Seeking consistency for the role of urinary macromolecules and glycosaminoglycans in calcium oxalate crystallization processes pertaining to the risk of renal stone formation using a multi-faceted basic science approach.

Dalielah Jappie, Allen Rodgers, Dawn Webber, Mayur Danny I Gohel

Journal: Clinica chimica acta; international journal of clinical chemistry 2021;521():76-84

PMID: 34197796

Abstract

BACKGROUND

The roles of urinary macromolecules (UMMs) in calcium oxalate (CaOx) renal stone formation have not been consistently established.

AIM

To unravel these roles using a multi-faceted, multi-technique approach employing a wide range of experimental variables on a rotational basis in strategically chosen combinations.

METHODS

Endogenous urinary glycosaminoglycans (GAGs) were investigated in fractions obtained after ultrafiltration of pooled human urine (HU). Exogenous GAGs (chondroitin sulphate, CS, and hyaluronic acid, HA) were studied in artificial (AU) and in individual HUs. Experiments were conducted in a batch crystallizer and in a mixed suspension, mixed product removal flow system. Crystallization was quantitatively followed using Coulter multisizer and flow cytometer techniques. Crystal aggregation in the presence and absence of exogenous CS and HA was measured by Zeta potential and crystal sedimentation.

RESULTS

Total UMMs (endogenous) and individual GAGs (exogenous) consistently promoted CaOx crystallization and disaggregation. Evidence of UMM-UMM and UMM-solution synergistic effects was consistently observed for achieving modulation of crystallization processes.

CONCLUSIONS

Total UMMs, the main modulatory component of which is GAGs, are promoters of CaOx crystal nucleation and inhibitors of CaOx crystal aggregation. These results allow researchers to disregard alternative roles that have been advocated in such studies.

Copyright © 2021 Elsevier B.V. All rights reserved.

Address: Department of Chemistry University of Cape Town, South Africa.; Department of Chemistry University of Cape Town, South Africa. Electronic address: [email protected].; School of Medical and Health Sciences, Tung Wah College, Hong Kong.

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