Association of autosomal dominant polycystic kidney disease with cerebral small vessel disease

Abstract

Cilia dysfunction in autosomal-dominant polycystic kidney disease (ADPKD) may impair the integrity of glymphatic system and be implicated in the progression of cerebral small vessel disease (SVD), although the link between the two diseases has not been investigated. We evaluated the association of ADPKD pathology with SVD pattern and severity. Overall, 304 individuals in an ADPKD (chronic kidney disease stage ≤4 and age ≥50 years) cohort and their age, sex, and estimated glomerular filtration rate (eGFR)-matched controls were retrospectively included. ADPKD severity was classified into 1 A-B, 1 C, and 1 D-E, according to age and height-adjusted total kidney volume. SVD parameters included white-matter hyperintensity (WMH) severity scale, enlarged perivascular space (ePVS) score, and degree of lacunes or cerebral microbleeds (CMBs). After adjustments for age, sex, eGFR, and cerebrovascular risk factor parameters, ADPKD was associated with higher ePVS scores ( P < 0.001), but not with the WMH severity or degree of lacunes or CMBs. In the ADPKD subgroup, higher ADPKD severity class was associated with higher ePVS scores ( P < 0.001), WMH severity ( P = 0.003), and degree of lacunes ( P = 0.002). ADPKD associated cilia dysfunction may induce chronic cerebral glymphatic system dysfunction, which may contribute to the specific progression of ePVS compared with other SVD markers.

Covert vascular brain injury in chronic kidney disease

“…Among patients with CKD, black patients had 2-fold higher odds of severe PVSs in the basal ganglia and centrum semiovale compared to whites and other racial groups ( 59 ). In a single hospital-based study for 304 patients with autosomal-dominant polycystic kidney disease (ADPKD), ADPKD was associated with a higher degree of PVSs, but not with the WMHs severity, lacunes, or CMBs, compared to age-, sex-, and eGFR-matched controls, suggesting that ADPKD-associated cilia dysfunction may induce chronic cerebral glymphatic system dysfunction ( 60 ).…”

Diffusion tensor imaging of the brain white matter microstructure in patients with chronic kidney disease and its correlation with cognition

“…Patients with CKD are at a higher risk of cognitive impairment, and older patients on dialysis have the highest absolute risk ( 4 ). Neuroimaging studies have shown that patients with CKD tend to have structural and functional changes, such as white matter hyperintensities, asymptomatic stroke, and brain atrophy ( 5 , 6 ). The white matter of the brain acts as a relay station for the central nervous system and is responsible for the exchange of information and communication between different gray matter areas ( 7 , 8 ).…”