OBJECTIVES: In recent clinical studies, saxagliptin exhibited nephroprotective potential by lowering albuminuria. In this study, we aimed to determine whether these kidney effects of saxagliptin were mediated by changes in markers of kidney tubular damage, including urinary neutrophil gelatinase-associated protein (uNGAL) and liver-type fatty acid-binding protein (uL-FABP). METHODS: Our study included 80 patients with type 2 diabetes, hypertension and mild to moderate diabetic kidney disease (DKD) with prevalent albuminuria. Patients were either randomly assigned to saxagliptin as add-on therapy or remained unchanged on their stable antidiabetic therapy as a control arm. RESULTS: Saxagliptin significantly reduced uNGAL with a median change of -25.4% (interquartile range [IQR], -35.6% to -12.2%) compared with the control group (median change, -0.91%; IQR, -12% to 11.88%; p<0.001) after 3 months. Similarly, patients given saxagliptin had a highly significant reduction in uL-FABP (median change, -24.4%; IQR, -30.5% to -15.1%) compared with controls (median change, -3.8%; IQR -10% to 12.5%; p<0.001). Median estimated glomerular filtration rate (eGFR) values after 3 months in the saxagliptin arm were significantly higher (76.5 mL/min per 1.73 m2; IQR, 70 to 92.75 mL/min per 1.73 m2) in the low-risk uNGAL group compared with controls (59.8 mL/min per 1.73 m2; IQR, 51 to 76.2 mL/min per 1.73 m2; p=0.002). Also, higher-although not significantly-posttreatment eGFR levels were observed in patients with low risk of uL-FABP (73 mL/min per 1.73 m2; IQR, 58 to 91.3 mL/min per 1.73 m2) compared with controls (57.3 mL/min per 1.73 m2; IQR, 49.5 to 72.6 mL/min per 1.73 m2; p=0.06). No significant increase was observed in high-risk patients for either marker when compared with controls. CONCLUSIONS: The albuminuria-lowering effect of saxagliptin may be due to inhibition of kidney tubular damage. Use of tubular markers may be a promising approach to identifying kidney responders to gliptins.