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Chronic Kidney disease of unknown cause (CKDu) is a leading cause of premature death in Nicaragua, primarily affecting young men in rural communities. Patients often suffer from acute kidney failure with no known cause, leaving the doctors clueless about prevention and treatment. Researchers have identified associations with CKDu, including exposure to agrichemicals, infectious disease, and working in sugarcane fields.
Using prospective longitudinal cohort data from Nicaragua, I estimated a multivariate three-state Hidden Markov model and a Markov model to examine the potential time-varying environmental, occupational, and lifestyle exposures that could impact kidney health and transition from healthy to unhealthy. The states in the Markov models reflect kidney health: healthy, borderline, and unhealthy. However, since the state of kidney health is unknown, we can model the distribution of the eGFR (estimated glomerular filtration rate), a measure of kidney function, and its annual rate of change. Multiple imputation is employed to impute the eGFR rate of change at baseline to estimate the state of kidney health at the start of the study. In addition to the data analysis, we ran a simulation study to analyze computation issues of the Hidden Markov model from the msm package.
The Hidden Markov model suggests that smoking regularly and sugarcane work maintain borderline kidney health. Drinking alcohol regularly both maintains and initiates transition to borderline and unhealthy kidney health. The Markov model also identified smoking regularly, sugarcane work, and drinking alcohol regularly as significant exposures that initiate the transition to unhealthy kidney state. The simulation study shows that rare exposures are responsible for some convergence issues even with larger sample size and longer study duration.
Women are less likely to be impacted by CKDu but social and cultural factors make it challenging to disentangle associations with sex from other environmental and occupational exposures. Future research is needed to further whether these exposures are proxies to the true underlying causes. Explaining the initiation of CKDu has great public health impacts. It can lead to developing prevention strategies and treatments, improving the understanding and awareness of this epidemic.
Zhang, Yixuan, "Unravelling the Mystery of Chronic Kidney Disease of Unknown Cause" (2023). Mathematics, Statistics, and Computer Science Honors Projects. 78.
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