To investigate how changes in eGFR can affect medical costs, a regional cohort of national health insurance beneficiaries in Japan was developed from a nationwide database system (Kokuho database, KDB), and non-individualized data were obtained. From 105,661 people, subjects on chronic dialysis and subjects without consecutive medical checkups were excluded. Finally, medical costs in the follow-up year categorized by annual changes in eGFR between baseline and the next year were longitudinally examined in 70,627 people ranging in age from 40 to 74 years. Global mean costs for subjects with a rapid decrease in eGFR (≤-30%/year) were the highest among all ΔeGFR categories. In men, the cost was 1.42 times that for a stable eGFR. A total of 6,268 (19.4%) men and 5,381 (14.0%) women with eGFR <60 ml/min/1.73 m2 were identified in the baseline year. The mean cost was higher with a low eGFR than without a low eGFR, and there were also higher proportions newly initiating dialysis in 2014 (low eGFR with rapid decrease in eGFR vs. with stable eGFR: 9.61% vs. 0.02% in women, P<0.001). Moreover, the costs for low eGFR subjects with a rapid decrease in eGFR were more than twice those of non-low eGFR subjects with a rapid decrease in eGFR and also compared to low eGFR subjects with a stable eGFR. Moreover, initiating chronic dialysis was considered one of the major causes of high medical costs in women with rapid eGFR decline. To the best of our knowledge, this is the first study of renal disease using a cohort developed from the KDB system recently established in Japan.