Protein-crystal Interactions in Calcium Oxalate Kidney Stone Formation

Abstract

We have studied the ability of urinary molecules in altering the precipitation of kidney stone-related calcium oxalate monohydrate (COM) crystals and correlated the resulting morphologies with those of idiopathic COM kidney stones. We found that weakly acidic but highly glycosylated polyelectrolytes (Tamm Horsfall protein (THP), fetuinA, hyaluronic acid) do not significantly affect crystallization, and that THP and fetuinA show the tendency to aggregate in the presence of nascent crystals. It is proposed that highly glycosylated polyelectrolytes encapsulate nascent urinary crystals, prevent their aggregation, and thus act supportive in crystal excretion. Strong effects on crystallization were observed in the presence of the highly acidic molecules osteopontin (OPN), citrate, and the non-urinary glycosaminoglycans heparin and dextran sulfate. OPN formed non-structured concretions comparable with those found in the core of stones, while citrate formed platelets closely resembling crystal shapes found in the mantle region. However, it is unclear how the columnar growth in the mantle takes place. It is assumed that changing polyelectrolyte compilations/concentrations affect stone forming processes (e.g. equilibria, enhanced self-assembly), perhaps resulting in these structures. We have indeed shown that peptides can induce the formation of such structures. Moreover, heparin and dextran sulfate inhibited COM formation; implicating that these molecules could assist OPN, citrate but also THP in preventing stone formation.