AIMS: To determine the associations between combined urinary protein (UP) and a reduced estimated glomerular filtration rate (eGFR) and the risk of starting dialysis with or without diabetes mellitus (DM). METHODS: A nationwide database with claims data on 335,778 people with and without DM aged 19-72 years in Japan was used to elucidate the impact of the severities of UP and eGFR on starting dialysis. Initiation of dialysis was determined from claims using ICD-10 codes and medical procedures. Using multivariate Cox modeling, we investigated the severities of UP and eGFR to predict the initiation of dialysis with and without DM. RESULTS: Both eGFR < 60 and UP(+) were independent predictors for starting dialysis with and without DM, and their values exhibited a synergistic risk of dialysis. eGFR < 60 presented a nearly twofold risk for starting dialysis compared to UP(+) regardless of DM. Risk of starting dialysis was increased with UP(+) and eGFR ≥ 60 accompanied by DM although this association was not observed without DM. Those who had UP(-) and eGFR < 60 had a high risk of starting dialysis regardless of DM. Compared with DM(-)UP(-)eGFR ≥ 60, HRs for starting dialysis for DM(+)UP(+)eGFR ≥ 60, DM(+)UP(-)eGFR < 60 and DM(+)UP(+)eGFR < 60 significantly increased 17.7 (10.6-29.7), 25.5 (13.8-47.1) and 358.1 (239.1-536.5) times, respectively. CONCLUSIONS: eGFR < 60 and UP(+) together presented an extremely high risk of dialysis especially with DM. UP( +) increased the risk of starting dialysis regardless of the eGFR with DM. Both patient education and a treatment strategy by physicians might be helpful to avoid the progression of renal failure.