Consequences of chronic kidney disease on neurodegenerative processes in 5/6Nx rat models

Recent findings reveal an increased risk of cognitive impairment in individuals with chronic kidney disease (CKD). To better understand the interactions between CKD and neurodegenerative diseases, twenty Sprague Dawley rats underwent either 5/6 Nephrectomy (Nx) or Sham operation through random allocation at two different time onsets: six or twelve weeks of age. Twenty-four weeks after surgery, renal function and histopathological parameters were evaluated. The 5/6Nx rats showed increased blood creatinine and urea levels as well as kidney inflammation at both time onsets. This renal damage appears to translate into brain damage, as assessed by markers of neuroinflammation (such as microglia and astrocytic activation) and perturbations in the blood-brain barrier (such as modified levels of tight junction proteins, perivascular astrocytes and the emergence of microhaemorrhages), in both models studied. Importantly, the impact on the brain differed based on the age of nephrectomy. To gain further insights into the underlying mechanisms linking renal impairment to neurodegenerative diseases, plasma analyses of inflammatory proteins and specific proteins like Reg1α—previously associated with chronic inflammatory processes and identified in patients with Alzheimer's disease and renal dysfunction—were conducted. Additionally, an assessment of uremic toxins capable of breaching the blood-brain barrier was carried out. This comprehensive approach aims to elucidate the intricate connections between renal dysfunction and the onset of neurodegenerative processes.