Anemia and Transfusion Medicine.

Peri-operative anemia is a common condition encountered in adult surgical patients. It is increasingly recognized as a predictor of post-operative morbidity and mortality. Evaluation and treatment of anemia pre-operatively can reduce transfusion needs and potentially improve outcomes in surgical patients. This article discusses anemia optimization strategies in peri-operative setting with special focus on use of intravenous iron therapy. Additionally, the authors describe the role of transfusion medicine and best practices around red blood cell, platelet, and plasma transfusions.

Comparison of the efficacy and adverse effects of oral ferrous succinate tablets and intravenous iron sucrose: a retrospective study.

OBJECTIVE: To analyse the clinical efficacy and adverse drug reactions (ADRs) of iron preparations. METHODS: A total of 374 patients with iron deficiency anaemia admitted to our hospital between 1 January and 31 December 2020 were included in this study. They were divided into 2 groups based on their medication regimens: Group A (n = 187) took oral ferrous succinate tablets, and Group B (n = 187) received intravenous iron sucrose. The remission of major symptoms, laboratory test results, ADRs and other related data were collected after 4 weeks of treatment. RESULTS: Compared with the pre-treatment baseline, haemoglobin (Hb), serum iron (SI), serum ferritin (SF) and the mean corpuscular volume (MCV) increased in both groups at 4 weeks of treatment (P < 0.05). After treatment, Group A had lower levels of Hb (108.41 ± 8.39 vs. 122.31 ± 6.04 g/L, t = 6.293, P < 0.001), SI (9.72 ± 4.24 vs. 15.62 ± 5.41 µmol/L, t = 5.482, P < 0.001) and SF (27.1 ± 10.82 vs. 39.82 ± 10.44 ug/L, t = 6.793, P < 0.001) compared with Group B. In contrast, there was no significant difference in the post-treatment level of MCV (P > 0.05). The overall response rate significantly differed between the 2 groups (78.61% vs. 90.91%, χ2 = 10.949, P < 0.001). The incidence of ADRs of both groups were similar, and the difference was not statistically significant (χ2 = 0.035, P = 0.851). CONCLUSION: Iron sucrose demonstrates favourable efficacy and safety in treating iron deficiency anaemia.

Erythropoiesis-stimulating agents for preventing acute kidney injury.

BACKGROUND: Acute kidney injury (AKI) is characterised by a rapid decline in kidney function and is caused by a variety of clinical conditions. The incidence of AKI in hospitalised adults is high. In animal studies, erythropoiesis-stimulating agents (ESA) have been shown to act as a novel nephroprotective agent against ischaemic, toxic, and septic AKI by inhibiting apoptosis, promoting cell proliferation, and inducing antioxidant and anti-inflammatory responses. As a result, ESAs may reduce the incidence of AKI in humans. Randomised controlled trials (RCTs) have been conducted on the efficacy and safety of ESAs, but no prior systematic reviews exist that comprehensively examine ESAs with respect to AKI prevention, although the effectiveness of these agents has been examined for a range of other diseases and clinical situations. OBJECTIVES: This review aimed to look at the benefits and harms of ESAs for preventing AKI in the context of any health condition. SEARCH METHODS: We searched the Cochrane Kidney and Transplant Register of Studies up to 30 August 2024 through contact with the Information Specialist using search terms relevant to this review. Studies in the Register are identified through searches of CENTRAL, MEDLINE, and EMBASE, conference proceedings, the International Clinical Trials Registry Platform (ICTRP) Search Portal and ClinicalTrials.gov. SELECTION CRITERIA: We included RCTs and quasi-RCTs (in which allocation to treatment was based on alternate assignment or order of medical records, admission dates, date of birth or other non-random methods) that compared ESAs with placebo or standard care in people at risk of AKI. DATA COLLECTION AND ANALYSIS: Three authors independently extracted data and assessed the risk of bias for included studies. We used random-effects model meta-analyses to perform quantitative synthesis of the data. We used the I2 statistic to measure heterogeneity amongst the studies in each analysis. We indicated summary estimates as a risk ratio (RR) for dichotomous outcomes and mean difference (MD) for continuous outcomes with their 95% confidence interval (CI). We assessed the certainty of the evidence for each main outcome using the Grades of Recommendation, Assessment, Development, and Evaluation (GRADE) approach. MAIN RESULTS: A total of 20 studies (36 records, 5348 participants) were included. The number of participants ranged from 10 to 1302, and most studies were carried out in single centres (13/20). All the included studies compared ESAs to placebo or usual care. Many of the studies were judged to have unclear or high risk of reporting bias, but were at low risk for other types of bias. ESAs, when compared to control interventions, probably makes little or no difference to the risk of AKI (18 studies, 5314 participants: RR 0.97, 95% CI 0.85 to 1.10; I² = 19%; moderate-certainty evidence), or death (18 studies, 5263 participants: RR 0.92, 95% CI 0.80 to 1.06; I² = 0%; moderate-certainty evidence), and may make little or no difference to the initiation of dialysis (14 studies, 2059 participants: RR 1.16, 95% CI 0.90 to 1.51; I² = 0%; low-certainty evidence). Even with standardised measurement of AKI, the studies showed no difference in results between different routes of administration (subcutaneous or intravenous), background diseases (cardiac surgeries, children or neonates, other adults at risk of AKI), or duration or dose of ESA. ESAs may make little or no difference to the risk of thrombosis when compared to control interventions (8 studies, 3484 participants: RR 0.92, 95% CI 0.68 to 1.24; I² = 0%). Similarly, ESAs may have little or no effect on kidney function measures and adverse events such as myocardial infarction, stroke or hypertension. However, this may be due to the low incidence of these adverse events. AUTHORS' CONCLUSIONS: In patients at risk of AKI, ESAs probably do not reduce the risk of AKI or death and may not reduce the need for starting dialysis. Similarly, there may be no differences in kidney function measures and adverse events such as thrombosis, myocardial infarction, stroke or hypertension. There are currently two ongoing studies that have either not been completed or published, and it is unclear whether they will change the results. Caution should be exercised when using ESAs to prevent AKI.

