Effects of micro and nano plastics on renal health

Abstract

Research on microplastics (MPs) and kidney health is rapidly expanding, yet major knowledge gaps remain. Human exposure remains poorly characterized, with limited data on MPs levels in drinking water, food, indoor air, urine, blood, and kidney tissues. Most animal models rely on high-dose, short-term exposures, whereas studies employing environmentally realistic doses and long-term designs are required to evaluate links with chronic kidney disease and fibrosis. Mechanistic insights are also incomplete; the roles of ferroptosis, pyroptosis, and complement activation, as well as the influence of particle size, shape, polymer type, and surface charge, warrant further investigation. Co-exposures are another critical issue, as MPs act as vectors for heavy metals, persistent organic pollutants, and plastic additives, while also interacting with the gut microbiota and immune system. Clinical implications are particularly concerning: Dialysis fluids, intravenous solutions, and medical devices may represent unrecognized sources of exposure. Addressing these gaps will require multidisciplinary approaches, harmonized detection methods, and clinical monitoring to assess the burden and health consequences of MPs in vulnerable populations. This review underscores the kidney as a potential target organ for MP accumulation and highlights the urgent need for human biomonitoring.

Key Words: Microplastics; Kidney; Nephrotoxicity; Ferroptosis; Pyroptosis; Oxidative stress; Co-exposure; Dialysis; Environmental health

Core Tip: Microplastics and nanoplastics are emerging environmental contaminants capable of reaching the human kidney through ingestion, inhalation, and medical exposure. Experimental data reveal that microplastics accumulate in renal tissue, inducing oxidative stress, endoplasmic reticulum stress, inflammation, autophagy, and ferroptosis. Co-exposure with metals or plastic additives enhances nephrotoxicity, while early human findings confirm their presence in kidney tissue and dialysis fluids. This review integrates mechanistic, experimental, and clinical evidence, highlighting the kidney as a vulnerable target organ and calling for standardized detection methods, multi-omics approaches, and biomonitoring to assess the health burden of plastic exposure.

INTRODUCTION

Microplastics (MPs) are plastic fragments smaller than 5 mm, generated through the degradation of larger plastics or intentionally produced as microbeads. Nanoplastics (NPs) are particles smaller than 1 μm. They are ubiquitous in water, soil and the atmosphere and contaminate food items such as honey, salt, beverages and seafood[1]. Human ingestion is estimated at 39000-52000 particles per person per year. Once ingested, MPs can cross biological barriers and have been detected in multiple organs (placenta, lungs, liver, blood, breast milk, semen and meconium)[2]. Evidence for renal deposition and toxicity has only begun to emerge. This review synthesizes experimental, mechanistic and epidemiological evidence describing how MPs affect kidney structure and function. While this review primarily focuses on MPs, NPs (≤ 100 nm) deserve particular attention because of their higher tissue penetration potential and ability to cross cellular and subcellular membranes. Experimental studies suggest that NPs exhibit distinct biodistribution patterns, accumulating more efficiently in renal tissue than larger particles and interacting directly with mitochondria and lysosomes[3,4]. However, detecting NPs in biological matrices remains technically challenging, as their size often falls below the resolution limits of micro-Fourier transform infrared and Raman spectroscopy, requiring advanced methods such as nanoparticle tracking analysis or pyrolysis-gas chromatography/mass spectrometry for reliable quantification. The literature base remains small and is dominated by in vitro and animal studies; however, recent detection of MPs in human kidneys and dialysis fluids indicates that renal exposure is a realistic concern[5].

ROUTES OF EXPOSURE AND RENAL ACCUMULATION - ENTRY PATHWAYS AND DISTRIBUTION

MPs enter the body mainly through ingestion of contaminated food/water, inhalation of airborne particles or intravenous infusion during medical procedures. MPs reach the kidneys via inhalation, oral ingestion and intravascular injection and can be excreted in urine[6]. Once in the bloodstream, particles can be filtered by the glomerulus, reabsorbed in the tubular epithelium or translocated across the nephron. Particle size influences nephrotoxicity: Toxicity does not scale linearly with size, and there is a specific range where renal toxicity is greatest[6].

