Introduction People with advanced diabetic nephropathy (DN) are at high risk for development of end-stage renal disease (ESRD) or death. Whether renin-angiotensin system inhibitors and some concomitant drugs could still continue to delay the onset of ESRD in the later stage of DN needs to be clarified. This study aimed to evaluate the relationship of the therapeutic methods as well as clinicopathologic variables with prognosis of patients with biopsy-proven DN during stage 4 of chronic kidney disease (CKD). Methods Forty-six DN patients who underwent renal biopsy in stage 4 CKD were enrolled from January 1, 2002, to December 31, 2019. Clinical data were abstracted retrospectively from the time of renal biopsy. Follow-up data were collected until April 1, 2020, or from the day of renal biopsy to either the occurrence of ESRD or death. The primary outcome was the composite of ESRD or death. Treatment effectiveness and the prognostic ability of clinicopathologic data were evaluated using multivariate Cox regression analyses. Results The median renal survival duration was 17.3 (95% confidence interval, 7.4-27.3 months). Primary endpoint events occurred in 29 individuals (63.0%) during follow-up, including 24 who reached ESRD and 5 who died before progression to ESRD. None of the clinicopathologic data, including pathologic cass of DN, were statistically independent prognostic factors for renal survival. Conventional therapies, such as use of renin-angiotensin system (RAS) inhibitors, a level of glycated hemoglobin (HbA1c) < 7%, and blood pressure < 130/80 mmHg, were also not statistically different between the stable and progressive groups. Conclusion Specific therapies including targeting blood pressure < 130/80 mmHg, HbA1c concentration < 7%, and use of RAS inhibitors could not effectively delay the onset of ESRD in the later stage of DN. Therefore, efforts to slow the progression of DN should focus on early diagnosis and treatment.