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Hypoxia‐inducible factor prolyl hydroxylase (HIF‐PH) inhibitors are a new class of agents for the treatment of anemia in chronic kidney disease (CKD). Unlike traditional treatments such as erythropoiesis‐stimulating agents (ESAs), HIF‐PH inhibitors are orally administered drugs and may increase endogenous erythropoietin and improve iron homeostasis. However, a significant concern is their possible side effect on blood pressure. The current mini‐review summarizes the data of 26 randomized controlled (placebo or ESAs) trials on six different HIF‐PH inhibitors with regard to their potential influence on blood pressure and hypertension in the management of anemia in CKD. Overall, the use of HIF‐PH inhibitors was associated with a higher risk of hypertension than placebo (pooled risk ratio 1.36, 95% confidence interval [CI] 1.16–1.59), but a lower risk of hypertension than ESA treatment (pooled risk ratio 0.92, 95% CI 0.86–0.98), especially in CKD patients not undergoing dialysis (pooled risk ratio 0.85, 95% CI 0.73–0.98). This review highlights the importance of blood pressure monitoring during the treatment of HIF‐PH inhibitors, especially out‐of‐office blood pressure measurement. [ABSTRACT FROM AUTHOR]

To explore independent influencing factors for clinical efficacy of roxadustat in hemodialysis patients. Hemodialysis patients treated with roxadustat were enrolled. The plasma trough concentrations of roxadustat were measured using liquid chromatography–tandem mass spectrometry (LC–MS/MS). A multiple logistic regression model was established to determine the factors that affect clinical efficacy of roxadustat in patients undergoing hemodialysis. A total of 67 hemodialysis patients were enrolled in the study. The results showed that age, blood trough concentration of roxadustat, and baseline hemoglobin (Hb) level were independent factors of clinical efficacy of roxadustat (OR = 1.06, p =.025 for age; OR = 1.001, p =.037 for plasma concentration; and OR = 0.941, p =.003 for baseline Hb), with an AUC score of 0.859. Age, blood trough concentration of roxadustat, and baseline Hb level were independent influencing factors of the response to roxadustat in hemodialysis patients. [ABSTRACT FROM AUTHOR]

Aims: To investigate the prevalence and influencing factors of drug-related problems (DRPs) in inpatients with kidney disease to provide reference data for pharmaceutical care. Methods: The basic information, diagnoses, and medication reconciliation (MR) of inpatients in the Department of Nephrology at our hospital between October 2020 and September 2021 were collected. The Chinese-modified DRP version based on the PCNE classification (Version 9.1) was used to assess, intervene and statistically analyze the results of the patients' DRPs. The influence factor of DRPs in inpatients with kidney disease was analyzed by the multivariate binary logistic regression. Results: Of 623 patients included in this study, 132 (21.80%) had DRPs. The prevalence of anemia was significantly higher in patients with DRPs than those without DRPs (43.18% vs. 28.72%, p < 0.05), the mean number of drug types consumed (7.25 ± 3.44 with DRPs vs. 5.93 ± 3.58 without DRPs, p < 0.05) and the proportion of ≥5 drugs (%) (79.55% with DRPs vs 58.04% without DRPs, p < 0.05) were significantly increased. In addition, the prevalence of hypertension (76.52% vs. 68.64%), diabetes (27.27% vs. 22.20%) and hyperuricemia (16.67% vs. 13.65%) in DRP patients were higher than those without DRPs, but there was no statistical difference (p > 0.05). The logistic regression analysis showed that patients with anemia (OR = 1.702, 95%CI: 1.146–2.529, p = 0.008), average number of medication types taken (OR = 1.089, 95%CI: 1.034–1.147, p = 0.001) significantly increased the risk of DRPs. The distribution of harm levels was as follows: 78 problems (59.09%) were level C, 29 (21.97%) were level B, 10 (7.58%) were level D, 7 (5.30%) were level A, 7 (5.30%) were level E, and 1 (0.76%) were level F. All DRPs were resolved after 128 interventions. Conclusion: Renal anemia, the average number of drug varieties consumed, and the proportion of ≥5 drugs are associated with the occurrence of DRPs. Pharmacists conducting MR services can reduce DRPs of inpatients in the department of nephrology and ensure patient drug safety. [ABSTRACT FROM AUTHOR]

Background: Five hypoxia-inducible factor prolyl hydroxylase inhibitors (HIF-PHIs) have been approved for marketing in Japan. However, marked differences exist in terms of drug potency, dose requirement, and pharmacokinetics. Methods: The primary evaluation in this study was the changes in hemoglobin levels, dose escalation, drug potency, and cost among HIF-PHIs, 3 months after the initiation of treatment. Results: All patients treated with HIF-PHI between August 2020 and December 2023 were enrolled in this study. In total, 124 patients were administered daprodustat (N = 37), enarodustat (N = 44), molidustat (N = 13), or vadadustat (N = 30). The mean hemoglobin levels of daprodustat, enarodustat, molidustat, and vadadustat at 3 months were 11.7 g/dL, 11.8 g/dL, 12.2 g/dL, and 11.3 g/dL, respectively. At 3 months, the mean doses of daprodustat, enarodustat, molidustat, and vadadustat increased by 110%, 177%, 125%, and 152%, respectively, from the initial dose. The HIF-PHI potency indices (HPI) of daprodustat, enarodustat, molidustat, and vadadustat at 3 months were 0.168, 0.307, 0.184, and 0.254, respectively. At 3 months, the mean daily costs of daprodustat, enarodustat, molidustat, and vadadustat were JPY 345, JPY 434, JPY 206, and JPY 565, respectively. Conclusion: The difference in dose escalation for anemia treatment among HIF-PHIs is due to differences in drug potency, where the HPI significantly differs among HIF-PHIs. The disparity between the HPI and the cost of the initial dose accounts for the variance in the daily costs of renal anemia treatment among HIF-PHIs. [ABSTRACT FROM AUTHOR]

Chronic kidney disease has emerged as a major health issue both in China and worldwide. Renal anemia frequently occurs in patients with chronic kidney disease, and its severity and incidence rate increase as the disease progresses. Over the last 30 years, the administration of exogenous EPO and EPO stimulants has been employed to alleviate renal anemia, suggesting that a relative deficiency in EPO may be a primary cause. However, this approach has overshadowed other contributing factors, particularly eryptosis, which results from the reduced lifespan of red blood cells. Numerous studies reveal that there are nephrogenic and extrarenal EPO secretion indicating that an absolute deficiency of EPO is not always present in patients. Therefore, this paper speculates that renal anemia may arise when EPO-driven erythropoiesis fails to adequately compensate for aggravating eryptosis. Other factors including iron metabolism disorder, uremic toxin accumulation, inflammatory state, oxidative stress, and secondary hyperparathyroidism affect EPO reactivity bone marrow hematopoiesis and eryptosis, leading to an imbalance between red blood cell production and destruction, and cause anemia ultimately. More further studies on the pathogenesis and treatment of renal anemia would be expected to provide evidence to support our opinion. [ABSTRACT FROM AUTHOR]

Background: Treatment of end stage renal disease (ESRD) is based on preserving renal functions. Since renal anemia is frequently detected, we use parenteral iron treatments in patients with chronic kidney disease (CKD). However, there need to be more precise and sufficient studies on the effect of these treatments on the rate of decrease in the glomerular filtration rate (GFR). Therefore, we conducted a study comparing the rates of change in renal function in patients who had used parenteral iron for at least five years. Methods: Our study is a retrospective cohort study, and 180 patients with CKD (86 women, 94 men, mean age: 63.5 ± 11.4 years) who had been followed and treated in nephrology outpatient clinics for at least five years and met the study criteria were included in the study. Patients were divided into three groups for iron therapy: not receiving iron therapy, iron carboxy maltose (ICM), and iron sucrose (IS) parenterally. Each group consisted of 60 people. The first and last creatinine and GFR values were compared for a 5-year follow-up in each group. Results: There was no significant difference between the two groups, those using and those not using iron, regarding creatinine increase and GFR decrease rate. Additionally, no significant difference was detected in the GFR decline rates of patients using ICM and IS. Conclusions: This study reduces the concerns that correcting anemia through parenteral iron therapy in patients with CKD may harm renal function. [ABSTRACT FROM AUTHOR]

