Detecting early loss of kidney function in a Sri Lankan cohort study of working age adults

Background: Chronic kidney disease of undetermined cause (CKDu) is a form of kidney disease not associated with traditional risk factors such as hypertension, diabetes or heavy proteinuria. 11.2% of men and 3.7% of women demonstrated low eGFR (a surrogate for CKDu) in the absence of these risk factors in a 2017 cross-sectional population-representative survey of adults in North Central Province, Sri Lanka. We therefore established a longitudinal cohort to track changes in kidney function over time and to identify risk factors for developing poor kidney health. Methods: This was a 6-year study of adults aged 20-60 years conducted in Puhudivula, Anuradhapura district. Exclusions included evidence of diabetes, hypertension or pre-existing CKD. We fitted hidden Markov models (HMMs) to estimate underlying state of kidney health and examine risk factors associated with departure from a healthy state. Results: We identified four kidney health trajectories in the population (n=425): always healthy (74%); unhealthy throughout (5%); transition from health to unhealthy (10%); and reversion from unhealthy to healthy (11%). Using smokeless tobacco, including betel quid, was associated with being in an unhealthy category (2.29 [1.17, 4.49]). Lagged exposure to smoking (2.26 [1.25, 4.10]), smokeless tobacco (1.98 [1.13, 3.48]) and weedkiller (1.72 [1.15, 2.59]) were associated with the point of transition to an unhealthy state. Conclusions: Almost a quarter of working age adults in this population demonstrated eGFR changes consistent with poor kidney health. Smokeless tobacco use was associated with both pre-existing evidence of poor kidney health and transitioning to the unhealthy category.