ArticleThe Journal of clinical investigation2022
Impaired renal reserve contributes to preeclampsia via the kynurenine and soluble fms-like tyrosine kinase 1 pathway.
Article in The Journal of clinical investigation, 2022. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 17 papers.
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Who cites it
17 citing papers in PubMed.
- Pregnancy-related disorders: molecular mechanisms and management.Molecular biomedicine · 2026Review
- Role of microbial metabolites in the pathogenesis of hypertensive disorders of pregnancy: From short‑chain fatty acids to tryptophan metabolites (Review).Molecular medicine reports · 2026Review
- Complement Activation in Maternal and Placental Pathology of Preeclampsia.Hypertension (Dallas, Tex. : 1979) · 2026Article
- Deletion of endothelial KLF4 as a model for preeclampsia.bioRxiv : the preprint server for biology · 2026Article
- The placenta at term: insights from the Loke Centre for Trophoblast Research 18th Annual Meeting, 2025.Biology open · 2026Article
- Tryptophan's Journey Through Pregnancy: The Role of Serotonin.International journal of tryptophan research : IJTR · 2026Review
- L-kynurenine or nicotinamide supplementations mitigate uterine decidualization impairments during early pregnancy of uninephrectomized mice.Frontiers in physiology · 2026Article
- Vitamin B12 Protects the Exacerbated Ischemia-Reperfusion Injury-Induced Chronic Kidney Disease in Mice with Genetically Increased Elmo1.Antioxidants (Basel, Switzerland) · 2025Article
- Kidney health outcomes of hypertensive disorders of pregnancy.Nature reviews. Nephrology · 2025Review
- Fenestrated Endothelial Cells across Organs: Insights into Kidney Function and Disease.International journal of molecular sciences · 2024Review
- Two decades of advances in preeclampsia research: molecular mechanisms and translational studies.The Journal of clinical investigation · 2024Article
- Protein Misfolding in Pregnancy: Current Insights, Potential Mechanisms, and Implications for the Pathogenesis of Preeclampsia.Molecules (Basel, Switzerland) · 2024Review
- Hemodynamic Renal Reserve Response in Conscious Normotensive and Hypertensive Mice.Kidney & blood pressure research · 2024Article
- A Novel Dual-Function Nitric Oxide Donor Therapy for Preeclampsia-A Proof-of-Principle Study in a Murine Model.Antioxidants (Basel, Switzerland) · 2023Article
- Novel mechanism of increased preeclampsia risk after kidney donation.Kidney international · 2023Article
- Human Chorionic Gonadotropin-Stimulated Interleukin-4-Induced-1 (IL4I1) Promotes Human Decidualization via Aryl Hydrocarbon Receptor.International journal of molecular sciences · 2023Article
- The curious case of tryptophan in pregnancy.The Journal of clinical investigation · 2022Article
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11 authors.
Funding
No grant is acknowledged in the PubMed record.
Abstract
To understand how kidney donation leads to an increased risk of preeclampsia, we studied pregnant outbred mice with prior uninephrectomy and compared them with sham-operated littermates carrying both kidneys. During pregnancy, uninephrectomized (UNx) mice failed to achieve a physiological increase in the glomerular filtration rate and during late gestation developed hypertension, albuminuria, glomerular endothelial damage, and excess placental production of soluble fms-like tyrosine kinase 1 (sFLT1), an antiangiogenic protein implicated in the pathogenesis of preeclampsia. Maternal hypertension in UNx mice was associated with low plasma volumes, an increased rate of fetal resorption, impaired spiral artery remodeling, and placental ischemia. To evaluate potential mechanisms, we studied plasma metabolite changes using mass spectrometry and noted that l-kynurenine, a metabolite of l-tryptophan, was upregulated approximately 3-fold during pregnancy when compared with prepregnant concentrations in the same animals, consistent with prior reports suggesting a protective role for l-kynurenine in placental health. However, UNx mice failed to show upregulation of l-kynurenine during pregnancy; furthermore, when UNx mice were fed l-kynurenine in drinking water throughout pregnancy, their preeclampsia-like state was rescued, including a reversal of placental ischemia and normalization of sFLT1 levels. In aggregate, we provide a mechanistic basis for how impaired renal reserve and the resulting failure to upregulate l-kynurenine during pregnancy can lead to impaired placentation, placental hypoperfusion, an antiangiogenic state, and subsequent preeclampsia.
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