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A larger body size has been shown to be associated with increased excretion of urinary lithogenic solutes, and an increased risk of nephrolithiasis has been reported in overweight patients. However, the type of stones produced in these subjects has not been ascertained. Based on a large series of calculi, we examined the relationship between body size and the composition of stones, in order to assess which type of stone is predominantly favoured by overweight. Among 18,845 consecutive calculi referred to our laboratory, 2,100 came from adults with recorded body height and weight. Excluding calculi from patients with diabetes mellitus, as well as struvite and cystine stones, the study material consisted of 1,931 calcium or uric acid calculi. All calculi were analysed by infrared spectroscopy and categorized according to their main component. Body mass index (BMI) values were stratified as normal BMI (< 25 kg/m2), overweight (BMI 25-29.9) or obese (BMI > or = 30). Overall, 27.1% of male and 19.6% of female stone formers were overweight, and 8.4 and 13.5% were obese, respectively. In males, the proportion of calcium stones was lower in overweight and obese groups than in normal BMI group, whereas the proportion of uric acid stones gradually increased with BMI, from 7.1% in normal BMI to 28.7% in obese subjects (P<0.0001). The same was true in females, with a proportion of uric acid stones rising from 6.1% in normal BMI to 17.1% in obese patients (P=0.003). In addition, the proportion of uric acid stones markedly rose with age in both genders (P<0.0001). The average BMI value was significantly higher in uric acid stone formers aged < 60 years than in all other groups, whereas it did not differ from other groups in those aged > or = 60 years. Stepwise regression analysis identified BMI and age as significant, independent covariates associated with the risk of uric acid stones. Our data provide evidence that overweight is associated with a high proportion of uric acid stones in patients less than 60 years of age, whereas beyond this limit, advancing age is the main risk factor.

Urinary stone incidence and composition have changed markedly over the past half-century in industrialized countries, in parallel with profound changes in living standards and dietary habits, with a dramatic increase in the incidence of calcium oxalate stones. However, studies evaluating the influence of age and gender on the distribution of the various types of urinary calculi are scarce. We report the results of a study based on 27,980 calculi (from 19,442 males and 8,538 females) analyzed by infrared spectroscopy between 1976 and 2001. The relationships between age and sex and stone composition were investigated using a multivariate approach, based on correspondence factor analysis (CFA). We found a male predominance for calcium oxalate and uric acid, a female preponderance for calcium phosphate and struvite stones, and an increasing prevalence of uric acid stones with age in both genders. CFA was able to reconstruct in blind the age curve from stone composition. The first two axes of the multidimensional classification, which correspond to age, included 86.9% of the total variance, indicating that age was the main factor involved in stone type. Superimposition of age classes and stone components showed a strong relationship between age and whewellite, weddellite, brushite, carbapatite, octacalcium phosphate and uric acid, while other substances (whitlockite, amorphous carbonated calcium phosphate, struvite, proteins, mucopolysaccharides, triglycerides or ammonium urate) appeared weakly related to age. In addition, CFA suggests the role of common lithogenic factors between weddellite, carbapatite and brushite, which clustered in the same area, whereas the various crystalline forms of phosphate stones segregated into two different clusters, suggesting distinct pathogenic factors. In conclusion, this study provides a picture of the present epidemiology of urinary stones in France. CFA helped to confirm: (1) an etiopathogenic distinction between weddellite and whewellite, (2) etiopathogenic associations between chemical compounds, which were only suspected on a clinical basis, and (3) suggested yet unrecognized associations, especially with respect to the heterogeneous group of phosphate stones.

A calcium oxalate crystal growth inhibitor was isolated from human urine using DEAE-Sephacel gel followed by Sephacryl S-300 chromatography and FPLC column. The isolated inhibitor was a uronic-acid-rich protein (UAP). It was found to be a glycoprotein with a molecular weight of 35,000 Da as determined by SDS-polyacrylamide gel electrophoresis. Inhibitory activity was demonstrated using a calcium oxalate crystallization system. In addition UAP, nephrocalcin (NC) or nephrocalcin-like (NC-like) activity was an effective inhibitor in this system. However, the inhibitory activity of UAP appeared to be higher than that of NC or NC-like activity. This finding suggests that NC or NC-like activity is not only urinary protein with strong inhibitory activity. UAP and probably other proteins also play a role in the control of urinary crystal growth.