ABSTRACT Hypoxia‐inducible factor prolyl hydroxylase (HIF‐PH) inhibitors are a new class of agents for the treatment of anemia in chronic kidney disease (CKD). Unlike traditional treatments such as erythropoiesis‐stimulating agents (ESAs), HIF‐PH inhibitors are orally administered drugs and may increase endogenous erythropoietin and improve iron homeostasis. However, a significant concern is their possible side effect on blood pressure. The current mini‐review summarizes the data of 26 randomized controlled (placebo or ESAs) trials on six different HIF‐PH inhibitors with regard to their potential influence on blood pressure and hypertension in the management of anemia in CKD. Overall, the use of HIF‐PH inhibitors was associated with a higher risk of hypertension than placebo (pooled risk ratio 1.36, 95% confidence interval [CI] 1.16–1.59), but a lower risk of hypertension than ESA treatment (pooled risk ratio 0.92, 95% CI 0.86–0.98), especially in CKD patients not undergoing dialysis (pooled risk ratio 0.85, 95% CI 0.73–0.98). This review highlights the importance of blood pressure monitoring during the treatment of HIF‐PH inhibitors, especially out‐of‐office blood pressure measurement.

Objective To study the clinical efficacy and safety of Roxadustat in the maintenance hemodialysis of HIV/AIDS patients with EPO resistance. Methods 60 cases of HIV/AIDS patients with EPO resistance undergoing maintenance hemodialysis treatment at the Blood Purification Center of the Third People's Hospital of Kunming from July 2022 to December 2023 were divided based on patient preference into a control group of 30 cases continuing Erythropoietin (EPO) treatment and an observation group of 30 cases treated with Roxadustat for 8 weeks. Changes in patients' hemoglobin (HGB), serum ferritin (SF), serum iron (SI), total iron binding capacity ( TIBC), high-sensitivity C-reactive protein ( hs-CRP), cytokines ( IL-1β, IL-6, IL-8, IL-10, TNF-α, IFN-γ, IFN-α) were recorded and compared before and after treatment in the two groups, along with monitoring the occurrence of adverse drug reactions. Results After 8 weeks of treatment, the levels of hemoglobin (HGB), serum iron (SI) and total iron binding capacity (TIBC) in observation group were significantly increased, and the differences were statistically significant (all P < 0.05), while the levels of serum ferritin (SF), IL-1β, IL- 6, IL-10 and TNF-α were significantly decreased, with statistically significant (all P < 0.05) . In the comparison between the two groups, the levels of hemoglobin (HGB) and total iron binding capacity (TIBC) in the observation group were higher than those in the control group, with statistically significant differences (all P < 0.05) . The levels of serum iron (SF), IL-1β, IL-6, IL-10, and TNF-α in the observation group were lower than those in the control group, with statistically significant differences (P < 0.05) . There were no serious adverse reactions in either group. Conclusion The use of Roxadustat in maintenance hemodialysis patients resistant to EPO and living with HIV/AIDS is safe and effective, significantly improving the patients' hemoglobin and iron metabolism levels, and can improve the patients' state of micro-inflammation. [ABSTRACT FROM AUTHOR]

Rehmannia glutinosa is widely recognized as a prominent medicinal herb employed by practitioners across various generations for the purpose of fortifying kidney yin. Within Rehmannia glutinosa, the compound known as catalpol (CAT) holds significant importance as a bioactive constituent. However, the protective effects of CAT on kidneys, including ameliorative effects on chronic kidney disease — most prominently renal anemia and renal fibrosis — have not been clearly defined. In this study, the kidney injury model of NRK-52E cells and C57BL/6N male mice was prepared by exposure to aristolochic acid I (AA-I), and it was discovered that CAT could ameliorate oxidative stress injury, inflammatory injury, apoptosis, renal anemia, renal fibrosis, and other renal injuries both in vivo and in vitro. Further treatment of NRK-52E cells with Nrf2 inhibitors (ML385) and activators (ML334), as well as NF-κB inhibitors (PDTC), validated CAT's ability to target Nrf2 activation. Furthermore, the expression of phosphorylated NF-κB p65, IL-6, and Cleaved-Caspase3 protein was inhibited. CAT also inhibited NF-κB, and then inhibited the expression of IL-6, p-STAS3, TGF-β1 protein. Therefore, CAT can regulate Nrf2/NF-κB signaling pathway, significantly correct renal anemia and renal fibrosis, and is conducive to the preservation of renal structure and function, thus achieving a protective effect on the kidneys. [ABSTRACT FROM AUTHOR]

Purpose: Renal anemia is a common complication of chronic kidney disease. Currently, recombinant human erythropoietin and roxadustat are the main treatments. In China, diabetic kidney disease is the primary cause of chronic kidney disease. However, high-quality evidence on the efficacy of roxadustat in patients with non-dialysis-dependent chronic kidney disease and diabetes mellitus is scarce. This study aimed to assess the clinical effect of roxadustat in such patients. Methods: Patients with non-dialysis-dependent anemia and diabetes mellitus who received roxadustat or recombinant human erythropoietin for ≥ 4 weeks were enrolled. We compared baseline characteristics, including age, gender, hypertension, and hemoglobin level, and then employed a 1:3 ratio propensity score matching. The primary efficacy outcomes were changes in hemoglobin levels. After propensity score matching, 212 patients were analyzed, including the roxadustat (n = 53) and recombinant human erythropoietin (n = 159) groups. Baseline characteristics were comparable, including hemoglobin level, estimated glomerular filtration rate, and glycated hemoglobin A1c (p > 0.05). Results: After 4, 12, and 24 weeks of treatment, the median hemoglobin levels in the roxadustat group were 97.5 g/L, 104 g/L, and 106.5 g/L, respectively, significantly surpassing the corresponding levels in the recombinant human erythropoietin group at 91 g/L, 94.5 g/L, and 94.5 g/L (p = 0.002, p = 0.025, p = 0.006, respectively). Additionally, subgroup analysis demonstrated better treatment efficacy of roxadustat patients with elevated high-sensitivity C-reactive protein and low albumin levels. Conclusion: In Chinese patients with anemia and diabetes not on dialysis, roxadustat efficiently and rapidly improved and maintained hemoglobin levels unaffected by elevated high-sensitivity C-reactive protein and low albumin levels. [ABSTRACT FROM AUTHOR]

Background: Erythropoietin resistance is present in some patients with chronic kidney disease, especially in those undergoing hemodialysis, and is often treated using roxadustat rather than iron supplements and erythropoiesis-stimulating agents (ESAs). However, some patients cannot afford full doses of roxadustat. This retrospective study investigated the efficacy of low-dose roxadustat combined with recombinant human erythropoietin (rhuEPO) therapy in 39 patients with erythropoietin-resistant renal anemia undergoing maintenance hemodialysis (3-4 sessions/week). Methods: The ability of the combination of low-dose roxadustat and rhuEPO to increase the hemoglobin concentration over 12 weeks was assessed. Markers of iron metabolism were evaluated. Eligible adults received 50-60% of the recommended dose of roxadustat and higher doses of rhuEPO. Results: The mean hemoglobin level increased from 77.67 ± 11.18 g/dL to 92.0 ± 8.35 g/dL after treatment, and the hemoglobin response rate increased to 72%. The mean hematocrit level significantly increased from 24.26 ± 3.99% to 30.04 ± 3.69%. The soluble transferrin receptor level increased (27.29 ± 13.60 mg/L to 38.09 ± 12.78 mg/L), while the total iron binding capacity (49.22 ± 11.29 mg/L to 43.91 ± 12.88 mg/L) and ferritin level (171.05 ± 54.75 ng/mL to 140.83 ± 42.03 ng/mL) decreased. Conclusion: Therefore, in patients with ESA-resistant anemia who are undergoing hemodialysis, the combination of low-dose roxadustat and rhuEPO effectively improves renal anemia and iron metabolism. [ABSTRACT FROM AUTHOR]

