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尿 L-FABP 与贫血:尿标志物在 2 型糖尿病中的不同作用。

Urinary L-FABP and anaemia: distinct roles of urinary markers in type 2 diabetes.

机构信息

Technical University Munich, Munich, Germany.

出版信息

Eur J Clin Invest. 2010 Feb;40(2):95-102. doi: 10.1111/j.1365-2362.2009.02220.x. Epub 2009 Nov 11.

Abstract

BACKGROUND

Urinary liver-type fatty acid binding protein (L-FABP) and kidney injury molecule (KIM)-1, novel urinary biomarkers of renal tubulointerstitial function, have previously been associated with acute ischaemic kidney injury. We studied the clinical significance of urinary L-FABP, KIM-1 and N-acetyl-beta-glucosaminidase (NAG) as potential markers of renal function and chronic ischaemic injury in patients with diabetic nephropathy.

MATERIAL AND METHODS

A total of 130 type 2 diabetes patients with early diabetic nephropathy and 40 healthy controls were studied. Urinary L-FABP, KIM-1, NAG, albumin excretion rate (AER) and creatinine clearance were obtained from 24-h urine samples, and correlated with measures of red blood cell count, renal function and metabolic control.

RESULTS

Urinary L-FABP was significantly increased in diabetes patients compared with healthy controls [8.1 (interquartile 0.6-11.6) vs. 2.4 (0.5-3.6) microg/g creatinine, P < 0.001] and correlated with AER (r = 0.276, P = 0.002), creatinine clearance (r = -0.189, P = 0.033) and haemoglobin levels (r = -0.190, P = 0.030). In multivariable linear regression analysis, haemoglobin (beta = -0.247, P = 0.015) and AER (beta = 0.198, P = 0.046) were significant predictors of urinary L-FABP. Prevalent anaemia was independently associated with a 6-fold risk for increased tubulointerstitial kidney damage (upper vs. lower two L-FABP tertiles: OR, 6.06; 95% CI: 1.65-22.23; P = 0.007). Urinary KIM-1 was not significantly associated with kidney function, AER, or measures of red blood cell count while urinary NAG was associated with parameters of glucose control and renal function.

CONCLUSIONS

Different urinary biomarkers may reflect distinct pathophysiological mechanisms of tubulointerstitial damage in early diabetic nephropathy: Urinary L-FABP could be a novel biomarker for chronic intrarenal ischaemia.

摘要

背景

尿肝脏型脂肪酸结合蛋白(L-FABP)和肾损伤分子(KIM)-1 是肾小管间质功能的新型尿生物标志物,先前与急性缺血性肾损伤相关。我们研究了尿 L-FABP、KIM-1 和 N-乙酰-β-D-氨基葡萄糖苷酶(NAG)作为糖尿病肾病患者肾功能和慢性缺血性损伤潜在标志物的临床意义。

材料与方法

共研究了 130 例 2 型糖尿病伴早期糖尿病肾病患者和 40 例健康对照者。从 24 小时尿液样本中获得尿 L-FABP、KIM-1、NAG、白蛋白排泄率(AER)和肌酐清除率,并与红细胞计数、肾功能和代谢控制的指标相关联。

结果

与健康对照组相比,糖尿病患者的尿 L-FABP 明显升高[8.1(四分位距 0.6-11.6)与 2.4(0.5-3.6)μg/g 肌酐,P<0.001],且与 AER(r=0.276,P=0.002)、肌酐清除率(r=-0.189,P=0.033)和血红蛋白水平(r=-0.190,P=0.030)相关。在多元线性回归分析中,血红蛋白(β=-0.247,P=0.015)和 AER(β=0.198,P=0.046)是尿 L-FABP 的显著预测因子。普遍贫血与肾小管间质肾损伤的风险增加 6 倍独立相关(上三分位与下三分位 L-FABP:比值比,6.06;95%可信区间:1.65-22.23;P=0.007)。尿 KIM-1 与肾功能、AER 或红细胞计数的指标无显著相关性,而尿 NAG 与血糖控制和肾功能的参数相关。

结论

不同的尿生物标志物可能反映了早期糖尿病肾病肾小管间质损伤的不同病理生理机制:尿 L-FABP 可能是慢性肾内缺血的新型生物标志物。

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