Clinical reports indicate a bidirectional relationship between mental illness and chronic systemic disease. Kidney injury and inflammation have been linked to brain dysfunction and alterations in learning and memory, as well as development of anxiety and depression, however, the underlying neurophysiological mechanisms remain elusive. In the current study, we investigated whether a chronic kidney disease (CKD) state is suffcient to produce deficits in rodent stress behaviors using a mild or severe model of CKD. Male rats were exposed to either 21 days of 0.75% adenine diet (AD) (model of mild CKD), or a combination of AD with unilateral nephrectomy (AD/Unx), prior to the start of AD (model of severe CKD). Control rats received sham surgery and remained on normal diet/chow throughout the experimental paradigm. CKD development in the rat models was determined by a significant increase in serum creatinine used as index for kidney function. Behavioral testing results demonstrate that mild CKD model, especially in combination with unilateral nephrectomy (severe CKD model), is accompanied by anhedonia (i.e., decreased sucrose preference) and increased anxiety-like behaviors in the novelty-suppressed feeding, open field and elevated plus maze tests. These findings suggest that impairment of kidney functionality is suffcient to increase behavioral emotionality in rodents consistent with development of depressive-like and anxiogenic phenotype. Ongoing studies are focused on identifying neurophysiological mechanisms linking renal disease with neurological abnormalities. Furthering our understanding of these mechanisms may aid in the development of improved treatments and prevention strategies for management of mental health comorbidities associated with kidney disease. Des Moines University IOER Research & Grant Award. This is the full abstract presented at the American Physiology Summit 2024 meeting and is only available in HTML format. There are no additional versions or additional content available for this abstract. Physiology was not involved in the peer review process.