生育和妊娠中的肾脏损伤：一项孟德尔随机化研究。
Kidney damage on fertility and pregnancy: A Mendelian randomization.
机构信息
Department of Reproductive Medicine, Affiliated Hospital of Nanjing University of Chinese Medicine, Jiangsu Province Hospital of Chinese Medicine, Nanjing, China.
The First College of Clinical Medical, Nanjing University of Chinese Medicine, Nanjing, China.
出版信息
PLoS One. 2023 Jul 21;18(7):e0288788. doi: 10.1371/journal.pone.0288788. eCollection 2023.
BACKGROUND
Low fertility and adverse pregnancy outcomes are commonly observed in women with chronic kidney disease (CKD). However, a causal relationship between low fertility and adverse pregnancy outcomes with CKD remains unclear. Besides, whether mild kidney dysfunction can affect fertility and pregnancy still needs exploration. Hence, this study aimed to investigate the causal effect of kidney damage on fertility and pregnancy using Mendelian randomization (MR).
METHODS
We first used two-sample MR to examine the effects of kidney damage on fertility and pregnancy. Next, we introduced the Bayesian model averaging MR analysis to detect major causal relationships and render the results robust. The genetic instruments and outcome data were derived from various large genome-wide association studies.
RESULTS
Adverse pregnancy outcomes: Our analyses supported a suggestive causal effect of CKD and estimated glomerular filtration rate (eGFR) rapid on stillbirth, with CKD having an odds ratio (OR) of 1.020 [95% confidence interval (CI) 1.002 to 1.038] and eGFR rapid having an OR of 1.026 (95% CI 1.004-1.048). We also discovered a suggestive causal effect of eGFR on spontaneous abortion, with an OR of 2.63 (95% CI 1.269 to 5.450). Moreover, increased urinary albumin-to-creatinine ratio (UACR) was regarded as a potential risk factor for pre-eclampsia (OR = 1.936; 95% CI 1.065 to 3.517) and gestational hypertension (OR = 1.700; 95% CI 1.002 to 2.886). Fertility assessment: The results indicated that eGFR and UACR had a suggestive causal relationship with the anti-Müllerian hormone level (eGFR beta: 1.004; UACR beta: 0.405).
CONCLUSIONS
Our study used MR to demonstrate a suggestive causal relationship between kidney damage and fertility and pregnancy. We reported that mild kidney dysfunction might be a risk factor for reduced fertility and adverse pregnancy outcomes. Dynamic renal detection may help preserve fertility and reduce the risk of pregnancy loss.
背景
慢性肾脏病（CKD）患者的生育力和妊娠结局通常较差。然而，CKD 患者生育力和妊娠结局较差与 CKD 之间是否存在因果关系尚不清楚。此外，轻度肾功能障碍是否会影响生育力和妊娠仍需探索。因此，本研究旨在使用孟德尔随机化（MR）研究肾脏损伤对生育力和妊娠的因果关系。
方法
我们首先使用两样本 MR 研究肾脏损伤对生育力和妊娠的影响。接下来，我们引入贝叶斯模型平均 MR 分析来检测主要的因果关系并使结果更稳健。遗传工具和结果数据来自各种大型全基因组关联研究。
结果
不良妊娠结局：我们的分析支持 CKD 和估算肾小球滤过率（eGFR）快速与死胎之间存在因果关系的假设，CKD 的比值比（OR）为 1.020[95%置信区间（CI）1.002 至 1.038]，eGFR 快速的 OR 为 1.026（95%CI 1.004-1.048）。我们还发现 eGFR 与自然流产之间存在因果关系的假设，OR 为 2.63（95%CI 1.269 至 5.450）。此外，增加的尿白蛋白/肌酐比值（UACR）被认为是子痫前期（OR=1.936；95%CI 1.065 至 3.517）和妊娠期高血压（OR=1.700；95%CI 1.002 至 2.886）的潜在危险因素。生育力评估：结果表明，eGFR 和 UACR 与抗苗勒管激素水平（eGFRβ：1.004；UACRβ：0.405）存在因果关系的假设。
结论
本研究使用 MR 证明了肾脏损伤与生育力和妊娠之间存在因果关系。我们报告称，轻度肾功能障碍可能是生育力下降和不良妊娠结局的危险因素。动态肾功能检测可能有助于保留生育力并降低妊娠丢失的风险。
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