A 6-year longitudinal cohort study of 425 working-age adults (20–60) in Anuradhapura district, Sri Lanka — excluding those with diabetes, hypertension, or pre-existing CKD — identified four distinct kidney health trajectories using hidden Markov models. Roughly 26% of participants showed eGFR changes consistent with poor kidney health. Smokeless tobacco use, including betel quid, carried a 2.29-fold odds of being in an unhealthy kidney state (95% CI: 1.17–4.49), while lagged smoking exposure (OR 2.26), smokeless tobacco (OR 1.98), and weedkiller exposure (OR 1.72) were each independently associated with transitioning to kidney dysfunction.
Chronic kidney disease of undetermined cause (CKDu) has devastated agricultural communities across South and Central Asia and Central America for decades, yet its etiology remains contested — with heat stress, heavy metals, agrochemicals, and herbal nephrotoxins all implicated. This study is notable for its longitudinal design and use of probabilistic state-transition modeling, which captures reversibility — a clinically underappreciated feature, as 11% of participants reverted to healthy states. The weedkiller association adds to a growing body of evidence implicating agrochemical nephrotoxicity, though the specific agent is unnamed here. Critical limitations include the small cohort (n=425), single geographic cluster, and reliance on eGFR as a surrogate rather than biopsy-confirmed CKD staging. As a preprint not yet peer-reviewed, these findings should be treated as preliminary. Still, the tobacco-kidney link in a non-traditional-risk-factor population represents a potentially actionable public health lever in affected agricultural regions.