Expression of proteins that inhibit calcium oxalate crystallization in vitro in the urine of normal and stone-forming individuals

The factors precipitating clinically active calcium oxalate (CaOx) urolithi asis are not known. This study examined the relationships between urinary p roteins that inhibit CaOx crystallization in vitro and the incidence of CaO x urolithiasis. The first hypothesis is that levels of urinary CaOx crystal lization inhibitors differ between clinically active stone formers (SFs) an d normal individuals. The second hypothesis is that lower levels of urinary CaOx crystallization inhibitors contribute to the two- to threefold greate r incidence of CaOx urolithiasis in males compared with females. These hypo theses were derived from previous observations on the expression of urinary inter-alpha -trypsin inhibitor trimer (I alpha TI-trimer) in normal and st one-forming individuals. The proteins of void urine samples from normal vol unteers (24 males, 19 females) and CaOx-SFs (26 males, 16 females) were res olved by sodium dodecyl sulfate-polyacrylamide gel electrophoresis. Immunor eactive I alpha TI-trimer, osteopontin, and prothrombin were detected by im munoblot plus enhanced chemiluminescence; the relative densities of the ban ds were then determined. With the exception of I alpha TI-trimer (P less th an or equal to 0.026, approximately twofold), there was no difference in th e relative densities of CaOx crystallization inhibitors in the urine of nor mal and CaOx stone-forming individuals. Thus, there does not appear to be a generalized increase or decrease in levels of CaOx crystallization inhibit ory proteins between normal and CaOx stone-forming individuals. The relativ e density of I alpha TI-trimer was approximately threefold greater in femal es than in males (P less than or equal to 0.001). Differences in the relati ve densities of the other CaOx crystallization inhibitors were small and of questionable physiological importance. These data do not support the hypot hesis that males have a greater incidence of CaOx urolithiasis because of a generalized decrease in urinary CaOx crystallization inhibitory protein le vels. (C) 2001 by the National Kidney Foundation, Inc.