 28 ]. Both parameters can be altered by infections or inflammation, thereby affecting their sensitivity and specificity [ 29 ]. Although bone marrow iron staining remains the gold standard for diagnosing iron deficiency, this procedure is invasive and costly, making it impractical for routine clinical application. The percentage of hypochromic red blood cells (HRC%) and the reticulocyte Hb content (CHr) are independent of inflammatory status and can reflect functional iron status [ 30 ]. It is recommended to evaluate iron deficiency using HRC%> 6% and CHr < 29 pg. However, it should be noted that prolonged sample transportation and storage may increase HRC% readings, so testing must be completed within 6 hours after blood collection. sTFR is derived mainly from ferroportin (FPN) on the membrane surface of normoblasts and mediates the entry of iron-containing sFt into cells. The sTFR level is proportional to the TFR level, which is determined mainly by the intracellular iron demand and erythropoietic activity [ 31 ]. Unlike other iron parameters, the sTFR level is not affected by inflammation, trauma, stress or other factors, and the concentration of sTFR increases rapidly in early iron deficiency, which is conducive to the early diagnosis of iron deficiency anemia [ 32 , 33 ]. The sTFR/logsFt ratio is an indicator of iron deficiency when the sFt level is elevated because of inflammation [ 34 ]. Iron metabolism disorders in CKD patients have attracted widespread attention, but iron metabolism disorders cannot be effectively corrected in a large proportion of CKD patients. As an HIF-PHI, roxadustat activates the HIF pathway by reversibly and transiently inhibiting the activity of PHD [ 35 ]. HIF is a crucial transcription factor that adapts to oxygen changes in the body. It forms a heterodimer composed of the oxygen-sensitive HIF-α subunit and the constitutive HIF-β subunit. Under normal conditions, HIF-α is rapidly degraded by PHD. During hypoxia or after PHI treatment, reduced PHD activity allows more HIF-α to enter the nucleus, where it recruits HIF-β and induces the expression of specific target genes, indirectly lowering hepcidin expression [ 36 ]. Hepcidin, which is secreted by hepatocytes, functions by controlling the activity of the cellular iron exporter ferroportin, which delivers iron to the plasma through intestinal iron absorption and from iron stores [ 37 ]. The hepcidin concentration in plasma is increased by iron loading and inflammation and is suppressed by erythropoietic stimulation and during pregnancy [ 6 ]. Therefore, when hepcidin is overproduced, iron cannot be released from iron-storing and iron-absorbing cells, leading to decreased circulating iron levels [ 38 ]. Since hepcidin is rapidly cleared from the circulation by the kidneys within minutes, its production rate can be swiftly adjusted to modify circulating concentrations and thereby regulate iron metabolism. In CKD patients, owing to increased hepcidin synthesis caused by the iron load and chronic inflammatory status and decreased hepcidin clearance in the kidney due to a decreased glomerular filtration rate, the two combined lead to elevated hepcidin levels in the plasma of CKD patients, especially in ESRD patients [ 39 ]. It is commonly believed that the absorption of oral iron supplements is inhibited by high hepcidin levels and that oral iron supplements may limit the bioavailability of iron supplements by inducing hepcidin expression, resulting in the formation of a negative feedback loop [ 40 ]. However, in our study, roxadustat significantly reduced hepcidin levels in PD patients receiving iron supplementation or not. This suppression of hepcidin in concert with the roxadustat-induced increases in the levels of transferrin, which increase iron-absorbing capacity, may explain the sufficiency of low-dose oral iron for anemia correction. HIF is a crucial transcription factor that helps the body adapt to oxygen changes, inducing a series of target genes related to erythropoiesis, angiogenesis, and energy metabolism to respond to hypoxic stress. In addition to suppressing hepcidin expression, HIF-1 enhances iron utilization by upregulating transferrin, ceruloplasmin, and TFR1. HIF-2 plays a key role in regulating iron uptake. Mice lacking intestinal epithelial HIF-2 exhibit reduced levels of duodenal cytochrome B, divalent metal transporter 1, and FPN in duodenal cells, decreasing intestinal iron absorption [ 41 ]. Therefore, the increased iron consumption observed in iron-deficient groups may result not only from enhanced hematopoietic function but may also be associated with improved iron utilization efficiency. Under hypoxic conditions, this system activates multiple genes to increase the cellular oxygen supply, in addition to regulating erythropoiesis and iron metabolism, including angiogenesis, lipid and glucose metabolism, glycolysis, mitochondrial function, inflammation and immunity, cell growth and survival, vasodilation, and cell migration [ 42 ]. Notably, this study has the following limitations: First, this trial was a single-center study, and the findings may not be generalizable to other populations. Second, this study examined changes in patients’ conditions after only 24 weeks of treatment, which may not have been long enough to assess the safety of roxadustat. HIF has been demonstrated to be associated with risks of angiogenesis and cancer, and further studies are needed before firm conclusions can be drawn [ 43 ]. Conclusions In conclusion, this 24-week prospective cohort study confirmed that the combination of roxadustat and oral iron supplementation is more effective than roxadustat alone in ameliorating anemia in PD patients. Roxadustat improves iron metabolism in patients by inhibiting the expression of hepcidin and inducing the expression of molecules required for the iron cycle. However, with increased iron utilization, some patients may develop absolute iron deficiency. In clinical practice, iron agents should be used individually according to the patient’s iron metabolism status, and monitoring should be strengthened to achieve efficient, safe and economical management of anemia in peritoneal dialysis patients. Abbreviations Full name Abbreviation chronic kidney disease CKD end-stage renal disease ESRD erythropoiesis-stimulating agents ESAs erythropoietin EPO ferroportin FPN hypoxia-inducible factor-prolyl hydroxylase inhibitor HIF-PHI peritoneal dialysis PD serum iron SI serum ferritin sFt serum soluble transferrin receptor sTFR total iron binding capacity TIBC transferrin saturation TSAT Declarations Ethics approval and consent to participate This study adhered to the Declaration of Helsinki and was approved by the Ethics Committee of the Affiliated Jintan Hospital of Jiangsu University (2025-KY-007). All the enrolled patients signed an informed consent form. Consent for publication Not applicable. Data a vailability statement The data that support the findings of this study are available on request from the corresponding author. Competing interests The authors declare that they have no competing interests. Funding This study was supported by the Science and Technology Project of Jintan District Health Bureau (JTYXH-2025-2-08) and a project of the Practice and Innovation Plan of Jiangsu Province (SJCX21_1147). Author contribution Zhang Xuejie completed the study conception and design, data analysis and interpretation, and thesis writing. Acknowledgements We would like to extend our sincere gratitude to The Affiliated Jintan Hospital of Jiangsu University for providing us with a conducive and comfortable platform during our study. We also deeply appreciate our dear colleagues for their reliable, tireless support and assistance. References Shaikh HMF. P.Anemiaofchronickidneydisease.In:StatPearls.TreasureIsland,FL:StatPearlsPublishing,LLC; 2025. Spinowitz FS. B.Update on anemia in ESRD and earlier stages of CKD: Core curriculum 2018 .. Am J Kidney Dis 2018; 71 :423–35. Pasricha SR, Tye–Din J, Muckenthaler MU, Swinkels DW. Iron deficiency Lancet 2021; 397 :233–48. Zhao PRL. 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Am J Clin Nutr 2017; 106 :S1606–14 S . Chernyavskaya BA. LM,Gurevich K, Roxadustat (FG–4592): correction of anemia in incident dialysis patients.J Am Soc Nephrol 2016; 27 :1225–33. Heras–Benito M. Renal anemia: current treatments and emerging molecules Rev Clin Esp (Barc) 2023; 223 :433–9. Gao GZ. H,etal.Study on HIF–PHI combined with iron supplement in treatment of renal anemia in rats .. BMC Nephrol 2025; 26 :125. Kapitsinou BEK. CP,Jalal DI. Iron deficiency in chronic kidney disease: updates on pathophysiology, diagnosis, and treatment .. J Am Soc Nephrol 2020; 31 :456–68. Janc BK. S, Młynarska E, Anemia of chronic kidney disease–a narrative review of its pathophysiology, diagnosis, and management.Biomedicines 2024; 12 :1191. Girelli DVL. M,Elliott S, Mark PB, Iron biology. Nephrol . Dial Transpl 2024; 39 :1404–15. Abe MT. H.Iron metabolism and inflammatory mediators in patients with renal dysfunction .. Int J Mol Sci 2024; 25 :3745. Thomas RLE. D,etal.Diagnosis and management of iron deficiency in CKD: a summary of the NICE guideline recommendations and their rationale.Am J Kidney Dis 2016; 67 :548–58. Yusra, Lismawati, Effendy DA, Kurniawan LL, Lydia A. Role of soluble transferrin receptor–an iron marker in hemodialysis patients. Indian J Nephrol 2022; 32 :555–9. Saboor. M, Zehra A, Hamali HA, Mobarki AA. Revisiting iron metabolism, iron homeostasis and iron deficiency anemia . Clin Lab 2021; 67 :660–6. Addo MZ. ME,Sharma AJ, Flores–Ayala RC, Brittenham GM. Physiologically based serum ferritin thresholds for iron deficiency in children and non–pregnant women: a US national health and nutrition examination surveys (NHANES) serial cross–sectional study . Lancet Haematol 2021; 8 :e572–82. Eisenga BJL. F,etal.Controversiesinoptimalanemiamanagement:conclusionsfromakidneydisease:improvingglobaloutcomes(KDIGO)conference.KidneyInt .2021;99:1280–95. Sato T, Takeda N. The roles of HIF–1α signaling in cardiovascular diseases J Cardiol 2023; 81 :202–8. Tsuchiya OC. K,Maeda K. Hypoxia–inducible factor prolyl hydroxylase inhibitors and iron metabolism .. Int J Mol Sci 2023; 24 :3037. Rana S, Prabhakar N. Iron disorders and hepcidin. Clin Chim Acta 2021; 523 :454–68. Nemeth E, Ganz T. Hepcidin–ferroportin interaction controls systemic iron homeostasis. Int J Mol Sci 2021; 22 :6493 Talbot CD. H.Iron, hepcidin, and immunity .. Adv Exp Med Biol 2025; 1480 :197–215. Reikvam SM. H.Hepcidin as a therapeutic target in iron overload.Expert Opin Ther Targets 2024; 28 :1039–46. ChoudhryH,Harris AL. Advances in hypoxia–inducible factor biology . Cell Metab 2018; 27 :281–98. Taylor CT, Scholz CC. The effect of HIF on metabolism and immunity. Nat Rev Nephrol 2022; 18 :573–87. Shi Y, Gilkes DM. HIF–1 and HIF–2 in cancer: structure, regulation, and therapeutic prospects. Cell Mol Life Sci. 2025;82:44. Additional Declarations No competing interests reported. 