Comprehensive perioperative blood management in patients undergoing elective bypass cardiac surgery: Benefit effect of health care education and systematic correction of iron deficiency and anemia on red blood cell transfusion.

STUDY OBJECTIVE: The aim of this study was to investigate the efficacy of a two-step patient blood management (PBM) program in red blood cell (RBC) transfusion requirements among patients undergoing elective cardiopulmonary bypass (CPB) surgery. DESIGN: Prospective, non-randomized, two-step protocol design. SETTING: Cardiac surgery department of Clinique Pasteur, Toulouse, France. PATIENTS: 897 patients undergoing for elective CPB surgery. INTERVENTIONS: We conducted a two-steps protocol: PBMe and PBMc. PBMe involved a short quality improvement program for health care workers, while PBMc introduced a systematic approach to pre- and postoperative correction of deficiencies, incorporating iron injections, oral vitamins, and erythropoiesis-stimulating agents. MEASUREMENTS: The PBM program's effectiveness was evaluated through comparison with a pre-PBM retrospective cohort after propensity score matching. The primary objective was the proportion of patients requiring RBC transfusions during their hospital stay. Secondary objectives were also analyzed. MAIN RESULTS: After matching, 343 patients were included in each group. Primary outcomes were observed in 35.7% (pre-PBM), 26.7% (PBMe), and 21.1% (PBMc) of patients, resulting in a significant reduction (40.6%) in the overall RBC transfusion rate. Both the PBMe and PBMc groups exhibited significantly lower risks of RBC transfusion compared to the pre-PBM group, with adjusted odds ratios of 0.59 [95% CI 0.44-0.79] and 0.44 [95% CI 0.32-0.60], respectively. Secondary endpoints included reductions in transfusions exceeding 2 units, total RBC units transfused, administration of allogeneic blood products, and total bleeding volume recorded on Day 1. There were no significant differences noted in mortality rates or the duration of hospital stays. CONCLUSIONS: This study suggests that health care education and systematic deficiency correction are associated with reduced RBC transfusion rates in elective CPB surgery. However, further randomized, controlled studies are needed to validate these findings and refine their clinical application.

Hypoxia-Inducible Factor Prolyl Hydroxylase Inhibitors in Kidney Disease.

