Analysis of brain iron deposition in an in vivo model of pediatric autosomal dominant polycystic kidney disease

Abstract Polycystic kidney disease (PKD) represents one form of chronic kidney disease (CKD) affecting the pediatric population. CKD in early life has been associated with neurocognitive deficits and disturbances in iron metabolism. Excess iron accumulation may exacerbate inflammatory and oxidative stress pathways linked to neurocognitive decline in CKD. No animal studies have yet investigated brain iron metabolism in early-life CKD, including PKD, or confirmed these findings through histological analysis. Utilizing a conditional Pkd2 knockout mouse, we investigated the effect of kidney disease on early brain development and brain iron deposition through neuroimaging and histology. By postnatal day 19, PKD mice had significantly increased blood urea nitrogen (BUN, mean = 141 mg/dL ± 0.6, p < 0.01) and cyst burden (mean = 83.1% ± 5.4, p < 0.01). Brain volumetrics did not differ longitudinally between groups; however, PKD mice had significantly shorter T2* relaxation times across multiple brain regions (total brain, gray and white matter, cerebral cortex, cerebellum, brainstem, hippocampus, and globus pallidus), indicating increased iron deposition. Perl’s Prussian blue staining confirmed increased iron in the cerebral cortex of PKD mice. These findings extend prior human CKD neuroimaging data and provide a platform to investigate mechanisms of iron-mediated neuroinjury in early-life CKD