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09:18:25","extension":"xml","order_by":33,"title":"","display":"","copyAsset":false,"role":"acdc-reference","size":142153,"visible":true,"origin":"","legend":"","description":"","filename":"0c6a6c5ecfd1435e9df47b016fecdc1b1structuring.xml","url":"https://assets-eu.researchsquare.com/files/rs-8336397/v1/fcaa8138f60b2ffa468a4882.xml"},{"id":99319937,"identity":"a8a2307c-8567-4b43-aaac-9ae96f7dac04","added_by":"auto","created_at":"2025-12-31 16:38:01","extension":"html","order_by":34,"title":"","display":"","copyAsset":false,"role":"acdc-reference","size":154754,"visible":true,"origin":"","legend":"","description":"","filename":"earlyproof.html","url":"https://assets-eu.researchsquare.com/files/rs-8336397/v1/3cebbdf5d037ff3f8eee0571.html"},{"id":99218314,"identity":"241a82f5-6eb4-4ab6-8aeb-c055ab5f6c26","added_by":"auto","created_at":"2025-12-30 09:18:24","extension":"png","order_by":1,"title":"Figure 1","display":"","copyAsset":false,"role":"figure","size":225647,"visible":true,"origin":"","legend":"\u003cp\u003ePatient flowchart. Among 391 PD patients who were regularly followed up, 106 eligible patients were included [no iron group, n=58 (54.72%); oral iron group, n=48 (45.28%)]. A total of 70 patients completed 24 weeks of treatment [no iron group, n=39 (67.24%); oral iron group, n=31 (64.58%)], 22.41 and 18.75% of patients were lost to follow-up, and 10.34% and 16.67% discontinued intervention in the no iron and oral iron groups, respectively.\u003c/p\u003e","description":"","filename":"1.png","url":"https://assets-eu.researchsquare.com/files/rs-8336397/v1/01a1b886426dfc360a7e5c4b.png"},{"id":99218313,"identity":"df8bcc9f-1966-4209-b730-beeb9e9fa16b","added_by":"auto","created_at":"2025-12-30 09:18:24","extension":"png","order_by":2,"title":"Figure 2","display":"","copyAsset":false,"role":"figure","size":14199,"visible":true,"origin":"","legend":"\u003cp\u003eRoxadustat doses in the no iron group and oral iron group.\u003c/p\u003e","description":"","filename":"2.png","url":"https://assets-eu.researchsquare.com/files/rs-8336397/v1/c8630f788537b7de16d116f6.png"},{"id":99318226,"identity":"4578c085-a5a0-47ad-9de7-1f955e1b3f48","added_by":"auto","created_at":"2025-12-31 16:32:13","extension":"png","order_by":3,"title":"Figure 3","display":"","copyAsset":false,"role":"figure","size":25110,"visible":true,"origin":"","legend":"\u003cp\u003eHepcidin levels in the no iron group and oral iron group.\u003c/p\u003e\n\u003cp\u003e**Significant difference between groups (P\u0026lt;0.01)\u003c/p\u003e","description":"","filename":"3.png","url":"https://assets-eu.researchsquare.com/files/rs-8336397/v1/15f8de785cad44da8aa0b820.png"},{"id":99218315,"identity":"9cbd241d-ea6b-4217-9dfa-96db093ec4e0","added_by":"auto","created_at":"2025-12-30 09:18:24","extension":"png","order_by":4,"title":"Figure 4","display":"","copyAsset":false,"role":"figure","size":40682,"visible":true,"origin":"","legend":"\u003cp\u003esTFR levels (a) and mean change from baseline by treatment (no iron versus oral iron) at week 8 and week 24 (b). sTFR/logsFt levels (c) and the proportion of patients with a TFR/logsFt ratio\u0026lt;1, a sTFR/logsFt ratio≥1 but \u0026lt;2 and a sTFR/logsFt ratio≥2 by treatment (no iron versus oral iron) at baseline, week 8 and week 24. (s). sTFR denotes serum soluble transferrin receptor, and sFt denotes serum ferritin.\u003c/p\u003e\n\u003cp\u003e*Significant difference between groups (P\u0026lt;0.05).\u003c/p\u003e","description":"","filename":"4.png","url":"https://assets-eu.researchsquare.com/files/rs-8336397/v1/18e16d73c6117381cb9ffeba.png"},{"id":99318141,"identity":"7ce6d6de-e40c-4b26-854d-455bcb37284e","added_by":"auto","created_at":"2025-12-31 16:31:36","extension":"png","order_by":5,"title":"Figure 5","display":"","copyAsset":false,"role":"figure","size":28471,"visible":true,"origin":"","legend":"\u003cp\u003eProportion of patients with absolute iron deficiency and functional iron deficiency (a) and Hb concentration \u0026lt;110 g/L, Hb concentration ≥110 g/L but \u0026lt;130 g/L and Hb concentration ≥130 g/L (b) by treatment (no iron versus oral iron) at baseline, week 8 and week 24. Hb denotes Hb.\u003c/p\u003e","description":"","filename":"5.png","url":"https://assets-eu.researchsquare.com/files/rs-8336397/v1/91cd9f13afa59f894d4b02fd.png"},{"id":104383636,"identity":"4cf621f5-3b7c-4638-8a9a-d5738cef1ce7","added_by":"auto","created_at":"2026-03-11 08:12:38","extension":"pdf","order_by":0,"title":"","display":"","copyAsset":false,"role":"manuscript-pdf","size":1166917,"visible":true,"origin":"","legend":"","description":"","filename":"manuscript.pdf","url":"https://assets-eu.researchsquare.com/files/rs-8336397/v1/1798fe8c-9da9-4b06-b508-bdadfaa6cc1b.pdf"}],"financialInterests":"No competing interests reported.","formattedTitle":"\u003cp\u003eEffect of oral iron on the ability of roxadustat to ameliorate anemia in peritoneal dialysis patients: A real-world 24-week study\u003c/p\u003e","fulltext":[{"header":"Background","content":"\u003cp\u003eRenal anemia is a common and severe complication in patients with CKD, particularly those with end-stage renal disease (ESRD) [\u003cspan citationid=\"CR1\" class=\"CitationRef\"\u003e1\u003c/span\u003e], and is closely associated with increased cardiovascular events, cognitive dysfunction, and all-cause mortality. PD, as a critical renal replacement therapy for end-stage renal disease (ESRD), involves complex pathophysiological mechanisms underlying anemia in patients. In addition to absolute or relative erythropoietin (EPO) deficiency, iron metabolism disorders\u0026mdash;particularly functional iron deficiency driven by microinflammatory states and characterized by elevated serum ferritin (sFt) levels and decreased transferrin saturation (TSAT) levels\u0026mdash;are the core factors contributing to refractory anemia and EPO resistance [\u003cspan citationid=\"CR2\" class=\"CitationRef\"\u003e2\u003c/span\u003e, \u003cspan citationid=\"CR3\" class=\"CitationRef\"\u003e3\u003c/span\u003e].\u003c/p\u003e \u003cp\u003eExtensive studies have confirmed that renal anemia is prevalent among peritoneal dialysis (PD) patients [\u003cspan citationid=\"CR4\" class=\"CitationRef\"\u003e4\u003c/span\u003e], with treatment relying on erythropoietin-stimulating agents (ESAs), iron supplements, and in severe cases, blood transfusions [\u003cspan citationid=\"CR5\" class=\"CitationRef\"\u003e5\u003c/span\u003e]. However, the conventional regimen of ESA combined with iron therapy faces challenges such as iron-regulated functional iron deficiency [\u003cspan citationid=\"CR6\" class=\"CitationRef\"\u003e6\u003c/span\u003e], inflammatory state interference [\u003cspan citationid=\"CR7\" class=\"CitationRef\"\u003e7\u003c/span\u003e], and potential adverse effects of intravenous iron [\u003cspan citationid=\"CR8\" class=\"CitationRef\"\u003e8\u003c/span\u003e, \u003cspan citationid=\"CR9\" class=\"CitationRef\"\u003e9\u003c/span\u003e]. Therefore, there is an urgent need for safer and more effective treatment options for anemia in PD patients.\u003c/p\u003e \u003cp\u003eTo address these issues, HIF-PHI are receiving increasing attention [\u003cspan citationid=\"CR10\" class=\"CitationRef\"\u003e10\u003c/span\u003e, \u003cspan citationid=\"CR11\" class=\"CitationRef\"\u003e11\u003c/span\u003e]. Roxadustat improves erythropoiesis at the physiological level and iron utilization by stabilizing hypoxia-inducible factor [\u003cspan citationid=\"CR12\" class=\"CitationRef\"\u003e12\u003c/span\u003e], upregulating endogenous EPO expression, and downregulating hepcidin synthesis [\u003cspan citationid=\"CR13\" class=\"CitationRef\"\u003e13\u003c/span\u003e, \u003cspan citationid=\"CR14\" class=\"CitationRef\"\u003e14\u003c/span\u003e]. Recent randomized, multicenter, double-blind clinical studies conducted in China have shown that roxadustat significantly improves the Hb levels in patients with CKD [\u003cspan citationid=\"CR15\" class=\"CitationRef\"\u003e15\u003c/span\u003e, \u003cspan citationid=\"CR16\" class=\"CitationRef\"\u003e16\u003c/span\u003e]. Other studies have also demonstrated that roxadustat is effective in treating renal anemia and reduces the need for blood transfusions and intravenous iron supplementation [\u003cspan additionalcitationids=\"CR18\" citationid=\"CR17\" class=\"CitationRef\"\u003e17\u003c/span\u003e\u0026ndash;\u003cspan citationid=\"CR19\" class=\"CitationRef\"\u003e19\u003c/span\u003e].This mechanism raises a key clinical question: Is traditional oral iron supplementation still necessary under roxadustat treatment?\u003c/p\u003e \u003cp\u003eThe microinflammatory state in peritoneal dialysis patients alters the actual levels of parameters such as TSAT and sFt by influencing transferrin and hepcidin levels [\u003cspan citationid=\"CR20\" class=\"CitationRef\"\u003e20\u003c/span\u003e]. Therefore, the level of sTFR unaffected by inflammation can provide more information for evaluating iron metabolism in CKD patients [\u003cspan citationid=\"CR21\" class=\"CitationRef\"\u003e21\u003c/span\u003e]. By leveraging the relationship between these two iron-deficiency-related variables, the sTFR/logFt ratio can enhance the diagnostic efficacy of using sTFR or sFt alone [\u003cspan citationid=\"CR22\" class=\"CitationRef\"\u003e22\u003c/span\u003e].\u003c/p\u003e \u003cp\u003eHere, we report a phase 3 study in which patients were not treated with roxadustat, ESAs, or iron during the first six weeks of enrolment and were assigned to receive either no iron supplementation or oral iron supplementation depending on whether they were taking iron supplements. The aim of this study was to evaluate the effect of roxadustat treatment on iron metabolism in peritoneal dialysis patients and to evaluate the exogenous iron requirement in the treatment of anemia in PD patients.\u003c/p\u003e"},{"header":"Methods","content":"\u003cdiv id=\"Sec3\" class=\"Section2\"\u003e \u003ch2\u003eStudy design\u003c/h2\u003e \u003cp\u003eThis study is a single-center prospective cohort study, selecting PD patients with regular follow-up. This study was approved by the Ethics Committee of the Affiliated Jintan Hospital of Jiangsu University (2025-KY-007) and completed the Chinese Clinical Trial Registration (registration number: ChiCTR2200057231). Patients were required to meet the following inclusion criteria: (1) Age 18\u0026ndash;75 years; (2) Regular PD for at least 6 weeks; (3) No prior treatment with ESAs, roxadustat, or iron supplements within 6 weeks before enrollment; (4) Mean Hb 60\u0026ndash;100 g/L. Patients were excluded if they met any of the following exclusion criteria: (1) Combined with other dialysis modalities; (2) Received iron supplements, ESAs, or roxadustat within 6 weeks; (3) Severe organic dysfunction of the heart, liver, lungs, or brain; (4) Incomplete clinical data.