Entry pathways into the kidney

MPs can reach the kidney through several routes, including ingestion, inhalation, and medical exposure. Ingestion of contaminated food and water is considered the dominant pathway. Once in the gastrointestinal tract, small particles, particularly those < 10 μm, are able to cross the intestinal barrier and enter systemic circulation. Mechanisms include paracellular leakage through impaired tight junctions, transcytosis by enterocytes or specialized M cells in Peyer’s patches, and transport via chylomicrons through the lymphatic circulation[7]. Inhaled airborne MPs may deposit in the lungs, cross the alveolar epithelium, and enter the bloodstream, from which they are subsequently distributed to peripheral organs, including the kidney[8]. In addition, iatrogenic sources have been reported: MPs and NPs have been detected in infusion and dialysis fluids, providing a direct route into circulation without the need to cross epithelial barriers[9].

Distribution and renal handling

Once in systemic circulation, the renal fate of MPs is dictated by particle size, surface charge, and protein corona formation[10]. Some particles undergo glomerular filtration and become retained in the glomerular basement membrane, while others are internalized by proximal tubular epithelial cells through endocytosis[11]. The “filtration-reabsorption-translocation” hypothesis suggests that MPs can be filtered at the glomerulus, partly reabsorbed in the proximal tubule, and subsequently translocated to the renal interstitium or back into systemic circulation[6].

Interactions within kidney tissue

At the cellular level, MPs are readily taken up by proximal tubular epithelial cells, as demonstrated in vitro with human cultured cells; internalization leads to lysosomal accumulation, defective degradation, and release of reactive oxygen species (ROS), triggering oxidative stress and mitochondrial injury[12]. Mitochondrial dysfunction further initiates endoplasmic reticulum (ER) stress, with glucose-regulated protein 78 (GRP78) and C/EBP homologous protein (CHOP) up-regulation, and activates apoptosis and autophagy pathways[13,14]. MPs also stimulate inflammatory signaling cascades, notably through nuclear factor kappa-B (NF-κB) activation and enhanced secretion of interleukin-1β (IL-1β), IL-6, and tumor necrosis factor-α (TNF-α). Co-exposures with environmental toxicants such as cadmium or bisphenol A (BPA) amplify these responses by increasing chemokine expression (C-C motif chemokine ligand 2, C-C motif chemokine receptor 2) and activating aryl hydrocarbon receptor pathways[15].

Structural and functional consequences

Animal studies corroborate these findings, showing that MPs induce glomerular collapse, tubular necrosis, interstitial fibrosis, capsule dilation, mitochondrial swelling, and tubular vacuolization[16]. Such injuries compromise renal structure and function, contributing to progressive nephrotoxicity. Moreover, MPs often act as carriers for other pollutants, including heavy metals, phthalates, and BPA, facilitating renal delivery and exacerbating toxicity[17]. Beyond classical toxicity, MPs have been implicated in ferroptosis, an iron-dependent form of lipid peroxidation, and in complement activation through the complement component 5a/complement component 5a receptor axis, both of which may contribute to chronic kidney injury[18,19].

Experimental evidence of accumulation

Experimental studies provide growing evidence that MPs can accumulate in kidney tissue in both animal models and humans. In one of the earliest investigations, Deng et al[20] exposed mice to pristine and fluorescent polystyrene MPs (5 μm and 20 μm) for four weeks and found that both particle sizes accumulated in the liver, gut, and kidney, with markedly higher levels observed for the smaller 5 μm fraction. The maximum concentration of 5 μm MPs in kidneys reached 0.946 mg/g and remained detectable even one week after exposure ceased. This accumulation was associated with altered energy and lipid metabolism, as evidenced by mitochondrial dysfunction, increased ROS production, and oxidative stress-related damage[20]. Similar findings were reported in juvenile rats, where 28-day oral exposure to 1 μm polystyrene MPs (2 mg/kg/day) reduced body weight and kidney index, caused intestinal injury, and induced histological lesions including glomerular collapse and tubular damage. Moreover, exposure disrupted blood urea nitrogen and creatinine levels and elevated inflammatory cytokines such as IL-1β, IL-6, and TNF-α, indicating functional impairment and systemic inflammation[21].

