Codsi Elisabeth, Garovic Vesna D, Gonzalez-Suarez Maria L, Milic Natasa, Borowski Kristi S, Rose Carl H, Davies Norman P, Kashani Kianoush B, Lieske John C, White Wendy M
Department of Maternal Fetal Medicine, Mayo Clinic, Rochester, Minnesota;
Department of Medicine, Division of Nephrology and Hypertension, Mayo Clinic, Rochester, Minnesota; and.
Am J Physiol Regul Integr Comp Physiol. 2017 May 1;312(5):R773-R778. doi: 10.1152/ajpregu.00509.2016. Epub 2017 Apr 24.
Glomerular damage is common in preeclampsia (PE), but the extent and etiology of tubular injury are not well understood. The aim of this study was to evaluate tubular injury in patients with PE and to assess whether it predates clinical disease. We performed a prospective cohort study of 315 pregnant women who provided urine samples at the end of the second trimester and at delivery. This analysis included women who developed PE ( = 15), gestational hypertension (GH; = 14), and normotensive controls (NC; = 44). Urinary markers of tubular injury, α1-microglobulin (A1M), retinol-binding protein (RBP), kidney-injury molecule-1 (KIM1), complement C5b-9, tissue inhibitor metalloproteinase-2 (TIMP-2), and insulin-like growth factor binding protein-7 (IGFBP-7) were measured by enzyme-linked immunosorbent assay (ELISA) and reported in relation to urine creatinine concentration. Second-trimester concentrations of all markers were similar among groups. At delivery, A1M concentrations were higher in the PE group than in the GH and NC groups as an A1M/creatinine ratio >13 (66.7, 8.3, and 35%, respectively, = 0.01). Concentrations of C5b-9 were higher in the PE group than in the GH and NC groups (medians 9.85, 0.05, and 0.28 ng/mg, respectively, = 0.003). KIM1, RBP, TIMP-2, and IGFBP-7 concentrations did not differ among groups at delivery. In conclusion, proximal tubular dysfunction, as assessed by A1M and C5b-9, developed during the interval between the end of the second trimester and delivery in patients with PE. However, this was not matched by abnormalities in markers previously associated with tubular cell injury (KIM-1, IGFBP-7, and TIMP-2).
肾小球损伤在子痫前期（PE）中很常见，但肾小管损伤的程度和病因尚不清楚。本研究的目的是评估PE患者的肾小管损伤，并评估其是否早于临床疾病出现。我们对315名孕妇进行了一项前瞻性队列研究，这些孕妇在孕中期结束时和分娩时提供了尿液样本。该分析包括发生PE的女性（n = 15）、妊娠期高血压（GH；n = 14）和血压正常的对照组（NC；n = 44）。通过酶联免疫吸附测定（ELISA）测量肾小管损伤的尿标志物，即α1-微球蛋白（A1M）、视黄醇结合蛋白（RBP）、肾损伤分子-1（KIM1）、补体C5b-9、组织金属蛋白酶抑制剂-2（TIMP-2）和胰岛素样生长因子结合蛋白-7（IGFBP-7），并报告其与尿肌酐浓度的关系。所有标志物在孕中期的浓度在各组之间相似。在分娩时，PE组的A1M浓度高于GH组和NC组，A1M/肌酐比值>13（分别为66.7%、8.3%和35%，P = 0.01）。PE组的C5b-9浓度高于GH组和NC组（中位数分别为9.85、0.05和0.28 ng/mg，P = 0.003）。分娩时，KIM1、RBP、TIMP-2和IGFBP-7浓度在各组之间没有差异。总之，通过A1M和C5b-9评估，PE患者在孕中期结束至分娩期间出现了近端肾小管功能障碍。然而，这与先前与肾小管细胞损伤相关的标志物（KIM-1、IGFBP-7和TIMP-2）的异常情况不相符。