\u003c/p\u003e \u003c/div\u003e\n\u003ch3\u003eCalculation sample size\u003c/h3\u003e\n\u003cp\u003eThe sample sizes (N1\u0026thinsp;=\u0026thinsp;34; N2\u0026thinsp;=\u0026thinsp;34) for the no iron group and the oral iron group were based on a multicenter randomized controlled clinical trial conducted [\u003cspan citationid=\"CR23\" class=\"CitationRef\"\u003e23\u003c/span\u003e], with a 1:1 ratio between the two groups. The sample sizes were calculated using PASS15.0 software, with two-tailed α\u0026thinsp;=\u0026thinsp;0.05 and the test efficiency was 90%. A total of 106 patients were enrolled based on actual conditions, with an estimated dropout rate of 30%.\u003c/p\u003e\n\u003ch3\u003eStudy drug administration\u003c/h3\u003e\n\u003cp\u003eThe initial dose of roxadustat [Enambojin (China) Pharmaceutical Technology Development Co., Ltd., Sinopharm H20180024 (50 mg), H20180023 (20 mg)] was determined based on the patient's weight: 100 mg (for weight between 45 and 60 kg) or 120 mg (for weight\u0026thinsp;\u0026ge;\u0026thinsp;60 kg) three times weekly, with dosage adjusted according to the instructions, and the maximum dose was 2.5 mg/kg. Patients in the oral iron group used ferrous succinate sustained-release tablets (Jinling Pharmaceutical Co., Ltd., Sinopharm H20010307), 0.2-0.4g daily. Intravenous iron administration was prohibited during the study.\u003c/p\u003e\n\u003ch3\u003eEnd points\u003c/h3\u003e\n\u003cp\u003eThe primary endpoints were: the proportion of patients achieving the treatment goal (defined as a Hb concentration of 110\u0026ndash;130 g/L), changes in iron biomarker levels from baseline to week 24, including sTFR, serum iron (SI), sFt, TSAT, and total iron binding capacity (TIBC), and the proportions of patients with absolute iron deficiency (defined as TSAT\u0026thinsp;\u0026lt;\u0026thinsp;20% and sFt\u0026thinsp;\u0026lt;\u0026thinsp;100 ng/mL) and functional iron deficiency (defined as TSAT\u0026thinsp;\u0026lt;\u0026thinsp;20% and sFt\u0026thinsp;\u0026ge;\u0026thinsp;100 ng/mL). The secondary endpoints were the incidence of hyperkalemia, metabolic acidosis, and peritonitis.\u003c/p\u003e \u003cdiv id=\"Sec7\" class=\"Section2\"\u003e \u003ch2\u003eStatistical analysis\u003c/h2\u003e \u003cp\u003eAll the data were analyzed with SPSS 25.0. Continuous variables with a normal distribution were expressed as mean\u0026thinsp;\u0026plusmn;\u0026thinsp;standard deviation and analyzed using the independent samples t-test. Non-normal data were presented as median and interquartile range and analyzed using the Wilcoxon rank sum test. Categorical data were expressed as percentages and analyzed using the chi-square test. A mixed-effects repeated measures model was employed to analyze the mean changes in iron biomarker levels, Hb levels, and lipid metabolism levels at week 24 compared to week 8 and baseline. A two-tailed P value\u0026thinsp;\u0026lt;\u0026thinsp;0.05 was considered statistically significant.\u003c/p\u003e \u003c/div\u003e"},{"header":"Results","content":"\u003cdiv id=\"Sec9\" class=\"Section2\"\u003e\n\u003ch2\u003ePatient characteristics and disposition\u003c/h2\u003e\n\u003cp\u003eAmong the 106 patients enrolled (no iron, 58; oral iron, 48), 18 (8.3%) discontinued the study within the first 8 weeks, 18 (8.3%) discontinued the study at weeks 8\u0026ndash;24, and the remaining 70 patients completed the 24-week study (Fig.\u0026nbsp;\u003cspan class=\"InternalRef\"\u003e1\u003c/span\u003e). The average daily iron dose for patients receiving oral iron therapy was 3.77 mg/kg. Demographic and baseline characteristics did not significantly differ between the cohorts (Table\u0026nbsp;\u003cspan class=\"InternalRef\"\u003e1\u003c/span\u003e). The mean baseline Hb concentration among the patients enrolled was 87.84\u0026thinsp;\u0026plusmn;\u0026thinsp;9.42 g/L.\u003c/p\u003e\n\u003cdiv class=\"gridtable\"\u003e\n\u003cdiv class=\"colspec\" align=\"left\"\u003e\u0026nbsp;\u003c/div\u003e\n\u003ctable id=\"Tab1\" border=\"1\"\u003e\u003ccaption\u003e\n\u003cdiv class=\"CaptionNumber\"\u003eTable 1\u003c/div\u003e\n\u003cdiv class=\"CaptionContent\"\u003e\n\u003cp\u003eCharacteristics of the patients at baseline *\u003c/p\u003e\n\u003c/div\u003e\n\u003c/caption\u003e\n\u003cthead\u003e\n\u003ctr\u003e\n\u003cth align=\"left\"\u003e\n\u003cp\u003eCharacteristic\u003c/p\u003e\n\u003c/th\u003e\n\u003cth align=\"left\"\u003e\n\u003cp\u003eNo iron (n\u0026thinsp;=\u0026thinsp;58)\u003c/p\u003e\n\u003c/th\u003e\n\u003cth align=\"left\"\u003e\n\u003cp\u003eOral iron (n\u0026thinsp;=\u0026thinsp;48)\u003c/p\u003e\n\u003c/th\u003e\n\u003cth align=\"left\"\u003e\n\u003cp\u003e\u003cem\u003eP\u003c/em\u003e Value\u003c/p\u003e\n\u003c/th\u003e\n\u003c/tr\u003e\n\u003c/thead\u003e\n\u003ctbody\u003e\n\u003ctr\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003eMale sex, \u003cem\u003en\u003c/em\u003e (%)\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"char\" char=\".\"\u003e\n\u003cp\u003e32 (55.17)\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"char\" char=\".\"\u003e\n\u003cp\u003e27 (56.25)\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"char\" char=\".\"\u003e\n\u003cp\u003e0.911\u003c/p\u003e\n\u003c/td\u003e\n\u003c/tr\u003e\n\u003ctr\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003eAge, years\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"char\" char=\".\"\u003e\n\u003cp\u003e48.40\u0026thinsp;\u0026plusmn;\u0026thinsp;13.04\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"char\" char=\".\"\u003e\n\u003cp\u003e46.63\u0026thinsp;\u0026plusmn;\u0026thinsp;14.38\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"char\" char=\".\"\u003e\n\u003cp\u003e0.508\u003c/p\u003e\n\u003c/td\u003e\n\u003c/tr\u003e\n\u003ctr\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003eBMI, kg/m\u003csup\u003e2\u003c/sup\u003e\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"char\" char=\".\"\u003e\n\u003cp\u003e23.84\u0026thinsp;\u0026plusmn;\u0026thinsp;3.80\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"char\" char=\".\"\u003e\n\u003cp\u003e23.27\u0026thinsp;\u0026plusmn;\u0026thinsp;3.49\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"char\" char=\".\"\u003e\n\u003cp\u003e0.427\u003c/p\u003e\n\u003c/td\u003e\n\u003c/tr\u003e\n\u003ctr\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003eDuration of PD, weeks\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"char\" char=\".\"\u003e\n\u003cp\u003e86.00 (45.25,139.25)\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"char\" char=\".\"\u003e\n\u003cp\u003e78.00 (37.25,115.00)\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"char\" char=\".\"\u003e\n\u003cp\u003e0.648\u003c/p\u003e\n\u003c/td\u003e\n\u003c/tr\u003e\n\u003ctr\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003eMean arterial pressure, mmHg\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"char\" char=\".\"\u003e\n\u003cp\u003e108.17\u0026thinsp;\u0026plusmn;\u0026thinsp;16.86\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"char\" char=\".\"\u003e\n\u003cp\u003e109.53\u0026thinsp;\u0026plusmn;\u0026thinsp;18.63\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"char\" char=\".\"\u003e\n\u003cp\u003e0.693\u003c/p\u003e\n\u003c/td\u003e\n\u003c/tr\u003e\n\u003ctr\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003eGlucose, mmol/L\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"char\" char=\".\"\u003e\n\u003cp\u003e5.06\u0026thinsp;\u0026plusmn;\u0026thinsp;1.53\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"char\" char=\".\"\u003e\n\u003cp\u003e5.78\u0026thinsp;\u0026plusmn;\u0026thinsp;2.35\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"char\" char=\".\"\u003e\n\u003cp\u003e0.063\u003c/p\u003e\n\u003c/td\u003e\n\u003c/tr\u003e\n\u003ctr\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003eHistory of hypertension, \u003cem\u003en\u003c/em\u003e (%)\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"char\" char=\".\"\u003e\n\u003cp\u003e52 (89.66)\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"char\" char=\".\"\u003e\n\u003cp\u003e42 (87.50)\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"char\" char=\".\"\u003e\n\u003cp\u003e0.727\u003c/p\u003e\n\u003c/td\u003e\n\u003c/tr\u003e\n\u003ctr\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003eHistory of diabetes mellitus, \u003cem\u003en\u003c/em\u003e (%)\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"char\" char=\".\"\u003e\n\u003cp\u003e12 (20.69)\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"char\" char=\".\"\u003e\n\u003cp\u003e8 (16.67)\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"char\" char=\".\"\u003e\n\u003cp\u003e0.598\u003c/p\u003e\n\u003c/td\u003e\n\u003c/tr\u003e\n\u003ctr\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003ePeritoneal transport type:\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\u0026nbsp;\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\u0026nbsp;\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\u0026nbsp;\u003c/td\u003e\n\u003c/tr\u003e\n\u003ctr\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003eHigh transport, \u003cem\u003en\u003c/em\u003e (%)\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"char\" char=\".\"\u003e\n\u003cp\u003e4 (6.90)\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"char\" char=\".\"\u003e\n\u003cp\u003e4 (8.33)\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\u0026nbsp;\u003c/td\u003e\n\u003c/tr\u003e\n\u003ctr\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003eHigh average transport, \u003cem\u003en\u003c/em\u003e (%)\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"char\" char=\".\"\u003e\n\u003cp\u003e13 (22.41)\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"char\" char=\".\"\u003e\n\u003cp\u003e12 (25.00)\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\u0026nbsp;\u003c/td\u003e\n\u003c/tr\u003e\n\u003ctr\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003eLow transport, \u003cem\u003en\u003c/em\u003e (%)\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"char\" char=\".\"\u003e\n\u003cp\u003e3 (5.17)\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"char\" char=\".\"\u003e\n\u003cp\u003e5 (10.42)\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"char\" char=\".\"\u003e\n\u003cp\u003e0.417\u003c/p\u003e\n\u003c/td\u003e\n\u003c/tr\u003e\n\u003ctr\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003eLow average transport, \u003cem\u003en\u003c/em\u003e (%)\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"char\" char=\".\"\u003e\n\u003cp\u003e21 (36.21)\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"char\" char=\".\"\u003e\n\u003cp\u003e20 (41.67)\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\u0026nbsp;\u003c/td\u003e\n\u003c/tr\u003e\n\u003ctr\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003eUnknown, \u003cem\u003en\u003c/em\u003e (%)\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"char\" char=\".\"\u003e\n\u003cp\u003e17 (29.31)\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"char\" char=\".