Background Limited data are now available to evaluate the relationship between serum magnesium level, anemia and mortality in the dialysis population. Methods Using data from the Japanese Dialysis Outcomes and Practice Patterns Study (J-DOPPS) phases 5 and 6, we analyzed the association between serum magnesium (s-Mg) levels and the erythropoiesis-stimulating agents resistance index (ERI) as the primary outcome. To estimate the longitudinal relationship, a mixed-effect model was used with ERI at each 4-month period as the dependent variable and quintiles of s-Mg at the previous 4-month period as the independent variable. We also examined incidence of infectious events, and the all-cause and cardiovascular disease (CVD)-related deaths as secondary outcomes by Cox regression with quintiles of s-Mg at baseline. Results Of the 4776 participants in J-DOPPS, 1650 were included in the analysis. The median of s-Mg at baseline was 2.5 mg/dL. A significant linear association of s-Mg with ERI (P for trend <.001) was revealed. Low and high s-Mg levels were not associated with the clinical outcomes of interest, except for the highest quintile of s-Mg being significantly associated with lower incidence of all-cause mortality and CVD-related deaths compared with the middle (reference) quintile. Conclusions We observed that lower s-Mg levels subsequently induced higher ERI and that mild higher s-Mg levels were possibly associated with good rather than poor outcomes in Japanese hemodialysis patients. Adjustment of s-Mg levels may be proposed as a new strategy at a low cost and risk to reduce the risk of premature mortality. [ABSTRACT FROM AUTHOR]

Introduction: Erythropoiesis-stimulating agents (ESAs) together with iron supplementation had been the standard treatment for anemia in chronic kidney disease (CKD) for the past decades. Recently, hypoxia-inducible factor-prolyl hydroxylase inhibitors (HIF-PHIs) have attracted attention as a novel treatment option. Areas covered: This review summarizes the effectiveness and the safety of HIF-PHIs based on previous clinical trials and discusses points to consider for their clinical use. Expert opinion: The results from clinical trials demonstrate that HIF-PHIs are non-inferior to ESAs in terms of the efficacy to maintain or improve blood hemoglobin levels. However, concerns about adverse events including cardiovascular outcomes, thrombotic events, and tumor progression have prevented HIF-PHIs from being widely approved for clinical use. Also, long-term safety has not been demonstrated yet. Practically, HIF-PHIs should be used with caution in patients with a history of thrombosis or active malignancy. Patients without them may be preferable for HIF-PHIs if those are bothered with regular injections of ESAs or are hyporesponsive to ESAs without obvious reasons, provided that the drugs were approved in the country. Even so, clinicians must take caution for signs of adverse events such as heart failure after prescribing the drugs. [ABSTRACT FROM AUTHOR]

Objective To explore independent influencing factors for clinical efficacy of roxadustat in hemodialysis patients.Methods Hemodialysis patients treated with roxadustat were enrolled. The plasma trough concentrations of roxadustat were measured using liquid chromatography–tandem mass spectrometry (LC–MS/MS). A multiple logistic regression model was established to determine the factors that affect clinical efficacy of roxadustat in patients undergoing hemodialysis.Results A total of 67 hemodialysis patients were enrolled in the study. The results showed that age, blood trough concentration of roxadustat, and baseline hemoglobin (Hb) level were independent factors of clinical efficacy of roxadustat (OR = 1.06, p = .025 for age; OR = 1.001, p = .037 for plasma concentration; and OR = 0.941, p = .003 for baseline Hb), with an AUC score of 0.859.Conclusions Age, blood trough concentration of roxadustat, and baseline Hb level were independent influencing factors of the response to roxadustat in hemodialysis patients.

AimsTo investigate the prevalence and influencing factors of drug-related problems (DRPs) in inpatients with kidney disease to provide reference data for pharmaceutical care.MethodsThe basic information, diagnoses, and medication reconciliation (MR) of inpatients in the Department of Nephrology at our hospital between October 2020 and September 2021 were collected. The Chinese-modified DRP version based on the PCNE classification (Version 9.1) was used to assess, intervene and statistically analyze the results of the patients’ DRPs. The influence factor of DRPs in inpatients with kidney disease was analyzed by the multivariate binary logistic regression.ResultsOf 623 patients included in this study, 132 (21.80%) had DRPs. The prevalence of anemia was significantly higher in patients with DRPs than those without DRPs (43.18% vs. 28.72%, p < 0.05), the mean number of drug types consumed (7.25 ± 3.44 with DRPs vs. 5.93 ± 3.58 without DRPs, p < 0.05) and the proportion of ≥5 drugs (%) (79.55% with DRPs vs 58.04% without DRPs, p < 0.05) were significantly increased. In addition, the prevalence of hypertension (76.52% vs. 68.64%), diabetes (27.27% vs. 22.20%) and hyperuricemia (16.67% vs. 13.65%) in DRP patients were higher than those without DRPs, but there was no statistical difference (p > 0.05). The logistic regression analysis showed that patients with anemia (OR = 1.702, 95%CI: 1.146–2.529, p = 0.008), average number of medication types taken (OR = 1.089, 95%CI: 1.034–1.147, p = 0.001) significantly increased the risk of DRPs. The distribution of harm levels was as follows: 78 problems (59.09%) were level C, 29 (21.97%) were level B, 10 (7.58%) were level D, 7 (5.30%) were level A, 7 (5.30%) were level E, and 1 (0.76%) were level F. All DRPs were resolved after 128 interventions.ConclusionRenal anemia, the average number of drug varieties consumed, and the proportion of ≥5 drugs are associated with the occurrence of DRPs. Pharmacists conducting MR services can reduce DRPs of inpatients in the department of nephrology and ensure patient drug safety.

Background/Aims Roxadustat, an oral medication for treating renal anemia, is a hypoxia-inducible factor prolyl hydroxylase inhibitor used for regulating iron metabolism and promoting erythropoiesis. To investigate the efficacy and safety of roxadustat in patients undergoing peritoneal dialysis (PD) with erythropoietin hyporesponsiveness. Methods Single-center, retrospective study, 81 PD patients (with erythropoietin hyporesponsiveness) were divided into the roxadustat group (n = 61) and erythropoiesis-stimulating agents (ESAs) group (n = 20). Hemoglobin (Hb), total cholesterol, intact parathyroid hormone (iPTH), brain natriuretic peptide (BNP), related indicators of cardiac function and high-sensitivity C-reactive protein (hs-CRP) were collected. Additionally, adverse events were also recorded. The follow-up period was 16 weeks. Results The two groups exhibited similar baseline demographic and clinical characteristics. At baseline, the roxadustat group had a mean Hb level of 89.8 ± 18.9 g/L, while the ESAs group had a mean Hb level of 95.2 ± 16.0 g/L. By week 16, the Hb levels had increased to 118 ± 19.8 g/L (p < 0.05) in the roxadustat group and 101 ± 19.3 g/L (p > 0.05) in the ESAs group. The efficacy of roxadustat in improving anemia was not influenced by baseline levels of hs-CRP and iPTH. Cholesterol was decreased in the roxadustat group without statin use. An increase in left ventricular ejection fraction and stabilization of BNP were observed in the roxadustat group. Conclusions For PD patients with erythropoietin hyporesponsiveness, roxadustat can significantly improve renal anemia. The efficacy of roxadustat in improving renal anemia was not affected by baseline levels of hs-CRP0 and iPTH.

