The Influence of Microplastics on CKD Progression

Andrew Kowalski, MD, FASN

Introduction

Recently the New England Journal of Medicine published an article detailing the plague of microplastics that were found in the plaque of carotid arteries. The discussion about various environmental impacts and the role of microscopic plastic particles have been circling around various medical communities, but it never caught traction. Healthcare providers focused on preventative measures were probably the loudest advocates of awareness.

It’s not like we did not now that microplastics exist, it just has never been a direct issues that we in the world or conventional medicine have dealt with. Even the general public has been exposed to the problems of microplastics. Less than a decade ago a large sandwich fast food company was exposed of having microplastics in their bread to extend shelf life. Plus we have all heard, or or even Googled, the infamous McDonalds cheeseburger that has remained untouched by mold or decay after 10-15 years. Microplastics are in everything and their use is to preserved shelf life of foods. I mean, I doubt bread made in the 1940’s had a shelf life of 3+ weeks…its just unnatural. Unfortunately, heavy preservatives, which includes microplastics, are the norm among packaged foods.

The problem is we just don’t know how large of an impact this will have on our health until years or decades from now. We need to start now and take charge of our health.

It is not new information that CKD is a significant public health burden, with increasing prevalence worldwide. While traditional risk factors such as diabetes, hypertension, and genetic predisposition are well established, we are now becoming more aware of the emerging environmental contaminants that are gaining recognition for their role in renal pathophysiology. And at the top of the list is microplastics, tiny plastic particles less than 5 mm in size. Recent studies have emerged as these particles being a potential nephrotoxic agent. This blog delves into the mechanisms by which microplastics may influence the progression of CKD, summarizing current research and highlighting future directions in this evolving field.

Image taken from Stanford Medicine, Katie Savchuk, Jan, 2025

Understanding Microplastics: Sources and Pathways

Microplastics originate from two primary sources:

• Primary microplastics, manufactured for use in cosmetics, cleaning products, and industrial applications.

• Secondary microplastics, resulting from the degradation of larger plastic waste through physical, chemical, and biological processes.

The majority of human contamination are due to these particles entering the human body primarily through ingestion (contaminated food and water) and inhalation (airborne microplastics). Once internalized, their small size allows them to migrate across epithelial barriers, potentially reaching systemic circulation and depositing in various organs—including the kidneys.

Specific dietary sources contributing to microplastic exposure in patients with CKD include seafood, drinking water, fruits, vegetables, and packaged foods. These sources are significant due to the pervasive presence of microplastics in the environment and their potential nephrotoxic effects.

• Seafood: Fish and shellfish are major dietary sources of microplastics. These organisms can ingest microplastics from their environment, leading to their accumulation in edible tissues. Consumption of contaminated seafood can result in the ingestion of plastics, which can then accumulate in human tissues, including the kidneys.

• Drinking Water: Both bottled and tap water have been found to contain microplastics. The ingestion of contaminated water is a direct route for microplastics to enter the human body, contributing to their accumulation in the kidneys and potentially exacerbating CKD.

• Fruits and Vegetables: microplastics can be present on the surface of fruits and vegetables due to contamination from soil, water, and air. Washing and peeling may reduce but not entirely eliminate contamination, leading to ingestion and potential accumulation.

• Packaged Foods: Foods packaged in plastic materials can be a source of microplastics. The degradation of plastic packaging can release microplastics into the food, which are then ingested and can accumulate in the body.

Microplastics and Systemic Toxicity

Several studies have demonstrated that microplastics can trigger oxidative stress, inflammation, and immune and cellular stress responses such as mitochondrial dysfunction and endoplasmic reticulum stress. These systemic effects, if persistent, can contribute to multi-organ damage:

• Oxidative Stress: microplastics, particularly polystyrene microplastics (PS-MPs), induce oxidative stress by generating reactive oxygen species (ROS) within renal cells. This oxidative stress disrupts the mitochondrial electron transport chain, leading to mitochondrial membrane damage, which further exacerbates ROS production. The accumulation of ROS can cause DNA damage, protein oxidation, and lipid peroxidation (the main cause of plaque build up in the blood vessels), ultimately impairing cellular function and viability.

