Anemia is a common complication for patients with chronic kidney disease (CKD) and is associated with cardiovascular comorbidities and reduced quality of life. The incidence of anemia increases as kidney function declines and affects approximately 32% of Japanese patients with stage 3-5 CKD. This review examined the current literature on anemia in CKD patients in Japan to provide an overview of the burden of anemia in CKD. Medline, Embase, and Igaku Chuo Zasshi databases were searched to identify relevant manuscripts and abstracts published from 2004 onward. The population included CKD patients with anemia, and the outcomes of interest were epidemiology, economic, humanistic, and treatment patterns. Observational studies, database analysis, and economic evaluation studies were included in the analysis. A total of 1151 references were identified, and 50 were eligible for final review. Economic burden was reported in most studies (n = 37) followed by treatment patterns (n = 26), and epidemiological (n = 25) and humanistic (n = 1) burdens. Prevalence of anemia varied largely (0-95%) based on the different definitions of anemia, and increased with CKD severity. Higher mortality was associated with erythropoiesis-stimulating agent (ESA) resistance and lower hemoglobin levels among patients treated with ESA. Drug dosage was the most reported economic burden (n = 33), followed by medical, and non-medical outcomes. Costs associated with anemia were considerable and depended on dialysis status and ESA treatment. Only one study reported data on quality of life, suggesting that further investigation on the humanistic burden of anemia in CKD is needed.

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Background Established cardiovascular risk assessment tools lack chronic kidney disease–specific clinical factors and may underestimate cardiovascular risk in non–dialysis-dependent chronic kidney disease (CKD) patients. Methods A retrospective analysis of a cohort of patients with stage 3–5 non–dialysis-dependent chronic kidney disease in the Salford Kidney Study (UK, 2002–2016) was performed. Multivariable Cox regression models with backward selection and repeated measures joint models were used to evaluate clinical risk factors associated with cardiovascular events (individual and composite cardiovascular major adverse cardiovascular events), mortality (all-cause and cardiovascular-specific), and need for renal replacement therapy. Models were established using 70% of the cohort and validated on the remaining 30%. Hazard ratios ([95% CIs]) were reported. Results Among 2192 patients, mean follow-up was 5.6 years. Cardiovascular major adverse cardiovascular events occurred in 422 (19.3%) patients; predictors included prior history of diabetes (1.39 [1.13–1.71]; P = 0.002) and serum albumin reduction of 5 g/L (1.20 [1.05–1.36]; P = 0.006). All-cause mortality occurred in 740 (33.4%) patients, median time to death was 3.8 years; predictors included reduction of estimated glomerular filtration of 5 mL/min/1.73 m2 (1.05 [1.01–1.08]; P = 0.011) and increase of phosphate of 0.1 mmol/L (1.04 [1.01–1.08]; P = 0.021), whereas a 10 g/L hemoglobin increase was protective (0.90 [0.85–0.95]; P < 0.001). In 394 (18.0%) patients who received renal replacement therapy, median time to event was 2.3 years; predictors included halving of estimated glomerular filtration rate (3.40 [2.65–4.35]; P < 0.001) and antihypertensive use (1.23 [1.12–1.34]; P < 0.001). Increasing age, albumin reduction, and prior history of diabetes or cardiovascular disease were risk factors for all outcomes except renal replacement therapy. Conclusions Several chronic kidney disease–specific cardiovascular risk factors were associated with increased mortality and cardiovascular event risk in patients with non–dialysis-dependent chronic kidney disease. Graphical abstract