Abstract The determinants of roxadustat treatment failure in renal anemia remain elusive. This study sought to develop a nomogram for predicting the risk of treatment failure of roxadustat in peritoneal dialysis (PD) with renal anemia. A retrospective cohort analysis from January 1, 2019, to January 31, 2023, included 204 PD patients with renal anemia, stratified by attainment group (Hb ≥ 110 g/L, n = 103) or non-attainment (Hb

Background/Objectives: Chronic kidney disease (CKD) and anemia are independent prognostic factors for heart failure. In recent years, hypoxia-inducible factor-prolyl hydroxylase (HIF-PH) inhibitors have become available for the treatment of renal anemia. This prospective randomized controlled study aimed to investigate the effects of switching from a continuous erythropoietin receptor activator (CERA) to one of four HIF-PH inhibitors in patients with chronic heart failure and renal anemia. Methods: Forty patients were randomized by the envelop method to receive treatment with roxadustat, daprodustat, vadadustat, or molidustat. The primary endpoint was the change in the hemoglobin (Hb) level. Secondary endpoints included changes in erythropoietin, changes in free T3, free T4, and thyroid-stimulating hormone (TSH), adverse effects, and drug dose increases and decreases. This study was preregistered in the University Hospital Medical Information Network Clinical Trials Registry (study ID: UMIN000041651). Results: We found no statistically significant difference between Hb levels with HIF-PH inhibitors and CERA, but at month 6, the Hb level was significantly higher with roxadustat than with vadadustat and daprodustat. Erythropoietin decreased significantly after switching to HIF-PH inhibitors. HIF-PH inhibitors had various significant effects on free T3, free T4, and TSH. No adverse events occurred. The doses of some drugs had to be increased or decreased. Conclusions: In patients with heart failure and renal anemia receiving CERA, Hb, NT-ProBNP, and renal function were similar after switching from CERA to HIF-PH inhibitors. The individual HIF-PH inhibitors appear to have different effects on anemia and thyroid function. However, because this was a single-center study with a limited sample size, the efficacy and potential limitations of HIF-PH inhibitors need to be further clarified. [ABSTRACT FROM AUTHOR]

Obejective: To investigate the clinical efficacy of relationship between serum 25-hydroxyvitamin D [25 (OH)D], neutrophil gelatinase-associated lipocalin (NGAL), Hepcidin （Hepcidin）and roxadustat capsules in the treatment of renal anemia in maintenance hemodialysis (MHD) patients. Methods: 137 MHD patients with renal anemia who were treated with roxadustat capsules in the Affiliated Hospital of Xuzhou Medical University from October 2020 to October 2022 were selected, and patients were divided into effective group (86 cases) and ineffective group (51 cases) according to the effect of 12 weeks of treatment. The serum levels of 25(OH) D, NGAL and Hepcidin were detected before treatment, the factors affecting the efficacy of roxadustat capsules were analyzed by multivariate Logistic regression model, the value of 25(OH)D, NGAL and Hepcidin in predicting the efficacy of roxadustat capsules were analyzed by receiver operating characteristic (ROC) curve. Results: The level of serum 25 (OH)D in ineffective group before treatment was lower than that in effective group (P<0.05), and the levels of NGAL and Hepcidin were higher than those in effective group (P<0.05). High level of NGAL and high level of Hepcidin were risk factors for ineffective treatment of renal anemia in MHD patients with roxadustat capsules (P<0.05), high level of 25 (OH)D, combined with hemofiltration or hemoperfusion, and urea clearance index (Kt/v) >1.2 were protective factors (P<0.05). The area under the curve (AUC) of 25 (OH)D, NGAL, and Hepcidin combined to predict the efficacy of rosastat capsules was 0.853, which was higher than the prediction of individual indicators. Conclusion: The serum 25 (OH) D level decreased and NGAL and Hepcidin level increased in patients with MHD renal anemia before treatment with roxadustat capsules, the above level changes were related to the treatment effect of roxadustat capsules, the combination of 25 (OH)D, NGAL and Hepcidin could improve the predictive value of the therapeutic effect of roxadustat capsules. [ABSTRACT FROM AUTHOR]

The determinants of roxadustat treatment failure in renal anemia remain elusive. This study sought to develop a nomogram for predicting the risk of treatment failure of roxadustat in peritoneal dialysis (PD) with renal anemia. A retrospective cohort analysis from January 1, 2019, to January 31, 2023, included 204 PD patients with renal anemia, stratified by attainment group (Hb ≥ 110 g/L, n = 103) or non-attainment (Hb < 110 g/L, n = 101) within 1 year treatment. Univariate and multivariate Cox proportional hazards regressions were employed to ascertain predictive factors and construct the nomogram. Nomogram efficacy was evaluated via C-index, time-dependent ROC, calibration plots, and decision curve analysis, with internal validation via tenfold cross-validation and 1000 bootstrap resampling iterations. The study identified PD duration, serum transferrin, cardiovascular comorbidities, and stains as significant predictors. The nomogram demonstrated moderate discrimination at 6 months (AUC: 0.717) and enhanced predictive accuracy at 12 months (AUC: 0.741). The predicted and actual risk probabilities were concordant, with clinical net benefits observed at six-month (8 to 53%) and twelve-month (27 to 84%) risk thresholds. This nomogram is a valuable tool for effectively predicting non-attainment risk and facilitating personalized management of renal anemia in PD patients treated with roxadustat. [ABSTRACT FROM AUTHOR]

OBJECTIVE: To probe into the effects of Danggui Buxue decoction combined with circling moxibustion on glomerular filtration function, vascular calcification, intestinal endotoxin level and hepcidin-25, β-hydroxybutyrate (β-HB) in patients with chronic kidney disease(CKD) 3-5 non-dialysis diabetes nephropathy complicated with renal anemia. METHODS: A total of 102 patients with CKD 3-5 non-dialysis diabetes nephropathy complicated with renal anemia admitted into nephropathy and rheumatology department of the hospital from Dec. 2021 to Feb. 2023 were extracted and divided into the research group and control group by random number table method, with 51 patients in each group. On the basis of routine treatment (diet control, moderate exercise, oral rosastatin), the control group was treated with circling moxibustion, while the research group received Danggui Buxue decoction on the basis of the control group. Both groups were treated continuously for 3 months. After treatment, the efficacy of two groups was analyzed, and the glomerular filtration function, vascular calcification score, peripheral blood lipopolysaccharide (LPS), interleukin-6 (IL-6), hepcidin-25 and β-HB levels were compared between two groups. RESULTS: The total effective rate of the research group was 96. 08% (49 / 51), significantly higher than that 84. 31% ( 43 / 51) of the control group, the difference was statistically significant (P<0. 05). Compared with the control group, patients in the research group after treatment had higher glomerular filtration rate, lower abdominal aortic vascular calcification score, lower LPS, IL-6, hepcidin-25 and β-HB levels in peripheral blood, and higher hemoglobin, ferritin, transferrin saturation and transferrin contents in peripheral blood, the differences were statistically significant ( P < 0. 05 ). CONCLUSIONS: The efficacy of Danggui Buxue decoction combined with circling moxibustion for improving anemia in patients with CKD 3-5 non-dialysis diabetes nephropathy complicated with renal anemia is significant, which can improve the glomerular filtration function and reduce the degree of vascular calcification, the mechanism may be related to reducing the level of lipopolysaccharide and regulating the level of hepcidin-25 and β-HB. [ABSTRACT FROM AUTHOR]

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Introduction: Hypoxia-inducible factor-prolyl hydroxylase (HIF-PH) inhibitors, used in the treatment of renal anemia, hold the potential to increase the production of vascular endothelial growth factors. Therefore, HIF-PH inhibitors may exacerbate retinal hemorrhage in diseases such as diabetic retinopathy. Here, we present a case involving the administration of an HIF-PH inhibitor, resulting in the exacerbation of retinal hemorrhage in a patient with diabetic retinopathy. Case Presentation: A 32-year-old man with diabetes mellitus and renal anemia caused by diabetic nephropathy was referred to our department for ophthalmic examination, revealing diabetic retinopathy with scattered retinal hemorrhages, exudates, and diabetic maculopathy in both eyes. Darbepoetin alfa was initially administered and switched to the HIF-PH inhibitor roxadustat on day 74. By day 88, fresh retinal hemorrhage was observed in the right eye. On day 132, the retinal hemorrhage had further worsened, with new preretinal hemorrhage in both eyes. Roxadustat was discontinued, replaced with darbepoetin alfa, resulting in retinal hemorrhage improvement by day 181 (49 days post-roxadustat cessation). On day 201, fundus hemorrhage further improved, optical coherence tomography showed no macular edema or subretinal fluid, and the retina was thinning. Fluorescein angiography showed neovascular vessels, active fluorescein leakage, and extensive avascular areas in both eyes, prompting pan-retinal photocoagulation. Visual acuity remained stable throughout treatment. Conclusion: Patients with advanced diabetic retinopathy taking HIF-PH inhibitors should be aware of retinal hemorrhage exacerbations. If observed, the treatment plan, including discontinuation of the HIF-PH inhibitor or switching to another agent, should be discussed with a diabetologist, nephrologist, and ophthalmologist.

