Clinically meaningful eGFR slope as a surrogate endpoint differs across CKD stages and slope evaluation periods: the CKD-JAC study.

Background: The slope of estimated glomerular filtration rate (eGFR) is a promising surrogate endpoint in patients with chronic kidney disease (CKD). However, current evidence is mainly derived from Western populations with CKD stages 1-3. In addition, stage-by-stage analysis has never been formally performed.

Methods: We analyzed data from the Chronic Kidney Disease Japan Cohort Study, which included a large proportion of patients with CKD stages 4 and 5. We estimated eGFR slopes over three evaluation periods (0.5, 1, and 2 years) using mixed effects models and examined their associations with kidney failure with replacement therapy across CKD stages.

Results: Of 2713 patients with an available 1-year eGFR slope, 985 subsequently initiated kidney replacement therapy. Overall, a slower eGFR decline was strongly associated with a lower risk of subsequent kidney failure with replacement therapy. The association was pronounced with higher baseline CKD stages and attenuated with shorter evaluation periods. The estimated deceleration in eGFR decline over 1 year associated with a 20% lower risk of subsequent kidney failure with replacement therapy was 1.91 (1.60-2.37), 1.12 (1.00-1.28), and 1.06 (0.81-1.60) ml/min/1.73 m per year in patients with CKD stages 3, 4, and 5, respectively.

Conclusion: Our results support the potential of eGFR slope as a surrogate across different stages of CKD in Asians and suggest that a shorter evaluation period than 2 years may be feasible for patients with late-stage CKD. Our findings provide valuable insights for the future design of clinical trials in CKD patients, especially those with more advanced CKD.