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Life sciences · Journal article
BMC Nephrology · October 1, 2026
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Over the past two decades, chronic kidney disease (CKD) of unknown aetiology (CKDu) has emerged as a significant public health challenge in several tropical, low- and middle-income countries. Despite rising rates of CKD that are not fully explained by traditional risk factors and accumulating evidence linking environmental exposures to CKD, CKDu remains largely unexamined in high-income settings such as the United States (US). This study aimed to examine the prevalence and risk factors of CKDu among US adults, using nationally representative data from NHANES. We analysed data from 38,970 adults aged 20–80 years who participated in the 2003–2018 NHANES cycles. Estimated glomerular filtration rate (eGFR) was calculated using the Chronic Kidney Disease–Epidemiology Collaboration equation. CKD was defined as eGFR < 60 mL/min/1.73 m². Suspected CKDu was defined as CKD in the absence of diabetes, hypertension, or heavy proteinuria (albumin-to-creatinine ratio ≥ 300 mg/g). Weighted logistic regression was used to assess associations between demographic, clinical, and environmental factors and CKDu. Overall, 3,211 adults had CKD (weighted prevalence 6.44%, 95% CI: 6.08–6.83), with suspected CKDu accounting for 16.9% of cases. In a subgroup of 18,742 adults without diabetes or hypertension, 440 had CKD (2.05%, 95% CI: 1.80–2.35). After further excluding individuals with heavy proteinuria, 426 of 18,647 participants met criteria for suspected CKDu (2.03%, 95% CI: 1.77–2.33). Older age, female sex, race/ethnicity, smoking, higher serum uric acid, elevated serum osmolality, and increased blood cadmium and lead levels were independently associated with suspected CKDu. Suspected CKDu affects approximately 2% of US adults and it was associated with older age, female sex, race/ethnicity, smoking, serum uric acid, serum osmolality, and blood cadmium and lead levels. These findings underscore an under-recognized burden in the US and highlight the need to further investigate environmental and occupational risk factors contributing to CKDu in high-income settings.