Heavy metal association with chronic kidney disease of unknown cause in central India: results from a case-control study Original paper
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Metals
Metals
Heavy metals play a significant and multifaceted role in the pathogenicity of microbial species.
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Dr. Umar
Read MoreClinical Pharmacist and Clinical Pharmacy Master’s candidate focused on antibiotic stewardship, AI-driven pharmacy practice, and research that strengthens safe and effective medication use. Experience spans digital health research with Bloomsbury Health (London), pharmacovigilance in patient support programs, and behavioral approaches to mental health care. Published work includes studies on antibiotic use and awareness, AI applications in medicine, postpartum depression management, and patient safety reporting. Developer of an AI-based clinical decision support system designed to enhance antimicrobial stewardship and optimize therapeutic outcomes.
Microbiome Signatures identifies and validates condition-specific microbiome shifts and interventions to accelerate clinical translation. Our multidisciplinary team supports clinicians, researchers, and innovators in turning microbiome science into actionable medicine.
Clinical Pharmacist and Clinical Pharmacy Master’s candidate focused on antibiotic stewardship, AI-driven pharmacy practice, and research that strengthens safe and effective medication use. Experience spans digital health research with Bloomsbury Health (London), pharmacovigilance in patient support programs, and behavioral approaches to mental health care. Published work includes studies on antibiotic use and awareness, AI applications in medicine, postpartum depression management, and patient safety reporting. Developer of an AI-based clinical decision support system designed to enhance antimicrobial stewardship and optimize therapeutic outcomes.
What was studied?
This study investigated heavy metal association with CKDu, focusing on whether exposure to arsenic (As), cadmium (Cd), lead (Pb), and chromium (Cr) differs in adults with chronic kidney disease of unknown cause (CKDu) compared with those who have traditional chronic kidney disease (CKD) or normal renal function. Conducted at a tertiary hospital in central India, the research directly measured blood and urine metal concentrations using inductively coupled plasma optical emission spectrometry, enabling a more reliable assessment of systemic metal burden than urine-only measurements. The investigators also evaluated environmental and behavioral exposures, including pesticide use and drinking water sources, to identify potential pathways contributing to CKDu. Visual data reinforce these findings through box plots showing markedly elevated blood arsenic in CKDu compared with CKD and healthy controls, alongside consistently higher cadmium, lead, and chromium levels in all renal dysfunction groups.
Who was studied?
Adults aged 18–70 years were enrolled between 2019 and 2022, comprising 60 CKDu patients, 62 CKD controls, and 54 healthy controls, all from central India. CKDu participants met strict diagnostic criteria excluding diabetes, longstanding hypertension, glomerular disease, obstruction, or kidney stones, with proteinuria below 2 g/g and eGFR <60 ml min 1.73 m² for at least three months. ckd controls had similar renal impairment but with identifiable etiologies and greater proteinuria. healthy were relatives of patients, confirmed to have normal egfr (>90 mL/min/1.73 m²), normal albumin-creatinine ratios, and no comorbidities. Groups were comparable in many behavioral variables, but CKDu patients reported disproportionately higher pesticide exposure and surface-water consumption.
Most important findings
The clearest signal was the disproportionately high blood arsenic in CKDu (median 91.97 µg/L), significantly exceeding levels in CKD (4.5 µg/L) and healthy controls (39.01 µg/L). Regression modeling (page 10) confirmed blood arsenic as independently associated with CKDu after accounting for age and sex. Urinary arsenic, by contrast, was highest in healthy participants—a pattern likely explained by reduced urinary excretion in CKD and CKDu due to lower GFR. Cadmium, lead, and chromium were consistently higher in both CKDu and CKD groups relative to healthy controls, with CKD generally showing the largest elevations. Urinary Cd, Pb, and Cr were undetectable in most healthy subjects. Strong correlations between these metals in both blood and urine (page 6) imply shared environmental co-exposures. Surface water use was another strong predictor of CKDu (OR ~3.18).
| Heavy Metal | CKDu vs CKD | CKDu vs Healthy | Key Note |
|---|---|---|---|
| Arsenic | Much higher | Higher | Only metal independently linked to CKDu |
| Cadmium | Slightly lower | Higher | Weak CKD-specific trend |
| Lead | Lower | Higher | Significant overall burden in kidney disease |
| Chromium | Slightly lower | Higher | Strong co-exposure correlations |
Key implications
This work identifies arsenic as a key environmental factor associated with CKDu in central India, implicating pesticide contamination and surface water as potential exposure routes. The broader heavy-metal burden in CKD and CKDu underscores systemic environmental toxicity as a shared contributor to renal injury. These findings highlight the importance of integrating environmental health assessment—including metal exposure history and water-source evaluation—into clinical evaluation of CKDu, and they offer mechanistic links to known microbial dysbiosis pathways relevant for microbiome-signature databases.
Citation
Atlani M, Kumar A, Ahirwar R, et al. Heavy metal association with chronic kidney disease of unknown cause in central India: results from a case-control study.BMC Nephrology. 2024;25:120. doi:10.1186/s12882-024-03564-4
Arsenic can disrupt both human health and microbial ecosystems. Its impact on the gut microbiome can lead to dysbiosis, which has been linked to increased disease susceptibility and antimicrobial resistance. Arsenic's ability to interfere with cellular processes, especially through its interaction with essential metals like phosphate and zinc, exacerbates these effects.
Cadmium (Cd) is a highly toxic heavy metal commonly found in industrial, agricultural, and environmental settings. Exposure to cadmium can occur through contaminated water, food, soil, and air, and it has been linked to a variety of health issues, including kidney damage, osteoporosis, and cancer. In agriculture, cadmium is often present in phosphate fertilizers and can accumulate in plants, entering the food chain. Its toxicity to living organisms makes cadmium a subject of regulatory concern worldwide, particularly in industrial waste disposal and environmental monitoring.
Lead exposure has a profound effect on the microbiome, disrupting microbial diversity, immune responses, and contributing to the development of antimicrobial resistance (AMR). Understanding how Pb interacts with microbial communities and impacts host-pathogen dynamics is essential for clinicians to mitigate long-term health risks and improve treatment strategies.
Dysbiosis in chronic kidney disease (CKD) reflects a shift toward reduced beneficial taxa and increased pathogenic, uremic toxin-producing species, driven by a bidirectional interaction in which the uremic environment disrupts microbial composition and dysbiotic metabolites accelerate renal deterioration.