Co-exposure has been shown to worsen kidney toxicity. For example, mice given drinking water with 5 μm MPs (10 mg/L) and cadmium (50 mg/L) for three months displayed greater kidney damage than those exposed to cadmium alone. The combined exposure led to renal capsule dilation, tubular necrosis, and mitochondrial damage, with MPs identified within renal tubular epithelium, suggesting their persistence in kidney tissue[22]. In a related model, Sprague-Dawley rats chronically co-exposed to polyethylene terephthalate (PET) MPs and the plasticizer dimethyl phthalate developed kidney hypertrophy and exhibited increased levels of oxidative DNA damage, measured by plasma 8-hydroxy-2’-deoxyguanosine, although no overt structural damage was detected. These results suggest that MPs may act as carriers for additives, enhancing systemic toxicity by facilitating their renal delivery[23].

Medical exposure constitutes an additional source of risk. Analysis of hemodialysis (HD) and peritoneal dialysis (PD) solutions revealed the presence of MPs in all samples, mainly fibers made of polyethylene, polyvinyl chloride, and ethylene-vinyl acetate. Mean concentrations were 0.29 ± 0.16 MPs/L in HD fluids and 0.34 ± 0.02 MPs/L in PD fluids, with particle sizes larger in HD (1.31 ± 0.98 mm) compared to PD (0.64 ± 0.43 mm). Importantly, PD patients were estimated to be exposed to approximately 50% more MPs per week than HD patients, highlighting an unrecognized but chronic exposure route in this vulnerable population and underscoring the need for improved filtration and polymer-free materials[5].

Finally, the first direct evidence of MPs in human renal tissue was reported in 2023[24]. Using micro-Raman spectroscopy, researchers analyzed urine from healthy volunteers and kidney tissue from nephrectomy specimens, detecting polymer fragments including polyethylene, polystyrene, and styrene-isoprene rubber, as well as pigment residues such as hematite and copper phthalocyanine. This study provided proof of principle that MPs can accumulate in both human renal tissue and urine, and it called for further investigations into renal deposition and clearance mechanisms[24].

Quantitative analyses provide clearer insight into the magnitude of renal exposure. In mice, kidney concentrations reached 0.946 mg/g tissue after four weeks of oral exposure to 5 μm polystyrene MPs, with particles still detectable one week post-treatment[20]. In humans, micro-Raman spectroscopy revealed 0.1-0.4 particles/mg in kidney tissue and urine samples, with particle sizes ranging from 4 μm to 15 μm[24]. Medical exposure adds a further burden: HD and PD fluids contained 0.29 ± 0.16 MPs/L and 0.34 ± 0.02 MPs/L, respectively[5]. Across animal studies, administered doses generally range from 0.1 mg/kg/day to 10 mg/kg/day, indicating that most models use concentrations well above estimated environmental exposure levels. These quantitative findings strengthen the evidence that MPs can reach and persist in the kidney under both experimental and clinical conditions.

In vitro and in vivo toxicological evidence

Evidence from in vitro models demonstrates that human kidney cells are direct targets of MP toxicity. In proximal tubular epithelial cells (human kidney 2), Tan et al[6] exposed cultures to 0.1 μm and 1 μm polystyrene MPs and observed rapid internalization, increased mitochondrial ROS, ER stress characterized by GRP78 and CHOP up-regulation, as well as induction of autophagy and inflammatory markers. These effects were reduced by the mitochondrial ROS scavenger MitoTEMPO, showing that mitochondrial dysfunction plays a key role in MP-induced toxicity. In vivo, MPs also accumulated in mouse kidneys, causing tissue damage and increasing ER stress and autophagy markers[25].

Similar effects have been reported in human embryonic kidney cells. Goodman et al[12] demonstrated that exposure to 1 μm polystyrene MPs (0-100 μg/mL, up to 72 hours) markedly suppressed cellular proliferation without causing overt cell death. Confocal microscopy revealed particle uptake and morphological changes, while flow cytometry revealed that more than 70% of cells internalized MPs after 48 hours. Exposure further elevated ROS levels and downregulated mRNA expression of key antioxidant enzymes, including superoxide dismutase 2 and catalase, as well as the glycolytic enzyme glyceraldehyde 3-phosphate dehydrogenase, indicating impaired antioxidant defense and energy metabolism.

