Kidney damage on fertility and pregnancy: A Mendelian randomization

Jin Ren; Qiuyan Huang; Xiaowei Lie; Xingli Tong; Qi Yao; Ge Zhou

doi:10.1371/journal.pone.0288788

Kidney damage on fertility and pregnancy: A Mendelian randomization

PLoS One. 2023 Jul 21;18(7):e0288788. doi: 10.1371/journal.pone.0288788. eCollection 2023.

Authors

Jin Ren^{1

2}, Qiuyan Huang^{1

2}, Xiaowei Lie¹, Xingli Tong¹, Qi Yao³, Ge Zhou¹

Affiliations

¹ Department of Reproductive Medicine, Affiliated Hospital of Nanjing University of Chinese Medicine, Jiangsu Province Hospital of Chinese Medicine, Nanjing, China.
² The First College of Clinical Medical, Nanjing University of Chinese Medicine, Nanjing, China.
³ Department of Pathology and Pathophysiology, Nanjing University of Chinese Medicine, Nanjing, Jiangsu Province, China.

Abstract

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.

Copyright: © 2023 Ren et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.

MeSH terms

Abortion, Spontaneous*
Bayes Theorem
Female
Genome-Wide Association Study
Glomerular Filtration Rate / genetics
Humans
Kidney
Mendelian Randomization Analysis
Pregnancy
Renal Insufficiency*
Renal Insufficiency, Chronic* / genetics

Grants and funding

Funding Statement: This study was supported by the National Natural Science Foundation of China (No. 82074479); the Natural Science Foundation of Jiangsu Province (No. BK20201503); the Special Foundation of Clinical Medicine of Jiangsu Provincial Bureau of Science and Technology (No. ZT202107); the Special funding for the training of outstanding young doctors (No. 2023QB0141). There was no additional external funding received for this study. The funding source did not have any influence on the study design, analyses, interpretation of data.