title: Factors Responsible for Plasma β-Amyloid Accumulation in Chronic Kidney Disease.
abstract: Disturbed brain-to-blood elimination of β-amyloid (Aβ) promotes cerebral Aβ accumulation in Alzheimer's disease. Considering that the kidneys are involved in Aβ elimination from the blood, we evaluated how chronic kidney disease (CKD) affects plasma Aβ. In 106 CKD patients stages 3-5 (including 19 patients on hemodialysis and 15 kidney recipients), 53 control subjects with comparable vascular risk profile and 10 kidney donors, plasma Aβ was determined using electrochemiluminescence immunoassay and gel electrophoresis followed by Western blotting. Plasma Aβ increased with CKD stage (control = 182.98 ± 76.73 pg/ml; CKD3A = 248.34 ± 103.77 pg/ml; CKD3B = 259.25 ± 97.74 pg/ml; CKD4 = 489.16 ± 154.16 pg/ml; CKD5 = 721.19 ± 291.69 pg/ml) and was not influenced by hemodialysis (CKD5D = 697.97 ± 265.91 pg/ml). Renal transplantation reduced plasma Aβ (332.57 ± 162.82 pg/ml), whereas kidney donation increased it (251.51 ± 34.34 pg/ml). Gel electrophoresis confirmed stage-dependent elevation namely of Aβ1-40, the most abundant Aβ peptide. In a multivariable regression including age, sex, estimated glomerular filtration rate (eGFR), potassium, hemoglobin, urine urea, and urine total protein, the factors eGFR (β = -0.42, p < 0.001), hemoglobin (β = -0.17, p = 0.020), and urine protein (β = 0.26, p = 0.008) were associated with plasma Aβ. In a regression including age, sex, eGFR, potassium, hemoglobin and the vascular risk factors systolic blood pressure, smoking, LDL, HDL, HbA1c, body mass index, brain-derived natriuretic peptide and fibrinogen, the factors eGFR (β = -0.53, p < 0.001), body mass index (β = -0.17, p = 0.022), and fibrinogen (β = 0.18, p = 0.024) were associated with plasma Aβ. Our results demonstrate a stage-dependent plasma Aβ increase that is augmented by loss of glomerulotubular integrity, low body weight, and inflammation, demonstrating a multifaceted role of renal dysfunction in Aβ retention.
authors.affiliation: Department of Neurology, University Hospital Essen, Hufelandstraße 55, 45122, Essen, Germany.
authors.forename: Janine
authors.initials: J
authors.lastname: Gronewold
authors.affiliation: Department of Psychiatry and Psychotherapy, LVR-Hospital Essen, Faculty of Medicine, University of Duisburg-Essen, Virchowstraße 174, 45147, Essen, Germany.|Department of Psychiatry and Psychotherapy, University Medical Center Goettingen, von-Siebold-Straße 5, Goettingen, Germany.
authors.forename: Hans-Wolfgang
authors.initials: HW
authors.lastname: Klafki
authors.affiliation: Department of Neurology, University Hospital Essen, Hufelandstraße 55, 45122, Essen, Germany.
authors.forename: Enrico
authors.initials: E
authors.lastname: Baldelli
authors.affiliation: Department of Neurology, University Hospital Essen, Hufelandstraße 55, 45122, Essen, Germany.
authors.forename: Britta
authors.initials: B
authors.lastname: Kaltwasser
authors.affiliation: Department of Neurology, University Hospital Essen, Hufelandstraße 55, 45122, Essen, Germany.
authors.forename: Ulla K
authors.initials: UK
authors.lastname: Seidel
authors.affiliation: Department of Neurology, University Hospital Essen, Hufelandstraße 55, 45122, Essen, Germany.
authors.forename: Olga
authors.initials: O
authors.lastname: Todica
authors.affiliation: Department of Nephrology, University Hospital Essen, Hufelandstraße 55, 45122, Essen, Germany.
authors.forename: Michaela
authors.initials: M
authors.lastname: Volsek
authors.affiliation: Department of Psychiatry and Psychotherapy, LVR-Hospital Essen, Faculty of Medicine, University of Duisburg-Essen, Virchowstraße 174, 45147, Essen, Germany.
authors.forename: Ute
authors.initials: U
authors.lastname: Haußmann
authors.affiliation: Department of Psychiatry and Psychotherapy, University Medical Center Goettingen, von-Siebold-Straße 5, Goettingen, Germany.
authors.forename: Jens
authors.initials: J
authors.lastname: Wiltfang
authors.affiliation: Department of Nephrology, University Hospital Essen, Hufelandstraße 55, 45122, Essen, Germany.
authors.forename: Andreas
authors.initials: A
authors.lastname: Kribben
authors.affiliation: Department of Nephrology, University Hospital Essen, Hufelandstraße 55, 45122, Essen, Germany.
authors.forename: Heike
authors.initials: H
authors.lastname: Bruck
authors.affiliation: Department of Neurology, University Hospital Essen, Hufelandstraße 55, 45122, Essen, Germany. dirk.hermann@uk-essen.de.
authors.forename: Dirk M
authors.initials: DM
authors.lastname: Hermann
mesh_terms: D000368:Aged; D016229:Amyloid beta-Peptides / Q000097:blood*; D016022:Case-Control Studies; D015331:Cohort Studies; D005260:Female; D006801:Humans; D007668:Kidney / Q000503:physiopathology; D008297:Male; D008875:Middle Aged; D051436:Renal Insufficiency, Chronic / Q000097:blood* / Q000503:physiopathology; D012307:Risk Factors; D014019:Tissue Donors
chemical_list: D016229:Amyloid beta-Peptides
keywords: Alzheimer’s disease; Chronic kidney disease; Neurovascular hypothesis; Peripheral sink hypothesis; Plasma β-amyloid; Vascular risk factor