Synergistic effects have also been documented when MPs interact with chemical pollutants. Verzola et al[15] investigated the combined effects of polyethylene MPs and BPA in proximal tubular cells. While MPs or BPA alone caused only mild toxicity, co-exposure significantly reduced cell viability, increased lipid peroxidation, upregulated oxidative stress pathways, and amplified pro-inflammatory responses (e.g. IL-1β). Heat shock protein 90 was downregulated, while the aryl hydrocarbon receptor was upregulated, suggesting that MPs can act as vectors for endocrine disruptors, exacerbating nephrotoxicity[15].

Animal studies reinforce these cellular findings. In juvenile rats, oral exposure to polystyrene MPs caused weight loss, reduced kidney index, intestinal and renal injury, and biochemical evidence of nephrotoxicity, including disrupted blood urea nitrogen and creatinine levels. Elevated pro-inflammatory cytokines (IL-1β, IL-6, TNF-α), ER stress, and apoptosis were also reported. Importantly, antioxidant treatment with N-acetylcysteine or the ER stress inhibitor salubrinal mitigated these effects, underscoring oxidative and ER stress as central mechanisms of renal injury[21]. In another study, kidney accumulation of MPs was associated with oxidative stress, evidenced by increased glutathione peroxidase and superoxide dismutase activities but decreased catalase activity, suggesting a compensatory response to sustained redox imbalance[20].

The toxicity of MPs has been shown to be particularly pronounced during co-exposure with metals and plasticizers. In mice, combined exposure to 5 μm MPs and cadmium exacerbated renal injury relative to cadmium alone, producing capsule dilation, tubular necrosis, mitochondrial damage, and evidence of autophagy, apoptosis, and fibrosis. MPs were also observed in renal tubular epithelium, indicating their capacity to penetrate and persist in kidney tissue[22]. Similarly, in Sprague-Dawley rats, chronic co-exposure to PET MPs and dimethyl phthalate elevated plasma 8-hydroxy-2’-deoxyguanosine, a marker of oxidative DNA damage, and induced kidney hypertrophy, even in the absence of overt histological lesions. These findings suggest synergistic toxicity between MPs and their associated additives[23]. Table 1 summarizes representative in vivo and in vitro studies linking MP exposure to renal toxicity.

Table 1 Summary of experimental evidence on microplastic-induced renal effects.

Model	Particle type/size	Dose/duration	Main findings	Ref.
Mouse	PS, 5-20 μm	0.5 mg/kg/day, 4 weeks	Kidney accumulation, mitochondrial dysfunction, ROS increase	Deng et al[20], 2017
Rat (juvenile)	PS, 1 μm	2 mg/kg/day, 28 days	Tubular damage, ER stress, inflammation increase	Wang et al[21], 2022
HK-2 cells	PS, 0.1-1 μm	10-100 μg/mL, 24-48 hours	Mitochondrial ROS, ER stress, autophagy increase	Tan et al[6], 2025
HK-2 + Cd	PS, 5 μm	Cd 50 mg/L + MPs 10 mg/L, 3 months	Exacerbated nephrotoxicity, fibrosis increase	Zou et al[22], 2022
HD/PD fluids	Mixed polymers	-	MPs detected in all samples, chronic exposure risk	Kara et al[5], 2025

PS: Polystyrene; ROS: Reactive oxygen species; ER: Endoplasmic reticulum; HK-2: Human kidney 2; Cd: Cadmium; MPs: Microplastics; HD: Hemodialysis; PD: Peritoneal dialysis.