BACKGROUND: Hypoxia-inducible factor (HIF) prolyl hydroxylase inhibitors are an oral treatment for anemia of chronic kidney disease (CKD). In this systematic review and meta-analysis, we assessed long-term safety of HIF prolyl hydroxylase inhibitors. METHODS: We searched MEDLINE, Embase, and Cochrane databases for randomized trials comparing HIF prolyl hydroxylase inhibitors with an erythropoiesis-stimulating agent (ESA) or placebo with greater than or equal to 48 weeks of follow-up. The primary outcome was major adverse cardiovascular event (MACE), defined as a composite of all-cause death, myocardial infarction, or stroke. Treatment effects were pooled using random-effects models. RESULTS: Twenty-five trials involving 26,478 participants were included. Of these, 13 trials enrolled 13,230 participants with dialysis-dependent CKD, and 12 trials enrolled 13,248 participants with nondialysis-dependent CKD. There was no evidence that HIF prolyl hydroxylase inhibitors and ESA had different effects on MACE in people with dialysis-dependent CKD (risk ratio, 0.99; 95% confidence interval [CI], 0.92 to 1.08) or people with nondialysis-dependent CKD (risk ratio, 1.08; 95% CI, 0.95 to 1.22). Similarly, there was no evidence that HIF prolyl hydroxylase inhibitors and placebo had different effects on MACE (risk ratio, 1.10; 95% CI, 0.96 to 1.27) in people with nondialysis-dependent CKD. The lack of difference between HIF prolyl hydroxylase inhibitors and ESA or placebo was observed for individual components of MACE and cardiovascular death. Safety of HIF prolyl hydroxylase inhibitors for other outcomes was comparable with ESA in dialysis-dependent CKD. In nondialysis-dependent CKD, dialysis access thrombosis, venous thromboembolism, infections, and hyperkalemia occurred more frequently with HIF prolyl hydroxylase inhibitors in placebo-controlled trials but not in ESA-controlled trials. CONCLUSIONS: There was no evidence of a difference in the long-term cardiovascular safety profile of HIF prolyl hydroxylase inhibitors and ESA in adults with dialysis-dependent CKD and adults with nondialysis-dependent CKD. (PROSPERO registration number, CRD42021278011.).

Ferric carboxymaltose and exercise capacity in heart failure with preserved ejection fraction and iron deficiency: the FAIR-HFpEF trial.

BACKGROUND AND AIMS: Evidence is lacking that correcting iron deficiency (ID) has clinically important benefits for patients with heart failure with preserved ejection fraction (HFpEF). METHODS: FAIR-HFpEF was a multicentre, randomized, double-blind trial designed to compare intravenous ferric carboxymaltose (FCM) with placebo (saline) in 200 patients with symptomatic HFpEF and ID (serum ferritin < 100 ng/mL or ferritin 100-299 ng/mL with transferrin saturation < 20%). The primary endpoint was change in 6-min walking test distance (6MWTD) from baseline to week 24. Secondary endpoints included changes in New York Heart Association class, patient global assessment, and health-related quality of life (QoL). RESULTS: The trial was stopped because of slow recruitment after 39 patients had been included (median age 80 years, 62% women). The change in 6MWTD from baseline to week 24 was greater for those assigned to FCM compared to placebo [least square mean difference 49 m, 95% confidence interval (CI) 5-93; P = .029]. Changes in secondary endpoints were not significantly different between groups. The total number of adverse events (76 vs. 114) and serious adverse events (5 vs. 19; rate ratio 0.27, 95% CI 0.07-0.96; P = .043) was lower with FCM than placebo. CONCLUSIONS: In patients with HFpEF and markers of ID, intravenous FCM improved 6MWTD and was associated with fewer serious adverse events. However, the trial lacked sufficient power to identify or refute effects on symptoms or QoL. The potential benefits of intravenous iron in HFpEF with ID should be investigated further in a larger cohort.

The clinical efficacy of combined ESA and Roxadustat treatment for renal anemia in hemodialysis patients with secondary hyperparathyroidism: A case series.

