SIENER, ROSWITHA, SARA GLATZ, CLAUDIA NICOLAY, AND ALBRECHT HESSE. The role of overweight and obesity in calcium oxalate stone formation. Obes Res. 2004;12:106 -113. Objective: The aim of the study was to assess the influence of overweight and obesity on the risk of calcium oxalate stone formation. Research Methods and Procedures: BMI, 24-hour urine, and serum parameters were evaluated in idiopathic calcium oxalate stone formers (363 men and 164 women) without medical or dietetic pretreatment. Results: Overweight and obesity were present in 59.2% of the men and in 43.9% of the women in the study population. Multiple linear regression analysis revealed a significant positive relationship between BMI and urinary uric acid, sodium, ammonium, and phosphate excretion and an inverse correlation between BMI and urinary pH in both men and women, whereas BMI was associated with urinary oxalate excretion only among women and with urinary calcium excretion only among men. Serum uric acid and creatinine concentrations were correlated with BMI in both genders. Because no association was established between BMI and urinary volume, magnesium, and citrate excretion, inhibitors of calcium oxalate stone formation, the risk of stone formation increased significantly with increasing BMI among both men and women with urolithiasis (p ϭ 0.015). The risk of calcium oxalate stone formation, median number of stone episodes, and frequency of diet-related diseases were highest in overweight and obese men. Discussion: Overweight and obesity are strongly associated with an elevated risk of stone formation in both genders due to an increased urinary excretion of promoters but not inhibitors of calcium oxalate stone formation. Overweight and obese men are more prone to stone formation than overweight women.

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A crucial role for cell-crystal interactions in the development of urolithiasis (UL) and nephrocalcinosis (NC) was previously observed in experiments with different cell lines mimicking renal epithelial cells. It was found that such cell-crystal interactions lead to tubular damage and/or or dysfunction. To find further proof for these observations, we measured the urinary N-acetyl-beta- d-glucosaminidase (NAG) excretion, a marker of proximal tubular damage, in children with UL or NC and in children with an increased risk of UL. We enrolled 142 children aged 4-16 years (mean 9.67+/-3.40 years), with 50 children having UL, 30 children with a history of UL (ULH), 20 patients with NC, 34 children with secondary hyperoxaluria (HyOx), and 8 children with idiopathic hypercalciuria (HC). Normal urinary NAG/Cr values were determined in a group of 70 healthy children aged 4-16 years (mean 10.06+/-3.97 years). The urinary NAG activity was measured using a colorimetric method and the results were expressed as molar creatinine (Cr) ratios. The highest median NAG/Cr ratios were found in children with UL plus hematuria (0.72 U/mM) and in children with UL (0.67 U/mM) or NC (0.48 U/mM), which were all significantly higher than those in controls (0.28 U/mmol, P<0.001 and P<0.05). The NAG/Cr ratios were increased above the upper normal reference interval of 0.63 U/mM (95th percentile) in 28 of 50 (56%) children with UL and in 9 of 20 (45%) children with NC. Although the ULH group also had significantly higher median NAG/Cr ratios (0.36 U/mM) compared with controls, the NAG/Cr ratio was only elevated in 4 of 30 (13%) patients. NAG values in children with secondary HyOx or HC were not different from controls. No correlation was found between the NAG/Cr ratios and the urinary excretion of oxalate or calcium. In conclusion, UL or NC may result in proximal tubular injury, which is rather the consequence of disease activity and of the mechanical influence of calculi, than of the metabolic background. The mechanism of cell damage in these conditions however, seems to be complex. Neither HyOx nor HC alone were sufficient to induce severe tubular damage expressed as an increase in NAG excretion in our patients.

In previous papers we introduced the Bonn-Risk Index (BRI) as a new method of evaluating an individual's actual risk of forming calcium oxalate (CaOx). A comparison of our results with the calculated urinary relative supersaturations (RS) with respect to CaOx, showed that samples with similar values of RS can have different values of BRI. We suggested that this may reflect the individual influence of the urinary macromolecular constituents which are not taken into account at the calculation of RS. To estimate the role of macromolecules on the value of BRI, we examined 45 unprepared 24-h urine samples from 24 persons (16 healthy subjects, eight CaOx stone-formers) with respect to BRI, RS, and the concentration of urinary Tamm-Horsfall-protein ([THP]). The crystallization experiments were carried out by the use of a laser-probe. Based on the data of BRI and RS, the effect of THP may shift from a minor promoter in stone-formers and persons "at risk", to an inert urinary constituent in healthy subjects and persons "without risk". However, the observed effects are small and at least in the latter group close to zero.

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