原发性肾病综合征患者血清、尿肝型脂肪酸结合蛋白的变化及其在肾组织表达的意义

Expression of L -FABP in serum, urine and renal tissues in the patients with primary nephrotic syndrome

目的通过检测原发性。肾病综合征（PNS）患者血清、尿肝型脂肪酸结合蛋白（L—FABP）的水平，观察肾组织L—FABP表达，研究其与病理类型的关系及在PNS合并急性肾损伤（AKI）时的变化和意义。方法45例PNS患者根据病理结果是否有急性肾小管坏死（ATN）分为：不伴有ATN的PNS未合并AKI组（PNS未合并AKI组）37例，其中系膜增生性肾炎（MsPGN）13例、轻微病变（MCD）5例、局灶节段性肾小球硬化（FSGS）9例、膜性肾病（MN）10例；伴有ATN的PNS合并AKI组（PNS合并AKI组）8例，病理类型均为MCD。另取10例健康体检者的血清、尿及10例因肾肿瘤行肾切除术但远离肿瘤部的正常肾组织作为对照组。酶联免疫吸附试验（ELISA）检测血清、尿中L—FABP水平，免疫组化法测定肾组织中L—FABP表达量。结果①PNS未合并AKI组各病理类型患者血清、尿L—FABP水平及肾组织L—FABP表达均高于对照组（P〈0．05），其中FSGS患者尿L—FABP水平及肾组织L—FABP表达高于其他病理类型（P〈0．05），血清L—FABP水平在各病理类型间差异无统计学意义（P〉0．05）。②PNS合并AKI组血清、尿L—FABP水平及肾组织L—FABP表达较PNS未合并AKI组升高（P〈0．05）。③血清、尿L—FABP及血肌酐（SCr）诊断AKI的ROC曲线下面积（AUC）分别为0．910、0．973、0．812。④血清、尿L—FABP水平分别与SCr、血尿素氮（BUN）、24h尿蛋白定量（24hUpro）、肾组织L—FABP表达呈正相关（r=0．331～0．764，P〈0．05），分别与血白蛋白（ALB）、尿渗透压（OSM）呈负相关（r=-0．665～-0．482，P〈0．05）。结论L—FABP可作为早期诊断PNS合并AKI的敏感指标。

Objective By detecting liver - type fatty acid binding protein （ L - FABP） levels in serum, urine and L - FABP expression in renal tissues in patients with primary nephrotic syndrome （ PNS）, to investigate its relationship with pathological type and PNS with acute kidney injury （AKI）. Methods 45 patients with PNS were divided into 2 groups according to whether they had acute tubular necrosis （ATN）. There were 37 cases of PNS without ATN and AKI （PNS without AKI group）. According to the pathological types, they were further divided into mesangial proliferative glomerolonephritis （MsPGN） group （13 cases）, minimal change disease （MCD） group （5 cases）, focal segmental glomerulosclerosis （FSGS） group （9 cases） , and membranous nephropathy （MN） group （ 10 cases）. There were 8 cases of PNS with ATN and AKI （PNS with AKI group）, in which all cases were MCD. Serum and urine of 10 healthy subject who received routine physical checkup and 10 normal renal tissues located far from renal tumor in patients with nephritic tumor served as control groups. The levels of L - FABP in serum and urine were detected by enzyme - linked immunosorbent assay （ELISA）. Immunohistochemical staining was used to detect the expression of L - FABP in renal tissues. Results （1） The levels of L - FABP in serum and urine and expression of L - FABP in renal tissues in patients with PNS were significantly higher than those of the control group （ P 〈 0.05 ）. Compared with the MsPGN group, MCD group and MN group, the urine L - FABP and renal L - FABP in the FSGS group increased significantly （P 〈 0.05 ）. However, there were no significant difference in serum among the 4 pathological types （ P 〉 0. 05 ）. （2） The serum and urine levels of L - FABP and the expression of L - FABP in renal tissures were enhanced in the PNS with AKI group compared with the PNS without AKI group （P 〈 0.05 ）. （3） The receiver operator characteristic curve＇s area under the curve （ROC -AUC） of serum, urine L - FABP and serum creatinine （SCr） for diagnosis of AKI were 0. 910, 0. 973,0. 812, respectively. （4） The serum and urine levels of L -FABP were positively correlated with SCr, blood urea nitrogen （BUN）, 24 h urine pro- tein （24hUpro） and expression of L - FABP in renal tissures （r =0. 331 -0. 764, P 〈0.05）, and were negatively correlated with albumin （ALB） and urine osmotic pressure （OSM） （r= -0. 665 - -0. 482, P〈O. 05）. Conclusion L - FABP can be used as a sensitive biomarker for the diagnosis of AKI at early time in patients with PNS. Key words： primary nephrotic syndrome; liver- type fatty acid binding protein; acute kidney injury