RATIONALE: Pharmacological mechanism of Roxadustat in the treatment of renal anemia. PATIENT CONCERNS: To investigate the efficacy and safety of combined Roxadustat and erythropoiesis stimulator (ESA) treatment of renal anemia in hemodialysis patients with secondary hyperparathyroidism. DIAGNOSES: A retrospective analysis was conducted on hemodialysis patients with renal anemia and secondary hyperparathyroidism treated with ESAs alone, who were admitted to our hospital from March 2022 to December 2022. INTERVENTIONS: The patients were treated with Roxadustat combined with ESAs for 3 months, during which oral iron supplementation was given, and the changes in Hb levels and laboratory-related indicators before and after the combined treatment were analyzed. OUTCOMES: The results showed that a total of 13 patients received combination therapy, with a significant increase in Hb compared to ESAs alone (t = -3.955, P = .002). The Hb qualification rate was 38.46%, and the ∆Hb response rate was 76.92%. The parathyroid hormone significantly decreased with a statistically significant difference (Z = -2.062b, P = .039). Hemoglobin (RBC), total iron binding capacity, and serum ferritin (male) were significantly increased compared to ESAs alone. Total cholesterol and low-density lipoprotein were significantly lower than ESAs alone. The differences in the changes in the above indicators were statistically significant (P < .05). There was no statistically significant difference in changes in other laboratory-related indicators (P > .05). No adverse reactions were observed during the combined treatment of 13 patients. LESSONS SUBSECTIONS: The combination of Roxadustat and ESAs can effectively improve renal anemia in hemodialysis patients with secondary hyperparathyroidism, as well as improve indicators of hyperparathyroidism and blood lipid levels with high levels of safety. This combined treatment thus provides a new and safe treatment method for these patients.

UK survey of patient and caregiver perspectives on the impact of chronic kidney disease-associated anaemia.

OBJECTIVE: Chronic kidney disease (CKD)-associated anaemia has substantial biopsychosocial impacts. This study explores the impact of CKD-associated anaemia and treatment preferences from the patient perspective. DESIGN: Cross-sectional survey. SETTING: Anonymised online survey implemented by Ipsos UK on behalf of the National Kidney Federation and GSK from October 2022 to January 2023. PARTICIPANTS: Data were collected from UK adults living with CKD (self-reported). PRIMARY AND SECONDARY OUTCOME MEASURES: Outcome measures were exploratory and not predefined. The cross-sectional survey was designed to explore the biopsychosocial impact of living with anaemia on individuals with CKD; their unmet needs; the treatment strategies typically implemented and the associated barriers/facilitators to adherence; the healthcare professional-patient relationship with regard to anaemia diagnosis and management. RESULTS: Of 101 participants, 90 (89%) were patients with CKD and 11 (11%) were informal carers. 96 (95%) participants reported symptom(s) relevant to their experience of CKD. 88 (87%) participants reported symptom(s) associated with anaemia and 61 (64%) expressed an impact on daily life including 18 (19%) unable to perform daily activities, 13 (14%) unable to go to work and 9 (9%) reporting poor social life/interactions. 85 (84%) participants reported they have received treatment for anaemia: intravenous iron (n=55, 54%), iron tablets (n=29, 29%), erythropoietin-stimulating agents (ESAs) via an autoinjector (n=28, 28%), ESA injections via a syringe (n=24, 24%), ESA injections via a dialysis machine (n=17, 17%), folic acid (n=22, 22%) and blood transfusion (n=17, 17%). Six of seven (86%) participants who received their ESA from a healthcare professional at home preferred injections whereas 13/27 (48%) participants who injected themselves at home preferred oral tablets. CONCLUSIONS: There is not a 'one-size-fits-all' approach to the management of CKD-associated anaemia. A personalised approach incorporating the treatment preferences of the individual should be explored when discussing treatment options.

Intravenous ferric carboxymaltose versus oral ferrous sulphate for the treatment of moderate to severe postpartum anaemia in Nigerian women (IVON-PP): protocol for an open-label randomised controlled type 1 hybrid effectiveness-implementation trial.

