Abstract

Objective: We studied tubular and glomerular damage in type 1 diabetic patients by measuring u-LFABP (urinary liver-type fatty acid-binding protein) and albuminuria. Subsequently, we evaluated the effect of ACE inhibition on u-LFABP in patients with diabetic nephropathy.

Research Design and Methods: Caucasians with type 1 diabetes (T1D): 58 with normoalbuminuria (u-albumin<30mg/24h), 45 with persistent microalbuminuria (30-300 mg/24h) and 45 with persistent macroalbuminuria (≥300 mg/24h). A control group consisted of 57 healthy individuals. The groups were matched by gender and duration of diabetes. In addition U-LFABP were measured in 48 T1D patients with diabetic nephropathy in a randomized crossover trial consisting of 2 months of treatment with lisinopril 20, 40, and 60 mg once daily in random order.

Results: In the cross sectional study, the median levels (IQR) of u-LFABP (μg/g creatinine) were significantly higher in normoalbuminuric vs. control group (2.6 (1.3-4.1) vs. 1.9 (0.8-3.0), p=0.02) and increased with increasing levels of albuminuria, microalbuminuric 4.2 (1.8-8.3), nephropathy group 71.2 (8.1-123.4), p<0.05 for all comparisons. U-LFABP correlates with urinary albumin/creatinine ratio (UACR) (R²=0.54, p <0.001).

Results: In the intervention study, all doses of lisinopril significantly reduced urinary albumine excretion rate (UAER) and u-LFABP from baseline. The reductions (95%CI) in u-LFABP were 43%, 46%, and 40% with increasing doses of lisinopril (NS).

Conclusion: Early and progressive rise in tubulointerstitial damage as reflected by increased u-LFABP levels occurs in type 1 diabetic patients and is associated with albuminuria. Furthermore, ACE inhibition reduces the tubular and glomerular damage and dysfunction.