01
Oct
Study Reveals Mechanisms of Kidney Injury and Cancer from Exposure to Weed Killer Glyphosate
(Beyond Pesticides, October 1, 2025) A novel study in Scientific Reports combines computational analyses with toxicological data to identify pathways affected by exposure to the weed killer glyphosate. The analyses identify glyphosate targets that correlate with kidney injury and kidney cancer, revealing pathways with significant glyphosate-induced alterations, including the dysregulation of nitrogen metabolism that leads to ammonia accumulation and oxidative stress, both of which contribute to renal (kidney) damage and carcinogenesis (development of cancer).
“This study provides a comprehensive investigation into the molecular mechanisms by which glyphosate may contribute to kidney injury and kidney cancer, employing an array of bioinformatics tools for target prediction, toxicity assessment, pathway enrichment analysis, molecular docking and molecular dynamics simulation,†the researchers state. The results of the analyses and simulations highlight the molecular mechanisms underlying glyphosate’s nephrotoxic (damaging to kidneys) and carcinogenic (cancer-causing) effects.
Study Importance and Background
Glyphosate, known as a broad-spectrum systemic herbicide, has been used for agricultural and nonagricultural purposes for decades and is the most extensively used herbicide worldwide. This widespread use is largely due to its application to genetically engineered, glyphosate-tolerant crops. Both glyphosate and its main metabolite (breakdown product), aminomethylphosphonic acid (AMPA), are detected in water, soil, and food, which then represent multiple pathways for exposure to nontarget organisms, including humans.
There is a wide body of science connecting glyphosate to threats to public health, wildlife, and the environment. Both research and litigation provide evidence of the carcinogenic potential of glyphosate, as well as toxicity to kidneys. Studies show both acute and chronic effects of glyphosate exposure, “triggering oxidative stress, inflammation, and apoptosis [cell death] in renal cells, culminating in structural and functional kidney damage.†(See scientific literature here, here, and here.)
Additional epidemiological research links glyphosate exposure with higher rates of renal diseases, including chronic kidney disease (CKD) and renal cell carcinoma. “Both in vitro [in a test tube or petri dish] and in vivo [in a living organism] studies reveal glyphosate’s capacity to disrupt mitochondrial function, modulate gene expression involved in detoxification, and generate reactive oxygen species (ROS), collectively contributing to renal cell injury,†the researchers point out. (See here and here.) They continue, “Given these findings, there is an urgent need to unravel the molecular pathways by which glyphosate may drive kidney injury and cancer progression, especially under conditions of prolonged exposure.â€
Methodology
To better understand the mechanisms through which glyphosate can impact kidney function and cancer development, without the limitations seen in traditional toxicological approaches with complex substances like glyphosate, this study utilizes network toxicology as a “transformative framework for dissecting the complex biological interactions triggered by chemical exposures.â€
As the authors explain, “Unlike traditional toxicology, which often focuses on individual molecular pathways or isolated targets, network toxicology employs systems biology to analyze the chemical’s impact across interconnected molecular networks.†This approach allows for analysis of glyphosate’s cellular and systemic effects that result in deleterious impacts on health.
Utilizing computational approaches allows for “the prediction and prioritization of potential interactions between small molecules like glyphosate and complex biological systems,†the researchers state. They continue, “Specifically, methodologies such as molecular docking and simulation analysis are employed to predict the binding affinity and favored orientation of glyphosate with proteins implicated in critical cellular processes—particularly those related to renal function and carcinogenesis (e.g., key enzymes, receptors, or transporters identified from network analyses).†For more information on the specific databases and computational tools within the study, see the methodology section for more details.
Study Results and Implications
Through network toxicological analyses and simulations, this study predicts glyphosate’s ability to incite kidney toxicity and carcinogenicity, which adds to the current body of science with existing toxicity data that indicates that increasing doses of glyphosate heighten risks of adverse health effects. The results include:
- The prediction of 47 drug targets of glyphosate, 20 of which overlap with kidney injury and 31 with kidney cancer, represents how glyphosate can modulate specific pathways through key targets to cause diseases, shown through the creation of a “drug-target-pathway network.†(See here.)
- Additional predictions from databases indicate “that glyphosate’s co-toxicity primarily involves kidney injury. Additionally, the databases predicted carcinogenicity, neurotoxicity, respiratory toxicity, and ototoxicity [ear poisoning] for glyphosate.â€
- Analyses of protein-protein interaction networks involving glyphosate-induced effects show ten targets for glyphosate-induced kidney injury and ten targets for kidney cancer. These targets include matrix metalloproteinases (MMPs) that play crucial roles in processes such as tissue remodeling, wound healing, and embryonic development, as well as in diseases such as cancer and chronic inflammation. The authors note, “While MMPs are known targets in cancer biology their specific implication in glyphosate-induced renal toxicity represents a significant mechanistic advancement elucidated by our network-based approach.â€
- Gene Ontology analyses reveal prominent biological processes, including proteolysis (breakdown of proteins), extracellular matrix disassembly, negative regulation of apoptosis, and collagen catabolic process for glyphosate-induced kidney injury and cancer.
