Excretion of the tubular protein liver fatty acid binding protein (L-FABP) is a potential novel biomarker of renal dysfunction. We examined whether urine L-FABP excretion adds prognostic information to the well-established risk markers, blood pressure (BP), albumin excretion and baseline GFR, regarding progression of chronic kidney disease (CKD). In a prospective study design a cohort of 74 stage 3-4 CKD patients (age 61 ± 13 years) were included. Glomerular filtration ratio (GFR, 51Cr-EDTA-clearance), 24-hour ambulatory BP, 24-hour urinary albumin/creatinine ratio (UAC) and urinary L-FABP/creatinine ratio (U-L-FABP/C) were determined at baseline and after 18 months of follow-up. For comparison 25 age-matched healthy controls were included. The U-L-FABP/C was elevated in CKD patients when compared to controls (mean U-L-FABP/C 2.3 [95% CI 1.7-2.9] μg/mmol vs 0.6 [0.5-0.7] μg/mmol, p < .001). In CKD patients, log U-L-FABP/C at baseline and at follow-up were positively associated (Pearson correlation coefficient r = 0.74, p < .001). Baseline log U-L-FABP/C was negatively correlated with baseline GFR (r = -0.32, p < .001) and directly correlated with UAC (r = 0.67, p < .001). The relative change in GFR from baseline to follow-up correlated with baseline UAC (p < .001), 24-hour systolic BP (p = 0.05) and log U-L-FABP/C (p < .001). Using multiple regression analysis adjusting for baseline GFR, UAC, BP, age and gender, baseline log U-L-FABP/C was associated with a decline in GFR only in patients with UAC <3 mg/mmol (n = 29, p = 0.001) and not in patients with UAC ≥3 mg/mmol (n = 44, p = 0.21). In conclusion urine L-FABP/C is permanently elevated in CKD patients, but only associated with GFR decline in those without albuminuria.