\"\u003e\n\u003cp\u003e7 (14.58)\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\u0026nbsp;\u003c/td\u003e\n\u003c/tr\u003e\n\u003ctr\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003ePathological diagnosis:\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\u0026nbsp;\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\u0026nbsp;\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\u0026nbsp;\u003c/td\u003e\n\u003c/tr\u003e\n\u003ctr\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003eChronic glomerulonephritis, \u003cem\u003en\u003c/em\u003e (%)\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"char\" char=\".\"\u003e\n\u003cp\u003e19 (32.76)\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"char\" char=\".\"\u003e\n\u003cp\u003e20 (41.67)\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\u0026nbsp;\u003c/td\u003e\n\u003c/tr\u003e\n\u003ctr\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003ePolycystic kidney, \u003cem\u003en\u003c/em\u003e (%)\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"char\" char=\".\"\u003e\n\u003cp\u003e4 (6.90)\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"char\" char=\".\"\u003e\n\u003cp\u003e4 (8.33)\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\u0026nbsp;\u003c/td\u003e\n\u003c/tr\u003e\n\u003ctr\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003eHypertension, \u003cem\u003en\u003c/em\u003e (%)\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"char\" char=\".\"\u003e\n\u003cp\u003e17 (29.31)\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"char\" char=\".\"\u003e\n\u003cp\u003e13 (27.08)\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\u0026nbsp;\u003c/td\u003e\n\u003c/tr\u003e\n\u003ctr\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003eDiabetes, \u003cem\u003en\u003c/em\u003e (%)\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"char\" char=\".\"\u003e\n\u003cp\u003e11 (18.97)\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"char\" char=\".\"\u003e\n\u003cp\u003e7 (14.58)\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"char\" char=\".\"\u003e\n\u003cp\u003e0.925\u003c/p\u003e\n\u003c/td\u003e\n\u003c/tr\u003e\n\u003ctr\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003eNephrotic syndrome, \u003cem\u003en\u003c/em\u003e (%)\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"char\" char=\".\"\u003e\n\u003cp\u003e4 (6.90)\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"char\" char=\".\"\u003e\n\u003cp\u003e2 (4.17)\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\u0026nbsp;\u003c/td\u003e\n\u003c/tr\u003e\n\u003ctr\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003eOthers, \u003cem\u003en\u003c/em\u003e (%)\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"char\" char=\".\"\u003e\n\u003cp\u003e3 (5.17)\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"char\" char=\".\"\u003e\n\u003cp\u003e2 (4.17)\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\u0026nbsp;\u003c/td\u003e\n\u003c/tr\u003e\n\u003ctr\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003esTFR, nmol/L\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"char\" char=\".\"\u003e\n\u003cp\u003e36.81\u0026thinsp;\u0026plusmn;\u0026thinsp;11.49\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"char\" char=\".\"\u003e\n\u003cp\u003e36.98\u0026thinsp;\u0026plusmn;\u0026thinsp;8.11\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"char\" char=\".\"\u003e\n\u003cp\u003e0.931\u003c/p\u003e\n\u003c/td\u003e\n\u003c/tr\u003e\n\u003ctr\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003eHepcidin, ng/ml\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"char\" char=\".\"\u003e\n\u003cp\u003e105.04\u0026thinsp;\u0026plusmn;\u0026thinsp;29.00\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"char\" char=\".\"\u003e\n\u003cp\u003e104.28\u0026thinsp;\u0026plusmn;\u0026thinsp;25.65\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"char\" char=\".\"\u003e\n\u003cp\u003e0.887\u003c/p\u003e\n\u003c/td\u003e\n\u003c/tr\u003e\n\u003ctr\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003eSI, \u0026micro;mol/L\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"char\" char=\".\"\u003e\n\u003cp\u003e14.53\u0026thinsp;\u0026plusmn;\u0026thinsp;6.33\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"char\" char=\".\"\u003e\n\u003cp\u003e12.35\u0026thinsp;\u0026plusmn;\u0026thinsp;6.49\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"char\" char=\".\"\u003e\n\u003cp\u003e0.085\u003c/p\u003e\n\u003c/td\u003e\n\u003c/tr\u003e\n\u003ctr\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003esFt, ng/ml\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"char\" char=\".\"\u003e\n\u003cp\u003e210.35 (81.47,354.95)\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"char\" char=\".\"\u003e\n\u003cp\u003e200.90 (55.14,322.65)\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"char\" char=\".\"\u003e\n\u003cp\u003e0.356\u003c/p\u003e\n\u003c/td\u003e\n\u003c/tr\u003e\n\u003ctr\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003esTFR/LogsFt\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"char\" char=\".\"\u003e\n\u003cp\u003e1.46\u0026thinsp;\u0026plusmn;\u0026thinsp;0.65\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"char\" char=\".\"\u003e\n\u003cp\u003e1.52\u0026thinsp;\u0026plusmn;\u0026thinsp;0.45\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"char\" char=\".\"\u003e\n\u003cp\u003e0.574\u003c/p\u003e\n\u003c/td\u003e\n\u003c/tr\u003e\n\u003ctr\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003eTSAT, %\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"char\" char=\".\"\u003e\n\u003cp\u003e34.57\u0026thinsp;\u0026plusmn;\u0026thinsp;15.32\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"char\" char=\".\"\u003e\n\u003cp\u003e29.18\u0026thinsp;\u0026plusmn;\u0026thinsp;14.75\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"char\" char=\".\"\u003e\n\u003cp\u003e0.070\u003c/p\u003e\n\u003c/td\u003e\n\u003c/tr\u003e\n\u003ctr\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003eTIBC, \u0026micro;mol/L\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"char\" char=\".\"\u003e\n\u003cp\u003e42.89\u0026thinsp;\u0026plusmn;\u0026thinsp;10.39\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"char\" char=\".\"\u003e\n\u003cp\u003e43.86\u0026thinsp;\u0026plusmn;\u0026thinsp;12.68\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"char\" char=\".\"\u003e\n\u003cp\u003e0.666\u003c/p\u003e\n\u003c/td\u003e\n\u003c/tr\u003e\n\u003ctr\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003eHemoglobin, g/L\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"char\" char=\".\"\u003e\n\u003cp\u003e87.81\u0026thinsp;\u0026plusmn;\u0026thinsp;9.01\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"char\" char=\".\"\u003e\n\u003cp\u003e87.88\u0026thinsp;\u0026plusmn;\u0026thinsp;10.00\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"char\" char=\".\"\u003e\n\u003cp\u003e0.972\u003c/p\u003e\n\u003c/td\u003e\n\u003c/tr\u003e\n\u003ctr\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003eRBC, 10\u003csup\u003e12\u003c/sup\u003e/L\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"char\" char=\".\"\u003e\n\u003cp\u003e2.98\u0026thinsp;\u0026plusmn;\u0026thinsp;0.37\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"char\" char=\".\"\u003e\n\u003cp\u003e2.90\u0026thinsp;\u0026plusmn;\u0026thinsp;0.39\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"char\" char=\".\"\u003e\n\u003cp\u003e0.270\u003c/p\u003e\n\u003c/td\u003e\n\u003c/tr\u003e\n\u003ctr\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003eEPO, mIU/mL\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"char\" char=\".\"\u003e\n\u003cp\u003e6.80 (3.86,10.70)\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"char\" char=\".\"\u003e\n\u003cp\u003e5.82 (3.71,8.53)\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"char\" char=\".\"\u003e\n\u003cp\u003e0.175\u003c/p\u003e\n\u003c/td\u003e\n\u003c/tr\u003e\n\u003ctr\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003eFolate, ng/mL\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"char\" char=\".\"\u003e\n\u003cp\u003e6.22 (4.50,20.00)\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"char\" char=\".\"\u003e\n\u003cp\u003e13.8 (4.64,20.00)\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"char\" char=\".\"\u003e\n\u003cp\u003e0.211\u003c/p\u003e\n\u003c/td\u003e\n\u003c/tr\u003e\n\u003ctr\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003eVitamin B\u003csub\u003e12\u003c/sub\u003e, pg/mL\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"char\" char=\".\"\u003e\n\u003cp\u003e479.50 (319.75,786.90)\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"char\" char=\".\"\u003e\n\u003cp\u003e436.50 (302.25,647.00)\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"char\" char=\".\"\u003e\n\u003cp\u003e0.351\u003c/p\u003e\n\u003c/td\u003e\n\u003c/tr\u003e\n\u003ctr\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003eK\u003csup\u003e+\u003c/sup\u003e, mmol/L\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"char\" char=\".\"\u003e\n\u003cp\u003e4.34\u0026thinsp;\u0026plusmn;\u0026thinsp;0.80\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"char\" char=\".\"\u003e\n\u003cp\u003e4.20\u0026thinsp;\u0026plusmn;\u0026thinsp;0.70\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"char\" char=\".\"\u003e\n\u003cp\u003e0.346\u003c/p\u003e\n\u003c/td\u003e\n\u003c/tr\u003e\n\u003ctr\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003e\u0026gt;5.5 mmol/L, \u003cem\u003en\u003c/em\u003e (%)\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"char\" char=\".\"\u003e\n\u003cp\u003e3 (5.17)\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"char\" char=\".\"\u003e\n\u003cp\u003e1 (0.21)\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"char\" char=\".\"\u003e\n\u003cp\u003e0.750\u003c/p\u003e\n\u003c/td\u003e\n\u003c/tr\u003e\n\u003ctr\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003eHCO\u003csup\u003e3\u0026minus;\u003c/sup\u003e, mmol/L\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"char\" char=\".\"\u003e\n\u003cp\u003e21.54\u0026thinsp;\u0026plusmn;\u0026thinsp;3.16\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"char\" char=\".\"\u003e\n\u003cp\u003e21.83\u0026thinsp;\u0026plusmn;\u0026thinsp;3.89\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"char\" char=\".\"\u003e\n\u003cp\u003e0.673\u003c/p\u003e\n\u003c/td\u003e\n\u003c/tr\u003e\n\u003ctr\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003e\u0026lt;22.0 mmol/L, \u003cem\u003en\u003c/em\u003e (%)\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"char\" char=\".\"\u003e\n\u003cp\u003e32 (55.17)\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"char\" char=\".\"\u003e\n\u003cp\u003e19 (39.58)\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"char\" char=\".