High prevalence of uric acid calculi in diabetic stone formers

Sir, Recently, Abate et al. [1] reported that patients with recurrent uric acid stones manifest clinical and metabolic abnormalities consistent with the metabolic syndrome. As the latter is often predictive of the development of diabetes mellitus type 2, one may hypothesize that diabetic patients may be at particular risk of developing uric acid nephrolithiasis. However, to the best of our knowledge, few studies have evaluated the prevalence of uric acid nephrolithiasis among the diabetic population and stone composition in diabetic stone formers. Meydan and co-workers [2] recently reported that 21% of diabetic patients were affected by urolithiasis as compared with only 8% in the non-diabetic population, but the chemical type of stones was not given. Pak et al. [3] reported that 33.9% of 59 stone-forming patients with type 2 diabetes had uric acid stones, as compared with only 6.2% among non-diabetic stone formers. Taking advantage of the large number of calculi analysed in our laboratory (more than 43 000 by June 2004), we compared the distribution of the main components of stones from 631 diabetic patients (438 males, 193 females; type 2 diabetes in 84%) and from 4087 non-diabetic stone formers (2883 males, 1254 females) matched for age [59.8±12.4 (SD) vs 59.7±11.9 years] and gender distribution (sex ratio 2.26 in both groups). The mean body mass index was higher in diabetic than in non-diabetic stone formers (28.8±6.3 vs 25.6±4.4 kg/m2; P<0.0001). Stone composition was determined quantitatively using Fourier transform infrared spectroscopy. The distribution of the main components of stones in males and females in the two groups (diabetics and non-diabetics) is shown in Table 1. Calcium oxalate was most prevalent as the main component of stones in both genders, but to a lesser extent in women than in men and in non-diabetic than in diabetic stone formers. No significant difference was observed for calcium phosphates (CaP) or magnesium ammonium phosphate (MAP) between the two groups. In contrast, uric acid was found as the main component of stones in a significantly higher proportion of diabetic than non-diabetic patients (28.5 vs 13.0%; P<0.0001), the difference being more marked in females (36.8 vs 9.7%) than in males (24.9 vs 14.7%). When taking into consideration calculi containing any proportion of uric acid (i.e. pure uric acid or mixed uric acid/calcium stones), the prevalence of uric acid-containing calculi was even higher in diabetic patients, at 35.4% vs 16.8% (P<0.0001) (40.3% vs 12.3% in women; 33.3% vs 18.8% in men). Pure uric acid stones represented 41.8% and 34.8% of uric acid-containing stones in diabetic and non-diabetic stone formers, respectively (not significant). There was no significant difference in stone composition between type 1 and type 2 diabetes, with the proportion of uric acid stones being 31.6% and 28.1%, respectively (Table 2). Overall, the proportion of uric acid stones was 2.2 times higher in diabetic than in non-diabetic stone formers, but the difference was strikingly more marked in women than in men with a ratio of 3.8 vs 1.7 (P = 0.003). Main component of stones in diabetic and non-diabetic stone formers Data for age are means±SD; all other data are percentages. aP<0.01, bP<0.001, cP<0.0001 vs men in the same group of patients. dP<0.02, eP<0.01, fP<0.001, gP<0.0001 vs non-diabetic patients. Main component of stones in diabetic and non-diabetic stone formers Data for age are means±SD; all other data are percentages. aP<0.01, bP<0.001, cP<0.0001 vs men in the same group of patients. dP<0.02, eP<0.01, fP<0.001, gP<0.0001 vs non-diabetic patients. Main component of stones in type 1 and type 2 diabetic stone formers Data for age are means±SD; all other data are percentages. aP<0.05, bP<0.01, cP<0.001 vs men in the same group of patients. Main component of stones in type 1 and type 2 diabetic stone formers Data for age are means±SD; all other data are percentages. aP<0.05, bP<0.01, cP<0.001 vs men in the same group of patients. It was shown recently that the metabolic syndrome presently affects >40% of the population aged ≥60 years in the US [4], which is in keeping with the observation that uric acid nephrolithiasis was highly prevalent in our diabetic stone formers who were aged 60 years as a mean. Of note, the increased proportion of uric acid stones with diabetes mellitus was especially marked in women who spontaneously form stones less frequently in general, and uric acid stones in particular, than do males; however, the reasons for this gender difference are still unexplained. In view of the relentlessly growing ‘epidemic’ of type 2 diabetes in Western countries, uric acid nephrolithiasis may become of clinical concern in diabetic patients, thus justifying preventive measures. In clinical practice, patients with diabetes type 2 or the metabolic syndrome should be checked for nephrolithiasis by abdominal ultrasound, especially if urine pH is ≤5.5. Conversely, onset of uric acid nephrolithiasis, especially if the subject is overweight, should prompt a check for diabetes type 2. In short, we propose searching for uric acid nephrolithiasis in diabetics and searching for diabetes in uric acid stone formers, especially women. Conflict of interest statement. None declared. 1Biochemistry A Laboratory2 Nephrology Department Necker Hospital Paris France Email: michel.daudon@nck.ap-hop-paris.fr