Chronic renal insufficiency does not induce behavioral and cognitive alteration in rats

In humans, chronic kidney disease (CKD) is associated with cognitive decline, increase in anxiety, or depression. The underlying mechanisms of these changes remain unclear. The aim of this study was to elucidate whether and how experimentally induced long-term CKD affects cognitive functions in rats. Thirty male Wistar rats underwent 5/6 nephrectomy (5/6 Nx), an established model of CKD, or sham surgery. Development of CKD was monitored using biochemical analyses and confirmed by renal histology. Behavioral tests of anxiety, depression and spatial behavior were performed before, and at 3 and 9 months after the surgery. CKD in 5/6 Nx rats was characterized by significant decrease of renal function, e.g., glomerular filtration rate, and progressive glomerulosclerosis, tubular atrophy, and interstitial fibrosis; and increased plasma uremic toxins. Mortality was higher in 5/6 Nx rats in comparison with controls. Compared to control group, the surviving 5/6 Nx rats presented similar general locomotor activity, depression traits, and spatial abilities (p=0.43, p=0.84, p=0.71, respectively). At 9 months, lower anxiety in the light-dark box test was observed in 5/6 Nx rats if compared with the control group (p=0.02). Despite the development of progressive CKD in 5/6 Nx rats, no expected behavioral changes were observed. Further experimental studies associating behavioral responses to severity of CKD are definitely needed to confirm the solely psychosocial aspect background of CKD-associated cognitive impairment in humans.