Defective or absent inhibition of agglomeration in the presence of normal inhibition of crystal growth in stone-formers with a high recurrence rate

Abstract

The nature and clinical significance of inhibitors of crystallization in human urine have been for many years an area of active research in the field of urolithiasis. Classically, inhibitors are defined as substances which inhibit crystal growth and agglomeration, both these processes being considered as a single entity. This has stemmed mainly from the lack of sufficient methods to quantify the two processes independently and not from experimental, very important process and microscopic examination of an average renal stone reveals clearly its agglomerate structure. We have developed methods for assessing in vitro the various crystallization processes independently and the theoretical and practical aspects of these have been published in a series of articles (1, 2, 3). These methods allow us to measure the effects of a substance on the solubility, growth and agglomeration of calcium oxalate monohydrate seed crystals separately. We have now applied these methods to the study of urines from healthy subjects and recurrent calcium oxalate stone formers who were selected from our stone patient population because of their very high recurrence rate (more than a stone per month) and resistance to known modes of treatment. These patients also had no RTA and cultures of their urines were sterile. Urines from both groups of subjects were diluted 1:5 and solubility (√L_c-,mM), growth constant (Ka,L. g^-1min^-1) and agglomeration inhibition ([tm], min) were measured as previously described (1, 2, 3). As a growth constant is specific for the type of seed crystal used, growth inhibition is expressed relatively to a normal saline control experiment and ranges from 0 to 100%. In addition, the following biochemical parameters were measured in 24 hr urine collections: creatinine, calcium, phosphate, magnesium, uric acid, oxalate citrate.