Introduction: Roxadustat, the first-in-class drug for the treatment of renal anemia, has demonstrated efficacy in renal anemia with microinflammation. Additional data are needed regarding the efficacy of roxadustat on renal anemia with systemic macroinflammation. Methods: Three cohorts of renal anemia based on the basic level of high-sensitivity CRP were included. Patients with hsCRP ≤2 mg/L were selected as non-inflammation (NI) group; 2< hsCRP ≤10 mg/L as microinflammation (MI) group; hsCRP≥10 mg/L as macroinflammation (MA) group. Patients received oral roxadustat three times per week for 52 weeks. The primary end point was the hemoglobin level over weeks 12–52. The second end point was the cumulative proportion of patients achieving hemoglobin response by the end of week 12. Results: A total of 107 patients with chronic kidney diseases (CKDs) were enrolled. Overall, the baseline hemoglobin level of patients was 79.99 ± 11.20 g/L. Roxadustat could significantly increase the hemoglobin level in all of the three groups and did not show any significant difference (p > 0.05, respectively). Meanwhile, compared with that of the NI group, there was no significant difference in hemoglobin response rate in the MA group both at week 12 (p = 0.06; 95% confidence interval [CI], 0.9531–13.75) and week 52 (p = 0.37; 95% CI, 0.5080–7.937). Moreover, the hemoglobin response was independent of baseline hsCRP level (p = 0.72, 95% CI, −0.1139 to 0.0794). More importantly, roxadustat significantly reduced ferritin and serum iron levels and increased total iron-binding capacity in the three groups, which showed no significant differences among the three groups (p > 0.05, respectively). Conclusion: Roxadustat significantly improves anemia in CKD patients with systemic macroinflammation.

Abstract Objective Hypoxia-inducible factor prolyl hydroxylase (HIF-PH) inhibitors are a new class of anti-anemia agents. We retrospectively evaluated the safety and efficacy of HIF-PH inhibitors in patients with heart failure (HF) complicated by anemia associated with chronic kidney disase. HIF-PH inhibitor treatment was initiated in 32 patients with chronic HF complicated by renal anemia and were followed up for 3 months. Results Hematocrit and hemoglobin levels markedly improved 3 months after HIF-PH inhibitor treatment. However, levels of NT-proBNP, which is an indicator of HF, did not decrease considerably. Based on the rate of change in NT-proBNP, we divided the patients into “responder” and “non-responder” groups. The results showed that considerably more patients had a ferritin level of less than 100 ng/mL in the non-responder group at baseline. There were substantially more patients with TSAT of less than 20% in the non-responder group at 1 month after HIF-PH inhibitor treatment. The cut-off values to maximize the predictive power of ferritin level at baseline and TSAT value at 1 month after treatment were 41.8 ng/ml and 20.75. HIF-PH inhibitor treatment can be expected to be effective for improving both anemia and HF if ferritin≥41.8 ng/ml at baseline or TSAT≥20.75 at 1 month after treatment.

Abstract Background The consequences of chronic kidney disease (CKD) can be addressed with a range of pharmacotherapies primarily prescribed by nephrologists. More accurate information regarding future CKD-related pharmacotherapy requirements could guide clinical decisions including follow-up frequency. Methods Following assignment to derivation and validation groups (2,1), variables predicting individually future use of vitamin D receptor agonists (VDRA), phosphate binders, erythropoiesis stimulating agents (ESAs) and iron were identified using logistic regression in a prospective cohort study containing demography, comorbidity, hospitalization, laboratory, and mortality data in patients with CKD stage G4/G5 across six European countries. Discriminative ability was measured using C-statistics, and predicted probability of medication use used to inform follow-up frequency. Results A total of 2196 patients were included in the analysis. During a median follow-up of 735 days 648 initiated hemodialysis and 1548 did not. Combinations of age, diabetes status and iPTH, calcium, hemoglobin and serum albumin levels predicted the use of ESA, iron, phosphate binder or VDRA, with C-statistics of 0.70, 0.64, 0.73 and 0.63 in derivation cohorts respectively. Model performance in validation cohorts were similar. Sixteen percent of patients were predicted to have a likelihood of receiving any of these medications of less than 20%. Conclusions In a multi-country CKD cohort, prediction of ESA and phosphate binder use over a two-year period can be made based on patient characteristics with the potential to reduce frequency of follow-up in individuals with low risk for requiring these medications.

Hypoxia-inducible factor prolyl hydroxylase inhibitors (HIF-PHIs) have emerged as a novel therapeutic class for treating anemia in patients with chronic kidney disease. Small molecule analogs of α-ketoglutarate (AKG), an essential substrate for 2-oxoglutarate-dependent dioxygenases (2-OGDDs), including prolyl hydroxylase domain proteins (PHDs), inhibit PHDs pharmacologically and thereby prevent HIF degradation. HIF stabilization alleviates anemia through several stimulatory effects on erythropoiesis, but it also affects the expression of many anemia-unrelated genes whose protein products exert important functions in vivo. Therefore, the pleiotropic effects of HIF stabilization under normoxic conditions deserve to be examined in more detail. Specifically, we believe that particular attention should be given to epigenetic modifications among the various AKG-based metabolic systems that may be altered by HIF-PHIs. It is noteworthy that AKG has been reported to exert health-protective actions. AKG-based metabolic systems include enzymes associated with the tricarboxylic acid cycle and amino acid metabolism, as well as 2-OGDD-mediated processes, which play important roles in many biological reactions. In this review, we examine the multifaceted effects of HIF-PHIs, encompassing not only their on-target effect of HIF stabilization but also their off-target inhibitory effects on various AKG-based metabolic systems. Furthermore, we examine its potential relevance to cardiovascular complications, based on clinical and animal studies suggesting its involvement in vascular calcification, thrombogenesis and heart failure. In conclusion, although HIF-PHIs offer a promising avenue for anemia treatment in CKD patients, their broader impact on multiple biological systems raises substantial concerns. The intricate interplay between HIF stabilization, AKG competition and cardiovascular complications warrants extensive, long-term investigations to ensure the safety and usefulness of HIF-PHIs in clinical practice. [ABSTRACT FROM AUTHOR]

Since zinc is involved in many aspects of the hematopoietic process, zinc supplementation can reduce erythropoiesis-stimulating agents (ESAs) in patients undergoing hemodialysis. However, it remains unclear whether hypoxia-inducible factor–prolyl hydroxylase inhibitors (HIF-PHIs) have similar reduction effects. HIF-PHI stabilizes HIF, which promotes hematopoiesis, although HIF-1α levels are downregulated by zinc. This study aimed to investigate the effect of zinc supplementation on the hematopoietic effect of HIF-PHI in patients undergoing hemodialysis. Thirty patients undergoing maintenance hemodialysis who underwent periods of treatment with roxadustat or darbepoetin alfa during the past 3 years were retrospectively observed. Participants who underwent periods with and without zinc supplementation were selected, with nine treated with darbepoetin alfa and nine treated with roxadustat. Similarly to the ESA responsiveness index (ERI), the hematopoietic effect of zinc supplementation was determined by the HIF-PHI responsiveness index (HRI), which was calculated by dividing the HIF-PHI dose (mg/week) by the patient's dry weight (kg) and hemoglobin level (g/L). Zinc supplementation significantly increased ERI (p < 0.05), but no significant change was observed (p = 0.931) in HRI. Although zinc supplementation did not significantly affect HRI, adequate zinc supplementation is required to alleviate concerns such as vascular calcification and increased serum copper during the use of HIF-PHI. [ABSTRACT FROM AUTHOR]

