OBJECTIVE This study was conducted to determine the utility of tubular (urinary/plasma neutrophil gelatinase-associated lipocalin [NGAL] and urinary kidney injury molecule 1 [KIM-1]) and glomerular (estimated glomerular filtration rate [eGFR]) biomarkers in predicting preeclampsia (PE) in pregnant women with type 1 diabetes mellitus (T1DM) who were free of microalbuminuria and hypertension at the first trimester.

RESEARCH DESIGN AND METHODS This was a prospective study of T1DM pregnancy. Maternal urinary and plasma NGAL, urinary KIM-1 (ELISA of frozen samples), and eGFR (Chronic Kidney Disease Epidemiology Collaboration equation) were determined at three study visits (V1: 12.4 ± 1.8; V2: 21.7 ± 1.4; V3: 31.4 ± 1.5 weeks’ gestation [mean ± SD]) in 23 women with T1DM with subsequent PE (DM+PE+), 24 who remained normotensive (DM+PE−), and, for reference, in 19 normotensive pregnant women without diabetes (DM−). The groups with diabetes were matched for age, diabetes duration, and parity. All subjects were normotensive and free of microalbuminuria or albuminuria at V1. All study visits preceded the onset of PE.

RESULTS Urinary creatinine-corrected NGAL (uNGALcc, ng/mg) was significantly elevated at V1 in DM+PE+ vs. DM+PE− women (P = 0.01); this remained significant after exclusion of leukocyte-positive samples (5 DM+PE+ and 2 DM+PE−) (P = 0.02). Accounting for BMI, HbA_1c, and total daily insulin dose, a doubling of uNGALcc at V1 conferred a sevenfold increase in risk for PE (P = 0.026). In contrast, neither plasma NGAL nor urinary KIM-1 predicted PE. Also at V1, eGFR was elevated in DM+PE+ vs. DM+PE− (P = 0.04).

CONCLUSIONS Early tubular and glomerular dysfunction may predict PE in first trimester women with T1DM, even if free of microalbuminuria. These data suggest that subclinical renal tubular and glomerular injury, if present early in pregnancy, may predispose women with T1DM to PE.

目的进行这项研究，以确定肾小管（尿/血浆中性粒细胞明胶酶相关的脂钙蛋白[NGAL]和尿肾损伤分子1 [KIM-1]）和肾小球（估计肾小球滤过率[eGFR]）生物标志物在预测先兆子痫中的效用。 1型糖尿病（T1DM）孕妇在孕早期没有微量白蛋白尿和高血压的情况下（PE）。

研究设计和方法这是对T1DM妊娠的前瞻性研究。在三个研究访问中确定了母体尿和血浆NGAL，尿KIM-1（冷冻样品的ELISA）和eGFR（慢性肾脏病流行病学协作方程）（V1：12.4±1.8； V2：21.7±1.4； V3：31.4± 23名患有T1DM并随后发生PE（DM + PE +）的T1DM妇女，1.5名仍处于正常血压状态（DM + PE-）的妊娠1.5周[平均值[SD]]，以及作为参考的19名无糖尿病的正常血压孕妇（DM- ）。糖尿病组的年龄，糖尿病病程和均等匹配。所有受试者均血压正常，在V1时无微量蛋白尿或蛋白尿。所有的研究访问都在体育运动发作之前进行。

结果DM + PE +与DM + PE-妇女相比，尿肌酐校正的NGAL（uNGALcc，ng / mg）在V1时显着升高（P = 0.01）。在排除白细胞阳性样本（5 DM + PE +和2 DM + PE-）之后，这一点仍然很明显（P = 0.02）。考虑到BMI，HbA _1c和每日总胰岛素剂量，uNGALcc在V1时加倍导致发生PE的风险增加了7倍（P = 0.026）。相反，血浆NGAL和尿KIM-1均不能预测PE。同样在V1，相对于DM + PE-，eGFR在DM + PE +中升高（P = 0.04）。

结论早期的肾小管和肾小球功能障碍可能预示着T1DM的早孕妇女发生PE，即使没有微量白蛋白尿也是如此。这些数据表明，亚临床的肾小管和肾小球损伤（如果出现在妊娠早期）可能使患有T1DM的女性易患PE。