Urinary liver-type fatty acid-binding protein and progression of diabetic nephropathy in type 1 diabetes

Abstract

Objective: Diabetic nephropathy (DN) has mainly been considered a glomerular disease, although tubular dysfunction may also play a role. This study assessed the predictive value for progression of a tubular marker, urinary liver-type fatty acid-binding protein (L-FABP), at all stages of DN.

Research design and methods: At baseline, 1,549 patients with type 1 diabetes had an albumin excretion rate (AER) within normal reference ranges, 334 had microalbuminuria, and 363 had macroalbuminuria. Patients were monitored for a median of 5.8 years (95% CI 5.7-5.9). In addition, 208 nondiabetic subjects were studied. L-FABP was measured by ELISA and normalized with urinary creatinine. Different Cox proportional hazard models for the progression at every stage of DN were used to evaluate the predictive value of L-FABP. The potential benefit of using L-FABP alone or together with AER was assessed by receiver operating characteristic curve analyses.

Results: L-FABP was an independent predictor of progression at all stages of DN. As would be expected, receiver operating characteristic curves for the prediction of progression were significantly larger for AER than for L-FABP, except for patients with baseline macroalbuminuria, in whom the areas were similar. Adding L-FABP to AER in the models did not significantly improve risk prediction of progression in favor of the combination of L-FABP plus AER compared with AER alone.

Conclusions: L-FABP is an independent predictor of progression of DN irrespective of disease stage. L-FABP used alone or together with AER may not improve the risk prediction of DN progression in patients with type 1 diabetes, but further studies are needed in this regard.

Figure 1

A: Urinary L-FABP levels across study groups at baseline. The L-FABP levels were significantly different among the study groups. Significant differences (P < 0.001) in L-FABP levels were observed between the macroalbuminuria group and all other groups. L-FABP levels in the microalbuminuria group were significantly different (P < 0.001) from healthy patients and those with type 1 diabetes and normal AER. Patients with type 1 diabetes and normal AER had significantly (P < 0.001) higher L-FABP levels than healthy patients. B: Urinary L-FABP levels across study groups at baseline in relation with progression status. L-FABP level is significantly higher (P < 0.001) for progressors across all groups (normal AER, microalbuminuria, and macroalbuminuria) compared with nonprogressors. The horizontal line in the middle of each box indicates the median; the top and bottom borders of the box mark the 75th and 25th percentiles, respectively, and the whiskers mark the 90th and 10th percentiles.

Figure 2

A: ROC curve analysis for L-FABP and AER in patients with type 1 diabetes and normal AER showed a trend toward an improvement of the risk prediction (P = 0.09) for L-FABP used together with AER (AUC_L-FABP&AER = 0.786) compared with AER used alone (AUC_AER = 0.778) in patients with type 1 diabetes and normal AER. B: ROC curve analysis for L-FABP and AER in the microalbuminuria group found no significant difference between AUC_AER (0.847) and AUC_L-FABP&AER (0.841). AUC_L-FABP (0.777) was significantly smaller than AUC_AER (P = 0.034). C: ROC curve analysis for L-FABP and AER in the macroalbuminuria group found no significant difference between AUC_AER (0.862) and AUC_L-FABP&AER (0.863). AUC_AER&L-FABP was significantly larger (P = 0.012) than AUC_L-FABP (0.850).