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. Despi te intense research, their relationship to calculogenesis remains cont roversial. In an attempt to study excretion of proteins in stone forme rs, their urinary profiles were analyzed and compared with those of he althy subjects. Two-dimensional gel electrophoresis was employed to ob tain high resolution separation of proteins. The urine of patients wit h histories of idiopathic calcium oxalate (CaOx) calculi contained 7 u nique proteins, and 2 others that appeared to be overexpressed. Except for alpha(1)-acid glycoprotein, the remaining 8 proteins are previous ly unknown constituents of urine with molecular weights of approximate ly 43, 39.5, 29, 26, 25.5, 26.5, 27 and 18.5 kD. Their isoelectric poi nts range from 5.5 to 8.0. Coelectrophoresis of pooled urinary protein s of male and female stone formers disclosed that all 9 proteins had i dentical 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 th ese proteins. This excludes the possibility that the proteins might be a consequence of abrasion of urothelial lining by the developing ston e(s). Recently defective Tamm-Horsfall mucoprotein (THM) has been impl icated 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 composit ion of THM. Whether this is attributable to a dissimilar amino acid se quence of this mucoprotein, remains to be probed.