• Inflammation: Microplastics trigger inflammatory responses in renal cells. Exposure to PS-MPs increases the expression of inflammatory markers and cytokines. This inflammatory response can lead to cellular damage and contribute to the progression of CKD.

• Fibrosis: Chronic exposure to microplastics can lead to renal fibrosis (scar tissue formation), a hallmark of CKD progression. Microplastics induce fibrosis through mechanisms such as ferroptosis, a form of regulated cell death associated with iron-dependent lipid peroxidation. This process involves the activation of TGF-β1 and subsequent fibroblast activation, leading to extracellular matrix deposition and tissue scarring.

• Cellular Stress Responses: microplastics cause significant cellular stress, including mitochondrial dysfunction. Mitochondrial dysfunction is characterized by increased mitochondrial ROS and the activation of stress-related proteins marked by the upregulation of stress markers and the activation of autophagy-related proteins like LC3 and Beclin 1. These stress responses can lead to cellular apoptosis and autophagy, further contributing to renal injury.

In summary, microplastics affect renal function at the cellular level by inducing oxidative stress, inflammation, fibrosis, and cellular stress responses such as mitochondrial dysfunction, which collectively contribute to the progression of CKD. These pathophysiological pathways are of particular concern in the context of CKD,

Image from: Deng, Y., Zhang, Y., Lemos, B. et al. Tissue accumulation of microplastics in mice and biomarker responses suggest widespread health risks of exposure. Sci Rep 7, 46687 (2017). https://doi.org/10.1038/srep46687

where systemic inflammation and oxidative damage are already prevalent.

The Kidney as a Target Organ

The kidneys are highly vascularized and responsible for filtering large volumes of blood. 20% of the blood of every heart beat enters the kidney, making them particularly vulnerable to circulating toxins, including microplastics and their associated chemicals.

Accumulation in Renal Tissue

Recent animal studies have shown microplastic accumulation in renal tissue, where they may:

• Interfere with glomerular filtration

• Induce tubular epithelial cell apoptosis (induce programmed cell death)

• Promote fibrotic changes (making scar tissue) through transforming growth factor-beta (TGF-β) signaling.

Disruption of Renal Cellular Function

Microplastics can impair renal cellular metabolism and ATP production (the main molecule responsible for energy). Cellular stress in proximal tubular cells can initiate inflammatory and fibrotic cascades, and therefore accelerate CKD progression.

Synergistic Effects in CKD Patients

As mentioned in previous blog posts, CKD patients are already in a state of heightened oxidative stress and inflammation, with compromised excretory and metabolic functions. The additional burden of microplastic exposure may:

• Accelerate loss of nephron mass (the main working unit of the kidney [about 1 million units in each kidney])

• Worsen proteinuria and glomerular hypertension

• Reduce the efficacy of renoprotective treatments. With what little we have to slow progression may end up having little to no protective effect.

The body does not efficiently rid itself of microplastics, and studies have shown that microplastics can be detected in human tissues and fluids, including urine, indicating that they can persist in the body for extended periods. The excretion of microplastics is primarily through feces and, to a lesser extent, urine. However, the efficiency of this excretion is limited, and microplastics can bioaccumulate in the kidneys.

Moreover, CKD-related changes in gastrointestinal permeability could enhance microplastic absorption, creating a feedback loop of toxicity.

Microplastics and the Gut-Kidney Axis

The gut-kidney axis is a bidirectional communication system between the gut microbiome and renal function. Polystyrene microplastics have been shown to impair the gut barrier, leading to increased levels of urinary complement-activated products, which are associated with CKD symptoms in mice. This suggests a significant role of the gut-kidney axis in microplastic-induced renal injury. Microplastics disrupt gut microbial diversity and promote the growth of pathogenic species that produce uremic toxins such as indoxyl sulfate and p-cresyl sulfate. These toxins are poorly cleared in CKD and contribute to cardiovascular and renal damage, reinforcing CKD progression.

Clinical and Epidemiological Evidence

Though human studies are limited, early findings suggest:

• Microplastics have been detected in human blood, arterial plaque, stool, and even the placenta!

• Epidemiological studies link higher environmental plastic exposure with increased markers of renal dysfunction, though causation remains to be definitively proven.