INTRODUCTION: Postpartum anaemia is often caused by iron deficiency with onset during the antepartum period and can be exacerbated by excessive blood loss at birth. Its prevalence is estimated as 50-80% in low-income and middle-income countries. It poses adverse consequences on the mother and negatively impacts her ability to care for her newborn. Prompt treatment of postpartum anaemia is thus important. Adherence to oral iron is reportedly low in Nigeria due to its side effects and forgetfulness by the mothers. Intravenous iron such as ferric carboxymaltose, given as a single dose, might help overcome adherence issues, but investigation in a high-quality randomised control trial in Nigeria is first required while evaluation of challenges around its implementation is also warranted. OBJECTIVE: To determine the clinical effectiveness, tolerability and safety, of using intravenous ferric carboxymaltose (intervention) vs oral ferrous sulphate (control) for treating moderate to severe iron deficiency anaemia in postpartum women and to evaluate implementation of ferric carboxymaltose in treating postpartum anaemia in Nigeria. METHODS AND ANALYSIS: This study is an open-label randomised controlled trial with a concurrent implementation study. It is a hybrid type 1 effectiveness-implementation design conducted in four states across Northern and Southern Nigeria. A total of 1400 eligible and consenting women with postpartum moderate to severe anaemia (haemoglobin concentration <100 g/L) will be randomised to intravenous ferric carboxymaltose; a single dose at 20 mg/kg to a maximum of 1000 mg infusion administered at enrolment (intervention) or oral ferrous sulphate; 200 mg (65 mg elemental iron) two times per day from enrolment until 6 weeks postpartum (control). The primary outcome, proportion of participants who are anaemic (Hb <110 g/L) at 6 weeks postpartum will be analysed by intention-to-treat. Haemoglobin concentration, full blood count, serum iron, serum ferritin, transferrin saturation and total iron binding capacity will be measured at specific intervals. Implementation outcomes such as acceptability and feasibility of using ferric carboxymaltose for postpartum anaemia treatment in Nigeria will be assessed. ETHICS AND DISSEMINATION: This study is approved by the ethics committee of the teaching hospitals, Ministry of Health of the four states as required, National Health Research Ethics Committee and the drug regulatory agency, National Agency for Food and Drug Administration and Control (NAFDAC). Findings of this research will be presented at conferences and will be published in international peer-reviewed journals and shared with stakeholders within and outside Nigeria. TRIAL REGISTRATION NUMBER: International standard randomised controlled trial number: ISRCTN51426226.

Prevalence, risk factors, and treatment of anemia in hospitalized older patients across geriatric and nephrological settings in Italy.

Anemia is a common but often underdiagnosed and undertreated geriatric syndrome in hospitalized older patients. In this retrospective multicenter study, we aimed at characterizing the prevalence, risk factors, diagnostic and treatment approach to anemia in older patients admitted to acute care hospitals, focusing on differences between nephrology and geriatrics units. Prevalence and risk factors for anemia, diagnostic inertia (lack of iron, vitamin B12, and folate status assessment), replacement inertia (omitted treatment with iron, vitamin B12 or folic acid), and erythropoiesis-stimulating agents (ESA) inertia were explored. 1963 patients aged 82.7 (6.8) years were included in the study; 66.7% of the study population had anemia; among anemic patients, diagnostic inertia and replacement inertia were common with rates of 22-31% and 50-87%, respectively; omitted treatment with ESA affected 67.2% of patients and was more prevalent in geriatric units. In most cases, patients with ESA inertia were not routinely screened for iron tests. COPD, cancer, eGFR 45-60 ml/min were associated with increased tendency to ESA inertia. In conclusion, anemia had a high prevalence in older patients discharged from acute care units, but it is often underdiagnosed and undertreated.

A real-world analysis of roxadustat effectiveness and safety in managing renal anemia among patients on maintenance hemodialysis: An observational study.

We aimed to compare the clinical efficacy and safety of roxadustat with erythropoiesis-stimulating agents, particularly erythropoietin (EPO), in the treatment of maintenance hemodialysis patients with renal anemia. A prospective cohort study was carried out at the Nephrology Department of the Nantong First People's Hospital and Nantong University Affiliated Hospital from December 2020 to December 2021. We compared hemoglobin (Hb) levels, serum ferritin (SF) levels, and adverse cardiovascular events between the roxadustat and EPO groups at 1, 3, and 6 months into the treatment. A total of 209 patients participated in the study, with 112 in the roxadustat group and 97 in the EPO group. At baseline, no statistically significant differences were observed between the 2 groups in terms of age, gender, weight, dialysis modality and duration, previous EPO dosage, Hb levels, SF levels, transferrin saturation, heart function classification, and blood pressure levels (P > .05). After 1 month, Hb levels in the roxadustat group were significantly higher than those in the EPO group (P < .05). However, no statistically significant differences were found between the 2 groups at 3 and 6 months (P > .05). Additionally, there were no significant differences in SF levels and the occurrence of adverse cardiovascular events between the 2 groups after treatment (P > .05). Roxadustat was superior to EPO in the initial treatment phase, while its cardiovascular safety was comparable to that of EPO.