Introduction: Hypoxia-inducible factor-prolyl hydroxylase (HIF-PH) inhibitors, used in the treatment of renal anemia, hold the potential to increase the production of vascular endothelial growth factors. Therefore, HIF-PH inhibitors may exacerbate retinal hemorrhage in diseases such as diabetic retinopathy. Here, we present a case involving the administration of an HIF-PH inhibitor, resulting in the exacerbation of retinal hemorrhage in a patient with diabetic retinopathy. Case Presentation: A 32-year-old man with diabetes mellitus and renal anemia caused by diabetic nephropathy was referred to our department for ophthalmic examination, revealing diabetic retinopathy with scattered retinal hemorrhages, exudates, and diabetic maculopathy in both eyes. Darbepoetin alfa was initially administered and switched to the HIF-PH inhibitor roxadustat on day 74. By day 88, fresh retinal hemorrhage was observed in the right eye. On day 132, the retinal hemorrhage had further worsened, with new preretinal hemorrhage in both eyes. Roxadustat was discontinued, replaced with darbepoetin alfa, resulting in retinal hemorrhage improvement by day 181 (49 days post-roxadustat cessation). On day 201, fundus hemorrhage further improved, optical coherence tomography showed no macular edema or subretinal fluid, and the retina was thinning. Fluorescein angiography showed neovascular vessels, active fluorescein leakage, and extensive avascular areas in both eyes, prompting pan-retinal photocoagulation. Visual acuity remained stable throughout treatment. Conclusion: Patients with advanced diabetic retinopathy taking HIF-PH inhibitors should be aware of retinal hemorrhage exacerbations. If observed, the treatment plan, including discontinuation of the HIF-PH inhibitor or switching to another agent, should be discussed with a diabetologist, nephrologist, and ophthalmologist. [ABSTRACT FROM AUTHOR]

OBJECTIVE: The aim of this study was to investigate the hemoglobin variability in patients undergoing maintenance hemodialysis during the application of erythropoietin (EPO) and roxadustat. PATIENTS AND METHODS: For this retrospective study, we analyzed the clinical records of 80 patients with renal anemia on maintenance hemodialysis (MHD) admitted to our hospital between January 2017 and December 2022. We adopted a self-control design comparing the hemoglobin variability of the values before and after roxadustat administration in each patient. The patients received EPO from January 2017 to December 2019 and roxadustat from January 2020 to December 2022. We compared the levels of serum ferritin, transferrin saturation, and hemoglobin and calculated the hemoglobin variabilities by comparing values before and after roxadustat treatments. RESULTS: We found higher transferrin saturation levels at different time points after the roxadustat treatments (p<0.01); meanwhile, the serum ferritin and hemoglobin levels were significantly higher after the roxadustat treatment (p<0.001). During the treatments with EPO and roxadustat, the transferrin saturation, serum ferritin, and hemoglobin levels differed significantly at different time points for each patient (p<0.05). After roxadustat administration, the hemoglobin levels were significantly higher than after EPO administration (p<0.001) and changed more rapidly after roxadustat administration than after EPO administration (p<0.05). The hemoglobin variability after roxadustat administration was significantly lower than that after EPO administration (p<0.05). CONCLUSIONS: Treatment with roxadustat led to higher hemoglobin levels and less hemoglobin variability than the treatment with EPO, with high transferrin saturation and higher ferritin levels in patients with renal anemia on MHD. [ABSTRACT FROM AUTHOR]

Context Roxadustat, a hypoxia-inducible factor prolyl hydroxylase (HIF-PH) inhibitor, a recently developed class of drugs for treatment of anemia in chronic kidney disease (CKD), is reported to have a structure unlike that of other HIF-PH inhibitors but similar to that of triiodothyronine and bind to the thyroid hormone receptor in vitro. However, reports on the effects of roxadustat on thyroid function are limited and not detailed, and it remains unknown whether other HIF-PH inhibitors also affect thyroid function. Objective To compare the effect of roxadustat with daprodustat, another HIF-PH inhibitor, on thyroid function in patients with renal anemia in CKD. Methods This retrospective observational study included a total of 26 patients with anemia in CKD who were treated with roxadustat or daprodustat; thyroid-stimulating hormone (TSH) and free thyroxine (FT4) were measured before and after treatment with the drugs. Results After initiation of roxadustat, TSH showed a significant decrease (2.4732 [1.7858-4.9016] μIU/mL before treatment and 0.659 [0.112-2.005] μIU/mL after treatment, P <.05); FT4 showed a significant decrease (0.93 [0.84-1.05] ng/dL before treatment and 0.70 [0.53-0.85] ng/dL after treatment, P <.01). After daprodustat initiation, neither TSH nor FT4 showed a significant change (TSH: 3.044 [1.853-4.171] μIU/mL before treatment and 2.893 [1.866-4.894] μIU/mL after treatment, P =.635; FT4 was 0.93 [0.81-1.00] ng/dL before treatment and 0.97 [0.87-1.05] ng/dL after treatment, P =.328). Conclusion Roxadustat decreases TSH and FT4 levels while daprodustat does not. [ABSTRACT FROM AUTHOR]

The recent research was done to assess the hematological and biochemical disorders in nephrotoxicity induced by gentamicin (100 mg/kg) in Wistar rats. The green-formulated silver nanoparticles (AgNPs) by Tribulus terrestris leaf were analyzed by XRD, energy-dispersive X-ray spectrometer, and field emission scanning electron microscopy. The shape of the recent nanoparticles was spherical in size of 48 nm. In the in vivo, the classical and novel kidney injury parameters were used to assess the nephroprotective properties of AgNPs in animal model. Gentamicin decreased significantly (P ≤ 0.01) the value of PCV, concentration of HB, and count of RBC. The value of serum iron, erythropoietin, Cr, and urea raised in the gentamicin group. Leucogram revealed thrombocytopenia, granulocytosis, and leukocytosis. AgNPs improved the iron, erythropoietin, thrombocytes, leukogram, and erythrogram. The levels of creatinine, urea, GGT, ALT, AST, and ALP significantly reduced and albumin and total protein increased in group treated with AgNPs. Also, AgNPs significantly raised the anti-inflammatory cytokines, i.e., IL3, TGFβ, IL10, IL5, and IL4, and decreased the pro-inflammatory cytokines, i.e., TNFα, IL18, IL12, IL6, and IL1. These findings may offer AgNPs as a nephroprotective agent that could be a suitable therapeutic supplement in blood disorders conditions.

Resumen: La anemia es una complicación frecuente de la enfermedad renal crónica (ERC) y se asocia con una disminución en la calidad de vida y a un mayor riesgo de transfusiones, de morbimortalidad y de progresión de la ERC. El Grupo de Trabajo en Anemia de la Sociedad Española de Nefrología realizó un estudio Delphi entre expertos en anemia de la ERC para consensuar respuestas a preguntas relevantes que no se hubieran podido resolver con la evidencia existente. Se empleó la metodología de consensos RAND/UCLA. Se definieron 15 preguntas con una estructura PICO, seguida de una revisión en bases de datos de literatura científica. A partir de la evidencia se formularon enunciados. Diecinueve expertos los evaluaron mediante un proceso iterativo tipo Delphi a dos rondas. Se consensuaron 16 enunciados en respuesta a 8 preguntas referidas a la ferropenia y suplementación con Fe (impacto y gestión de ferropenia con o sin anemia, marcadores de ferropenia, seguridad de hierro i.v.) y a 7 relacionadas con agentes estimuladores de la eritropoyesis (AEE) y/o con estabilizadores del factor inducible por la hipoxia (HIF), alcanzándose consenso en todos ellos (individualización del objetivo de Hb, impacto y gestión de resistencia a AEE, AEE en el periodo inmediato post trasplante y estabilizadores de HIF: impacto sobre la ferrocinética, interacción con inflamación y seguridad cardiovascular). Existe una necesidad de estudios clínicos que aborden los efectos de la corrección del déficit de Fe con independencia de la anemia y el impacto del tratamiento de esta con diversos AEE sobre la calidad de vida, la progresión de ERC y los eventos cardiovasculares. Abstract: Anemia is a common complication of chronic kidney disease (CKD) and is associated with a decrease in quality of life and an increased risk of transfusions, morbidity and mortality, and progression of CKD. The Anemia Working Group of the Sociedad Española de Nefrología conducted a Delphi study among experts in anemia in CKD to agree on relevant unanswered questions by existing evidence. The RAND/UCLA consensus methodology was used. We defined 15 questions with a PICO structure, followed by a review in scientific literature databases. Statements to each question were developed based on that literature review. Nineteen experts evaluated them using an iterative Two-Round Delphi-like process. Sixteen statements were agreed in response to 8 questions related to iron deficiency and supplementation with Fe (impact and management of iron deficiency with or without anemia, iron deficiency markers, safety of i.v. iron) and 7 related to erythropoiesis stimulating agents (ESAs) and/or hypoxia-inducible factor stabilizers (HIF), reaching consensus on all of them (individualization of the Hb objective, impact and management of resistance to ESA, ESA in the immediate post-transplant period and HIF stabilizers: impact on ferrokinetics, interaction with inflammation and cardiovascular safety). There is a need for clinical studies addressing the effects of correction of iron deficiency independently of anemia and the impact of anemia treatment with various ESA on quality of life, progression of CKD and cardiovascular events.