MECHANISMS OF MP-INDUCED NEPHROTOXICITY

Oxidative stress and mitochondrial dysfunction

Oxidative stress represents the initial and most consistent mechanism of MP-induced renal toxicity. Once internalized, MPs trigger excessive mitochondrial generation of ROS, leading to depolarization of the mitochondrial membrane and impaired adenosine triphosphate synthesis. This mitochondrial dysfunction disrupts redox balance and initiates downstream stress signaling. In human kidney cells, MP exposure increases mitochondrial ROS, activates NF-κB, and elevates pro-inflammatory cytokines such as IL-1β, IL-6, and TNF-α[25]. In juvenile rats, chronic exposure induces similar effects, characterized by elevated oxidative stress markers and altered antioxidant enzyme activities[21]. In human embryonic kidney cells, MPs increase intracellular ROS while downregulating superoxide dismutase 2, catalase, and glyceraldehyde 3-phosphate dehydrogenase, confirming compromised antioxidant defenses[12]. Co-exposure with cadmium intensifies these effects, producing mitochondrial swelling, cristae disruption, and lipid peroxidation[22]. Together, these findings establish mitochondrial ROS overproduction as a central event in the initiation of MP-induced nephrotoxicity.

ER stress and apoptosis

Mitochondrial ROS overflow subsequently activates ER stress, which contributes to apoptotic cell death. ER stress is marked by the up-regulation of molecular chaperones such as GRP78 and pro-apoptotic mediators like CHOP. In cultured human kidney cells, MP-induced mitochondrial dysfunction triggers these pathways, leading to enhanced cytokine release and cellular injury[25]. In juvenile rats, ER stress and apoptosis occur concurrently, with increased caspase-3 activity and a higher Bax/Bcl-2 ratio; both effects are reversed by antioxidants or ER stress inhibitors such as salubrinal[21]. These observations indicate that mitochondrial-ER crosstalk is a key driver of MP-induced renal apoptosis and structural damage.

Inflammation

Inflammatory signaling constitutes a major downstream consequence of oxidative and ER stress. MP exposure activates NF-κB and promotes secretion of inflammatory cytokines in human proximal tubular cells, while in vivo studies show elevated renal IL-1β, IL-6, and TNF-α levels following MP ingestion[21]. Co-exposure to MPs and BPA further amplifies these responses, upregulating IL-1β, C-C motif chemokine ligand 2, and other chemokines[26]. Chronic inflammation contributes to tubular damage, interstitial fibrosis, and progressive renal functional decline. Persistent activation of inflammatory pathways may therefore represent a unifying mechanism linking MP exposure to chronic kidney injury.

Autophagy and ferroptosis

Autophagy and ferroptosis represent two interconnected stress responses that modulate cell survival under MP exposure. In human kidney 2 cells and mouse kidneys, MPs upregulate autophagy markers, which are reduced by antioxidant treatment[25]. This suggests that autophagy initially serves a protective role in clearing damaged organelles. However, sustained exposure or co-exposure with cadmium shifts this balance toward apoptosis and fibrosis, reflecting the limits of this compensatory response[22]. Recent findings also implicate ferroptosis, an iron-dependent form of lipid peroxidation, as a contributor to MP-induced renal fibrosis and chronic injury[18]. Together, these pathways highlight the multifaceted nature of cellular stress responses elicited by MPs.

Gut-kidney axis and immune activation

Beyond direct renal effects, MPs can disrupt the gut-kidney axis, promoting systemic inflammation and immune activation. Oral MP exposure alters gut microbiota composition, compromises intestinal barrier integrity, and facilitates translocation of inflammatory mediators into circulation[27]. This process may activate complement pathways such as complement component 5a/complement component 5a receptor, which have been implicated in MP-induced renal inflammation[6,19]. The gut-kidney axis thus represents an important indirect pathway through which MPs and their associated immune effects can aggravate renal injury.

Influence of particle characteristics and adsorbed pollutants

Toxicity depends on particle size, shape, polymer type and surface charge. It has been observed that smaller particles penetrate tissues more readily and accumulate to higher concentrations. Toxicity mechanisms are unlikely to be uniform across all MP types. Polymer chemistry, additives, and particle morphology strongly influence biological interactions. For instance, polyethylene and polypropylene are generally less reactive but can cause oxidative stress through physical abrasion and surface oxidation, whereas polyvinyl chloride and PET tend to release more toxic additives (plasticizers, antimony catalysts, or residual monomers) and may generate stronger inflammatory and oxidative responses. Particle shape also plays a crucial role: Fibers persist longer in tissues and induce frustrated phagocytosis and chronic inflammation, whereas spherical or fragmented particles are more readily internalized by epithelial and immune cells, leading to mitochondrial and ER stress. Hence, the nephrotoxicity observed across studies likely reflects both chemical composition and geometry, emphasizing the need for comparative studies using standardized particle characterization[3]. Fibres may persist longer than fragments. MPs can adsorb heavy metals or organic pollutants and release additives such as phthalates and BPA, exacerbating toxicity. Combined exposure to MPs and BPA or cadmium produced stronger oxidative and inflammatory responses than either pollutant alone[3,28].

