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

Abstract

To the Editor: The incidence of end-stage renal failure due to diabetic nephropathy has increased dramatically over the past 20 years. It is widely accepted that the rate of functional decline correlates with the severity of renal tubulointerstitial lesions. Previous studies have shown that renal function in patients with type 2 diabetes correlates better with tubulointerstitial changes than with glomerular pathology [1]. Further studies on tubulointerstitial injury in patients with diabetic nephropathy may provide additional insight into the pathogenesis of diabetic nephropathy and lead to the identification of therapeutic targets. Several factors play an important role in the progression of renal injury. Oxidative stress is both a cause and consequence of interstitial inflammation [2]. Tissue hypoxia resulting from angiotensin-induced vasoconstriction or from structural disruption of peritubular capillaries is a final common pathway in the development of tubulointerstitial fibrosis. Liver-type fatty acid-binding protein (L-FABP) is produced in the proximal tubules, where it plays a key role in fatty acid metabolism. Stresses to the proximal tubules tend to overload fatty acids in the cytoplasm and thereby damage tubules with the release of inflammatory factors. In this way, tubulointerstitial inflammation is provoked, and renal function deteriorates over time. 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]. Unique renoprotective properties of angiotensin II receptor antagonist, which are independent of blood pressure lowering but related to decreased oxidative stress and correction of chronic hypoxia, have been reported [5]. Telmisartan, a highly selective angiotensin II type I receptor antagonist, reduces blood pressure and proteinuria effectively and safely in patients with moderate or advanced-stage renal insufficiency due to various types of nephropathy [6]. Long-term administration of high doses of telmisartan seems to improve the efficacy of the drug to decrease proteinuria and slow progression to end-stage renal failure in nondiabetic hypertensive renal disease [7]. The aim of the present study was to determine whether telmisartan affects the urinary L-FABP level as a marker of proximal tubule injury in patients with type 2 diabetic nephropathy and renal insufficiency.The subjects were 30 type 2 diabetic nephropathy patients with renal insufficiency (18 men, 12 women; mean age 52.0 years; mean serum creatinine 221.0 μmol/l; mean systolic blood pressure 154 mmHg; mean diastolic blood pressure 96 mmHg) and 30 age-matched healthy subjects (18 men, 12 women; mean age 50.0 years; mean serum creatin...

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

“…Our finding is in accordance with earlier studies in type 2 diabetic patients (23), which showed a significant decrease in U-LFABP when these patients were treated with an angiotensin II receptor antagonist. Experimental studies in diabetic rats have shown that renin-angiotensin-aldosterone system blockade reduces antiapoptotic factors (24) and that oxidative stress in tubular cells is reduced and chronic hypoxia is corrected independent of the blood pressure–lowering effect (25) and thereby preserves tubular function.…”

Predictive value of serum cystatin C, β2-microglobulin, and urinary liver-type fatty acid-binding protein on the development of contrast-induced nephropathy

“…However, Nakamura et al reported that the urinary L-FABP level before angiography was higher in the CIN group and was a useful predictor of CIN [21]. A possible reason for the difference between these studies might be due to medications at the time of PCI, as some drugs such as angiotensin receptor blocker or statin reduce urinary L-FABP levels [22,23]. L-FABP plays a key role in fatty acid metabolism in the proximal tubules and is induced by fatty acids themselves.…”

Urinary liver-type fatty acid-binding protein predicts adverse outcomes in acute kidney injury

“…In preclinical studies, renal L-FABP expression protected against tubulointerstitial damage in models of proximal tubule protein overload, as well as against unilateral ureteral obstruction 14,15. Clinical studies have established L-FABP as a promising biomarker in both chronic kidney disease16-18 and AKI 19-21. In addition, Nakamura et al 22.…”