TY - JOUR
T1 - Risk factors for neurocognitive impairment and the relation with structural brain abnormality in children and young adults with severe chronic kidney disease
AU - Lijdsman, Sophie
AU - Oostrom, Kim J
AU - van Sandwijk, Marit S
AU - Bouts, Antonia H
AU - van Hoeck, Koen
AU - de Jong, Huib
AU - Oosterlaan, Jaap
AU - Bemelman, Frederike J
AU - Königs, Marsh
AU - Groothoff, Jaap W
N1 - Funding Information: This study was partly funded by the Dutch Kidney Foundation. Publisher Copyright: © 2022, The Author(s).
PY - 2022/11/2
Y1 - 2022/11/2
N2 - Background: Severe chronic kidney disease (CKD) in children and young adults has shown to be associated with abnormal brain development, which may contribute to neurocognitive impairments. We aimed to investigate risk factors for neurocognitive impairment and investigate the relation with structural brain abnormalities in young severe CKD patients. Methods: This cross-sectional study includes 28 patients with severe CKD (eGFR < 30), aged 8–30 years (median 18.5 years), on different treatment modalities (pre-dialysis [n = 8], dialysis [n = 8], transplanted [n = 12]). We assessed neurocognitive functioning using a comprehensive test battery and brain structure by magnetic resonance imaging metrics of brain volume and white matter integrity (fractional anisotropy [FA] and mean diffusivity [MD] measured with diffusion tensor imaging). Multivariate regression and mediation analyses were performed between clinical CKD parameters, brain structure, and neurocognitive outcome. Results: A combination of risk factors (e.g., longer time since kidney transplantation, longer dialysis duration and late CKD onset) was significantly associated with lower intelligence and/or worse processing speed and working memory. Lower FA in a cluster of white matter tracts was associated with lower intelligence and mediated the relation between clinical risk factors and lower intelligence. Conclusions: Young severe CKD patients with a prolonged duration of kidney replacement therapy, either dialysis or transplantation are at particular risk for impairments in intelligence, processing speed, and working memory. Disrupted white matter integrity may importantly contribute to these neurocognitive impairments. Prospective, longitudinal studies are needed to elucidate the mechanisms involved in CKD and treatment that affect white matter integrity and neurocognitive outcome in young patients. Graphical abstract: [Figure not available: see fulltext.].
AB - Background: Severe chronic kidney disease (CKD) in children and young adults has shown to be associated with abnormal brain development, which may contribute to neurocognitive impairments. We aimed to investigate risk factors for neurocognitive impairment and investigate the relation with structural brain abnormalities in young severe CKD patients. Methods: This cross-sectional study includes 28 patients with severe CKD (eGFR < 30), aged 8–30 years (median 18.5 years), on different treatment modalities (pre-dialysis [n = 8], dialysis [n = 8], transplanted [n = 12]). We assessed neurocognitive functioning using a comprehensive test battery and brain structure by magnetic resonance imaging metrics of brain volume and white matter integrity (fractional anisotropy [FA] and mean diffusivity [MD] measured with diffusion tensor imaging). Multivariate regression and mediation analyses were performed between clinical CKD parameters, brain structure, and neurocognitive outcome. Results: A combination of risk factors (e.g., longer time since kidney transplantation, longer dialysis duration and late CKD onset) was significantly associated with lower intelligence and/or worse processing speed and working memory. Lower FA in a cluster of white matter tracts was associated with lower intelligence and mediated the relation between clinical risk factors and lower intelligence. Conclusions: Young severe CKD patients with a prolonged duration of kidney replacement therapy, either dialysis or transplantation are at particular risk for impairments in intelligence, processing speed, and working memory. Disrupted white matter integrity may importantly contribute to these neurocognitive impairments. Prospective, longitudinal studies are needed to elucidate the mechanisms involved in CKD and treatment that affect white matter integrity and neurocognitive outcome in young patients. Graphical abstract: [Figure not available: see fulltext.].
KW - Brain structure
KW - Cognition
KW - Diffusion tensor imaging
KW - Executive functioning
KW - Kidney replacement therapy
UR - http://www.scopus.com/inward/record.url?scp=85141140767&partnerID=8YFLogxK
U2 - https://doi.org/10.1007/s00467-022-05781-1
DO - https://doi.org/10.1007/s00467-022-05781-1
M3 - Article
C2 - 36322259
SN - 0931-041X
JO - Pediatric nephrology (Berlin, Germany)
JF - Pediatric nephrology (Berlin, Germany)
ER -