RT Journal Article
SR Electronic
T1 Tubular and Glomerular Injury in Diabetes and the Impact of ACE Inhibition
JF Diabetes Care
JO Diabetes Care
FD American Diabetes Association
SP 1684
OP 1688
DO 10.2337/dc09-0429
VO 32
IS 9
A1 Nielsen, Stine E.
A1 Sugaya, Takeshi
A1 Tarnow, Lise
A1 Lajer, Maria
A1 Schjoedt, Katrine J.
A1 Astrup, Anne Sofie
A1 Baba, Tsuneharu
A1 Parving, Hans-Henrik
A1 Rossing, Peter
YR 2009
UL http://care.diabetesjournals.org/content/32/9/1684.abstract
AB 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.