Biomarker evidence of neurodegeneration in chronic kidney disease, in a general population

Abstract Background Progressive decline in cognition and renal function are both related to ageing. The estimated global prevalence of dementia was 55 million people in 2019, a number expected to increase to 139 million by 2050. Furthermore, chronic kidney disease (CKD) is the second fastest growing cause of death globally. Few studies have examined the link between these conditions. In this study, we examine CKD and estimated glomerular filtration rate (eGFR) in relation to plasma neurofilament light protein (P‐NfL) and volumetric magnetic resonance imaging (MRI) measures of Alzheimer’s disease‐specific and general neurodegeneration. Method Using a cross‐sectional design, 744 participants from the Gothenburg H70 Birth cohort 1944 study, conducted in 2014‐2016, underwent MRI examination and blood draws. Plasma NfL concentration was measured using a Single molecule array (Simoa) assay. eGFR was calculated from creatinine and used for CKD diagnosis. CKD was defined as an estimated glomerular filtration rate below 60 mL/min/1.73 m 2 . Measurements of biomarker evidence of neurodegeneration were compared between participants with and without CKD. Correlations were also performed against eGFR. A logistic regression model adjusting for known risk factors for CKD was performed. Result P‐NfL was significantly higher in participants with CKD (p<0.001). No difference was seen in any MRI variables. Only P‐NfL correlated with eGFR (R = ‐0.25, p<0.001), and there was a significant correlation both in participants with and without CKD (R = ‐0.44, p<0.001 and R = ‐0.18, p<0.001 respectively). Furthermore, in a logistic regression model, P‐NfL was a significant predictor of CKD independent of known risk factors including age, sex, education, smoking, hypertension, diabetes, BMI, fasting glucose, LDL‐cholesterol, CRP, and homocysteine (OR (CI); 3.231 (1.743: 5.990), p<0.001). Conclusion Our observations suggest that neurodegeneration measured as P‐NfL is a predictor of CKD, independent of hypertension and diabetes. The origin of NfL, and the potential influence on the utilization of P‐NfL as a marker of neurodegeneration in individuals with CKD, should be assessed in future studies.