#2560 HEMOGLOBIN VARIABILITY AND ADVERSE CLINICAL EVENTS IN PATIENTS WITH NON-DIALYSIS-DEPENDENT CHRONIC KIDNEY DISEASE AND ANEMIA IN CONTINUOUS CARE
Authors: Takahiro Kuragano , Okami Suguru , Tanaka Sachiko , Uenaka Hidetoshi , Kimura Takeshi , Ishida Yosuke , James Glen , Hayasaki Takanori 
Published: June 2023

Abstract

Background and Aims
Anemia management in non-dialysis dependent chronic kidney disease (NDD-CKD) patients has attracted attention with the introduction of new treatment options, such as prolyl hydroxylase domain enzyme inhibitors (HIF-PHI). However, studies reporting comprehensive information on anemia management in NDD-CKD patients are limited. While previous studies reported increased risks of adverse clinical events associated with hemoglobin (Hb) fluctuation in hemodialysis patients, limited information is available in NDD-CKD patients.

Method
A retrospective cohort study was performed using a Japanese nationwide electronic medical record-based hospital database. Patients with stage ≥3a NDD-CKD, aged ≥18 years, and at least one recorded Hb &lt;11 g/dL between January 1st 2013 and April 30th 2021 were included. Patients already receiving any anemia treatment (erythropoiesis stimulating agent (ESA), iron, or HIF-PHI) were excluded. Hb levels were collected at the index date (the date of the first recorded Hb &lt;11 g/dL) and during the follow-up period. Clinical events included all-cause death, cardiovascular (CV) events (myocardial infarction, unstable angina pectoris, stroke, or hospitalization for heart failure), dialysis introduction, and red-blood-cell transfusion. Time-dependent Cox proportional hazard models, adjusted by clinically relevant variables were applied to assess the risk of clinical events associated with transitioning Hb fluctuation patterns, categorized into six groups: within the target Hb range (11–13 g/dL); consistently below the target (low); consistently above the target (high); low-amplitude fluctuation around the upper limit of the target (LAH); low-amplitude fluctuation around the lower limit of the target (LAL); and, high amplitude fluctuation across the target (HA).

Results
Of 162,170 patients with CKD, 26,626 (16.4%) NDD-CKD patients with Hb &lt;11 g/dL were identified (median follow-up length, 1.9 years). The mean age was 75.9 years, and 37.8% were female. In overall patients, the mean (±SD) Hb levels at index and at 3, 6, and 12 months of follow up were 9.9±1.2 g/dL, 10.6±1.5 g/dL, 10.8±1.6 g/dL, and 10.9±1.6 g/dL, respectively. The proportion of patients with Hb &lt;10 g/dL at index and at 12 months were 34.3% and 23.9%, respectively. In the subgroup of patients treated with ESA or HIF-PHI (n = 8,876), the mean Hb (±SD) levels had increased from 9.3±1.3 g/dL to 10.3±1.5 g/dL at 3 months, 10.5±1.5 g/dL at 6 months, and 10.6±1.5 g/dL at 12 months after treatment initiation. In this subgroup, the proportion of patients with Hb &lt;10 g/dL had decreased from 70.0% to 30.1% at 12 months. Fig. 1 shows the Hb levels and proportions of patients with Hb &lt;10 g/dL by treatment type. During the follow-up period, 5,991 (22.5%) deaths, 3,545 (13.3%) CV events, 4,231 (15.9%) dialysis introductions, and 5,561 (20.9%) red-blood-cell transfusions were observed. The risks of clinical events were significantly higher in the low and LAL Hb groups than in the target Hb group (Fig. 2). The hazard ratios (95% CIs) for death, CV events, dialysis introduction, and red-blood-cell transfusion in the low Hb group, compared to the target Hb group were 1.35 (1.20–1.52), 1.90 (1.58–2.27), 1.75 (1.39–2.20), and 2.80 (2.28–3.43), respectively, and in the LAL Hb group were 1.28 (1.14–1.43), 1.71 (1.43–2.04), 1.85 (1.48–2.33), and 1.64 (1.33–2.02), respectively. In HA Hb group, significantly higher risks for dialysis introduction and red-blood-cell transfusion were observed.

Conclusion
This study reports comprehensive information on anemia management in NDD-CKD patients in clinical practice. Despite treatment for Hb correction, 20–30% of patients persistently remained at low Hb levels. The increased risk of adverse clinical events associated with Hb fluctuations suggest that stable Hb control within the target range is important to reduce the risk of mortality and morbidity in patients with NDD-CKD and anemia.