A spotlight on using HIF-PH inhibitors in renal anemia.

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.

A Randomized Trial of the Impact of Ferric Citrate on Erythropoietin and Intravenous Iron Use in Patients Receiving Dialysis.

INTRODUCTION: Ferric citrate (FC) is an FDA-approved iron-based phosphate binder for adults with dialysis-dependent chronic kidney disease. This study investigated the impact of FC as the primary phosphate-lowering therapy on utilization of erythropoiesis-stimulating agents (ESAs) and intravenous (IV) iron. METHODS: In this randomized, open-label, active-controlled, multicenter study (NCT04922645), patients on dialysis and receiving ESAs were randomized to receive FC or remain on standard of care (SOC) phosphate-lowering therapy for up to 6 months. Primary endpoints were the difference in change from baseline to efficacy evaluation period (EEP) in mean monthly ESA and IV iron doses. Secondary endpoints included treatment differences in hemoglobin, phosphate, TSAT, and ferritin levels. RESULTS: Two hundred nine patients were randomized to FC and had a day 1 dosing visit (n = 103) or SOC (n = 106). The two groups had similar baseline laboratory characteristics; however, atherosclerotic CV disease, peripheral vascular disease, and congestive heart failure were more common in the SOC group. The mean treatment difference in ESA monthly dose was -30.8 µg (FC vs. SOC; p = 0.02). An absolute though non-statistically significant change in mean monthly IV iron dose of -37.2 mg (p = 0.17) was observed with FC. Mean hemoglobin, TSAT, and ferritin all increased from baseline to the EEP with FC versus SOC. Serious adverse events occurred in 28% of patients receiving FC versus 37% in those receiving SOC. CONCLUSIONS: In patients receiving dialysis, treatment with FC as compared to remaining on SOC phosphate binders resulted in reductions in mean monthly ESA and IV iron dose.

Treatment of Anemia Associated with Chronic Kidney Disease: Plea for Considering Physiological Erythropoiesis.

Traditionally, the treatment of anemia associated with chronic kidney disease (CKD) involves prescribing erythropoiesis-stimulating agents (ESAs) or iron preparations. The effectiveness and safety of ESAs and iron have been established. However, several clinical issues, such as hyporesponsiveness to ESAs or defective iron utilization for erythropoiesis, have been demonstrated. Recently, a new class of therapeutics for renal anemia known as hypoxia-inducible factor (HIF)/proline hydroxylase (PH) inhibitors has been developed. Several studies have reported that HIF-PH inhibitors have unique characteristics compared with those of ESAs. In particular, the use of HIF-PH inhibitors may maintain target Hb concentration in patients treated with a high dose of ESAs without increasing the dose. Furthermore, several recent studies have demonstrated that patients with CKD with defective iron utilization for erythropoiesis had a high risk of cardiovascular events or premature death. HIF-PH inhibitors increase iron transport and absorption from the gastrointestinal tract; thus, they may ameliorate defective iron utilization for erythropoiesis in patients with CKD. Conversely, several clinical problems, such as aggravation of thrombotic and embolic complications, diabetic retinal disease, and cancer, have been noted at the time of HIF-PH inhibitor administration. Recently, several pooled analyses of phase III trials have reported the non-inferiority of HIF-PH inhibitors regarding these clinical concerns compared with ESAs. The advantages and issues of anemia treatment by ESAs, iron preparations, and HIF-PH inhibitors must be fully understood. Moreover, patients with anemia and CKD should be treated by providing a physiological erythropoiesis environment that is similar to that of healthy individuals.

Pure red cell aplasia secondary to erythropoietin therapy.

We report a case series of two patients with chronic kidney disease (CKD) who developed erythropoietin-induced pure red cell aplasia following a change in erythropoietin preparation. Both patients responded well to immunosuppressive treatments, but unfortunately developed severe infections as a result of being immunosuppressed.