Nucleation of calcium oxalate crystals by albumin: Involvement in the prevention of stone formation

Background. Urine is supersaturated in calcium oxalate, which means that it will contain calcium oxalate crystals that form spontaneously. Their size must be controlled to prevent retention in ducts and the eventual developme nt of a lithiasis. This is achieved, in part, by specific inhibitors of cry stal growth. We investigated whether promoters of crystal nucleation could also participate in that control, because for the same amount of salt that will precipitate from a supersaturated solution, increasing the number of c rystals will decrease their average size and facilitate their elimination. Methods. Albumin was purified from commercial sources and from the urine of healthy subjects or idiopathic calcium stone formers. Its aggregation prop erties were characterized by biophysical and biochemical techniques. Albumi n was then either attached to several supports or left free in solution and incubated in a metastable solution of calcium oxalate. Kinetics of calcium oxalate crystallization were determined by turbidimetry. The nature and ef ficiency of nucleation were measured by examining the type and number of ne oformed crystals. Results. Albumin, one of the most abundant proteins in urine, was a powerfu l nucleator of calcium oxalate crystals in vitro, with the polymers being m ore active than monomers. In addition, nucleation by albumin apparently led exclusively to the formation of calcium oxalate dihydrate crystals, wherea s calcium oxalate monohydrate crystals were formed in the absence of albumi n. An analysis of calcium oxalate crystals in urine showed that the dihydra te form was present in healthy subjects and stone formers, whereas the mono hydrate, which is thermodynamically more stable and constitutes the core of most calcium oxalate stones, was present in stone formers only. Finally, u rinary albumin purified from healthy subjects contained significantly more polymers and was a stronger promoter of calcium oxalate nucleation than alb umin from idiopathic calcium stone formers. Conclusions. Promotion by albumin of calcium oxalate crystallization with s pecific formation of the dihydrate form might be protective, because with r apid nucleation of small crystals, the saturation levels fall; thus, larger crystal formation and aggregation with subsequent stone formation may be p revented. We believe that albumin may be an important factor of urine stabi lity.