\"\u003e\n\u003cp\u003e0.129\u003c/p\u003e\n\u003c/td\u003e\n\u003c/tr\u003e\n\u003ctr\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003eP, mmol/L\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"char\" char=\".\"\u003e\n\u003cp\u003e2.16\u0026thinsp;\u0026plusmn;\u0026thinsp;2.90\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"char\" char=\".\"\u003e\n\u003cp\u003e1.68\u0026thinsp;\u0026plusmn;\u0026thinsp;0.52\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"char\" char=\".\"\u003e\n\u003cp\u003e0.254\u003c/p\u003e\n\u003c/td\u003e\n\u003c/tr\u003e\n\u003ctr\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003ePTH, pg/mL\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"char\" char=\".\"\u003e\n\u003cp\u003e230.35 (109.10,446.85)\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"char\" char=\".\"\u003e\n\u003cp\u003e269.30 (158.50,394.23)\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"char\" char=\".\"\u003e\n\u003cp\u003e0.501\u003c/p\u003e\n\u003c/td\u003e\n\u003c/tr\u003e\n\u003ctr\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003eTotal cholesterol, mmol/L\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"char\" char=\".\"\u003e\n\u003cp\u003e3.89\u0026thinsp;\u0026plusmn;\u0026thinsp;1.26\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"char\" char=\".\"\u003e\n\u003cp\u003e4.16\u0026thinsp;\u0026plusmn;\u0026thinsp;1.13\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"char\" char=\".\"\u003e\n\u003cp\u003e0.252\u003c/p\u003e\n\u003c/td\u003e\n\u003c/tr\u003e\n\u003ctr\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003eTriglyceride, mmol/L\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"char\" char=\".\"\u003e\n\u003cp\u003e1.58\u0026thinsp;\u0026plusmn;\u0026thinsp;0.96\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"char\" char=\".\"\u003e\n\u003cp\u003e1.49\u0026thinsp;\u0026plusmn;\u0026thinsp;0.70\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"char\" char=\".\"\u003e\n\u003cp\u003e0.593\u003c/p\u003e\n\u003c/td\u003e\n\u003c/tr\u003e\n\u003ctr\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003eHDL-C, mmol/L\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"char\" char=\".\"\u003e\n\u003cp\u003e0.91\u0026thinsp;\u0026plusmn;\u0026thinsp;0.37\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"char\" char=\".\"\u003e\n\u003cp\u003e0.92\u0026thinsp;\u0026plusmn;\u0026thinsp;0.23\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"char\" char=\".\"\u003e\n\u003cp\u003e0.834\u003c/p\u003e\n\u003c/td\u003e\n\u003c/tr\u003e\n\u003ctr\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003eLDL-C, mmol/L\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"char\" char=\".\"\u003e\n\u003cp\u003e2.36\u0026thinsp;\u0026plusmn;\u0026thinsp;1.06\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"char\" char=\".\"\u003e\n\u003cp\u003e2.52\u0026thinsp;\u0026plusmn;\u0026thinsp;0.92\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"char\" char=\".\"\u003e\n\u003cp\u003e0.415\u003c/p\u003e\n\u003c/td\u003e\n\u003c/tr\u003e\n\u003ctr\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003eC-reactive protein, mg/L\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"char\" char=\".\"\u003e\n\u003cp\u003e1.70 (0.50,5.30)\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"char\" char=\".\"\u003e\n\u003cp\u003e2.30 (0.70,12.20)\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"char\" char=\".\"\u003e\n\u003cp\u003e0.129\u003c/p\u003e\n\u003c/td\u003e\n\u003c/tr\u003e\n\u003ctr\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003e\u0026gt;\u0026thinsp;4.9 mg/L, \u003cem\u003en\u003c/em\u003e (%)\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"char\" char=\".\"\u003e\n\u003cp\u003e16 (27.59)\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"char\" char=\".\"\u003e\n\u003cp\u003e14 (29.17)\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"char\" char=\".\"\u003e\n\u003cp\u003e0.857\u003c/p\u003e\n\u003c/td\u003e\n\u003c/tr\u003e\n\u003ctr\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003eeGFR, ml/min\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"char\" char=\".\"\u003e\n\u003cp\u003e6.21\u0026thinsp;\u0026plusmn;\u0026thinsp;2.31\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"char\" char=\".\"\u003e\n\u003cp\u003e6.71\u0026thinsp;\u0026plusmn;\u0026thinsp;2.17\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"char\" char=\".\"\u003e\n\u003cp\u003e0.254\u003c/p\u003e\n\u003c/td\u003e\n\u003c/tr\u003e\n\u003ctr\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003eCreatinine, \u0026micro;mol/L\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"char\" char=\".\"\u003e\n\u003cp\u003e820.17\u0026thinsp;\u0026plusmn;\u0026thinsp;206.05\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"char\" char=\".\"\u003e\n\u003cp\u003e821.81\u0026thinsp;\u0026plusmn;\u0026thinsp;230.67\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"char\" char=\".\"\u003e\n\u003cp\u003e0.969\u003c/p\u003e\n\u003c/td\u003e\n\u003c/tr\u003e\n\u003c/tbody\u003e\n\u003ctfoot\u003e\n\u003ctr\u003e\n\u003ctd colspan=\"4\"\u003e\u003csup\u003e*Measurement data with a normal distribution are expressed as the means \u0026plusmn; standard deviations, and nonnormally distributed data are expressed as medians and interquartile ranges. Only patients who completed the 24\u0026minus;week study are listed (roxadustat, 70; ESA, 36). No significant between\u0026minus;group differences were found in baseline characteristics. sTFR denotes serum soluble transferrin receptor, Hepc denotes hepcidin, SI denotes serum iron, sFt denotes serum ferritin, TSAT denotes transferrin saturation, TIBC denotes total iron\u0026minus;binding capacity, UIBC denotes unsaturated iron\u0026minus;binding capacity, RBC denotes red blood cell count, EPO denotes erythropoietin, PTH denotes parathyroid hormone, HDL\u0026minus;C denotes high\u0026minus;density lipoprotein, LDL\u0026minus;C denotes low\u0026minus;density lipoprotein, WBC denotes white blood cell count, and eGFR denotes estimated glomerular filtration rate\u003c/sup\u003e.\u003c/td\u003e\n\u003c/tr\u003e\n\u003c/tfoot\u003e\n\u003c/table\u003e\n\u003c/div\u003e\n\u003cp\u003eRoxadustat doses administered\u003c/p\u003e\n\u003c/div\u003e\n\u003cp\u003eAt week 24, the mean dose of roxadustat was 94.29\u0026thinsp;\u0026plusmn;\u0026thinsp;48.02 mg, whereas it was 112.45\u0026thinsp;\u0026plusmn;\u0026thinsp;12.33 mg at week 1 (starting dose). At week 12 (P\u0026thinsp;=\u0026thinsp;0.019), week 20 (P\u0026thinsp;=\u0026thinsp;0.009) and week 24 (P\u0026thinsp;\u0026lt;\u0026thinsp;0.001), the mean dose of roxadustat in the oral iron group was significantly lower than that in the no iron group. At week 24, the mean dose of roxadustat was 80.00\u0026thinsp;\u0026plusmn;\u0026thinsp;47.96 mg in the oral iron group and 105.64\u0026thinsp;\u0026plusmn;\u0026thinsp;45.53 mg in the no iron group (Fig.\u0026nbsp;\u003cspan class=\"InternalRef\"\u003e2\u003c/span\u003e).\u003c/p\u003e\n\u003cdiv id=\"Sec11\" class=\"Section2\"\u003e\n\u003ch2\u003eChanges in iron metabolism indicators\u003c/h2\u003e\n\u003cp\u003eAt week 8, the change in the hepcidin concentration from baseline was \u0026minus;\u0026thinsp;11.23\u0026thinsp;\u0026plusmn;\u0026thinsp;24.14 ng/ml in the oral iron group and \u0026minus;\u0026thinsp;13.47\u0026thinsp;\u0026plusmn;\u0026thinsp;24.98 ng/ml in the no iron group (Fig.\u0026nbsp;\u003cspan class=\"InternalRef\"\u003e3\u003c/span\u003e). At week 24, the difference in the hepcidin concentration between the two groups was 0.061\u0026thinsp;\u0026plusmn;\u0026thinsp;20.35 ng/ml, and the changes in the hepcidin concentration from baseline were \u0026minus;\u0026thinsp;24.33\u0026thinsp;\u0026plusmn;\u0026thinsp;20.35 ng/ml and \u0026minus;\u0026thinsp;25.15\u0026thinsp;\u0026plusmn;\u0026thinsp;24.80 ng/ml, respectively (Fig.\u0026nbsp;\u003cspan class=\"InternalRef\"\u003e3\u003c/span\u003e).\u003c/p\u003e\n\u003cp\u003eAt week 8, the sTFR levels in the oral iron group and the no iron group increased by 1.49\u0026thinsp;\u0026plusmn;\u0026thinsp;9.87 nmol/L and 4.25\u0026thinsp;\u0026plusmn;\u0026thinsp;10.31 nmol/L, respectively, from baseline (Fig.\u0026nbsp;\u003cspan class=\"InternalRef\"\u003e4\u003c/span\u003ea). The intergroup difference was \u0026minus;\u0026thinsp;2.76 nmol/L (95% CI, \u0026minus;\u0026thinsp;7.08 to 1.56). By week 24, the change from baseline in the oral iron group was 5.49\u0026thinsp;\u0026plusmn;\u0026thinsp;8.82 nmol/L, and in the no iron group, it was 11.15\u0026thinsp;\u0026plusmn;\u0026thinsp;10.29 nmol/L, with an intergroup difference of -5.66 nmol/L (95% CI, -10.30 to -1.02) (Fig.\u0026nbsp;\u003cspan class=\"InternalRef\"\u003e4\u003c/span\u003eb). In the oral iron group, the LogsFt level remained clinically stable, with a change from baseline of 0.02\u0026thinsp;\u0026plusmn;\u0026thinsp;0.42% (95% CI, -7.04 to 0.53), and the TIBC and SI levels increased, with changes from baseline of 4.74\u0026thinsp;\u0026plusmn;\u0026thinsp;9.31 \u0026micro;mol/L (95% CI, 0.54\u0026ndash;10.01) and 3.30\u0026thinsp;\u0026plusmn;\u0026thinsp;5.910 \u0026micro;mol/L (95% CI, 0.41\u0026ndash;6.17), respectively. In the no iron group, the SI level remained clinically stable, with a change from baseline of -1.81\u0026thinsp;\u0026plusmn;\u0026thinsp;7.78 \u0026micro;mol/L (95% CI, -4.66 to 1.05); the LogsFt level decreased from baseline by 0.21\u0026thinsp;\u0026plusmn;\u0026thinsp;0.38 (95% CI, -0.36 to -0.02), and the TIBC level increased from baseline by 8.35\u0026thinsp;\u0026plusmn;\u0026thinsp;10.15 \u0026micro;mol/L (95% CI, 4.89\u0026ndash;13.22). The sTFR/LogsFt ratio remained stable in the oral iron group and significantly increased in the no iron group (Fig.\u0026nbsp;\u003cspan class=\"InternalRef\"\u003e4\u003c/span\u003ec): at week 24 of the study, the proportion of patients with a sTFR/LogsFt ratio\u0026thinsp;\u0026gt;\u0026thinsp;2 was 51.28% in the no iron group and 19.35% in the oral iron group (Fig.\u0026nbsp;\u003cspan class=\"InternalRef\"\u003e4\u003c/span\u003ed).\u003c/p\u003e\n\u003cp\u003eAt week 8, the change in the TSAT level from baseline in the oral iron group was 1.79\u0026thinsp;\u0026plusmn;\u0026thinsp;13.69%, whereas it was \u0026minus;\u0026thinsp;6.50\u0026thinsp;\u0026plusmn;\u0026thinsp;14.24% in the no iron group. At week 24, the difference in TSAT levels between the two groups was 8.29 nmol/L (95% CI, 0.87 to 15.70), and the changes in TSAT levels from baseline were 4.31\u0026thinsp;\u0026plusmn;\u0026thinsp;15.05 nmol/L and \u0026minus;\u0026thinsp;9.37\u0026thinsp;\u0026plusmn;\u0026thinsp;15.74 nmol/L, respectively (Table\u0026nbsp;\u003cspan class=\"InternalRef\"\u003e2\u003c/span\u003e).