Crystalluria

Abstract: SUMMARY 1. The particle size distributions of calcium oxalate crystals were measured at 37°C in fresh urine from recurrent, idiopathic stone-formers and their controls under the same conditions of dietary and fluid intake. The crystals excreted by the controls were small and belonged to a unimodal distribution, whereas those excreted by the stoneformers belonged to a distribution which contained a second peak of much larger particles. The proportion of large crystals in the urines of the stone-formers was significantly higher than in the urines of the controls. 2. The difference in the proportion of large particles passed by the two groups was accentuated by adding a small quantity of sodium oxalate to their diets. Whereas the controls continued to excrete only small crystals of calcium oxalate, the stone-formers passed most of their crystals as large particles. 3. Further investigations showed that the urines of the controls contained a potent inhibitor of the growth and aggregation of calcium oxalate crystals in vitro and that the inhibitor was deficient in the urines of the recurrent stone-formers. 4. It is suggested that the inhibitor in normal urine may allow calcium oxalate to be passed harmlessly in the form of small particles, whereas the lower inhibitory activity in the urines of the recurrent stone-formers is insufficient to prevent the growth of the primary crystals into the large aggregates seen in these urines. By blocking the formation of abnormally large crystals and aggregates the inhibitor may therefore play an important role in preventing crystalluria leading to stone formation.

Abstract: Drug-induced calculi represent 1–2% of all renal calculi. The drugs reported to produce calculi may be divided into two groups. The first one includes poorly soluble drugs with high urine excretion that favour crystallisation in the urine. Among them, drugs used for the treatment of patients with human immunodeficiency, namely atazanavir and other protease inhibitors, and sulphadiazine used for the treatment of cerebral toxoplasmosis, are the most frequent causes. Besides these drugs, about 20 other molecules may induce nephrolithiasis, such as ceftriaxone or ephedrine-containing preparations in subjects receiving high doses or long-term treatment. Calculi analysis by physical methods including infrared spectroscopy or X-ray diffraction is needed to demonstrate the presence of the drug or its metabolites within the calculi. Some drugs may also provoke heavy intra-tubular crystal precipitation causing acute renal failure. Here, the identification of crystalluria or crystals within the kidney tissue in the case of renal biopsy is of major diagnostic value. The second group includes drugs that provoke the formation of urinary calculi as a consequence of their metabolic effects on urinary pH and/or the excretion of calcium, phosphate, oxalate, citrate, uric acid or other purines. Among such metabolically induced calculi are those formed in patients taking uncontrolled calcium/vitamin D supplements, or being treated with carbonic anhydrase inhibitors such as acetazolamide or topiramate. Here, diagnosis relies on a careful clinical inquiry to differentiate between common calculi and metabolically induced calculi, of which the incidence is probably underestimated. Specific patient-dependent risk factors also exist in relation to urine pH, volume of diuresis and other factors, thus providing a basis for preventive or curative measures against stone formation.