Mercury Exposure and Nephrotoxicity: A Comprehensive Review – Mr Yakubu Adam Writes

Abstract: Mercury, a ubiquitous environmental pollutant, poses significant risks to human health, including nephrotoxicity. This review aims to provide a comprehensive overview of the association between mercury exposure and nephrotoxicity, encompassing epidemiological evidence, underlying mechanisms, and clinical implications. Epidemiological studies have consistently reported associations between mercury exposure and various markers of renal dysfunction and injury.

Mechanistic studies have elucidated oxidative stress, inflammation, and mitochondrial dysfunction as key pathways underlying mercury-induced nephrotoxicity. Clinical manifestations of mercury nephrotoxicity range from subclinical renal impairment to acute kidney injury and chronic kidney disease. Early detection and mitigation of mercury exposure are crucial for preventing renal damage and mitigating the burden of nephrotoxicity. Future research should focus on clarifying dose-response relationships, identifying susceptible populations, and exploring interventions to prevent or ameliorate mercury-induced nephrotoxicity.

Keywords: Mercury, nephrotoxicity, renal dysfunction, kidney injury, oxidative stress, inflammation

Introduction

Mercury is a naturally occurring element that exists in various forms, including elemental (or metallic), inorganic, and organic mercury compounds. While mercury has industrial and medical applications, its widespread use has led to environmental contamination and human exposure, primarily through consumption of contaminated fish and seafood, occupational exposure, and proximity to industrial sources [1]. Mercury is recognized as a potent toxicant, with adverse effects on multiple organ systems, including the central nervous system, cardiovascular system, and kidneys [2].

Nephrotoxicity refers to kidney damage or dysfunction caused by exposure to nephrotoxic agents, including heavy metals such as mercury. Mercury-induced nephrotoxicity has been documented in both experimental studies and human populations, with manifestations ranging from subclinical renal impairment to acute kidney injury (AKI) and chronic kidney disease (CKD) [3]. The kidneys play a crucial role in regulating fluid and electrolyte balance, excreting waste products, and maintaining acid-base homeostasis. Therefore, impairment of renal function can have profound implications for overall health and wellbeing.

This review aims to provide a comprehensive overview of the association between mercury exposure and nephrotoxicity, encompassing epidemiological evidence, underlying mechanisms, and clinical implications. Understanding the mechanisms of mercury-induced nephrotoxicity is essential for developing preventive strategies and therapeutic interventions to mitigate the adverse effects of mercury exposure on kidney health.

Epidemiological Evidence: Epidemiological studies have consistently reported associations between mercury exposure and various markers of renal dysfunction and injury. These include abnormalities in renal function tests such as serum creatinine, estimated glomerular filtration rate (eGFR), and urinary biomarkers of kidney injury such as albuminuria, proteinuria, and renal

tubular dysfunction [4]. Several population-based studies have demonstrated dose-response relationships between mercury exposure and the prevalence or incidence of CKD, suggesting a causal relationship [5]. Moreover, vulnerable populations such as children, pregnant women, and individuals with pre-existing kidney disease may be particularly susceptible to the nephrotoxic effects of mercury [6].

Mechanisms of Mercury-Induced Nephrotoxicity: The mechanisms underlying mercury- induced nephrotoxicity are complex and multifactorial, involving oxidative stress, inflammation, mitochondrial dysfunction, and direct cellular damage [7]. Mercury has a high affinity for sulfhydryl (-SH) groups in proteins, leading to disruption of enzymatic function and cellular signaling pathways. Reactive oxygen species (ROS) generated during the metabolism of mercury can induce oxidative stress, resulting in lipid peroxidation, DNA damage, and mitochondrial dysfunction [8]. In addition, mercury can activate pro-inflammatory pathways and promote the release of inflammatory cytokines, contributing to renal inflammation and tissue injury [9]. Furthermore, mercury can directly target renal tubular epithelial cells, leading to cell death, necrosis, and apoptosis [10].

Clinical Manifestations: Clinical manifestations of mercury nephrotoxicity vary depending on the duration, route, and dose of exposure. Acute exposure to high levels of mercury vapor or inorganic mercury salts can cause fulminant AKI, characterized by oliguria, proteinuria, hematuria, and acute tubular necrosis [11]. Chronic exposure to lower levels of mercury, such as through dietary intake of methylmercury-contaminated fish, may lead to progressive renal impairment and CKD [12]. Long-term exposure to mercury has also been associated with an increased risk of hypertension, cardiovascular disease, and other adverse health outcomes, further exacerbating the burden of renal disease [13].

Prevention and Management: Preventing mercury exposure is the most effective strategy for reducing the risk of mercury-induced nephrotoxicity. This includes minimizing occupational exposure to mercury vapors and fumes, educating the public about the sources of mercury contamination in the environment, and implementing regulations to limit mercury emissions from industrial processes [14]. Additionally, dietary interventions, such as consuming fish low in mercury and avoiding mercury-containing herbal remedies, can help reduce the risk of mercury toxicity [15]. In cases of acute mercury poisoning, prompt medical intervention is necessary to prevent irreversible kidney damage and systemic toxicity. Treatment may involve supportive measures such as hydration, diuresis, and chelation therapy to enhance mercury elimination [16].

Future Directions: Future research should focus on elucidating dose-response relationships between mercury exposure and nephrotoxicity, identifying susceptible populations, and exploring interventions to prevent or ameliorate the adverse effects of mercury on kidney health. Longitudinal cohort studies are needed to assess the long-term renal effects of chronic low-level mercury exposure and to identify early biomarkers of nephrotoxicity. In addition, experimental studies using animal models can help elucidate the underlying mechanisms of mercury-induced nephrotoxicity and evaluate the efficacy of novel therapeutic agents in mitigating renal damage.

Conclusion

Mercury exposure is associated with nephrotoxicity, as evidenced by epidemiological studies, mechanistic research, and clinical observations. The nephrotoxic effects of mercury are mediated by oxidative stress, inflammation, mitochondrial dysfunction, and direct cellular damage. Preventing mercury exposure and implementing early intervention strategies are essential for mitigating the burden of mercury-induced nephrotoxicity and preserving kidney health. Future research should focus on clarifying dose-response relationships, identifying susceptible populations, and exploring interventions to prevent or ameliorate the adverse effects of mercury on kidney function.

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