- Significant signaling pathways involved in glyphosate-induced kidney injury include bladder cancer, adherens junction (provides adhesion between cells), endocrine resistance, relaxin signaling pathway, estrogen signaling pathway, fluid shear stress and atherosclerosis, nitrogen metabolism, proteoglycans in cancer, diabetic cardiomyopathy (heart muscle disease), and lipid and atherosclerosis. The pathways related to glyphosate-induced kidney cancer include nitrogen metabolism, metabolic pathways, bladder cancer, adherens junction, endocrine resistance, relaxin signaling pathway, estrogen signaling pathway, and fluid shear stress [frictional forces impacting blood flow] and atherosclerosis. As a note, nitrogen metabolism is the pathway with the highest enrichment [higher statistical significance] in both glyphosate-induced kidney injury and kidney cancer, which offers insight into less-explored mechanisms of glyphosate toxicity.
“In summary, this study employed a robust computational strategy to propose that glyphosate may exert nephrotoxic and carcinogenic effects primarily through disrupting extracellular matrix integrity via interactions with MMPs and PLG [plasminogen, an enzyme involved in breaking down blood clots and other processes such as inflammation], and by dysregulating nitrogen metabolism,†the researchers state. These results advance the mechanistic understanding of glyphosate toxicity, beyond general oxidative stress, which is crucial in understanding the health risks from both short-term and long-term exposure.
Previous Research
Studies upon studies highlight the adverse effects associated with the widely used weed killer glyphosate, ranging from endocrine disruption and reproductive dysfunction to neurotoxicity and developmental impacts, among others. As shared in previous Daily News, in 2013, the Center for Public Integrity highlighted that glyphosate bonds with toxic heavy metals in the environment, such as cadmium and arsenic, forming stable compounds. These compounds are present in food and water for consumption and do not break down until they reach the kidneys. Thus, farmworkers exposed to glyphosate are likely to have these toxic metals in their kidneys. Additionally, in 2019, researchers Sararath Guanatilake, MD, and Channa Jayasumana, PhD, were awarded the Freedom and Responsibility Award from the American Association for the Advancement of Science for their work in uncovering the link between glyphosate and chronic kidney disease. (See Daily News coverage here.)
A previous Daily News, entitled “Kidney, Liver Damage Linked to Chronic, Low-Dose Glyphosate Exposure,†highlights a research study published in Environmental Health that links chronic, ultra-low dose exposure to glyphosate in drinking water to adverse impacts on the health of the liver and kidneys. Further research finds glyphosate causes changes to DNA function, resulting in chronic diseases such as kidney and liver diseases, diabetes, and Parkinson’s. Multigenerational effects from glyphosate exposure are also documented, with research associating cancer development with DNA alterations through oxidative stress mechanisms. (See Weed Killer Glyphosate Linked to Multi-Generational Adverse Health Effects and EPA Overlooks Glyphosate and Roundup Ingredients’ Cancer, DNA Damage, and Multigenerational Effects for more information.)
Mitigating Health Threats: The Organic Solution
As Beyond Pesticides has advocated for over 40 years, organic agriculture and land management practices offer a holistic approach that protects health and the environment from the harmful effects of petrochemical pesticides and fertilizers. Adopting organic methods mitigates health threats in the current case of glyphosate and kidneys, as well as all other toxic chemicals that are not allowed under organic standards.
As stated in previous Daily News, kidneys are one of the most important organs for filtering waste out of the body. However, kidneys are often the main target of pesticide toxicity mediated through oxidative stress, as well as other mechanisms elucidated in the current study. Therefore, human and ecological health must be protected by shifting to organic systems and supporting the organic movement by buying and growing organic food.
Organic methods provide many health and environmental benefits, eliminating the need for chemical-intensive practices. Research shows that switching to an organic diet has health benefits, even showing that glyphosate levels in the human body can decrease by 70% after one week. (See here and here.)
Get involved! Contribute your voice and help protect organic integrity through continuous improvement of organic standards. The Fall National Organic Standards Board (NOSB) meeting is scheduled for November 4 – 6, 2025. The public meeting of the NOSB is preceded by an opportunity for public comments in writing and via online webinars on October 28 and 30, 2025, from 12 pm to 5 pm ET, that concern how organic food is produced.
Please copy Beyond Pesticides’ comments and fill out the form here before clicking the blue button “Click here to go to Regulations.gov.” After pasting comments into Regulations.gov, we encourage you to please consider personalizing and adding text before final submission! For a complete discussion of topics, see Keeping Organic Strong and the Fall 2025 issues page.
All unattributed positions and opinions in this piece are those of Beyond Pesticides.
Source:
Dong, Y. and Zhu, J. (2025) Network toxicology reveals glyphosate mechanisms in kidney injury and cancer, Scientific Reports. Available at: https://pmc.ncbi.nlm.nih.gov/articles/PMC12375789/.