\u003c/p\u003e\n\u003cdiv class=\"gridtable\"\u003e\n\u003cdiv class=\"colspec\" align=\"left\"\u003e\u0026nbsp;\u003c/div\u003e\n\u003ctable id=\"Tab2\" border=\"1\"\u003e\u003ccaption\u003e\n\u003cdiv class=\"CaptionNumber\"\u003eTable 2\u003c/div\u003e\n\u003cdiv class=\"CaptionContent\"\u003e\n\u003cp\u003eIron biomarker levels*\u003c/p\u003e\n\u003c/div\u003e\n\u003c/caption\u003e\n\u003cthead\u003e\n\u003ctr\u003e\n\u003cth rowspan=\"2\" align=\"left\"\u003e\u0026nbsp;\u003c/th\u003e\n\u003cth colspan=\"3\" align=\"left\"\u003e\n\u003cp\u003eNo iron\u003c/p\u003e\n\u003c/th\u003e\n\u003cth colspan=\"3\" align=\"left\"\u003e\n\u003cp\u003eOral iron\u003c/p\u003e\n\u003c/th\u003e\n\u003c/tr\u003e\n\u003ctr\u003e\n\u003cth align=\"left\"\u003e\n\u003cp\u003eBaseline\u003c/p\u003e\n\u003cp\u003e(\u003cem\u003en\u003c/em\u003e\u0026thinsp;=\u0026thinsp;58)\u003c/p\u003e\n\u003c/th\u003e\n\u003cth align=\"left\"\u003e\n\u003cp\u003eWeek 8\u003c/p\u003e\n\u003cp\u003e(\u003cem\u003en\u003c/em\u003e\u0026thinsp;=\u0026thinsp;49)\u003c/p\u003e\n\u003c/th\u003e\n\u003cth align=\"left\"\u003e\n\u003cp\u003eWeek 24\u003c/p\u003e\n\u003cp\u003e(\u003cem\u003en\u003c/em\u003e\u0026thinsp;=\u0026thinsp;39)\u003c/p\u003e\n\u003c/th\u003e\n\u003cth align=\"left\"\u003e\n\u003cp\u003eBaseline\u003c/p\u003e\n\u003cp\u003e(\u003cem\u003en\u003c/em\u003e\u0026thinsp;=\u0026thinsp;48)\u003c/p\u003e\n\u003c/th\u003e\n\u003cth align=\"left\"\u003e\n\u003cp\u003eWeek 8\u003c/p\u003e\n\u003cp\u003e(\u003cem\u003en\u003c/em\u003e\u0026thinsp;=\u0026thinsp;39)\u003c/p\u003e\n\u003c/th\u003e\n\u003cth align=\"left\"\u003e\n\u003cp\u003eWeek 24\u003c/p\u003e\n\u003cp\u003e(\u003cem\u003en\u003c/em\u003e\u0026thinsp;=\u0026thinsp;31)\u003c/p\u003e\n\u003c/th\u003e\n\u003c/tr\u003e\n\u003c/thead\u003e\n\u003ctbody\u003e\n\u003ctr\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003e\u003csup\u003eSI, \u0026micro;mol/L\u003c/sup\u003e\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003e14.53\u0026thinsp;\u0026plusmn;\u0026thinsp;6.33\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003e14.28\u0026thinsp;\u0026plusmn;\u0026thinsp;8.22\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003e12.72\u0026thinsp;\u0026plusmn;\u0026thinsp;7.78\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003e12.35\u0026thinsp;\u0026plusmn;\u0026thinsp;6.49\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003e14.86\u0026thinsp;\u0026plusmn;\u0026thinsp;6.34\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003e15.65\u0026thinsp;\u0026plusmn;\u0026thinsp;5.91\u003csup\u003e\u003cstrong\u003ea\u003c/strong\u003e\u003c/sup\u003e\u003c/p\u003e\n\u003c/td\u003e\n\u003c/tr\u003e\n\u003ctr\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003e\u003csup\u003eLogsFt, \u0026micro;g/ml\u003c/sup\u003e\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003e2.23\u0026thinsp;\u0026plusmn;\u0026thinsp;0.43\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003e2.04\u0026thinsp;\u0026plusmn;\u0026thinsp;0.42\u003csup\u003e\u003cstrong\u003ea\u003c/strong\u003e\u003c/sup\u003e\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003e2.04\u0026thinsp;\u0026plusmn;\u0026thinsp;0.38\u003csup\u003e\u003cstrong\u003ea\u003c/strong\u003e\u003c/sup\u003e\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003e2.16\u0026thinsp;\u0026plusmn;\u0026thinsp;0.45\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003e2.02\u0026thinsp;\u0026plusmn;\u0026thinsp;0.40\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003e2.18\u0026thinsp;\u0026plusmn;\u0026thinsp;0.42\u003c/p\u003e\n\u003c/td\u003e\n\u003c/tr\u003e\n\u003ctr\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003e\u003csup\u003e\u0026lt;2 \u0026micro;g/l\u0026minus; \u003cem\u003en\u003c/em\u003e (%)\u003c/sup\u003e\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003e15 (25.86)\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003e22 (44.88)\u003csup\u003e\u003cstrong\u003ea\u003c/strong\u003e\u003c/sup\u003e\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003e19 (48.72)\u003csup\u003e\u003cstrong\u003ea\u003c/strong\u003e\u003c/sup\u003e\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003e17 (35.42)\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003e18 (46.15)\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003e11 (35.48)\u003c/p\u003e\n\u003c/td\u003e\n\u003c/tr\u003e\n\u003ctr\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003e\u003csup\u003eTSAT, %\u003c/sup\u003e\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003e34.57\u0026thinsp;\u0026plusmn;\u0026thinsp;15.32\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003e29.43\u0026thinsp;\u0026plusmn;\u0026thinsp;15.28\u003csup\u003e\u003cstrong\u003ea\u003c/strong\u003e\u003c/sup\u003e\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003e25.20\u0026thinsp;\u0026plusmn;\u0026thinsp;15.74\u003csup\u003e\u003cstrong\u003eC\u003c/strong\u003e\u003c/sup\u003e\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003e29.18\u0026thinsp;\u0026plusmn;\u0026thinsp;14.75\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003e31.65\u0026thinsp;\u0026plusmn;\u0026thinsp;12.73\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003e33.49\u0026thinsp;\u0026plusmn;\u0026thinsp;15.05\u003csup\u003e\u003cstrong\u003eb\u003c/strong\u003e\u003c/sup\u003e\u003c/p\u003e\n\u003c/td\u003e\n\u003c/tr\u003e\n\u003ctr\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003e\u003csup\u003e\u0026lt;20%, \u003cem\u003en\u003c/em\u003e (%)\u003c/sup\u003e\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003e10 (17.24)\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003e16 (32.65)\u003csup\u003e\u003cstrong\u003ea\u003c/strong\u003e\u003c/sup\u003e\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003e19 (48.72)\u003csup\u003e\u003cstrong\u003ea\u003c/strong\u003e\u003c/sup\u003e\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003e15 (31.25)\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003e6 (15.38)\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003e9 (29.03)\u003c/p\u003e\n\u003c/td\u003e\n\u003c/tr\u003e\n\u003ctr\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003e\u003csup\u003eTIBC, \u0026micro;mol/L\u003c/sup\u003e\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003e42.89\u0026thinsp;\u0026plusmn;\u0026thinsp;10.39\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003e48.71\u0026thinsp;\u0026plusmn;\u0026thinsp;10.62\u003csup\u003e\u003cstrong\u003ea\u003c/strong\u003e\u003c/sup\u003e\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003e51.94\u0026thinsp;\u0026plusmn;\u0026thinsp;9.73\u003csup\u003e\u003cstrong\u003ea\u003c/strong\u003e\u003c/sup\u003e\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003e43.86\u0026thinsp;\u0026plusmn;\u0026thinsp;12.68\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003e46.93\u0026thinsp;\u0026plusmn;\u0026thinsp;7.61\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003e48.59\u0026thinsp;\u0026plusmn;\u0026thinsp;9.31\u003csup\u003e\u003cstrong\u003ea\u003c/strong\u003e\u003c/sup\u003e\u003c/p\u003e\n\u003c/td\u003e\n\u003c/tr\u003e\n\u003c/tbody\u003e\n\u003c/table\u003e\n\u003c/div\u003e\n\u003cp\u003e*Measurement data with a normal distribution are expressed as the means\u0026thinsp;\u0026plusmn;\u0026thinsp;standard deviations, and nonnormally distributed data are expressed as medians and interquartile ranges. SI denotes serum iron, sFt denotes serum ferritin, TSAT denotes transferrin saturation, and TIBC denotes total iron-binding capacity.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003ea:\u0026nbsp;\u003c/strong\u003eSignificant difference from baseline (\u003cem\u003eP\u003c/em\u003e\u0026thinsp;\u0026lt;\u0026thinsp;0.05);\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eb:\u0026nbsp;\u003c/strong\u003eSignificant difference between the groups (\u003cem\u003eP\u003c/em\u003e\u0026thinsp;\u0026lt;\u0026thinsp;0.05);\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eC:\u0026nbsp;\u003c/strong\u003eSignificant difference from baseline (P\u0026thinsp;\u0026lt;\u0026thinsp;0.05) and between the groups (P\u0026thinsp;\u0026lt;\u0026thinsp;0.05).\u003c/p\u003e\n\u003cp\u003eAt week 24, 7.69% of the patients in the no iron group and 16.13% of the patients in the oral iron group had functional iron deficiency, with no significant difference between the groups (P\u0026thinsp;=\u0026thinsp;0.270). Moreover, we observed that the percentage of patients with absolute iron deficiency remained stable in the oral iron group (P\u0026thinsp;=\u0026thinsp;0.852) and increased significantly in the no iron group (P\u0026thinsp;=\u0026thinsp;0.011) (Fig.\u0026nbsp;\u003cspan class=\"InternalRef\"\u003e5\u003c/span\u003ea).\u003c/p\u003e\n\u003c/div\u003e\n\u003cdiv id=\"Sec12\" class=\"Section2\"\u003e\n\u003ch2\u003eChanges in Hb levels\u003c/h2\u003e\n\u003cp\u003eAt week 24, the logEPO levels in the oral iron group and the no iron group increased by 0.11\u0026thinsp;\u0026plusmn;\u0026thinsp;0.08 mIU/mL and 0.15\u0026thinsp;\u0026plusmn;\u0026thinsp;0.42 mIU/mL, respectively, from baseline, with a between-group difference of -0.04 mIU/mL (95% CI, -0.24 to 0.17). During the treatment with roxadustat, the Hb levels in both groups significantly increased from baseline. At week 24, the increase in the Hb concentration was 29.57\u0026thinsp;\u0026plusmn;\u0026thinsp;15.59 g/L in the oral iron group and 19.37\u0026thinsp;\u0026plusmn;\u0026thinsp;18.44 g/L in the no iron group. The between-group difference was 10.20 g/L (95% CI, 1.93 to 18.48). At week 24, 70.97% of the patients in the oral iron group had Hb concentrations\u0026thinsp;\u0026ge;\u0026thinsp;110 g/L and \u0026lt;\u0026thinsp;130 g/L, and the proportion was 51.28% in the no iron group (Fig.\u0026nbsp;\u003cspan class=\"InternalRef\"\u003e5\u003c/span\u003eb).\u003c/p\u003e\n\u003c/div\u003e\n\u003cdiv id=\"Sec13\" class=\"Section2\"\u003e\n\u003ch2\u003eSafety\u003c/h2\u003e\n\u003cp\u003eRoxadustat was well tolerated in the patients. One patient in the no iron group died during the follow-up period, and the investigators determined that it was unrelated to roxadustat.\u003c/p\u003e\n\u003cp\u003eHypertension requiring increased or altered antihypertensive medication was the most common adverse event, with 35 patients in the no iron group and 15 in the oral iron group. In the 24-week study, roxadustat did not increase the incidence of hyperkalemia in PD patients (P\u0026thinsp;=\u0026thinsp;0.651). In the no iron group, 5.17% of patients had hyperkalemia (defined as serum potassium concentration\u0026thinsp;\u0026gt;\u0026thinsp;5.50 mmol/L) at baseline, and 0.00% had hyperkalemia at week 24. In the oral iron group, this proportion was 2.08% at baseline and 3.23% at week 24. The incidence of acidosis was significantly lower in the no iron group (P\u0026thinsp;\u0026lt;\u0026thinsp;0.001) and remained stable in the oral iron group.\u003c/p\u003e\n\u003cp\u003eHigh-sensitivity C-reactive protein levels were evaluated, and the proportion of patients with C-reactive protein levels above the normal range remained stable throughout the study. Eleven cases of peritonitis occurred during the 24-week study (4 in the no iron group; 7 in the oral iron group). The severity of peritonitis was mild or moderate, and both types were resolved with antibiotic treatment; no patients stopped using roxadustat due to peritonitis.