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

Abstract

BackgroundThe roles of urinary macromolecules (UMMs) in calcium oxalate (CaOx) renal stone formation have not been consistently established. AimTo 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. MethodsEndogenous 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. ResultsTotal 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. ConclusionsTotal 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.