Evidence for the presence of abnormal proteins in the urine of recurrent stone formers.

Two-thirds of matrix of all urinary stones consists of proteins. Despite intense research, their relationship to calculogenesis remains controversial. In an attempt to study excretion of proteins in stone formers, their urinary profiles were analyzed and compared with those of healthy subjects. Two-dimensional gel electrophoresis was employed to obtain high resolution separation of proteins. The urine of patients with histories of idiopathic calcium oxalate (CaOx) calculi contained 7 unique proteins, and 2 others that appeared to be overexpressed. Except for alpha 1-acid glycoprotein, the remaining 8 proteins are previously unknown constituents of urine with molecular weights of approximately 43, 39.5, 29, 26, 25.5, 26.5, 27 and 18.5 kD. Their isoelectric points range from 5.5 to 8.0. Coelectrophoresis of pooled urinary proteins of male and female stone formers disclosed that all 9 proteins had identical charges and molecular weights, regardless of the donors' sex. Analyses of urines of idiopathic recurrent CaOx stone formers who had no radiologically detectable calculi also revealed the presence of these proteins. This excludes the possibility that the proteins might be a consequence of abrasion of urothelial lining by the developing stone(s). Recently defective Tamm-Horsfall mucoprotein (THM) has been implicated in urinary stone formation. Coelectrophoresis of pooled urinary proteins of healthy subjects and stone formers denoted that it had an identical charge and molecular weight in both groups. This suggested that stone formation could not be ascribed to a difference in composition of THM. Whether this is attributable to a dissimilar amino acid sequence of this mucoprotein, remains to be probed.