Human evidence and epidemiological insights

Evidence linking MPs exposure to human kidney disease is emerging but remains sparse. A scoping review of MPs in human tissues reported that MPs were present in kidneys and confirm systemic translocation and accumulation potential of MPs in various organs and tissues, especially the kidney and the urinary tract[29]. Another paper focusing on the urinary tract concluded that MPs or NPs are detected in kidney, urine or bladder cancer samples[30].

Patients requiring dialysis may receive significant MPs exposure through dialysis fluids, as described earlier[24]. These findings demonstrate that renal exposure to MPs is not merely theoretical. However, no epidemiological studies have yet linked MPs levels to kidney disease incidence or progression. Observational studies with quantitative MPs measurements in blood, urine and renal tissues are needed to evaluate correlations with kidney function, hypertension, or chronic kidney disease.

Direct evidence of renal deposition was provided in 2023, when the first detection of MPs fragments in human kidneys and urine was reported. Using micro-Raman spectroscopy, researchers identified polymer particles, including polyethylene, polystyrene, and styrene-isoprene rubber, as well as pigment residues such as hematite and copper phthalocyanine in nephrectomy tissues and urine from healthy volunteers[24]. Another concern arises from patients requiring dialysis, who may be exposed to substantial quantities of MPs through dialysis fluids. A recent analysis detected MPs in all HD and PD solutions examined, suggesting an unrecognized source of chronic exposure in this vulnerable patient group[5]. Quantitative measurements further strengthen the evidence of renal accumulation.

Taken together, these findings demonstrate that renal exposure to MPs is no longer merely hypothetical but has been confirmed in human samples and medical settings. Nevertheless, epidemiological studies directly linking MPs burden to kidney disease incidence, progression, or outcomes are still lacking. Future observational research should incorporate quantitative measurements of MPs in blood, urine, and renal tissues, coupled with clinical endpoints such as glomerular filtration rate, hypertension, or chronic kidney disease progression, in order to clarify causal relationships and establish the public health relevance of MPs exposure.

Most human detection studies have relied on micro-Fourier transform infrared and micro-Raman spectroscopy, which remain the gold standards for identifying and characterizing polymer particles in biological samples. However, these methods are limited by particle size resolution (typically > 1 μm) and are highly sensitive to environmental contamination, making rigorous quality control, procedural blanks, and contamination-free sampling essential for reliable results. Importantly, the presence of MPs in kidney or urinary tissues does not necessarily imply toxicity. Detection confirms exposure and translocation but does not demonstrate causality or functional impairment. Establishing a link between MP burden and renal dysfunction will require studies that integrate quantitative analyses, histopathology, and clinical endpoints. Altogether, current human data establish exposure but not causality, emphasizing that presence does not equate to toxicity.

Knowledge gaps and future directions

At present, no epidemiological data directly link internal MP burden to renal or systemic clinical outcomes. This absence constitutes the principal limitation of current evidence and underscores the need for human biomonitoring and longitudinal studies integrating exposure metrics with kidney function endpoints[29].

A key priority is the development of standardized detection methods. Current analytical techniques, such as micro-Raman spectroscopy, Fourier transform infrared spectroscopy, and pyrolysis gas chromatography/mass spectrometry, vary widely in sensitivity and specificity, which makes it difficult to compare findings across studies. Harmonized protocols for sample collection, digestion, and MP identification will be essential to ensure consistency and reliability.

Another important gap concerns human exposure assessment. Very little is known about MP concentrations in drinking water, food, and indoor air at levels relevant to renal exposure. Future studies should aim to quantify MP loads in human urine, blood, and kidney tissues across diverse populations and link them to dietary habits or environmental exposures. A controlled human study involving MP supplementation could provide valuable insight into absorption and distribution mechanisms, but such an approach would raise significant ethical concerns.