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More longitudinal data are needed to establish a direct link between microplastic exposure and CKD progression in humans.

Research Gaps and Future Directions

Key areas for future research include:

• Establishing dose-response relationships between microplastic exposure and renal damage

• Understanding the role of co-exposures (e.g., heavy metals, endocrine disruptors) carried by microplastics

• Developing biomarkers for early detection of microplastic-induced nephrotoxicity

• Evaluating the effectiveness of filtration technologies in reducing human microplastic exposure

Mitigation Strategies

Until more definitive evidence emerges, preventive measures should focus on:

• Reducing plastic usage and waste at the societal level

• Strengthening regulations around plastic additives and food packaging

• Enhancing water purification systems, especially in regions with high CKD prevalence

On an individual level, CKD patients and at-risk populations may benefit from:

• Avoiding consumption of heavily processed and packaged foods

• Using glass or stainless-steel containers over plastic

• Advocating for clean environmental practices in their communities

Conclusion

Microplastics represent a novel and concerning environmental threat with the potential to exacerbate many chronic conditions including CKD. While definitive causal pathways are still being elucidated, the convergence of epidemiological trends, mechanistic studies, and toxicological insights points to a pressing need for awareness, research, and action. Protecting renal health in the 21st century will likely evolve to look significantly different than initially imagined and may require not only clinical vigilance but also environmental stewardship.

References

1. The Kidney-Related Effects of Polystyrene Microplastics on Human Kidney Proximal Tubular Epithelial Cells HK-2 and Male C57bl/6 Mice. Wang YL, Lee YH, Hsu YH, et al. Environmental Health Perspectives. 2021;129(5):57003. doi:10.1289/EHP7612.

2. The Emerging Role of Microplastics in Systemic Toxicity: Involvement of Reactive Oxygen Species (ROS). Das A. The Science of the Total Environment. 2023;895:165076. doi:10.1016/j.scitotenv.2023.165076.

3. Di (2-Ethylhexyl) Phthalate and Polystyrene Microplastics Co-Exposure Caused Oxidative Stress to Activate NF-κB/NLRP3 Pathway Aggravated Pyroptosis and Inflammation in Mouse Kidney. Li S, Gu X, Zhang M, Jiang Q, Xu T. The Science of the Total Environment. 2024;926:171817. doi:10.1016/j.scitotenv.2024.171817.

4. Chronic Exposure to Polystyrene Microplastics Induces Renal Fibrosis via Ferroptosis. Hong R, Shi Y, Fan Z, et al. Toxicology. 2024;509:153996. doi:10.1016/j.tox.2024.153996.

5. Effects of Microplastics on the Kidneys: A Narrative Review. de Oliveira RB, Pelepenko LE, Masaro DA, et al. Kidney International. 2024;106(3):400-407. doi:10.1016/j.kint.2024.05.023.

5. Microplastics in Our Diet: A Growing Concern for Human Health. Bocker R, Silva EK. The Science of the Total Environment. 2025;968:178882. doi:10.1016/j.scitotenv.2025.178882.

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7. Effects of Microplastics on the Kidneys: A Narrative Review. de Oliveira RB, Pelepenko LE, Masaro DA, et al. Kidney International. 2024;106(3):400-407. doi:10.1016/j.kint.2024.05.023.

8. Microplastics and Kidneys: An Update on the Evidence for Deposition of Plastic Microparticles in Human Organs, Tissues and Fluids and Renal Toxicity Concern. La Porta E, Exacoustos O, Lugani F, et al. International Journal of Molecular Sciences. 2023;24(18):14391. doi:10.3390/ijms241814391.

9. Polystyrene Microplastics Induce Kidney Injury via Gut Barrier Dysfunction and C5a/C5aR Pathway Activation. Liang Y, Liu D, Zhan J, et al. Environmental Pollution (Barking, Essex : 1987). 2023;342:122909. doi:10.1016/j.envpol.2023.122909.

10. The Kidney-Related Effects of Polystyrene Microplastics on Human Kidney Proximal Tubular Epithelial Cells HK-2 and Male C57bl/6 Mice. Wang YL, Lee YH, Hsu YH, et al. Environmental Health Perspectives. 2021;129(5):57003. doi:10.1289/EHP7612.