Abstract Background Hypoxia-inducible factor-prolyl hydroxylase inhibitors (HIF-PHIs) have improved the treatment of renal anemia, especially in patients resistant to erythropoiesis-stimulating agents (ESAs). HIF facilitates maintain gut microbiota homeostasis, which plays an important role in inflammation and iron metabolism, which are in turn key factors affecting ESA resistance. The current study aimed to investigate the effects of roxadustat on inflammation and iron metabolism and on the gut microbiota in patients with ESA resistance. Methods We conducted a self-controlled, single-center study including 30 patients with ESA resistance undergoing maintenance hemodialysis. All patients received roxadustat without iron agents for renal anemia. Hemoglobin and inflammatory factors were monitored. Fecal samples were collected before and after 3 months’ administration and the gut microbiota were analyzed by 16S ribosomal RNA gene sequencing. Results Hemoglobin levels increased after treatment with roxadustat for 3 months (P

Background: Renal anemia, a common complication and threat factor of chronic kidney disease (CKD), has long been treated with injectable erythropoietin-stimulating agents (ESAs). As concerns regarding cardiovascular safety and erythropoietin resistance to ESAs have emerged, alternative therapies are urgently needed. Hypoxia-inducible factor prolyl hydroxylase inhibitor (HIF-PHI), an oral agent, has been proven to be effective in improving renal anemia. However, the effects of HIF-PHIs on nondialysis-dependent CKD (NDD-CKD) have yet to be supported by updated meta-analyses. Methods: A meta-analysis of clinical randomized controlled trials (RCTs) on HIF-PHI treatment of NDD-CKD patients based on PubMed, EMBASE, and Cochrane databases as of July 16th, 2023, was conducted. The primary outcomes were the level of hemoglobin (Hb) postintervention and the ratio of Hb responses. Most of the analysis was conducted via RevMan 5.3 software using a random-effects model. Stata (version 15.0) was used to analyze the publication bias. Results: Twenty-two studies with a total of 7178 subjects in the HIF-PHI group, 3501 subjects in the ESA group and 2533 subjects in the placebo group were enrolled. HIF-PHIs increased the level of Hb and improved iron metabolism but were not inferior to ESAs in terms of safety. Conclusions: HIF-PHIs may be a convenient and safe alternative to ESAs in patients with NDD-CKD and anemia. [ABSTRACT FROM AUTHOR]

This cohort study was designed to explore whether roxadustat or erythropoietin could affect thyroid function in patients with renal anemia. The study involved 110 patients with renal anemia. Thyroid profile and baseline investigations were carried out for each patient. The patients were divided into two groups: 60 patients taking erythropoietin served as the control group (rHuEPO group) and 50 patients using roxadustat served as the experimental group (roxadustat group). The results indicated that there were no significant differences in serum total thyroxine (TT4), total triiodothyronine (TT3), free triiodothyronine (FT3), free thyroxine (FT4) or thyroid stimulating hormone (TSH) between the two groups at baseline. After treatment, TSH, FT3, and FT4 were significantly lower in the roxadustat group than in the rHuEPO group (p < 0.05). After adjusting for age, sex, dialysis modality, thyroid nodules and causes of kidney disease, Cox regression showed that roxadustat was an independent influencing factor on thyroid dysfunction (HR 3.37; 95% CI 1.94–5.87; p < 0.001). After 12 months of follow-up, the incidence of thyroid dysfunction was higher in the roxadustat group than in the rHuEPO group (log-rank p < 0.001). Roxadustat may lead to a higher risk of thyroid dysfunction, including low TSH, FT3 and FT4, than rHuEPO in patients with renal anemia. [ABSTRACT FROM AUTHOR]

Enarodustat (JTZ-951) is an oral hypoxia-inducible factor-prolyl hydroxylase (HIF-PH) inhibitor for the treatment of anemia with chronic kidney disease. Carcinogenicity of enarodustat was evaluated in a 26-week repeated oral dose study in Transgenic rasH2 (Tg.rasH2) mice and a 2-year repeated oral dose study in Sprague-Dawley (SD) rats. The highest dose levels were set at 6 mg/kg in the Tg.rasH2 mouse study and at 1 mg/kg in the SD rat study based on the maximum tolerated doses in the 3-month and 6-month dose-range finding studies, respectively. Enarodustat did not increase the incidence of any tumors or affect survival in these carcinogenicity studies. Pharmacology-related findings including increases in blood RBC parameters were observed at the highest dose levels for each study. The AUC-based exposure margins as protein-unbound drug base are 16.3-/26.0-fold multiple (males/females) for Tg.rasH2 mice and 1.6-/1.1-fold multiple for SD rats when compared with the estimated exposure in human with chronic kidney disease at 8 mg/day (maximum recommended human dose). In conclusion, enarodustat was considered to have no carcinogenic potential at the clinical dose. [ABSTRACT FROM AUTHOR]

Patients undergoing hemodialysis often require zinc supplementation owing to hypozincemia, which may reduce serum copper concentrations. However, hypoxia-inducible factor–prolyl hydroxylase inhibitors (HIF-PHIs), which are used to treat renal anemia, have been reported to increase serum copper. Therefore, this study investigates the effectiveness of a combination of HIF-PHIs and zinc for the stabilization of serum copper and zinc concentrations during zinc supplementation for patients undergoing hemodialysis with renal anemia and hypozincemia. The serum zinc and copper concentrations were retrospectively compared over an 8-month period in 20 patients being administered roxadustat (an HIF-PHI) and 20 controls. The changes in concentrations were tracked in participants taking roxadustat who initiated or increased zinc supplementation. The serum zinc concentrations of the participants were significantly higher (p < 0.001) during zinc supplementation, regardless of roxadustat administration. Post-roxadustat, the serum copper concentrations were significantly higher than those pre-roxadustat or in non-roxadustat-treated participants, irrespective of zinc supplementation (p < 0.005). Even post-roxadustat, the serum copper concentrations were significantly lower, with no increase during zinc supplementation (p < 0.040). When zinc supplementation was initiated or increased in participants taking roxadustat, copper and zinc concentrations were normalized. Thus, combining zinc supplementation with roxadustat prevents both an excessive increase in serum copper and a decrease in serum zinc. [ABSTRACT FROM AUTHOR]

Purpose: This study aims to evaluate the effectiveness and cost-effectiveness of recombinant human erythropoietin (rHuEPO) and Roxadustat in treating renal anemia, particularly in athletic patients undergoing regular hemodialysis. Methods: Between January 2020 and December 2021, 150 athletic patients on continuous ambulatory regular hemodialysis were enrolled. They were divided equally into rHuEPO and Roxadustat groups. We assessed hemoglobin (Hb), hematocrit (Hct), serum ferritin (SF), and transferrin (TRF) levels, along with adverse reactions, allergic responses, coagulation function, and liver and kidney function parameters (ALT, CCr) before and after treatment. The study also compared the cost-effectiveness of these treatments. Results: Basic demographic information (gender, duration of illness, weight, dialysis method, age) showed no significant difference between groups (P > 0.05). The Roxadustat group demonstrated a significantly higher total effective rate (92.00%) compared to the rHuEPO group (74.67%), with P < 0.05. Posttreatment, improvements in Hb, Hct, SF, TRF, and coagulation and liver and kidney function indices were observed in both groups, with Roxadustat showing superior outcomes (P < 0.05). Adverse reactions were lower in the Roxadustat group (9.33%) compared to the rHuEPO group (24.00%), P < 0.05. Roxadustat's Incremental Cost-Effectiveness Ratio (ICER) was 41,134.10 yuan, deemed tolerable against the backdrop of thrice the per capita GDP. Conclusion: Both Roxadustat and rHuEPO are effective in treating renal anemia in athletes. However, Roxadustat shows superior efficacy, safety, ease of oral administration, patient acceptance, and cost-effectiveness. It becomes the preferred choice for athletic patients with a willingness to pay exceeding 41,134.10 yuan, marking it as the most economically viable option. [ABSTRACT FROM AUTHOR]