Background and Aims Anaemia is a common complication of chronic kidney disease (CKD) that is associated with fatigue, shortness of breath, and lethargy. CKD anaemia is commonly treated with oral or intravenous (IV) iron and IV or subcutaneous (SC) erythropoiesis-stimulating agents (ESAs). The objectives of this study were to understand patients’ experiences with CKD anaemia and their preferences related to treatment. Method Qualitative 60-minute semi-structured interviews were conducted with ESA-treated adult CKD patients with anaemia, either non–dialysis-dependent (ND) or dialysis-dependent (DD), and with practicing nephrologists in France, Germany, Spain, the UK, and Japan. The patients’ interviews, appropriately tailored for ND and DD patients, comprised three sections: 1) patients’ views on the burden of the disease and its treatment; 2) discussion of vignettes describing different treatment options; and 3) non-experimental choice questions between two hypothetical treatments including mode of administration, need for iron supplement, and risk of adverse events (AEs). Results A total of 51 patients were enrolled (ND, n=6 per country except for France [n=7]; DD [haemodialysis or peritoneal dialysis], n=4 per country). Two nephrologists per country were interviewed. The most commonly reported symptoms associated with anaemia were tiredness (ND, 77%; DD, 85%) and shortness of breath (ND, 42%; DD, 30%); these two symptoms were also reported by nephrologists, who considered clinical efficacy the most important aspect of treatment. In Japan, dizziness was the most common (n=5/6, 83%) symptom among ND patients. Anaemia symptoms were reported to negatively affect different aspects of patients’ lives, including the ability to carry out daily activities (ND, 61%; DD, 65%), work (ND, 42%; DD, 50%), and exercise (ND, 26%; DD, 30%). ESA treatments were perceived to be effective in improving patients’ symptoms and quality of life. Many patients had not experienced AEs associated with treatment and were not concerned about them, however patients who had experienced gastrointestinal (GI) AEs due to oral iron were sensitive to the risk of GI effects. Out of 23 ND patients who were asked, 19 (83%) preferred an oral treatment due to the convenience of administration, and to avoid injection pain and drug storage requirements associated with SC administration. Self-administering SC ESAs was a concern among Japanese ND patients, who often had a healthcare professional administer the medication. Haemodialysis patients (n=12), who often receive IV ESAs during their dialysis sessions, were less likely to prefer oral treatments due to lack of perceived convenience. Peritoneal dialysis patients (n=8), who often receive home dialysis and SC ESAs, preferred oral treatment to avoid self-administration and storage requirements, and to make travel easier. Limitations of the study included the small number of participants and amendments to the eligibility criteria implemented during data collection, including more relaxed requirements for blood pressure, blood transfusion, and insulin use. Conclusion Patients considered the available treatment options to effectively treat CKD anaemia. Besides efficacy, patients’ primary concern was the mode of administration of their medication, rather than safety considerations.

Introduction: Information about patient preferences for the treatment of anaemia associated with chronic kidney disease (CKD) is scarce. Hence, our aim was to examine how patients with non-dialysis-dependent CKD valued attributes of alternative hypothetical anaemia treatments. Methods: A discrete choice experiment (DCE) was conducted in adult patients who reported a clinical diagnosis of CKD-related anaemia. Treatment attributes included mode and frequency of administration, need for iron supplementation, risk of gastrointestinal side effects, risk of major cardiovascular events and impact on energy levels (as defined by the vitality section of the SF-6D health index). Logit models were used to analyse patients' preferences. Results: The DCE was completed by 200 patients in four countries. Patients preferred an oral mode of administration. Patients were willing to tolerate a 5.1% (95% CI 2.0-8.3%) increase in the risk of a major cardiovascular event and an 11.7% (95% CI 5.0-18.5%) increase in the risk of gastrointestinal side effects to switch from an at-home subcutaneous injection administered once every 2 weeks to an at-home oral pill administered three times a week. Patients were willing to tolerate a 20.3% (95% CI 15.0-25.6%) increase in the risk of gastrointestinal side effects and an 8.9% (95% CI 6.1-11.7%) increase in the risk of a major cardiovascular event to transition from 'Sometimes having a lot of energy' to 'Always having a lot of energy'. Conclusions: Patients with non-dialysis-dependent CKD-related anaemia demonstrated clear treatment preferences and were willing to accept increased gastrointestinal or cardiovascular risks in exchange for more energy or an oral treatment.