Investigating the Patterns of Renal Function Variability in Early-Stage Chronic Kidney Disease by Cluster Analysis

Background: Chronic kidney disease (CKD) is a significant global health concern, with increasing focus on predicting renal prognosis. While renal prognosis is often studied in advanced CKD, variability in renal function and its implications for long-term outcomes in early-stage CKD remain insufficiently examined. This study aimed to investigate renal prognosis in early-stage CKD within the general population, focusing on patterns of renal function variability and factors associated with high variability. Methods: This retrospective nationwide cohort study included participants from various geographical regions across Japan, representing a diverse general population. A total of 1,765 adults with early-stage CKD (eGFR 45–59 mL/min/1.73 m ² ), based on two initial screening results, were analyzed. The primary outcome was the pattern of eGFR variability identified by cluster analysis using three parameters: mean residual (difference between linear prediction and observed value), maximum residual, and range. In addition, we used a logistic regression model in order to assess associations between clinical factors and the high-risk cluster. Results: We identified three distinct clusters based on eGFR variability using cluster analysis. Among these clusters, one exhibited significantly high variability with a high residual (median of mean residuals of 10.9 mL/min/1.73 m ² and median of maximum residuals of 22.6 mL/min/1.73 m ² ) and a wide range (median of range of 25.1 mL/min/1.73 m ² ) (referred to as the "high variability cluster"). This cluster, comprising 4.6% of patients with early-stage CKD, demonstrated a more pronounced decline in eGFR over time. Factors such as younger age, proteinuria, antihypertensive drug use, and hyperglycemia were associated with the high variability cluster. Conclusions: This study highlights the presence of distinct eGFR variability patterns in early-stage CKD and identifies a subgroup at high risk for rapid renal decline. Monitoring eGFR variability provides critical insights into long-term prognosis and may inform targeted interventions. Considering these findings, early detection and management of patients with early CKD may improve disease progression and reduce the risk of adverse outcomes. Trial registration: This study is an observational study using a database and does not involve a health care intervention on human participants. Therefore, trial registration is not applicable.