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


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 (> or =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] microg/g creatinine, P = 0.02) and increased with increasing levels of albuminuria (microalbuminuric group 4.2 [1.8-8.3] microg/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 (R(2) = 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.
Nielsen
Stine E
SE
Steno Diabetes Center, Copenhagen, Denmark. sene@steno.dk
Sugaya
Takeshi
T
Tarnow
Lise
L
Lajer
Maria
M
Schjoedt
Katrine J
KJ
Astrup
Anne Sofie
AS
Baba
Tsuneharu
T
Parving
Hans-Henrik
HH
Rossing
Peter
P
D000328:Adult; D000419:Albuminuria / Q000188:drug therapy* / Q000652:urine*; D000806:Angiotensin-Converting Enzyme Inhibitors / Q000627:therapeutic use*; D016022:Case-Control Studies; D003404:Creatinine / Q000652:urine; D003430:Cross-Sectional Studies; D003922:Diabetes Mellitus, Type 1 / Q000150:complications / Q000652:urine; D003928:Diabetic Nephropathies / Q000188:drug therapy* / Q000652:urine*; D050556:Fatty Acid-Binding Proteins / Q000652:urine; D005260:Female; D006801:Humans; D017706:Lisinopril / Q000627:therapeutic use; D008297:Male; D008875:Middle Aged
D000806:Angiotensin-Converting Enzyme Inhibitors; D050556:Fatty Acid-Binding Proteins; D003404:Creatinine; D017706:Lisinopril