\u003c/p\u003e\n\u003c/div\u003e"},{"header":"Discussion","content":"\u003cp\u003eIn this 24-week clinical study involving patients with PD, roxadustat significantly improved iron metabolism by reducing hepcidin levels and mobilizing stored iron. However, with an increase in the iron utilization rate, the proportion of patients with absolute iron deficiency in the no iron group increased significantly, suggesting that appropriate iron supplementation is necessary during roxadustat treatment. Additionally, roxadustat effectively alleviated anemia in PD patients without increasing the incidence of hyperkalemia or acidosis. Roxadustat increased the mean Hb concentration by 8 g/L within 8 weeks of treatment, independent of whether oral iron was administered. During the last 8 weeks of the treatment period, greater changes in Hb levels were observed in the oral iron group than in the no iron group. In contrast to EPO analogues, roxadustat modestly increased endogenous EPO levels. Mild supplementation with oral iron (median: 200 mg per day) resulted in a marked change in Hb levels.\u003c/p\u003e \u003cp\u003eThe mechanism of renal anemia is complex, and reduced EPO levels and iron metabolism disorders are considered the main causes [\u003cspan citationid=\"CR24\" class=\"CitationRef\"\u003e24\u003c/span\u003e, \u003cspan citationid=\"CR25\" class=\"CitationRef\"\u003e25\u003c/span\u003e]. PD patients often experience iron metabolism disorders due to chronic inflammation, blood loss, use of anemia medications, intestinal absorption defects, and reduced reabsorption [\u003cspan citationid=\"CR26\" class=\"CitationRef\"\u003e26\u003c/span\u003e, \u003cspan citationid=\"CR27\" class=\"CitationRef\"\u003e27\u003c/span\u003e]. In clinical practice, the sFt level is typically used as an indicator of iron storage status, whereas the TSAT level serves as a measure of iron utilization [\u003cspan citationid=\"CR28\" class=\"CitationRef\"\u003e28\u003c/span\u003e]. Both parameters can be altered by infections or inflammation, thereby affecting their sensitivity and specificity [\u003cspan citationid=\"CR29\" class=\"CitationRef\"\u003e29\u003c/span\u003e]. Although bone marrow iron staining remains the gold standard for diagnosing iron deficiency, this procedure is invasive and costly, making it impractical for routine clinical application. The percentage of hypochromic red blood cells (HRC%) and the reticulocyte Hb content (CHr) are independent of inflammatory status and can reflect functional iron status [\u003cspan citationid=\"CR30\" class=\"CitationRef\"\u003e30\u003c/span\u003e]. It is recommended to evaluate iron deficiency using HRC%\u0026gt; 6% and CHr\u0026thinsp;\u0026lt;\u0026thinsp;29 pg. However, it should be noted that prolonged sample transportation and storage may increase HRC% readings, so testing must be completed within 6 hours after blood collection. sTFR is derived mainly from ferroportin (FPN) on the membrane surface of normoblasts and mediates the entry of iron-containing sFt into cells. The sTFR level is proportional to the TFR level, which is determined mainly by the intracellular iron demand and erythropoietic activity [\u003cspan citationid=\"CR31\" class=\"CitationRef\"\u003e31\u003c/span\u003e]. Unlike other iron parameters, the sTFR level is not affected by inflammation, trauma, stress or other factors, and the concentration of sTFR increases rapidly in early iron deficiency, which is conducive to the early diagnosis of iron deficiency anemia [\u003cspan citationid=\"CR32\" class=\"CitationRef\"\u003e32\u003c/span\u003e, \u003cspan citationid=\"CR33\" class=\"CitationRef\"\u003e33\u003c/span\u003e]. The sTFR/logsFt ratio is an indicator of iron deficiency when the sFt level is elevated because of inflammation [\u003cspan citationid=\"CR34\" class=\"CitationRef\"\u003e34\u003c/span\u003e].\u003c/p\u003e \u003cp\u003eIron metabolism disorders in CKD patients have attracted widespread attention, but iron metabolism disorders cannot be effectively corrected in a large proportion of CKD patients. As an HIF-PHI, roxadustat activates the HIF pathway by reversibly and transiently inhibiting the activity of PHD [\u003cspan citationid=\"CR35\" class=\"CitationRef\"\u003e35\u003c/span\u003e]. HIF is a crucial transcription factor that adapts to oxygen changes in the body. It forms a heterodimer composed of the oxygen-sensitive HIF-α subunit and the constitutive HIF-β subunit. Under normal conditions, HIF-α is rapidly degraded by PHD. During hypoxia or after PHI treatment, reduced PHD activity allows more HIF-α to enter the nucleus, where it recruits HIF-β and induces the expression of specific target genes, indirectly lowering hepcidin expression [\u003cspan citationid=\"CR36\" class=\"CitationRef\"\u003e36\u003c/span\u003e]. Hepcidin, which is secreted by hepatocytes, functions by controlling the activity of the cellular iron exporter ferroportin, which delivers iron to the plasma through intestinal iron absorption and from iron stores [\u003cspan citationid=\"CR37\" class=\"CitationRef\"\u003e37\u003c/span\u003e]. The hepcidin concentration in plasma is increased by iron loading and inflammation and is suppressed by erythropoietic stimulation and during pregnancy [\u003cspan citationid=\"CR6\" class=\"CitationRef\"\u003e6\u003c/span\u003e]. Therefore, when hepcidin is overproduced, iron cannot be released from iron-storing and iron-absorbing cells, leading to decreased circulating iron levels [\u003cspan citationid=\"CR38\" class=\"CitationRef\"\u003e38\u003c/span\u003e]. Since hepcidin is rapidly cleared from the circulation by the kidneys within minutes, its production rate can be swiftly adjusted to modify circulating concentrations and thereby regulate iron metabolism. In CKD patients, owing to increased hepcidin synthesis caused by the iron load and chronic inflammatory status and decreased hepcidin clearance in the kidney due to a decreased glomerular filtration rate, the two combined lead to elevated hepcidin levels in the plasma of CKD patients, especially in ESRD patients [\u003cspan citationid=\"CR39\" class=\"CitationRef\"\u003e39\u003c/span\u003e]. It is commonly believed that the absorption of oral iron supplements is inhibited by high hepcidin levels and that oral iron supplements may limit the bioavailability of iron supplements by inducing hepcidin expression, resulting in the formation of a negative feedback loop [\u003cspan citationid=\"CR40\" class=\"CitationRef\"\u003e40\u003c/span\u003e]. However, in our study, roxadustat significantly reduced hepcidin levels in PD patients receiving iron supplementation or not. This suppression of hepcidin in concert with the roxadustat-induced increases in the levels of transferrin, which increase iron-absorbing capacity, may explain the sufficiency of low-dose oral iron for anemia correction.\u003c/p\u003e \u003cp\u003eHIF is a crucial transcription factor that helps the body adapt to oxygen changes, inducing a series of target genes related to erythropoiesis, angiogenesis, and energy metabolism to respond to hypoxic stress. In addition to suppressing hepcidin expression, HIF-1 enhances iron utilization by upregulating transferrin, ceruloplasmin, and TFR1. HIF-2 plays a key role in regulating iron uptake. Mice lacking intestinal epithelial HIF-2 exhibit reduced levels of duodenal cytochrome B, divalent metal transporter 1, and FPN in duodenal cells, decreasing intestinal iron absorption [\u003cspan citationid=\"CR41\" class=\"CitationRef\"\u003e41\u003c/span\u003e]. Therefore, the increased iron consumption observed in iron-deficient groups may result not only from enhanced hematopoietic function but may also be associated with improved iron utilization efficiency.\u003c/p\u003e \u003cp\u003eUnder hypoxic conditions, this system activates multiple genes to increase the cellular oxygen supply, in addition to regulating erythropoiesis and iron metabolism, including angiogenesis, lipid and glucose metabolism, glycolysis, mitochondrial function, inflammation and immunity, cell growth and survival, vasodilation, and cell migration [\u003cspan citationid=\"CR42\" class=\"CitationRef\"\u003e42\u003c/span\u003e]. Notably, this study has the following limitations: First, this trial was a single-center study, and the findings may not be generalizable to other populations. Second, this study examined changes in patients\u0026rsquo; conditions after only 24 weeks of treatment, which may not have been long enough to assess the safety of roxadustat. HIF has been demonstrated to be associated with risks of angiogenesis and cancer, and further studies are needed before firm conclusions can be drawn [\u003cspan citationid=\"CR43\" class=\"CitationRef\"\u003e43\u003c/span\u003e].\u003c/p\u003e"},{"header":"Conclusions","content":"\u003cp\u003eIn conclusion, this 24-week prospective cohort study confirmed that the combination of roxadustat and oral iron supplementation is more effective than roxadustat alone in ameliorating anemia in PD patients. Roxadustat improves iron metabolism in patients by inhibiting the expression of hepcidin and inducing the expression of molecules required for the iron cycle. However, with increased iron utilization, some patients may develop absolute iron deficiency. In clinical practice, iron agents should be used individually according to the patient\u0026rsquo;s iron metabolism status, and monitoring should be strengthened to achieve efficient, safe and economical management of anemia in peritoneal dialysis patients.