Mansour Sherry G, Puthumana Jeremy, Coca Steven G, Gentry Mark, Parikh Chirag R
Program of Applied Translational Research, Department of Medicine, Yale University, School of Medicine, New Haven, CT, USA.
Section of Nephrology, Yale University School of Medicine, 60 Temple Street, Suite 6C, New Haven, CT, 06510, USA.
BMC Nephrol. 2017 Feb 20;18(1):72. doi: 10.1186/s12882-017-0490-0.
Fibrosis is the unifying pathway leading to chronic kidney disease. Identifying biomarkers of fibrosis may help predict disease progression.
We performed a systematic review to evaluate the reliability of blood and urine biomarkers in identifying fibrosis on biopsy as well as predicting renal outcomes. Using MEDLINE and EMBASE, a two-stage search strategy was implemented. Stage I identified a library of biomarkers correlating with fibrosis on biopsy. Stage II evaluated the association between biomarkers identified in stage I, and renal outcomes. Only biomarkers with moderate positive correlation with fibrosis (r > 0.40) or acceptable area under the curve (AUC >0.65) advanced to stage II.
Stage I identified 17 studies and 14 biomarkers. Five biomarkers met criteria to advance to stage II, but only three were independently associated with renal outcomes. Transforming growth factor β (TGF-β) correlated with fibrosis (r = 0.60), and was associated with 1.7-3.9 times the risk of worsening renal function in 426 patients. Monocyte chemoattractant protein-1 (MCP-1) diagnosed fibrosis with AUC of 0.66 and was associated with 2.3-11.0 times the risk of worsening renal function in 596 patients. Matrix metalloproteinase-2 (MMP-2) correlated with fibrosis (r = 0.41), and was associated with 2.5 times the risk of worsening renal function.
Given the heterogeneity of the data due to diverse patient populations along with differing renal outcomes, a meta-analysis could not be conducted. Nonetheless we can conclude from the published data that TGF-β, MCP-1 and MMP-2 may identify patients at risk for renal fibrosis and hence worse renal outcomes.
纤维化是导致慢性肾脏病的共同途径。识别纤维化生物标志物可能有助于预测疾病进展。
我们进行了一项系统评价，以评估血液和尿液生物标志物在通过活检识别纤维化以及预测肾脏结局方面的可靠性。使用MEDLINE和EMBASE，实施了两阶段检索策略。第一阶段确定了与活检时纤维化相关的生物标志物库。第二阶段评估了第一阶段确定的生物标志物与肾脏结局之间的关联。只有与纤维化呈中度正相关（r > 0.40）或曲线下面积可接受（AUC > 0.65）的生物标志物进入第二阶段。
第一阶段确定了17项研究和14种生物标志物。5种生物标志物符合进入第二阶段的标准，但只有3种与肾脏结局独立相关。转化生长因子β（TGF-β）与纤维化相关（r = 0.60），在426例患者中，其与肾功能恶化风险增加1.7至3.9倍相关。单核细胞趋化蛋白-1（MCP-1）诊断纤维化的AUC为0.66，在596例患者中，其与肾功能恶化风险增加2.3至11.0倍相关。基质金属蛋白酶-2（MMP-2）与纤维化相关（r = 0.41），与肾功能恶化风险增加2.5倍相关。
由于患者群体多样以及肾脏结局不同，数据存在异质性，因此无法进行荟萃分析。尽管如此，我们可以从已发表的数据中得出结论，TGF-β、MCP-1和MMP-2可能识别出有肾纤维化风险从而肾脏结局较差的患者。
