Objective To explore the diagnostic role of phosphatidylethanolamine binding protein 4 (PEBP4) in patients with chronic kidney disease (CKD) receiving nursing interventions. Methods ELISA was used to evaluate serum PEBP4 levels. Receiver-operating characteristic curve analysis was used to assess diagnostic accuracy. Spearman correlation analysis was used to assess the relationships between PEBP4 levels and biochemical indexes. Results Serum PEBP4 was high in CKD patients compared with healthy individuals. PEBP4 levels were positively correlated with pathological stage in CKD patients. PEBP4 had higher sensitivity for diagnosis of CKD than common indexes including blood urea nitrogen, creatinine and C-reactive protein. Among CKD patients treated with calcium channel blockers, serum PEBP4 levels declined notably and were associated with concentrations of K+, Na+, Cl− and Ca2+. Nursing interventions significantly decreased serum PEBP4 levels. A significant association between serum PEBP4 level and ionic concentration was observed in CKD patients receiving nursing interventions. Conclusions This prospective study demonstrated that PEBP4 level might represent an effective diagnostic biomarker in CKD patients. PEBP4 also acted as a valuable care compliance factor for determining the necessity for nursing interventions. Nursing interventions restored ion channel function and subsequently resulted in decreased PEBP4 levels and proteinuria.