Iron deficiency and cognitive functioning in kidney transplant recipients: findings of the TransplantLines biobank and cohort study

Abstract

Background: Neurocognitive impairment is common in kidney transplant recipients (KTRs). Adequate brain functioning requires energy and neurotransmitter activity, for which iron is essential. We aimed to investigate iron deficiency (ID) as a potentially modifiable risk factor for cognitive impairment in KTRs.

Methods: We analyzed stable KTRs participating in the TransplantLines Biobank and Cohort study. Participants underwent neuropsychological tests for memory, mental speed, and attention and executive functioning. ID was defined as ferritin <100 µg/mL or 100-299 µg/mL with transferrin saturation (TSAT) ≤20%. Associations between iron status and norm scores of neurocognitive outcomes, corrected for age, sex and education, were assessed using multivariable linear regression analyses adjusted for potential confounders including hemoglobin.

Results: We included 166 KTRs [median (IQR) age 57 (45-65) years, 59% male, estimated glomerular filtration rate 51±18 mL/min/1.73 m2]. Time since transplantation was 5.8 (1.0-12.0) years. Prevalence of ID was 65%. ID was independently associated with lower scores for mental speed (std.β = -0.19, P = .02) and attention and executive functioning (std.β = -0.19, P = .02), and tended to be associated with worse memory (std.β = -0.16, P = .07). Lower plasma ferritin levels were associated with worse memory (std.β = 0.23, P = .007), mental speed (std.β = 0.34, P < .001), and attention and executive functioning (std.β = 0.30, P = .001). Lower TSAT was associated with worse memory (std.β = 0.19, P = .04) and mental speed (std.β = 0.27, P = .003), and tended to be associated with worse attention and executive functioning (std.β = 0.16, P = .08).

Conclusions: Iron-deficient KTRs performed worse on neurocognitive tasks measuring memory, mental speed, and attention and executive functioning. These findings set the stage for prospective studies addressing whether ID correction restores cognitive function after kidney transplantation.

Keywords: cognitive function; iron; kidney transplant recipients.