Presence or Absence of Inhibitor of Calcium-Oxalate Crystal Growth in Urine of Normals and of Stone-Formers

Urine glycoprotein crystal growth inhibitors. Evidence for a molecular abnormality in calcium oxalate nephrolithiasis.

“…A lesser degree of kinetic crystal growth inhibition at any given concentration means that ifpatients excrete as much inhibitor as normals they will have less total effective inhibition ofcrystal growth, and therefore a greater potential for forming stones. We (1) and others (3,5,9,14) have found less overall inhibition of calcium oxalate crystal growth by urine from stone formers compared with normal; part of this deficit may be due to the intrinsic molecular disorder we describe here.…”

“…Added at dilutions of even 1:100, urine greatly slows the rate at which calcium oxalate monohydrate crystals grow in a metastably supersaturated calcium oxalate solution (1)(2)(3)(4)(5)(6). The upper limit of metastability for calcium oxalate is higher in urine than in simple salt solutions (7), because urine inhibits the process of nucleation-i.e., the transformation of solution ions into a solid phase-and slows the growth of very small nuclei so they cannot be detected.…”

“…The crystal growth inhibitor moleculeswhich we wish to abbreviate as GCI molecules-appear to account for a considerable proportion of the inhibitory effects of urine (12,13), and are the focus of this report. We (1) and others (5,9,14) have found that urine from stone-forming patients inhibits calcium oxalate crystal growth less than normal urine, and have reasoned that patients who form stones may do so in part because they produce GCT molecules that are less inhibitory than normal ones, or excrete intrinsically normal GOCI molecules in abnormally small quantities. We present here evidence for the former: compared with normal GCI molecules, GCI molecules isolated from the urine ofpatients with nephrolithiasis are less effective as inhibitors; they are also abnormal in their composition, and in their physical properties at the air-water interface.…”

Inhibitors and Promoters of Stone Formation

“…A simplified version of this approach is to set the supersaturation in a straight solution or whole urine to a known level, and to determine to what extent precipitation has occurred, either in the solution or on a nucleator such as a glass rod or a wire after a defined time lapse (5,9,90,91,(94)(95)(96)(97)(98). While this technique is acceptable in straight solutions whith defined ion concentrations, it is valid in whole urine only if the supersaturation can be determined (9).…”

“…Nature of the inhibitory activity. As for calcium phosphate, urine has been found to inhibit strongly the precipitation of calcium oxalate (93,94,96). The same is true for pyrophosphate (32,83,90,93,95,97,99,100), citrate, and magnesium (93), as well as for a great number of substances, i.e., dyes (95,97) (e.g;, methylene blue (102)), phytate (95), polyelectrolytes (95), urinary macromolecules (90), and especially metals (95,97,101) and heparin (103).…”