\u003c/p\u003e"},{"header":"Abbreviations","content":"\u003cdiv class=\"DefinitionList\"\u003e \u003cdiv class=\"DefinitionListEntry\"\u003e \u003cdiv class=\"Term\"\u003eFull name\u003c/div\u003e \u003cdiv class=\"Description\"\u003e \u003cp\u003eAbbreviation\u003c/p\u003e \u003c/div\u003e \u003c/div\u003e \u003cdiv class=\"DefinitionListEntry\"\u003e \u003cdiv class=\"Term\"\u003echronic kidney disease\u003c/div\u003e \u003cdiv class=\"Description\"\u003e \u003cp\u003eCKD\u003c/p\u003e \u003c/div\u003e \u003c/div\u003e \u003cdiv class=\"DefinitionListEntry\"\u003e \u003cdiv class=\"Term\"\u003eend-stage renal disease\u003c/div\u003e \u003cdiv class=\"Description\"\u003e \u003cp\u003eESRD\u003c/p\u003e \u003c/div\u003e \u003c/div\u003e \u003cdiv class=\"DefinitionListEntry\"\u003e \u003cdiv class=\"Term\"\u003eerythropoiesis-stimulating agents\u003c/div\u003e \u003cdiv class=\"Description\"\u003e \u003cp\u003eESAs\u003c/p\u003e \u003c/div\u003e \u003c/div\u003e \u003cdiv class=\"DefinitionListEntry\"\u003e \u003cdiv class=\"Term\"\u003eerythropoietin\u003c/div\u003e \u003cdiv class=\"Description\"\u003e \u003cp\u003eEPO\u003c/p\u003e \u003c/div\u003e \u003c/div\u003e \u003cdiv class=\"DefinitionListEntry\"\u003e \u003cdiv class=\"Term\"\u003eferroportin\u003c/div\u003e \u003cdiv class=\"Description\"\u003e \u003cp\u003eFPN\u003c/p\u003e \u003c/div\u003e \u003c/div\u003e \u003cdiv class=\"DefinitionListEntry\"\u003e \u003cdiv class=\"Term\"\u003ehypoxia-inducible factor-prolyl hydroxylase inhibitor\u003c/div\u003e \u003cdiv class=\"Description\"\u003e \u003cp\u003eHIF-PHI\u003c/p\u003e \u003c/div\u003e \u003c/div\u003e \u003cdiv class=\"DefinitionListEntry\"\u003e \u003cdiv class=\"Term\"\u003eperitoneal dialysis\u003c/div\u003e \u003cdiv class=\"Description\"\u003e \u003cp\u003ePD\u003c/p\u003e \u003c/div\u003e \u003c/div\u003e \u003cdiv class=\"DefinitionListEntry\"\u003e \u003cdiv class=\"Term\"\u003eserum iron\u003c/div\u003e \u003cdiv class=\"Description\"\u003e \u003cp\u003eSI\u003c/p\u003e \u003c/div\u003e \u003c/div\u003e \u003cdiv class=\"DefinitionListEntry\"\u003e \u003cdiv class=\"Term\"\u003eserum ferritin\u003c/div\u003e \u003cdiv class=\"Description\"\u003e \u003cp\u003esFt\u003c/p\u003e \u003c/div\u003e \u003c/div\u003e \u003cdiv class=\"DefinitionListEntry\"\u003e \u003cdiv class=\"Term\"\u003eserum soluble transferrin receptor\u003c/div\u003e \u003cdiv class=\"Description\"\u003e \u003cp\u003esTFR\u003c/p\u003e \u003c/div\u003e \u003c/div\u003e \u003cdiv class=\"DefinitionListEntry\"\u003e \u003cdiv class=\"Term\"\u003etotal iron binding capacity\u003c/div\u003e \u003cdiv class=\"Description\"\u003e \u003cp\u003eTIBC\u003c/p\u003e \u003c/div\u003e \u003c/div\u003e \u003cdiv class=\"DefinitionListEntry\"\u003e \u003cdiv class=\"Term\"\u003etransferrin saturation\u003c/div\u003e \u003cdiv class=\"Description\"\u003e \u003cp\u003eTSAT\u003c/p\u003e \u003c/div\u003e \u003c/div\u003e \u003c/div\u003e"},{"header":"Declarations","content":"\u003cp\u003e\u003cstrong\u003e\u003cem\u003eEthics approval and consent to participate\u003c/em\u003e\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eThis study adhered\u0026nbsp;to\u0026nbsp;the\u0026nbsp;Declaration\u0026nbsp;of\u0026nbsp;Helsinki and was approved by the Ethics Committee of the Affiliated Jintan Hospital of Jiangsu University (2025-KY-007). All the enrolled patients signed an informed consent form.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003e\u003cem\u003eConsent for publication\u003c/em\u003e\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eNot applicable.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003e\u003cem\u003eData a\u003c/em\u003e\u003c/strong\u003e\u003cstrong\u003e\u003cem\u003evailability\u0026nbsp;\u003c/em\u003e\u003c/strong\u003e\u003cstrong\u003e\u003cem\u003estatement\u003c/em\u003e\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eThe data that support the findings of this study are available on request from the corresponding author.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003e\u003cem\u003eCompeting interests\u003c/em\u003e\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eThe authors declare that they have no competing interests.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003e\u003cem\u003eFunding\u003c/em\u003e\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eThis study was supported by the Science and Technology Project of Jintan District Health Bureau (JTYXH-2025-2-08) and a project of the Practice and Innovation Plan of Jiangsu Province (SJCX21_1147).\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003e\u003cem\u003eAuthor contribution\u003c/em\u003e\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eZhang Xuejie completed the study conception and design, data analysis and interpretation, and thesis writing.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003e\u003cem\u003eAcknowledgements\u003c/em\u003e\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eWe would like to extend our sincere gratitude to The Affiliated Jintan Hospital of Jiangsu University for providing us with a conducive and comfortable platform during our study. We also deeply appreciate our dear colleagues for their reliable, tireless support and assistance.\u003c/p\u003e"},{"header":"References","content":"\u003col\u003e\u003cli\u003e\u003cspan\u003eShaikh HMF. \u003csup\u003eP.Anemiaofchronickidneydisease.In:StatPearls.TreasureIsland,FL:StatPearlsPublishing,LLC;\u003c/sup\u003e2025.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eSpinowitz FS. \u003csup\u003eB.Update on anemia in ESRD and earlier stages of CKD: Core curriculum 2018\u003c/sup\u003e.. \u003csup\u003eAm J Kidney Dis\u003c/sup\u003e 2018;\u003csup\u003e71\u003c/sup\u003e:423\u0026ndash;35.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003e\u003csup\u003ePasricha SR, Tye\u0026ndash;Din J, Muckenthaler MU, Swinkels DW. 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Int J Mol Sci\u003c/sup\u003e 2021;\u003csup\u003e22\u003c/sup\u003e:6493\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eTalbot CD. \u003csup\u003eH.Iron, hepcidin, and immunity\u003c/sup\u003e.. \u003csup\u003eAdv Exp Med Biol\u003c/sup\u003e 2025;\u003csup\u003e1480\u003c/sup\u003e:197\u0026ndash;215.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eReikvam SM. \u003csup\u003eH.Hepcidin as a therapeutic target in iron overload.Expert Opin Ther Targets\u003c/sup\u003e 2024;\u003csup\u003e28\u003c/sup\u003e:1039\u0026ndash;46.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003e\u003csup\u003eChoudhryH,Harris AL. Advances in hypoxia\u0026ndash;inducible factor biology\u003c/sup\u003e. \u003csup\u003eCell Metab\u003c/sup\u003e 2018;\u003csup\u003e27\u003c/sup\u003e:281\u0026ndash;98.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003e\u003csup\u003eTaylor CT, Scholz CC. The effect of HIF on metabolism and immunity. 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Cell Mol Life Sci. 2025;82:44.\u003c/span\u003e\u003c/li\u003e\u003c/ol\u003e"}],"fulltextSource":"","fullText":"","funders":[],"hasAdminPriorityOnWorkflow":false,"hasManuscriptDocX":true,"hasOptedInToPreprint":true,"hasPassedJournalQc":"","hasAnyPriority":false,"hideJournal":true,"highlight":"","institution":"","isAcceptedByJournal":false,"isAuthorSuppliedPdf":false,"isDeskRejected":"","isHiddenFromSearch":false,"isInQc":false,"isInWorkflow":false,"isPdf":false,"isPdfUpToDate":true,"isWithdrawnOrRetracted":false,"journal":{"display":true,"email":"[email protected]","identity":"researchsquare","isNatureJournal":false,"hasQc":true,"allowDirectSubmit":true,"externalIdentity":"","sideBox":"","snPcode":"","submissionUrl":"/submission","title":"Research Square","twitterHandle":"researchsquare","acdcEnabled":true,"dfaEnabled":false,"editorialSystem":"","reportingPortfolio":"","inReviewEnabled":false,"inReviewRevisionsEnabled":true},"keywords":"Peritoneal dialysis (PD), Anemia, Hypoxia inducible factor-prolyl hydroxylase inhibitors (HIF-PHIs), Iron metabolism","lastPublishedDoi":"10.21203/rs.3.rs-8336397/v1","lastPublishedDoiUrl":"https://doi.org/10.21203/rs.3.rs-8336397/v1","license":{"name":"CC BY 4.0","url":"https://creativecommons.org/licenses/by/4.0/"},"manuscriptAbstract":"\u003cp\u003e\u003cstrong\u003eBackground\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eRoxadustat is an orally bioavailable hypoxia-inducible factor prolyl hydroxylase inhibitor (HIF-PHI) that regulates iron metabolism in patients with chronic kidney disease (CKD) primarily by reducing hepcidin levels and mobilizing internal iron stores. With increased iron utilization, iron deficiency may occur in some patients, and more data are needed to evaluate the exogenous iron requirements of peritoneal dialysis (PD) patients receiving roxadustat to treat anemia.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eMethods\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eWe performed a prospective cohort study of anemic (Hb ≤ 100.0 g/L) patients undergoing PD. One hundred six patients received no iron or oral iron while they were treated with roxadustat for 24 weeks. The primary endpoints included Hb compliance rates, changes in iron biomarker levels and the proportion of patients with absolute iron deficiency and functional iron deficiency.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eResults\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eCompared with no iron supplementation, oral iron supplementation significantly increased Hb levels (difference, 10.20 g/L; 95% CI, 1.93 to 18.48) and Hb compliance rates (oral iron, 70.97%; no iron, 51.28%); attenuated the increase in serum soluble transferrin receptor (sTFR) levels (difference, -5.66 nmol/L; 95% CI, -10.30 to -1.02) and sTFR/logsFt levels (difference, -0.32; 95% CI, -0.54 to -0.11); and reduced the proportion of patients with absolute iron deficiency (oral iron, 16.13%; no iron, 28.21%). Hepcidin levels decreased significantly from baseline in both groups, by 23.94% in PD patients receiving no iron (n = 39) and by 23.33% in PD patients receiving oral iron (n = 31).\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eConclusions\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eCompared with no iron supplementation, oral iron supplementation can significantly reduce the incidence of absolute iron deficiency and significantly improve the efficacy of roxadustat in the treatment of anemia in PD patients. These results suggest that adequate iron supplementation is necessary during roxadustat therapy.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eTrial registration\u003c/strong\u003e: This study was registered on the Chinese Clinical Trial Registry on March 4, 2022 (registration number: ChiCTR2200057231).\u003c/p\u003e","manuscriptTitle":"Effect of oral iron on the ability of roxadustat to ameliorate anemia in peritoneal dialysis patients: A real-world 24-week study","msid":"","msnumber":"","nonDraftVersions":[{"code":1,"date":"2025-12-30 09:18:19","doi":"10.21203/rs.3.rs-8336397/v1","editorialEvents":[{"type":"communityComments","content":0}],"status":"published","journal":{"display":true,"email":"[email protected]","identity":"researchsquare","isNatureJournal":false,"hasQc":true,"allowDirectSubmit":true,"externalIdentity":"","sideBox":"","snPcode":"","submissionUrl":"/submission","title":"Research Square","twitterHandle":"researchsquare","acdcEnabled":true,"dfaEnabled":false,"editorialSystem":"","reportingPortfolio":"","inReviewEnabled":false,"inReviewRevisionsEnabled":true}}],"origin":"","ownerIdentity":"aeded724-81e3-49bc-848a-c192e67f636b","owner":[],"postedDate":"December 30th, 2025","published":true,"recentEditorialEvents":[],"rejectedJournal":[],"revision":"","amendment":"","status":"posted","subjectAreas":[],"tags":[],"updatedAt":"2026-03-11T08:10:57+00:00","versionOfRecord":[],"versionCreatedAt":"2025-12-30 09:18:19","video":"","vorDoi":"","vorDoiUrl":"","workflowStages":[]},"version":"v1","identity":"rs-8336397","journalConfig":"researchsquare"},"__N_SSP":true},"page":"/article/[identity]/[[...version]]","query":{"redirect":"/article/rs-8336397","identity":"rs-8336397","version":["v1"]},"buildId":"8U1c8b4HqxoKbykW_rLl7","isFallback":false,"isExperimentalCompile":false,"dynamicIds":[84888],"gssp":true,"scriptLoader":[]}