Tubular and Glomerular Injury in Diabetes and the Impact of ACE Inhibition

Abstract

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

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

RESULTS In the cross-sectional study, levels of U-LFABP were significantly higher in normoalbuminuric patients versus those in the control group (median 2.6 [interquartile range 1.3–4.1] vs. 19 [0.8–3.0] μg/g creatinine, P = 0.02) and increased with increasing levels of albuminuria (microalbuminuric group 4.2 [1.8–8.3] μg/g creatinine and nephropathy group 71.2 [8.1–123.4], P < 0.05 for all comparisons). U-LFABP correlates with the urinary albumin-to-creatinine ratio (R² = 0.54, P < 0.001). In the intervention study, all doses of lisinopril significantly reduced urinary albumin excretion rate and U-LFABP from baseline. The reductions in U-LFABP were 43, 46, and 40% with increasing doses of lisinopril (NS).

CONCLUSIONS An early and progressive increase 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.