Clinical evaluation of urinary excretion of liver-type fatty acid-binding protein as a marker for the monitoring of chronic kidney disease: A multicenter trial

Kamijo, Aki; Sugaya, Takeshi; Hikawa, Akihisa; Yamanouchi, Masaya; Hirata, Yasunobu; Ishimitsu, Toshihiko; Numabe, Atsushi; Takagi, Masao; Hayakawa, Hiroshi; Tabei, Fumiko; Sugimoto, Tsuneaki; Mise, Naofumi; Kimura, Kenjiro

doi:10.1016/j.lab.2004.12.003

Cited by 111 publications

(113 citation statements)

References 29 publications

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“…18,19 Increased oxidative stress induced by hyperglycemia may contribute to the pathogenesis of diabetic complications including nephropathy. 20 Diabetic hyperglycemia is associated with increased production of reactive oxygen species.…”

Section: Discussionmentioning

confidence: 99%

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

et al. 2011

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The present study aimed to determine whether either of two calcium channel blockers affected urinary albumin excretion or urinary levels of 8-hydroxy-2¢-deoxyguanosine (8-OHdG) and liver-type fatty acid-binding protein (L-FABP) in hypertensive diabetic patients with chronic kidney disease (CKD) who were already being treated with maximum doses of the angiotensin II receptor blocker olmesartan. We conducted an open-label, randomized, parallel-controlled study on type 2 diabetic patients with stable glycemic control who were receiving fixed doses of antidiabetic agents. The patients received either 8 mg per day azelnidipine, which was increased up to 16 mg per day (azelnidipine group; n¼34), or 2.5 mg per day amlodipine, which was increased up to 5 mg per day (amlodipine group; n¼33), over a 24-week period. Mean systolic and diastolic blood pressure decreased significantly in both groups, but there was no significant difference between the two groups at the end of the study. Serum creatinine levels and estimated glomerular filtration rate did not differ significantly between the two groups, whereas the urinary albumin/creatinine ratio and 8-OHdG and L-FABP levels decreased significantly in the azelnidipine group compared with the amlodipine group. Plasma aldosterone level was significantly decreased in the azelnidipine group, and its changes correlated significantly with those of urinary 8-OHdG and L-FABP. Our results suggest that the addition of azelnidipine to the maximal recommended dose of olmesartan was more effective in reducing albuminuria and oxidant stress in hypertensive diabetic patients with CKD than the addition of amlodipine. Hypertension Research (2011) 34, 935-941; doi:10.1038/hr.2011.67; published online 9 June 2011 Keywords: aldosterone; calcium channel blocker; chronic kidney disease; diabetic nephropathy; oxidant stress INTRODUCTIONThe importance of strict blood pressure (BP) control in patients with chronic kidney disease (CKD) was emphasized by the Japanese Society of Hypertension recommendations of a target BP of o130/ 80 mm Hg for hypertensive patients with CKD. This target is further reduced to o125/75 mm Hg for diabetic nephropathy patients whose urinary protein excretion is 41 g per day. 1 Reduction in proteinuria using suitable therapeutic interventions, similar to renin-angiotensin system (RAS) blockade an antihypertensive treatment regimen, is associated with a slower decline in renal function compared with other treatment groups with similar BPs. 2,3 RAS blockade with angiotensin-converting enzyme inhibitors or angiotensin II type-1 receptor blockers (ARBs) is currently considered the most effective pharmacological approach for renoprotection. These agents reduce proteinuria more effectively than other antihypertensive drugs, and therefore, RAS inhibitors should be titrated to maximal recommended doses. 1,4 However, it is difficult to control BP with mono-

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Section: Discussionmentioning

confidence: 99%

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

et al. 2011

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“…11,12 Urinary liver-type fatty-acid-binding protein (L-FABP) is a useful biomarker for renal tubulointerstitial injury and can be used to monitor both hemodynamic and drug responses in animal models and CKD patients. 13,14 In addition, urinary L-FABP is more sensitive than urinary protein in predicting the progression of CKD. 13 In the present study, the urinary excretion levels of 8-OHdG and L-FABP were used as markers of oxidative stress and tubular injury, respectively.…”

Section: Introductionmentioning

confidence: 99%

“…13,14 In addition, urinary L-FABP is more sensitive than urinary protein in predicting the progression of CKD. 13 In the present study, the urinary excretion levels of 8-OHdG and L-FABP were used as markers of oxidative stress and tubular injury, respectively. In addition, the antioxidative and antiproteinuric effects of cilnidipine were compared with those of amlodipine in hypertensive patients who were receiving treatment with a RAS inhibitor.…”

Section: Introductionmentioning

confidence: 99%

Renoprotective and antioxidant effects of cilnidipine in hypertensive patients

Soeki

Kitani²,

Kusunose

et al. 2012

Hypertens Res

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Cilnidipine, an L/N-type calcium channel blocker (CCB), has been reported to have more beneficial effects on proteinuria progression in hypertensive patients than amlodipine, an L-type CCB. The N-type calcium channel blockade that inhibits renal sympathetic nerve activity might reduce glomerular hypertension by facilitating vasodilation of the efferent arterioles. However, the precise mechanism of the renoprotective effect of cilnidipine remains unknown. Because cilnidipine exerted significantly higher antioxidant activity than amlodipine in cultured human mesangial cells, we hypothesized that cilnidipine might exert a renoprotective effect by suppressing oxidative stress. A total of 35 hypertensive patients receiving a renin-angiotensin system inhibitor were randomly assigned to a cilnidipine (n ¼ 18; 10 mg per day cilnidipine titrated to 20 mg per day) or amlodipine (n ¼ 17; 5 mg per day amlodipine titrated to 10 mg per day) group; the target blood pressure (BP) was set at 130/85 mmHg. After 6 months of treatment, systolic and diastolic BPs were significantly reduced in both of the groups, without any significant difference between the groups. The urinary albumin, 8-hydroxy-2 0 -deoxyguanosine (OHdG) and liver-type fatty-acid-binding protein (L-FABP) to creatinine ratios significantly decreased in the cilnidipine group (Po0.05) compared with those in the amlodipine group. The reductions in urinary albumin, 8-OHdG and L-FABP were not correlated with the change in systolic BP. In conclusion, cilnidipine, but not amlodipine, ameliorated urinary albumin excretion and decreased urinary 8-OHdG and L-FABP in the hypertensive patients. Cilnidipine probably exerts a greater renoprotective effect through its antioxidative properties.

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“…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].…”

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confidence: 96%

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

Nakamura

Sugaya²,

Koide

2006

Diabetologia

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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...

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Clinical evaluation of urinary excretion of liver-type fatty acid-binding protein as a marker for the monitoring of chronic kidney disease: A multicenter trial

Cited by 111 publications

References 29 publications

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

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

Renoprotective and antioxidant effects of cilnidipine in hypertensive patients

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

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