Animal studies to date have mostly used relatively high doses of MPs, typically in the range of 2-10 mg per kilogram for several weeks. A major limitation in the current toxicological data is that many experimental studies employ exposure levels that are far higher than plausible human environmental exposures. At such high doses, mechanisms such as oxidative stress, lysosomal overload, and particle-induced inflammation may dominate, but these responses may not scale linearly to the low, chronic exposures typical in humans. Thus, quantitative extrapolation from rodent high-dose experiments to human risk must be done with caution. In regulatory toxicology practice, effects observed in animals are typically adjusted by safety (uncertainty) factors, often 100-fold or more, to account for interspecies differences and variability among humans. Until more data become available on internal human micro- and NP burdens, exposure kinetics, and dose-response at environmentally relevant levels, it is prudent to interpret high-dose animal findings as hazard signals rather than direct risk predictions. There is a need for long-term experiments with environmentally realistic doses to determine whether MPs contribute to chronic kidney disease or fibrosis.

Mechanistic studies are also lacking. Further work should clarify the involvement of ferroptosis, pyroptosis, and complement activation, while exploring how particle size, shape, polymer type, and surface chemistry influence renal toxicity. Multi-omics approaches could help reveal subtle metabolic and epigenetic alterations induced by chronic exposure.

Since MPs rarely occur in isolation, co-exposure scenarios must be considered. MPs can adsorb heavy metals, persistent organic pollutants, and plastic additives, potentially acting as vectors for nephrotoxic agents. Interactions with the gut microbiota and immune responses are particularly relevant and require deeper investigation.

The clinical implications deserve urgent attention. Dialysis fluids, intravenous solutions, and medical devices may represent overlooked sources of exposure. To mitigate these risks, the use of polymer-free or low-leaching medical materials should be prioritized wherever feasible, particularly in dialysis circuits, infusion sets, and blood-contact devices. Development of advanced filtration systems capable of removing micro- and NPs from dialysis and infusion fluids represents an immediate technical goal. In parallel, quality-control standards for medical solutions should include MP quantification, and manufacturers should disclose polymer composition and additive content. Finally, the adoption of biocompatible or biodegradable alternatives, coupled with improved waste management in hospital settings, could substantially reduce inadvertent MP exposure among chronically treated patients[31]. Manufacturers and regulators should work toward polymer-free materials or improved filtration strategies to limit contamination. Monitoring MP levels in medical solutions and assessing their impact on patient outcomes should become a priority for clinical research.

Emerging approaches such as multi-omics profiling (transcriptomics, metabolomics, and proteomics) combined with machine learning-based biomarker discovery offer powerful tools to elucidate subtle molecular signatures of chronic MP exposure. These integrative analyses could identify key pathways linking oxidative, inflammatory, and fibrotic responses across renal cell types. In addition, urinary MP quantification holds promise as a non-invasive biomarker of internal exposure, enabling population-level monitoring and correlation with kidney function parameters in epidemiological studies.

CONCLUSION

MPs are emerging contaminants that can enter the human body through ingestion, inhalation and medical procedures. Experimental studies show that MPs accumulate in the kidneys of rodents and are internalized by human kidney cells, where they elicit oxidative stress, ER stress, inflammation, autophagy and apoptosis. Co-exposure with plastic additives or metals enhances nephrotoxicity. Preliminary human data demonstrate the presence of MPs fragments in kidney tissues and dialysis fluids, highlighting a tangible exposure pathway.

Nevertheless, the absence of epidemiological data linking internal MP burden to renal outcomes remains the major limitation preventing human risk assessment. Future research should prioritize harmonized detection methods for biological matrices to enable inter-study comparability. The development of validated biomarkers, particularly urinary MP quantification, could provide a non-invasive approach for human biomonitoring and exposure surveillance. In parallel, long-term, low-dose animal studies that replicate realistic oral, inhalation, and medical exposure levels are required to elucidate chronic effects and dose-response relationships. Integrating these approaches within standardized analytical and regulatory frameworks will be essential to move from hazard identification toward quantitative risk assessment and evidence-based clinical guidance.