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

Abstract

Promotion by albumin of calcium oxalate crystallization with specific formation of the dihydrate form might be protective, because with rapid nucleation of small crystals, the saturation levels fall; thus, larger crystal formation and aggregation with subsequent stone formation may be prevented. We believe that albumin may be an important factor of urine stability.

Modulation of Calcium Oxalate Dihydrate Growth by Selective Crystal-face Binding of Phosphorylated Osteopontin and Polyaspartate Peptide Showing Occlusion by Sectoral (Compositional) Zoning

“…It has been reported that the occurrence of COM, the more thermodynamically stable polymorph of calcium oxalate, is often at the core of most kidney stones and is approximately twice as frequent as COD (2), although both crystal types typically exist to some degree in most stones (3,4). COM is commonly found in the urine of "stone formers," but seldom is seen in healthy urine; on the other hand, COD crystals are typically found in the urine of both healthy people and stone formers and are routinely excreted during urination (5)(6)(7). Importantly, in patients with severe uremia and hypercalciuria, elongated, large rod-shaped COD crystals are not only often observed but are the sole mineral phase present in the kidneys in these pathologies (8,9).…”

Albumin and Its Role in Urolithiasis

“…Albumin preferentially leads to the formation of COD (CaOx dehydrate) crystals over COM (CaOx monohydrate), a similarly favorable formation of COD has also been reported with the use of (BSA), a homolog of HSA [26,27]. These crystals are small and are easily removed in comparison to their larger counterparts (COM crystals).…”

“…Furthermore, quite contradictory to its nature as a promoter of nucleation in CaOx crystals, albumin inhibits aggregation in a concentration-dependent manner. Although, this involvement in the nucleation process might just be benign [26].…”

“…In HAP -CaP crystals, a concentrated albumin-rich extract showed equal potency in inhibiting HAP crystal growth when compared to an albumin-free serum showcasing the protein's efficacy in comparison to other serum components [31]. Furthermore, albumin, a known drug binding agent has been seen to bind other urinary macromolecules as well [26].…”

“…The binding of albumin has been suggested to be face-specific and competitive with protein showing a penchant for the side faces in inorganic COM crystals, whereas the carboxyl groups of albumin have been suspected to be preferentially involved in the nucleation process in CaOx crystals [26,32]. Moreover, the forms of albumin used for in vitro studies are not the exact representations of the albumin present in the urine as it is a transport protein and is present in a complexed form with other molecules, dubiousness over the present data further prevails when one reaches farther out to take into consideration the complex environment of the urine.…”