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Factors Responsible for Plasma β-Amyloid Accumulation in Chronic Kidney Disease

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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.

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Acknowledgments

We thank Gisela Behrendt for administrative and technical support.

Funding

The study was supported by the Federal Ministry of Education and Research (BMBF/NGFN 01GR0808), which was not involved in study design, collection, analysis and interpretation of data, writing the report, and in the decision to submit the article for publication.

Conflicts of Interest

The authors declare that they have no competing interests.

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Authors and Affiliations

  1. Department of Neurology, University Hospital Essen, Hufelandstraße 55, 45122, Essen, Germany

    Janine Gronewold, Enrico Baldelli, Britta Kaltwasser, Ulla K. Seidel, Olga Todica & Dirk M. Hermann

  2. Department of Psychiatry and Psychotherapy, LVR-Hospital Essen, Faculty of Medicine, University of Duisburg-Essen, Virchowstraße 174, 45147, Essen, Germany

    Hans-Wolfgang Klafki & Ute Haußmann

  3. Department of Nephrology, University Hospital Essen, Hufelandstraße 55, 45122, Essen, Germany

    Michaela Volsek, Andreas Kribben & Heike Bruck

  4. Department of Psychiatry and Psychotherapy, University Medical Center Goettingen, von-Siebold-Straße 5, Goettingen, Germany

    Hans-Wolfgang Klafki & Jens Wiltfang

Authors
  1. Janine Gronewold
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  2. Hans-Wolfgang Klafki
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  3. Enrico Baldelli
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  6. Olga Todica
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  7. Michaela Volsek
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  9. Jens Wiltfang
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  10. Andreas Kribben
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Corresponding author

Correspondence to Dirk M. Hermann.

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Gronewold, J., Klafki, HW., Baldelli, E. et al. Factors Responsible for Plasma β-Amyloid Accumulation in Chronic Kidney Disease. Mol Neurobiol 53, 3136–3145 (2016). https://doi.org/10.1007/s12035-015-9218-y

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  • DOI: https://doi.org/10.1007/s12035-015-9218-y

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