Preprint Article Version 1 Preserved in Portico This version is not peer-reviewed

Wnt/β-Catenin Pathway Proteins in End-Stage Renal Disease

Version 1 : Received: 11 February 2021 / Approved: 12 February 2021 / Online: 12 February 2021 (10:08:22 CET)

How to cite: Al-Hakeim, H.; Asad, H.; Maes, M. Wnt/β-Catenin Pathway Proteins in End-Stage Renal Disease . Preprints 2021, 2021020296 (doi: 10.20944/preprints202102.0296.v1). Al-Hakeim, H.; Asad, H.; Maes, M. Wnt/β-Catenin Pathway Proteins in End-Stage Renal Disease . Preprints 2021, 2021020296 (doi: 10.20944/preprints202102.0296.v1).

Abstract

Background. Wnt-pathway proteins play a vital role in kidney development and defects in the Wnt-pathway are associated with kidney disorders. However, the knowledge on the role of Wnt/β-catenin pathway proteins in end-stage renal disease (ESRD) is limited.Aim of the study. To delineate the association of ESRD and Wnt-proteins including the agonistR-spondin 1, the transducer β-catenin and the antagonists Dickkopf-related protein 1 (DKK1) and sclerostin.Methods. Serum Wnt-pathway proteins levels were measured by ELISA, while other biochemicals were measured spectrophotometrically in 60 ESRD patients and 30 normal controls.Results. DKK1 and sclerostin were significantly higher in ESRD than in controls, and β-catenin and the catenin + R-Sponin-1 / DKK1 + sclerostin ratio, reflecting the ratio of agonist and transducer on antagonists (AT/ANTA), were significantly lower in ESRD. Logistic regression analysis showed that ESRD was significantly predicted by increased levels of DDK1 and sclerostin and lowered β-catenin (p<0.001). eGFR was significantly associated with DKK1 and sclerostin (inversely), β-catenin (positively) and the AT/ANTA ratio (r=0.468, p<0.001). DKK1 levels were significantly and positively correlated with urea, creatinine, and copper. DKK1 and sclerostin were inversely associated with hemoglobin and packet cell volume. Catenin was significantly negatively associated with copper, urea and creatinine.Conclusion. Wnt/β-catenin pathway proteins show significant alterations in ESRD, indicating significantly increased levels of antagonists and, therefore, attenuated Wnt/β-catenin pathway activity. The latter is associated with lowered eGFR and increased serum copper levels. Wnt/β-catenin pathway proteins are possible drug targets to treat ESRD or its consequences.

Keywords

End-Stage Renal Disease, Chronic Kidney Disease, Wnt-Pathway, R-Spondin 1, β-Catenin, Dickkopf-Related Protein 1, and Sclerostin.

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