Glomerular and tubular damage markers are elevated in patients with diabetes.
Glomerular and tubular damage markers are elevated in patients with diabetes.
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DOI：
10.2337/dc10-1545
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发表时间：
2011-04
期刊：
影响因子：
16.2
通讯作者：
Gansevoort RT
中科院分区：
文献类型：
--
作者：
Nauta FL;Boertien WE;Bakker SJ;van Goor H;van Oeveren W;de Jong PE;Bilo H;Gansevoort RT
我们在一项横断面研究中调查了糖尿病患者（n = 94）和非糖尿病对照组（n = 45）的血清和尿液损伤标志物水平，以研究肾小球（IgG）、近端肾小管（肾小管）和肾小球疾病之间的关系。（肾损伤分子[KIM]-1、N-乙酰-β-d-氨基葡萄糖苷酶[NAG]、中性粒细胞明胶酶相关脂质运载蛋白[NGAL]和胱抑素C），和远端肾小管（心脏脂肪酸结合蛋白[H-FABP]）损伤标志物与肾脏疾病严重程度的关系，通过白蛋白尿和估计肾小球滤过率（eGFR）进行评估。在新鲜晨尿样本和血浆中一式三份测量损伤标志物。在糖尿病患者中，41例为正常白蛋白尿，41例为微量白蛋白尿，12例为大量白蛋白尿。尿NAG（9倍），NGAL（1.5倍）和H-FABP（3.5倍）在正常白蛋白尿的糖尿病患者与非糖尿病对照组相比显着升高。除KIM-1外，每个白蛋白尿分层的所有标志物的尿浓度均升高。除KIM-1外，所有尿损伤标志物均与白蛋白尿显著相关，与年龄、性别和相应生物标志物的血浆浓度无关（标准β值在0.35和0.87之间;所有P值均≤ 0.001）。在单变量模型中，除KIM-1外，所有尿液损伤标志物均与eGFR显著相关（标准βs在-0.38和-0.21之间;所有P < 0.04）。校正年龄、性别、相应损伤标记物的血浆浓度和白蛋白尿后，只有H-FABP与eGFR的相关性仍然显著（标准β-0.26; P = 0.037）。肾小球和肾小管标志物与蛋白尿相关，与eGFR无关，表明蛋白尿反映肾小球和肾小管间质损伤。只有尿H-FABP与eGFR相关，而与蛋白尿无关，因此，尿H-FABP可能是评估糖尿病肾病的一个有前景的尿损伤标志物。
We investigated in a cross-sectional study the levels of serum and urinary damage markers in diabetic patients (n = 94) and nondiabetic control subjects (n = 45) to study the association of glomerular (IgG), proximal tubular (kidney injury molecule [KIM]-1, N-acetyl-β-d-glucosaminidase [NAG], neutrophil gelatinase–associated lipocalin [NGAL], and cystatin C), and distal tubular (heart fatty acid–binding protein [H-FABP]) damage markers with kidney disease severity, as assessed by albuminuria and estimated glomerular filtration rate (eGFR). Damage markers were measured in triplicate in fresh morning urine samples and in plasma. Of the diabetic patients, 41 were normoalbuminuric, 41 were microalbuminuric, and 12 were macroalbuminuric. Urinary NAG (ninefold), NGAL (1.5-fold), and H-FABP (3.5-fold) were significantly elevated in normoalbuminuric diabetic patients compared with nondiabetic control subjects. Urinary concentrations of all markers increased per albuminuria stratum, except KIM-1. All urinary damage markers, except KIM-1, were significantly associated with albuminuria, independent of age, sex, and plasma concentrations of the corresponding biomarker (standard βs between 0.35 and 0.87; all P ≤ 0.001). All urinary damage markers, except KIM-1, were significantly associated with the eGFR in univariate models (standard βs between −0.38 and −0.21; all P < 0.04). After adjusting for age, sex, plasma concentration of the corresponding damage marker, and albuminuria, only the association of H-FABP with eGFR remained significant (standard β −0.26; P = 0.037). Glomerular and tubular markers are associated with albuminuria, independently of eGFR, suggesting that albuminuria reflects both glomerular and tubulointerstitial damage. Only urinary H-FABP is associated with eGFR independently of albuminuria and, therefore, may be a promising urinary damage marker to assess diabetic kidney disease.