Holzscheiter Leon, Beck Claus, Rutz Sandra, Manuilova Ekaterina, Domke Ingrid, Guder Walter G, Hofmann Walter
Clin Chem Lab Med. 2014 Apr;52(4):537-46. doi: 10.1515/cclm-2013-0693.
New urinary biomarkers like neutrophil gelatinase-associated lipocalin (NGAL), liver-type fatty acid binding protein (L-FABP), and kidney injury molecule-1 (KIM-1) open the opportunity to detect kidney injuries in early stages. Our study aimed at evaluating NGAL, L-FABP, and KIM-1 in comparison to established markers of urine protein differentiation for detection of renal dysfunction.
On the basis of the PROTIS expert system (for differentiation of glomerulo-/tubulopathy) urine and plasma samples of 263 randomly selected patients were routinely examined (urine: total protein, albumin, IgG, α1-microglobulin, creatinine, and dip stick results for leukocytes, blood, protein, glucose, pH, and nitrite; plasma: creatinine and cystatin C) followed by the analysis of the new urine biomarkers NGAL (CMIA), L-FABP (ECLIA), and KIM-1 (ELISA).
Of the three new markers L-FABP showed the highest correlation with α1-microglobulin (r=0.76, p<0.01) and was closest associated with the degree of tubular proteinuria assessed by the PROTIS system. NGAL distinguished the PROTIS proteinuria groups with distinctive tubular proteinurias from the controls as well, but revealed a marked diagnostic influence by leukocyturia. Urinary KIM-1 revealed only a weak diagnostic value for the detection of renal injury.
Urinary NGAL and L-FABP proved to be promising candidates for detecting injuries of the renal tubular system over a broad range of clinical conditions. L-FABP showed a better diagnostic performance and a lower interference by leukocyturia and hematuria than NGAL. Both markers may serve as sensitive tissue injury markers in addition to the established markers of renal functional impairment.
新型尿液生物标志物，如中性粒细胞明胶酶相关脂质运载蛋白（NGAL）、肝型脂肪酸结合蛋白（L-FABP）和肾损伤分子-1（KIM-1），为早期检测肾损伤提供了机会。我们的研究旨在评估NGAL、L-FABP和KIM-1，并与用于检测肾功能不全的尿液蛋白鉴别既定标志物进行比较。
基于PROTIS专家系统（用于肾小球/肾小管疾病的鉴别），对263例随机选择患者的尿液和血浆样本进行常规检查（尿液：总蛋白、白蛋白、IgG、α1-微球蛋白、肌酐以及白细胞、血液、蛋白质、葡萄糖、pH值和亚硝酸盐的试纸检测结果；血浆：肌酐和胱抑素C），随后分析新型尿液生物标志物NGAL（化学发光微粒子免疫分析）、L-FABP（电化学发光免疫分析）和KIM-1（酶联免疫吸附测定）。
在这三种新型标志物中，L-FABP与α1-微球蛋白的相关性最高（r = 0.76，p < 0.01），并且与PROTIS系统评估的肾小管蛋白尿程度关联最为紧密。NGAL也能将具有明显肾小管蛋白尿的PROTIS蛋白尿组与对照组区分开来，但白细胞尿对其诊断有显著影响。尿KIM-1在检测肾损伤方面仅显示出较弱的诊断价值。
在广泛的临床情况下，尿NGAL和L-FABP被证明是检测肾小管系统损伤的有前景的候选标志物。L-FABP表现出比NGAL更好的诊断性能，且受白细胞尿和血尿的干扰更小。除了既定的肾功能损害标志物外，这两种标志物都可作为敏感的组织损伤标志物。
