Effect of Pitavastatin on Urinary Liver-Type Fatty Acid–Binding Protein Levels in Patients With Early Diabetic Nephropathy

Abstract

OBJECTIVE -Liver-type fatty acid-binding protein (L-FABP) is expressed in renal proximal tubules and is reported to be a useful marker for progression of chronic glomerulonephritis. The aim of this study was to determine whether urinary L-FABP levels are altered at various stages of diabetic nephropathy and whether pitavastatin affects urinary L-FABP levels in early diabetic nephropathy.RESEARCH DESIGN AND METHODS -Fifty-eight patients with type 2 diabetes (34 men and 24 women, median age 52 years) and 20 healthy, age-matched subjects (group E) were recruited for the study. The diabetic patients included 12 patients without nephropathy (group A), 20 patients with microalbuminuria (group B), 14 patients with macroalbuminuria and normal renal function (group C), and 12 patients with chronic renal failure but not undergoing hemodialysis (blood creatinine Ͼ1.2 mg/dl; mean 2.5 mg/dl, group D). Twenty group B patients were randomly assigned to receive 1 mg/day pitavastatin (10 patients, group B1) or placebo (10 patients, group B2). Treatment was continued for 12 months. Urinary L-FABP levels were measured by enzyme-linked immunosorbent assay. Urinary 8-hydroxydeoxyguanosine and serum free fatty acids (FFAs) were also measured in group B.RESULTS -Urinary L-FABP levels in groups A-D were 6.2 Ϯ 4.6 g/g creatinine, 19.6 Ϯ 13.5 g/g creatinine, 26.8 Ϯ 20.4 g/g creatinine, and 52.4 Ϯ 46.8 g/g creatinine, respectively. Urinary L-FABP levels in groups B-D were significantly higher than those in healthy subjects (group E, 5.8 Ϯ 4.0 g/g creatinine) (group B, P Ͻ 0.05; group C, P Ͻ 0.01; group D, P Ͻ 0.01). In group B1, urinary albumin excretion (UAE) and urinary L-FABP levels were decreased after pitavastatin treatment (UAE before, 110 Ϯ 74 g/min; 6 months, 88 Ϯ 60 g/min, P Ͻ 0.05; 12 months, 58 Ϯ 32 g/min, P Ͻ 0.01; L-FABP before, 18.6 Ϯ 12.5 g/g creatinine; 6 months, 12.2 Ϯ 8.8 g/g creatinine, P Ͻ 0.05; 12 months, 8.8 Ϯ 6.4 g/g creatinine, P Ͻ 0.01). In group B2, UAE and L-FABP levels showed little change during the experimental period. In group B1, urinary 8-hydroxydeoxyguanosine was decreased 12 months after pitavastatin treatment (before 32.5 Ϯ 19.5 ng/mg creatinine, after 18.8 Ϯ 14.5 ng/mg creatinine, P Ͻ 0.01), but in group B2, these showed little difference during the experimental period. In both groups B1 and B2, serum FFAs showed little difference during the experimental period.CONCLUSIONS -Urinary L-FABP levels appear to be associated with the progression of diabetic nephropathy, and pitavastatin may be effective in ameliorating tubulointerstitial damage in early diabetic nephropathy. Diabetes Care 28:2728 -2732, 2005D iabetes-associated nephropathy is the leading cause of end-stage renal disease. The pathogenesis of diabetic nephropathy is multifactorial, and the precise mechanisms are unclear. It is now widely accepted that the rate of functional deterioration correlates with the degree of renal tubulointerstitial fibrosis (1). Epithelial cells of the proximal tubules play a major role in orchestrating events in the...

Additive antioxidative effects of azelnidipine on angiotensin receptor blocker olmesartan treatment for type 2 diabetic patients with albuminuria

“…8,9 Urinary liver-type fatty acid-binding protein (L-FABP) is an important marker of tubulointerstitial changes in diabetic nephropathy, whereas oxidative stress is a pathogenetic factor underlying diabetes complications such as nephropathy. 10 For this reason, 8-hydroxy-2¢-deoxyguanosine (8-OHdG) has been reported to serve as a sensitive biomarker of oxidative DNA damage in vivo, demonstrating significantly increased urinary excretion levels with severe tubulointerstitial damage. 11,12 In addition, aldosterone induces oxidative stress in vascular cells through NADPH oxidase activation, which has a central role in endothelial dysfunction and atherosclerotic vascular disease.…”

Angiotensin II receptor antagonist reduces urinary liver-type fatty acid-binding protein levels in patients with diabetic nephropathy and chronic renal failure

“…Urinary excretion of L-FABP increases with the deterioration of kidney function and is a useful clinical marker for monitoring chronic kidney disease [3]. We have reported that urinary L-FABP may be a useful clinical marker for type 2 diabetic nephropathy [4].…”

“…Urinary excretion of L-FABP increases with the deterioration of kidney function and is a useful clinical marker for monitoring chronic kidney disease [3]. We have reported that urinary L-FABP may be a useful clinical marker for type 2 diabetic nephropathy [4].Several treatments have been shown to halt or retard the progression of diabetic nephropathy. Suppression of the renin-angiotensin system is currently the most widely used therapy in clinical practice [2].…”

“…Telmisartan 40 mg/day significantly reduced both proteinuria and urinary L-FABP after 6 months (p<0.05) and after 12 months (p<0.01), effects also achieved with telmisartan 80 mg/day at 6 (p< 0.01) and at 12 months (p<0.001). Decreases in proteinuria and urinary L-FABP levels were significantly more pronounced in the 80-mg group than in the 40-mg group (p<0.01).50:490-492 DOI 10.1007/s00125-006-0545-L-FABP has been shown to be a novel clinical marker that can help predict and monitor the progression of renal disease [4]. Inhibition of the renin-angiotensin system plays a major part in management of type 2 diabetes patients with nephropathy.…”

“…L-FABP has been shown to be a novel clinical marker that can help predict and monitor the progression of renal disease [4]. Inhibition of the renin-angiotensin system plays a major part in management of type 2 diabetes patients with nephropathy.…”