Wasung Michael E, Chawla Lakhmir S, Madero Magdalena
Division of Nephrology, Department of Medicine, Instituto Nacional de Cardiología Ignacio Chávez, Mexico City, Mexico.
Department of Medicine, Division of Intensive Care Medicine, and the Division of Nephrology, Washington, DC, Veterans Affairs Medical Center, and the Department of Anesthesiology and Critical Care Medicine, George Washington University.
Clin Chim Acta. 2015 Jan 1;438:350-7. doi: 10.1016/j.cca.2014.08.039. Epub 2014 Sep 3.
Acute kidney injury (AKI) and chronic kidney disease (CKD) are conditions that substantially increase morbidity and mortality. Although novel biomarkers are being used in practice, the diagnosis of AKI and CKD is still made with surrogate markers of GFR, such as serum creatinine (SCr), urine output and creatinine based estimating equations. SCr is limited as a marker of kidney dysfunction in both settings and may be inaccurate in several situations, such as in patients with low muscle mass or with fluid overload. New biomarkers have the potential to identify earlier patients with AKI and CKD and in the future potentially intervene to modify outcomes.
In particular KIM-1 and NGAL are considered excellent biomarkers in urine and plasma for the early prediction of AKI; however cycle arrest biomarkers have emerged as novel markers for risk stratification of AKI. Urine TIMP-2 and IGFBP7 performed better than any other biomarkers reported to date for predicting the development of moderate or severe AKI. Biomarker combinations are required to increase diagnostic accuracy in an acute setting. NGAL, cystatin C, and FGF-23 are promising and accurate biomarkers for CKD detection. Equations combining cystatin C and SCr perform better than the equations using either cystatin C or SCr alone, especially in situations where CKD needs to be confirmed. Combining creatinine, cystatin C and urine albumin to creatinine ratio improves risk stratification for kidney disease progression and mortality.
Recent advances in molecular biology have resulted in promising biomarkers for AKI and CKD diagnoses; however more research is necessary to implement them successfully into clinical practice in order to facilitate early diagnosis, guide interventions and monitor disease progression. The following review describes the most important biomarkers studied in kidney disease and will discuss the use and the value of these biomarkers in different clinical settings.
急性肾损伤（AKI）和慢性肾脏病（CKD）会显著增加发病率和死亡率。尽管新型生物标志物已应用于临床实践，但AKI和CKD的诊断仍基于肾小球滤过率（GFR）的替代指标，如血清肌酐（SCr）、尿量以及基于肌酐的估算方程。在这两种情况下，SCr作为肾功能障碍的标志物都存在局限性，在某些情况下可能不准确，如肌肉量低或存在液体超负荷的患者。新型生物标志物有可能更早地识别出AKI和CKD患者，并在未来有可能进行干预以改善预后。
特别是肾损伤分子-1（KIM-1）和中性粒细胞明胶酶相关脂质运载蛋白（NGAL）被认为是尿液和血浆中早期预测AKI的优秀生物标志物；然而，细胞周期停滞生物标志物已成为AKI风险分层的新型标志物。尿组织金属蛋白酶抑制因子-2（TIMP-2）和胰岛素样生长因子结合蛋白7（IGFBP7）在预测中度或重度AKI的发生方面比迄今报道的任何其他生物标志物表现更好。在急性情况下，需要联合使用生物标志物以提高诊断准确性。NGAL、胱抑素C和成纤维细胞生长因子-23（FGF-23）是用于CKD检测的有前景且准确的生物标志物。联合胱抑素C和SCr的方程比单独使用胱抑素C或SCr的方程表现更好，尤其是在需要确诊CKD的情况下。联合肌酐、胱抑素C和尿白蛋白与肌酐比值可改善肾脏疾病进展和死亡率的风险分层。
分子生物学的最新进展为AKI和CKD的诊断带来了有前景的生物标志物；然而，要将它们成功应用于临床实践还需要更多研究，以便促进早期诊断、指导干预并监测疾病进展。以下综述描述了在肾脏疾病中研究的最重要的生物标志物，并将讨论这些生物标志物在不同临床环境中的应用和价值。
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