Protein primary structure correlates with calcium oxalate stone matrix preference.

Despite the apparent importance of matrix proteins in calcium oxalate kidney stone formation, the complexity of the protein mixture continues to elude explanation. Based on a series of experiments, we have proposed a model where protein aggregates formed from a mixture containing both strongly charged polyanions and strongly charged polycations could initiate calcium oxalate crystal formation and crystal aggregation to create a stone. These protein aggregates also preferentially adsorb many weakly charged proteins from the urine to create a complex protein mixture that mimics the protein distributions observed in patient samples.

Osteopontin is a critical inhibitor of calcium oxalate crystal formation and retention in renal tubules.

Calcium nephrolithiasis is the most common form of renal stone disease, with calcium oxalate (CaOx) being the predominant constituent of renal stones. Current in vitro evidence implicates osteopontin (OPN) as one of several macromolecular inhibitors of urinary crystallization with potentially important actions at several stages of CaOx crystal formation and retention. To determine the importance of OPN in vivo, hyperoxaluria was induced in mice targeted for the deletion of the OPN gene together with wild-type control mice.