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      Clinical Value of Crystalluria and Quantitative Morphoconstitutional Analysis of Urinary Calculi

      a , b,c

      Nephron Physiology

      S. Karger AG

      Morphology, Stone analysis, Crystalluria, Crystal volume, Infrared spectroscopy

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          Morphoconstitutional analysis of urinary calculi, i.e. morphologic examination combined with Fourier transform infrared spectroscopy (FTIR), is of decisive interest for the diagnosis of rare but severe inherited or acquired stone diseases such as cystine, 2,8-dihydroxyadenine, xanthine, struvite, ammonium urate or drug-containing calculi as well as primary hyperoxalurias. In the absence of early diagnosis and proper management, these diseases may lead to progressive loss of renal function. Among common forms of calcium oxalate (CaOx) stones, predominant CaOx monohydrate (whewellite) is mainly associated with hyperoxaluric conditions whereas predominant CaOx dihydrate (weddellite) is mainly associated with hypercalciuria, and this distinction is of interest to orient metabolic evaluation and preventive measures. Crystalluria examination, also based on morphology and FTIR, is a valuable diagnostic method when no stone is available for analysis. Presence of specific crystals (cystine, 2,8-dihydroxyadenine, struvite, ammonium urate) is diagnostic by itself. In all types of nephrolithiasis, serial crystalluria determination appears as a simple, cheap and reliable method to evaluate the risk of stone formation and assess the effectiveness of preventive measures. Determination of urinary crystal volume was in our experience a useful tool in the management of patients with cystinuria or primary hyperoxaluria in the post-transplantation period. In conclusion, both accurate morphologic and FTIR analysis of stones and serial crystalluria determination should be more largely used, in view of their value in the diagnosis and management of renal stone formers.

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          Most cited references 13

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          Predictive value of kidney stone composition in the detection of metabolic abnormalities.

          To determine if kidney stone composition can predict the underlying medical diagnosis, and vice versa. We studied 1392 patients with kidney stones who underwent a complete ambulatory evaluation and who submitted one or more stones for analysis. We ascertained the associations between medical diagnosis and stone composition. The most common kidney stones were composed of calcium oxalate (n = 1041 patients [74.8%]), mixed calcium oxalate-calcium apatite (n = 485 [34.8%]), and calcium apatite alone (n = 146 [10.5%]). The most common medical diagnoses were hypocitraturia (n = 616 patients [44.3%]), absorptive hypercalciuria (n = 511 [36.7%]), and hyperuricosuria (n = 395 [28.4%]). Calcium apatite and mixed calcium oxalate-calcium apatite stones were associated with the diagnoses of renal tubular acidosis and primary hyperparathyroidism (odds ratios >/=2), but not with chronic diarrheal syndromes. As the phosphate content of the stone increased from calcium oxalate to mixed calcium oxalate-calcium apatite, and finally to calcium apatite, the percentage of patients with renal tubular acidosis increased from 5% (57/1041) to 39% (57/146), and those with primary hyperparathyroidism increased from 2% (26/1041) to 10% (14/146). Calcium oxalate stones were associated with chronic diarrheal syndromes, but not with renal tubular acidosis. Pure and mixed uric acid stones were strongly associated with a gouty diathesis, and vice versa. Chronic diarrheal syndromes and uric acid stones were associated with one another, and brushite stones were associated with renal tubular acidosis. As expected, there was a very strong association between infection stones and infection, and between cystine stones and cystinuria. Stone composition has some predictive value in diagnosing medical conditions, and vice versa, especially for noncalcareous stones.
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            Cystine crystal volume determination: a useful tool in the management of cystinuric patients.

            We prospectively determined cystine crystal volume (Vcys) in urine specimens from all consecutive patients with cystine urolithiasis followed at our institution over the past decade, in order to assess its predictive value as to the risk of recurrent cystine stone formation. A total of 57 patients (29 males, 28 females) with homozygous cystinuria entered in the study between January 1990 and December 2000, including 15 children aged less than 15 years and 42 patients aged 15 years or more. The clinical and radiological course was followed until December 2001, for a total of 243 patient-years of follow-up. From study entry until the end of follow-up, we serially examined first voided morning urine specimens in all patients, with determination of the number of cystine crystals per mm3, and the average size of crystals, thus allowing us to calculate Vcys using a simple formula based on crystal geometry. Recurrence was diagnosed on the basis of serial radiographic examinations using X-rays and echography. Overall, cystine crystals were present in 179 (39%) of the 460 examined urine specimens. Cystine crystalluria was significantly more frequent among the 27 patients who developed new cystine stones (SF) than in the other 30 who remained stone-free (63.3 vs 25.5% of samples, P or =50% of serially examined urine samples was more frequently found in patients with recurrent stone formation than in non-recurrent patients (24/27 vs 2/30, P or =3,000 micro3/mm3 was observed at least once prior to each of the 63 stone recurrences observed in 27 patients (2.3 per patient on the average). In addition, Vcys reflected the efficacy of treatment, with Vcys mean values of 12,097 +/- 3,214 micro3/mm3 at baseline, falling to 2,648 +/- 658 micro3/mm3 on basic therapy (hyperdiuresis plus alkalinization) alone, 1,141 +/- 522 micro3/mm3 on tiopronin therapy (median dose 1,000 mg/day) and 791 +/- 390 micro3/mm3 on D-penicillamine therapy (median dose 900 mg/day) whereas captopril had no effect (5,114 +/- 2,128 micro3/mm3). Based on the results of the present study, cystine crystalluria appears to accurately reflect active stone formation in cystinuric patients. Determination of total Vcys provides a simple, cheap and accurate means of predicting the risk of cystine stone recurrence with a Vcys value > or =3000 micro3/mm3 as the threshold risk value. We propose that serial Vcys determination be performed simultaneously with the measurement of urine pH and specific gravity to optimally monitor the medical treatment of cystine patients.
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              Saturation-inhibition index as a measure of the risk of calcium oxalate stone formation in the urinary tract.

              Studies were carried out on multiple urine samples from eight patients with recurrent idiopathic calcium oxalate stone formation and eight normal persons to define an index of the risk of forming calcium oxalate stones. Under the same conditions of dietary and fluid intake the urine samples of the patients with stone formation were more supersaturated with calcium oxalate (P less than 0.001) and had lower concentrations of protective inhibitors of crystallization (P less than 0.001) than those of the controls. However, the best separation between the groups was defined by a discriminant line relating inhibitory activity and urine saturation. A measure of the risk of forming large crystals, the saturation-inhibition index, was defined as the distance of each urine from the discriminant line. The patients with stone formation had a significantly higher mean saturation-inhibition index than the controls (P less than 0.001). Both the percentage of large calcium oxalate crystals excreted (P less than 0.001) and the stone episode rate (P less than 0.005) were significantly correlated with the saturation-inhibition index.

                Author and article information

                Nephron Physiol
                Nephron Physiology
                S. Karger AG
                October 2004
                19 October 2004
                : 98
                : 2
                : p31-p36
                Departments of aBiochemistry and bNephrology, and cINSERM U507, Necker Hospital, AP-HP, Paris, France
                80261 Nephron Physiol 2004;98:p31–p36
                © 2004 S. Karger AG, Basel

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                Figures: 1, Tables: 1, References: 25, Pages: 1
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