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 development of a lithiasis. This is achieved, in part, by specific inhibitors of crystal 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 crystals 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 properties were characterized by biophysical and biochemical techniques. Albumin 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 efficiency of nucleation were measured by examining the type and number of neoformed crystals.


RESULTS
Albumin, one of the most abundant proteins in urine, was a powerful nucleator of calcium oxalate crystals in vitro, with the polymers being more active than monomers. In addition, nucleation by albumin apparently led exclusively to the formation of calcium oxalate dihydrate crystals, whereas calcium oxalate monohydrate crystals were formed in the absence of albumin. An analysis of calcium oxalate crystals in urine showed that the dihydrate form was present in healthy subjects and stone formers, whereas the monohydrate, which is thermodynamically more stable and constitutes the core of most calcium oxalate stones, was present in stone formers only. Finally, urinary albumin purified from healthy subjects contained significantly more polymers and was a stronger promoter of calcium oxalate nucleation than albumin from idiopathic calcium stone formers.


CONCLUSIONS
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.
Cerini
C
C
INSERM U315, Physiologie et Pathologie Digestives, Hôpital Sainte-Marguerite, Marseille, France.
Geider
S
S
Dussol
B
B
Hennequin
C
C
Daudon
M
M
Veesler
S
S
Nitsche
S
S
Boistelle
R
R
Berthézène
P
P
Dupuy
P
P
Vazi
A
A
Berland
Y
Y
Dagorn
J C
JC
Verdier
J M
JM
D000328:Adult; D000418:Albumins / Q000032:analysis / Q000737:chemistry* / Q000494:pharmacology; D000419:Albuminuria / Q000378:metabolism*; D002129:Calcium Oxalate / Q000737:chemistry* / Q000494:pharmacology / Q000652:urine*; D002851:Chromatography, High Pressure Liquid; D003460:Crystallization; D004591:Electrophoresis, Polyacrylamide Gel; D005260:Female; D006801:Humans; D066298:In Vitro Techniques; D007669:Kidney Calculi / Q000737:chemistry* / Q000378:metabolism / Q000517:prevention & control; D007700:Kinetics; D008297:Male; D008863:Microspheres; D008875:Middle Aged; D012685:Sepharose; D012995:Solubility; D014556:Urine / Q000737:chemistry
D000418:Albumins; D002129:Calcium Oxalate; D012685:Sepharose