Evaluation of Klotho gene expression and NGAL levels following acute kidney injury during pregnancy hypertensive disorders

• Published in: Pregnancy hypertension 2022-12, Vol.30, p.161-170
• Main Authors: Jiang, Yuxin, Jiang, Wenyan, Li, Yuejia, Gu, Weinan, Huang, Hongdi, Wei, Qixi, Bai, Ge, Wang, Jianhong, Rizak, Joshua D., Zhou, Zhu
• Format: Article
• Language: English
• Subjects: Acute kidney injury; Hypertensive disorder; Klotho; NGAL; Oxidative stress; Pregnancy
• ISSN: 2210-7789; 2210-7797
• DOI: 10.1016/j.preghy.2022.08.008

•Acute Kidney Injury is a serious complication during pregnancy related hypertension.•Klotho protein levels are reduced following acute kidney injury during pregnancy.•Klotho protein levels are negatively correlated to oxidative stress.•Malondialdehyde was found to have a mediating effect of Klotho on creatinine levels.•Klotho protein is a potential therapeutic target for acute kidney injury in pregnancy. This study examined the relationship between hypertensive disorders and acute kidney injury (AKI) during pregnancy by evaluating Klotho (KL) gene expression and Neutrophil gelatinase-associated lipocalin (NGAL) levels in pregnant women. Pregnant women were divided into 3 groups: (1) Pregnancy related hypertensive disorders with AKI (PR-AKI) (9 cases), (2) hypertensive disorders pregnancy (HDP) (40 cases), and (3) normal pregnancy (30 cases). For each group, Klotho gene transcription levels in the blood, Klotho and NGAL proteins levels, Malondialdehyde (MDA) and superoxide dismutase (SOD) activity levels were measured in serum. Statistical comparisons were made among the three groups. Klotho/β-actin transcript levels and serum KL protein concentrations were significantly decreased in hypertensive disorder pregnancies with AKI complications. Serum NGAL protein levels were significantly increased in the hypertensive disorder pregnancies with AKI complications. Total serum Klotho protein was negatively correlated with creatinine, while serum NGAL was positively correlated with serum creatinine, urea nitrogen, uric acid, systolic blood pressure, diastolic blood pressure and 24 h urine protein levels. Serum levels of MDA and SOD were significantly increased in the hypertensive disorder pregnancy with AKI and the overall MDA concentration was negatively correlated with Klotho protein concentration. Klotho protein was found to have a direct effect on creatinine, and a mediating effect of MDA was found. Decreased expression of Klotho protein in correlation with increased levels of oxidative stress are found during of AKI complications in pregnancy hypertensive disorders.