Tubular and glomerular injury in diabetes and the impact of ACE inhibition

Stine E. Nielsen, Takeshi Sugaya, Lise Tarnow, Maria Lajer, Katrine J. Schjoedt, Anne Sofie Astrup, Tsuneharu Baba, Hans Henrik Parving, Peter Rossing

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    Abstrakt

    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 DESIGNANDMETHODS - 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 albuminto-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 re-flected 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.

    OriginalsprogEngelsk
    Sider (fra-til)1684-1688
    Antal sider5
    TidsskriftDiabetes Care
    Vol/bind32
    Udgave nummer9
    DOI
    StatusUdgivet - 1 sep. 2009

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