Early detection of acute kidney injury (AKI) is crucial for patients with chronic kidney disease (CKD) because the staging of AKI is associated with in-hospital mortality and CKD is a risk factor for the development of AKI.1 The definition of AKI is primarily based on serum creatinine (sCr) as a surrogate marker for glomerular filtration rate (GFR). However, sCr level may not reflect an acute decline of GFR, and it may be affected by several factors including age, sex, muscle mass, and chronic illness.2 The present study investigated the clinical significance of plasma neutrophil gelatinase-associated lipocalin (pNGAL) as a biomarker in the diagnosis of AKI and AKI superimposed on CKD. This retrospective observational study included 343 patients with AKI. The patients were classified into two groups; AKI (n=90) and AKI superimposed on CKD (n=253). AKI and CKD were defined by the 2012 Kidney Disease: Improving Global Outcomes Clinical Practice Guideline. The cut-off value of pNGAL was 200 ng/mL. The levels of sCr and pNGAL obtained at baseline and at 48 hr after the onset of AKI were analyzed. The interval change of sCr, estimated GFR (eGFR) and pNGAL during the first 48 hr (a value at baseline-a value at 48 hr) was described as ΔsCr, ΔeGFR and ΔpNGAL, respectively. In the present study, the level of pNGAL was inversely correlated with eGFR calculated by the CKD-EPI equation (r=−0.376, p<0.001), and positively correlated with sCr (r=0.421, p<0.001). The levels of sCr at baseline and at 48 hr were higher, and those of eGFR were lower in the AKI superimposed on CKD group than the AKI group. In addition, pNGAL levels at baseline and at 48 hr were higher in the AKI superimposed on CKD group as compared with the AKI group. However, the value of the ΔpNGAL was higher in the AKI group as compared with the AKI superimposed on CKD group (159.5±261.5 in the AKI group vs. 10.1±229.7 in the AKI on CKD group, p=0.001) although the values of the ΔsCr and ΔeGFR did not differ between the both groups (Table 1). Many clinical studies have demonstrated the clinical value of pNGAL for the diagnosis and prognosis of AKI.3 However, the clinical significance of pNGAL in differentiating AKI and AKI superimposed on CKD have not yet been established.4 Our results suggest that pNGAL may be a useful marker of GFR and the analysis of ΔpNGAL may be helpful to differentiate AKI from AKI superimposed on CKD.