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Aim: End-stage renal disease (ESRD) not only threatens a patient's life expectancy but also burdens the family and society with medical expenses. The mortality and prevalence rates are extremely high in Taiwan. Thus, this articleinvestigated the effectiveness of an innovative self-management program on the physiology, psychology, and management of patients with pre-ESRD., Methods: This study was designed as a randomized, controlled trial and was set in the department of nephrology in a regional teaching hospital in Taiwan. In total, 112 patients with pre-ESRD were assigned randomly to either an experimental (n = 67) or a control (n = 45) group. The baseline data collection included physiological indicators, psychological factors (depression, anxiety), and measures of self-efficacy and self-management. Routine hospital care was provided for the control group after the pretest and an innovative self-management intervention was used in the experimental group for 4 weeks after the pretest. The effectiveness of the intervention was evaluated 3 months later., Results: Improvements in the physiological indicators, such as blood urea nitrogen and creatinine, and the psychological indicators, such as depression, self-efficacy, and self-management, reached statistical significance., Conclusion: The innovative self-management program effectively decreased patients' functional indicators (blood urea nitrogen, creatinine) and level of depression and enhanced their self-efficacy and self-management., (© 2017 Japan Academy of Nursing Science.)