Precipitation mechanisms of Ca-oxalate in the presence of Ca-phosphates and osteopontin molecules related to kidney stone formation

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Kidney stones are a major health problem with increasing relevance in our society. Although the causes and mechanisms of calcium oxalate (CaOx) nephrolithiasis are not entirely clear, in many cases a plaque or other seed particle of hydroxyapatite is formed prior to CaOx precipitation from urine in the kidneys. The proposed research project focuses on the mineralogical aspects of nephrolithiasis including mineral precipitation, epitaxy, mineral replacement and microstructural and textural development of crystals depending on ion concentration and pH as well as on the interaction with relevant protein additives. Specifically, osteopontin as well as osteopontin-derived phosphorylated peptides have been shown to inhibit nucleation, crystal growth and aggregation of calcium oxalate monohydrate (COM, whewellite), which is the major constituent of CaOx kidney stones. Applying specific regions of the osteopontin macromolecules in the experiments will allow a detailed assessment of the structure-function relation during protein-mineral interaction. It is expected that this research has high potential to generate new insights into the relevant mineral precipitation mechanisms, which will increase the fundamental understanding of kidney stone formation as a basis for future developments in the prevention of nephrolithiasis.