LAUSR

Chronic kidney disease (CKD) is associated with an increased risk of cognitive impairment. In several models of CKD in rodents, we highlighted that CKD was associated with cognitive impairment and increased blood-brain barrier (BBB) permeability, quantified using 99mTc-DTPA scintigraphy imaging (SPECT/CT). BBB permeability was both correlated with cognitive impairment and with indoxyl sulfate (IS) levels. Inactivation of Aryl Hydrocarbon Receptor (AhR), receptor of the IS, protected the CKD mouse from the IS-induced BBB permeability. The objective of the BREIN study is to confirm the existence of an increased BBB permeability in humans with CKD. The prospective cohort study BREIN (NCT04328415) prospectively included patients with end-stage kidney disease (ESKD), and healthy volunteers (Ctrl) matched in age (±5 years), gender, and educational level to a patient. In patients and volunteers, BBB permeability was quantified by brain 99mTc-DTPA SPECT/CT performed by a senior nuclear physician and as percentage of injected activity (%IA). A battery of neuro-cognitive tests was performed, serum uremic toxins accumulation and AhR activation were assessed in all participants. 15 ESKD patients and 14 healthy volunteers were included. In ESKD patients had higher BBB permeability compared to controls: 0.29 0.07 vs. 0.14 0.06%IA, p < 0.0001. ESKD patients displayed lower MoCA score: 22.0 ± 5.0 vs. 27.3 ± 2.8, p = 0.008, impaired short-term memory (doors test): 12.5 ± 3.4 vs. 16.5 ± 3.4, p = 0.009, higher Beck depression score 8.1 ± 9.1 vs. 2.7 ± 3.4, p = 0.046, and slightly more daily cognitive complaints: 42.5 ± 29.3 vs. 29.8 ± 14.0 p = 0.153. ESKD patients displayed higher IS levels (2.8 ± 2.3 mmol/L vs. 0.9 ± 0.7 mmol/L, p = 0.006) and AhR activation (37.5 ± 17.8% vs. 24.7 ± 10.4%, p = 0.027). In ESKD patients, no significant correlation was found between BBB permeability and scores in cognitive tests, or serum uremic toxins levels. This study confirms that ESKD patients display an increased BBB permeability compared to matched healthy volunteers, as well as cognitive and impairment. Association with uremic toxins and cognitive impairment needs to be assessed in larger cohorts.