Clinical Significance of Urinary Liver-Type Fatty Acid–Binding Protein in Diabetic Nephropathy of Type 2 Diabetic Patients

Abstract

OBJECTIVEUrinary liver-type fatty acid–binding protein (L-FABP) is a promising indicator of tubular but not glomerular damage. The aim of this study was to evaluate the clinical usefulness of urinary L-FABP as a prognostic biomarker in impaired diabetic nephropathy in type 2 diabetes.RESEARCH DESIGN AND METHODSThis investigation involved a cross-sectional and longitudinal analysis of the relationship between urinary L-FABP levels and progressive nephropathy. Urinary L-FABP was measured with enzyme-linked immunosorbent assay. In the cross-sectional analysis, the association of urinary L-FABP, with the severity of diabetic nephropathy, was investigated in 140 patients with type 2 diabetes and in 412 healthy control subjects. Of the patients in the former study, 104 have been followed for 4 years. The progression of diabetic nephropathy was defined as progressive albuminuria, end-stage renal disease, or induction of hemodialysis.RESULTSUrinary L-FABP levels were progressively increased in subjects with normo-, micro-, or macroalbuminuria and further increased in patients with end-stage renal disease. In the longitudinal analysis, high urinary L-FABP levels were associated with the increase in albuminuria, progression to end-stage renal disease, or induction of hemodialysis. This was particularly demonstrated in the subgroup of patients without renal dysfunction (n = 59), where high urinary L-FABP levels were associated with the progression of diabetic nephropathy.CONCLUSIONSUrinary L-FABP accurately reflected the severity of diabetic nephropathy in type 2 diabetes, and its level was high in the patients with normoalbuminuria. Moreover, higher urinary L-FABP was a risk factor for progression of diabetic nephropathy.

Urinary Biomarkers and Risk of ESRD in the Atherosclerosis Risk in Communities Study

“…Although several studies have reported associations of L-FABP with renal outcomes in adults with diabetes (16,17), associations of L-FABP with clinical outcomes have not been widely studied among patients without diabetes. Characteristics of L-FABP in our study sample suggest that there are differences in the analysis and interpretation compared with prior work in persons with diabetes, because a substantial proportion of our study population had L-FABP values that were below the lower LOD established in our performance laboratory, requiring us to model L-FABP categorically rather than continuously.…”

Clinical impact of albuminuria in diabetic nephropathy

“…In this sense, biomarker studies to identify the presence and predict the progression of diabetic nephropathy have been investigated worldwide (15). Recently, Kamijo-Ikemori et al reported that urinary levels of liver-type fatty acid-binding protein (L-FABP) accurately reflected the 6 severity of diabetic nephropathy in type 2 diabetes (16). Importantly, urinary L-FABP levels were high in the patients with normoalbuminuria, suggesting its usefulness to detect earlier nephropathy in these patients.…”

Predictors of diabetic nephropathy

“…Results demonstrated that the level of u-LFABP reflects the severity of DN (P< 0.05). High u-LFABP level was considered a risk factor for the progression of DN (adjusted HR 7.285, 95% CI 2.425 -21.883, P < 0.0001), suggesting its ability as an early screening tool as well as predictor of DN [61]. Although these findings introduce u-LFABP, a urinary marker of tubular inflammation, as a supplement to albuminuria in predicting DN development in both type 1 and type 2 diabetic patients, other studies produced contradicting results [62].…”

“…These results should be intercepted with caution since u-LFABP was analyzed in a single 24h urine sample, urine samples were in a single 24h urine sample, urine samples were frozen at -20°C for ~18 years before analysis and urine samples before 1990 were lost so the analyzed urine samples were from 1990-2008 (although this is thought to only underrate the predictive power of u-LFABP) [60]. Moreover, another group of investigators assessed u-LFABP in predicting DN development in type 2 diabetic patients [61]. It included both a cross-sectional analysis, including 140 type 2 diabetic patients and 412 healthy individuals, and a longitudinal analysis, where 104 patients were followed for 4 years.…”