#3919 Klotho protein associated with worse cognitive function in chronic kidney disease patients

Abstract Background and Aims Cognitive decline is a major concern among patients with chronic kidney disease (CKD), significantly impacting quality of life and increasing mortality. Despite the relevance, its underlying mechanisms remain unclear. Klotho, a protein with neuroprotective properties primarily produced by the kidneys, is known to have reduced levels in individuals with CKD. This study explores the association between Klotho levels and cognitive performance in CKD patients. Method Cross-sectional study including adults with CKD assessed at a medical center in Northeast Brazil. Clinical and laboratory data were obtained, including Klotho, FGF23, VCAM-1, ANG1, and ANG2 biomarkers. Cognitive function was assessed through the application of the following neuropsychological tests: Rey's Auditory-Verbal Learning Test (RAVLT), Five Digit Test (FDT), Corsi's Cube Task (CCT), Stroop Test, Trial Making Test (TMT) and Phonemic and Semantic fluency tasks. Patients were classified according to their eGFR into 3 groups: control group, with no CKD; mild CKD (group A), eGFR ≥ 45 mL/min/ 1.73 m2; moderate/severe CKD (group B), eGFR < 45 mL/min/1,73 m2. Results A total of 52 patients were included in the study, mostly female (59.6%), with a mean age of 53.3 ± 15.4 years. Group A had 29 (55.7%) patients, group B had 11 (21.1%), and the control group had 12 (23.0%). When compared to control, groups A and B had significantly lower Klotho levels (0.2 [0.17–1.46] and 0.38 [0.17–3.18] vs. 1.61 [0.28–2.03] ng/mL, P = 0.01), higher FGF23 (0.7 [0–2.3] and 4 [0.5–11.6] vs. 0.2 [0–4] ng/mL, P = 0.05) and VCAM-1 levels (726 ± 275 and 920 ± 162 vs. 604 ± 180 ng/mL, P = 0.01). Klotho levels were associated with a deficit in RAVLT's learning (0.19 [0.15–0.88] vs. 1.54 [0.2–2.22], P = 0.02) and retention index (0.2 [0.18–0.43] vs. 0.33 [0.17–1.79], P = 0.52); and FDT's time to count (0.19 [0.15–0.43] vs. 1.74 [0.2–2.27], P = 0.01), to choose (0.21 [0.15–1.53] vs. 1.59 [0.19–2.22], P < 0.01), to shift (0.2 [0.15–1.49] vs. 1.78 [ 0.21–3.18], P < 0.01), and inhibition time (0.19 [ 0.13–1.46] vs. 1.09 [0.19–2.23], P < 0.01]. Conclusion Lower Klotho levels were associated with more advanced CKD and worse cognitive performance in patients without prior cerebrovascular diseases. These findings highlight the potential use of Klotho as an early biomarker of cognitive deficit among CKD patients.