The impact of non-AKI eGFR Variability on CKD progression in individuals with type 2 diabetes and preserved kidney function

Introduction: Variability in estimated glomerular filtration rate (eGFR) has been associated with increased risks of mortality and chronic kidney disease (CKD) progression in people with type 2 diabetes mellitus (T2DM) and impaired kidney function. However, its significance in individuals with preserved kidney function remains unclear.

Methods: In this nationwide retrospective population-based study of individuals with T2DM, eGFR variability was calculated by fitting a linear regression model to longitudinal data to estimate both the individual eGFR slope over the 5-year period as well as the variability in model residuals provided by the SD of the model residuals using longitudinal serum creatinine (SCr) measurements obtained during the first 5 years after diagnosis. Cox proportional hazards models were then applied to assess the association between eGFR variability and progression to stage G3b CKD among participants with preserved kidney function.

Results: This study included 98,322 participants who had an eGFR > 60 ml/min per 1.73 m² at diagnosis, remained alive with an eGFR > 60 ml/min per 1.73 m² 5 years after diagnosis, and were subsequently followed for a mean of 5.1 years. Greater eGFR variability was associated with an increased risk of progression to stage G3b CKD— hazard ratios (HRs) for the second, third, and fourth quartiles of variability versus the first quartile were 1.56 (95% confidence interval [CI]: 1.38–1.75), 1.85 (95% CI: 1.65–2.08), and 2.56 (95% CI: 2.29–2.86), respectively. This association persisted after adjustment for multiple variables—HR: 1.57; 95% CI: 1.40–1.77 for the fourth quartiles of variability versus the first quartile.

Conclusion: eGFR variability in the absence of acute kidney injury (AKI) is associated with CKD progression in individuals with T2DM and preserved kidney function.