*Purpose: Chronic renal allograft injury (CRAI) remains a major cause of allograft loss in kidney transplant recipients (KTRs). The aim of this study was to identify urinary biomarkers associated with CRAI and rapid renal function decline in KTRs.

*Methods: This study included 30 KTRs whose estimated GFR was less than 60 mL/min/1.73m² (CRAI group), and 20 KTRs with normal allograft function (control group). To identify potential urinary biomarkers, we performed SDS-PAGE followed by liquid chromatography-mass spectrometry (LC-MS/MS). Several urinary proteins including Apolipoprotein A4 (APOA4) were validated by ELISA. Rapid renal function decline was defined as estimated GFR decline of >3 mL/min/1.73m²/year or initiation of dialysis for 3 years after baseline sampling.

*Results: Among protein profiles identified by proteomics, urinary APOA4 levels were different between CRAI group and control group (15615.0 vs. 2447.9, P<0.001). Urinary APOA4 levels measured by ELISA were also higher in CRAI group (170914.0±166309.5 vs. 14187.5±19959.8 ng/mL, P<0.001). APOA4 levels had high association with CRAI group compared to control group (AUC 0.883 [0.794-0.973], P<0.001) in ROC curve. Among 50 KTRs, 19 patients (38%) were classified as rapid renal function decline group. Urinary APOA4 levels were higher in rapid renal function decline group than stable renal function group (215430.5±181781.3 vs. 42515.9±72438.4 ng/mL, P=0.001). Log-transformed APOA4 values predicted rapid renal function decline in KTRs (odds ratio 6.70 [95% CI 2.56-22.83]).

*Conclusions: These results suggest that urinary APOA4 level might be a potential biomarker for detection of CRAI and could be used as predictor for rapid renal function decline in KTRs.

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