Copyright of Practical Pharmacy & Clinical Remedies is the property of Editorial Department of Practical Pharmacy & Clinical Remedies and its content may not be copied or emailed to multiple sites or posted to a listserv without the copyright holder's express written permission. However, users may print, download, or email articles for individual use. This abstract may be abridged. No warranty is given about the accuracy of the copy. Users should refer to the original published version of the material for the full abstract. (Copyright applies to all Abstracts.)

Hypoxia‐inducible factor prolyl‐hydroxylase inhibitor (HIF‐PHI) is a novel agent for the treatment of renal anemia. HIF‐PHI increases endogenous erythropoietin production by inhibiting the degradation of an erythropoietin transcription factor. Although beneficial effects are expected from HIF‐PHI, its novel mechanism raises concerns regarding the risk of potential adverse events. The cases of hypothyroidism, which had not been reported in clinical trials, were reported after the administration of roxadustat in a real‐world setting. However, the effects of HIF‐PHIs on thyroid function have not yet been fully evaluated. This study aimed to assess the clinical impact of HIF‐PHIs on thyroid function using the Japanese Adverse Drug Event Report database, a spontaneous reporting system in Japan, because HIF‐PHIs were made available in Japan before they were available in other countries. Although a disproportionality signal for hypothyroidism was detected with roxadustat (reporting odds ratio [ROR]:22.1, 95% confidence interval [CI]:18.3‐26.7, no signals were detected with another HIF‐PHI, daprodustat (ROR:1.3, 95%CI:0.3‐5.4), and epoetin beta pegol (ROR:1.2, 95%CI:0.5‐2.7). Signals of hypothyroidism due to roxadustat were also detected regardless of age or sex. Approximately 50% of hypothyroidism cases were reported within 50 days of starting roxadustat use. These results indicate that roxadustat use may be related to the development of hypothyroidism. The need for monitoring of thyroid function should be alerted during roxadustat administration regardless of age or sex. [ABSTRACT FROM AUTHOR]

Renal anemia is a prevalent complication of chronic kidney disease （CKD）， which severely affects the prognosis of patients. The pathogenesis of renal anemia is complicated， and the core of which is erythropoietin deficiency and iron metabolism disorder. For years， renal anemia has been mainly treated based on erythropoiesis-stimulating and iron agents. Blood transfusion is used as a remedial treatment. Other therapeutic interventions include alleviating malnutrition， supplementing folic acid and vitamin B12， adequate dialysis and controlling hyperparathyroidism， etc.， which yield low efficacy. In recent years， clinical application of hypoxia-inducible factor prolyl hydroxylase inhibitors has brought another innovation in the treatment of renal anemia， and some potential approaches for the treatment of renal anemia have been reported. In this article， recent research progresses upon the treatment of renal anemia in CKD patients were reviewed， aiming provide new ideas for clinical treatment of this disease.

AbstractPurpose This cohort study was designed to explore whether roxadustat or erythropoietin could affect thyroid function in patients with renal anemia.Methods The study involved 110 patients with renal anemia. Thyroid profile and baseline investigations were carried out for each patient. The patients were divided into two groups: 60 patients taking erythropoietin served as the control group (rHuEPO group) and 50 patients using roxadustat served as the experimental group (roxadustat group).Results The results indicated that there were no significant differences in serum total thyroxine (TT4), total triiodothyronine (TT3), free triiodothyronine (FT3), free thyroxine (FT4) or thyroid stimulating hormone (TSH) between the two groups at baseline. After treatment, TSH, FT3, and FT4 were significantly lower in the roxadustat group than in the rHuEPO group (p

Background: In the primary analysis of the PREDICT trial, a higher hemoglobin target (11–13 g/dl) with darbepoetin alfa did not improve renal outcomes compared with a lower hemoglobin target (9–11 g/dl) in advanced chronic kidney disease (CKD) without diabetes. Prespecified secondary analyses were performed to further study the effects of targeting higher hemoglobin levels on renal outcomes. Methods: Patients with an estimated glomerular filtration rate (eGFR) 8–20 ml/min/1.73 m2 without diabetes were randomly assigned 1:1 to the high- and low-hemoglobin groups. The differences between the groups were evaluated for the following endpoints and cohort sets: eGFR and proteinuria slopes, assessed using a mixed-effects model in the full analysis set and the per-protocol set that excluded patients with off-target hemoglobin levels; the primary endpoint of composite renal outcome, evaluated in the per-protocol set using the Cox model. Results: In the full analysis set (high hemoglobin, n = 239; low hemoglobin, n = 240), eGFR and proteinuria slopes were not significantly different between the groups. In the per-protocol set (high hemoglobin, n = 136; low hemoglobin, n = 171), the high-hemoglobin group was associated with reduced composite renal outcome (adjusted hazard ratio: 0.64; 95% confidence interval: 0.43–0.96) and an improved eGFR slope (coefficient: + 1.00 ml/min/1.73 m2/year; 95% confidence interval: 0.38–1.63), while the proteinuria slope did not differ between the groups. Conclusions: In the per-protocol set, the high-hemoglobin group demonstrated better kidney outcomes than the low-hemoglobin group, suggesting a potential benefit of maintaining higher hemoglobin levels in patients with advanced CKD without diabetes. Clinical trial registration: Clinicaltrials.gov (identifier: NCT01581073). [ABSTRACT FROM AUTHOR]

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Background: Erythropoiesis-stimulating agents (ESAs) are the standard treatment for patients with renal anemia to increase hemoglobin (Hb) levels and reduce the need for blood transfusions. However, treatments targeting high Hb levels require high doses of ESAs administered intravenously, which is associated with an elevated risk of adverse cardiovascular events. Furthermore, there have been some problems such as hemoglobin variability and low achievement of target hemoglobin due to the shorter half-lives of ESAs. Consequently, erythropoietin-promoting medications, such as hypoxia-inducible factor-prolyl hydroxylase (HIF-PH) inhibitors, have been developed. This study aimed to evaluate changes in the Treatment Satisfaction Questionnaire for Medicine version II (TSQM-II) domain scores relative to baseline in each trial, to assess patient satisfaction with molidustat versus darbepoetin alfa. Methods: This post-hoc analysis of two clinical trials compared treatment satisfaction with an HIF-PH inhibitor, molidustat, versus a standard ESA, darbepoetin alfa, as part of therapy in patients with non-dialysis chronic kidney disease (CKD) and renal anemia. Results: Exploratory outcome data using the TSQM-II showed that both arms in both trials had enhanced treatment satisfaction over the course of the study period, as well as improvements in most TSQM-II domains at week 24 of treatment. Molidustat was associated with convenience domain scores at multiple time points depending on the trial. More patients were highly satisfied with the convenience of molidustat than that of darbepoetin alfa. Patients treated with molidustat had increased global satisfaction domain scores compared with those treated with darbepoetin alfa; however, the differences in global satisfaction domain scores were not significant. Conclusion: These patient-reported satisfaction outcomes support the use of molidustat as a patient-centered treatment option for CKD-related anemia. Registration of clinical trials: ClinicalTrials.gov Identifier: NCT03350321 (November 22, 2017). ClinicalTrials.gov Identifier: NCT03350347 (November 22, 2017). [ABSTRACT FROM AUTHOR]