Cryogel formation in a cold urine sample as a marker of aberrant post‑translational uromodulin modification

Background. Since the 16th century the phenomenon of “Sedimentum lateritium” (SL) has been known. It consists in the formation of a gel-like substance, cryogel (CG), in some cooled urine samples, along with salt sediment. The diagnostic value of the CG formation effect was studied in a series of studies based on a laboratory model – a cold urine sample (CUS) [1].

Aim. To determine the diagnostic significance of the SL phenomenon for detecting disorders of uromodulin posttranslational processing.

Materials and methods. The analysis of CG formation is grounded in current concepts of the renal proteome, focusing on the functional characteristics of different isoforms of uromodulin (UMO, Tamm-Horsfall protein). CG is considered as the result of the “sol-gel” phase transition of stereochemically modified cylindrical UMO isoforms with a hydrodynamic size of about 400 nm and a molecular weight of 28х10⁶D -UMO (28).

Results. Gel formation in colloidal solutions presupposes the presence of filamentous high molecular weight compounds (HMWC), the interaction of which forms the overall structure of the gel. The most studied structures in urine that meet these characteristics are the isoforms of UMO in urolithiasis. A stable violation of the postgenomic processing of UMO leads to a change in the colloidal stability of urine and an increase in the crystallization of inorganic urine components.

Conclusion. Our results indicate that CG formation is a universal sensitive biomarker for impaired post-translational processing of UMO in nephron epithelial cells. This phenomenon characterizes renal damage of diverse etiologies and marks the onset of chronic kidney disease (CKD).

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