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- Research Methods and Procedures
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 = 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.
- Top of page
- Research Methods and Procedures
The evaluation of BMI revealed a high prevalence of overweight and obesity among the study population. Overweight was significantly more frequent in men than in women with calcium oxalate stone disease. It is known that overweight, dietary pattern, and the frequency of diet-related diseases are linked together. In the present study, overweight and obesity were associated with an increased risk of diet-related diseases in men compared with women: 49% of the overweight and 74% of the obese men but only 44% of the overweight and 59% of the obese women had one to three of the comorbidities (hypertension, cardiovascular disease, gallstone disease, diabetes, hyperuricemia, or gout). Overweight and related diseases are primarily caused by an energy-rich diet that is poorly balanced in terms of macro- (protein, fat, and carbohydrates) and micronutrients (6). A case control study indicated that subjects on a low-fat or weight reduction diet had a substantially reduced risk of urolithiasis (7).
The present data support the hypothesis that an elevated BMI is associated with an increased risk of calcium oxalate stone formation. The evaluation of urinary risk profile in calcium oxalate stone patients revealed a positive relationship between BMI and urinary uric acid, sodium, ammonium, and phosphate excretion and an inverse correlation between BMI and urinary pH in both genders.
Urinary uric acid contributes substantially to the risk of calcium oxalate stone formation because high concentrations of uric acid lead to decreased solubility of calcium oxalate and might be associated with a reduced inhibitory activity of glycosaminoglycans on the crystallization of calcium oxalate (8). In the present study, serum and urinary uric acid levels increased with increasing BMI among both men and women in the study population, although urinary excretion and serum concentrations of uric acid were higher and increased to a greater extent in men compared with women. Moreover, the prevalence of hyperuricemia and gout was 30% in overweight and obese men compared with 18% in the normal-weight men in the study population. The increases in serum and urinary uric acid levels in calcium oxalate stone formers are suggested to be predominantly related to increased dietary purine intake and to a lower extent to elevated endogenous uric acid production (9). Because serum creatinine increased with increasing BMI, the data indicate that increased serum uric acid concentration in overweight and obese patients is mainly attributed to a slightly impaired renal clearance of uric acid rather than overproduction (10). The evaluation of a national data base from 5942 unselected patients with urinary stones of various composition confirmed elevated serum and urinary uric acid levels in morbidly obese men (defined as body weight >120 kg) and women (>100 kg) compared with nonobese men (<100 kg) and women (<85 kg) cohorts. In contrast to our findings, obesity was more frequent among women in the study population, representing 3.8% and 12.6% of the men and women, respectively (11).
Urinary sodium excretion was strongly correlated with BMI among men and women. The evaluation of obesity-related diseases showed that hypertension occurred in 25% of the overweight and obese but in only 7% of the normal-weight study population. Limitation of sodium chloride intake and the reduction of body weight are considered as effective measures for reducing blood pressure (12, 13).
The present study revealed a significant positive relationship between BMI and urinary calcium excretion, one of the main risk factors for calcium oxalate stone formation, only among men. A high intake of calcium, animal protein, and sodium are suggested to increase urinary calcium excretion in calcium oxalate stone patients. A recent randomized prospective trial showed that restricted intake of animal protein and salt, combined with a normal calcium intake, is more effective than the traditional low-calcium diet in reducing the risk of recurrent calcium oxalate stones in men with idiopathic hypercalciuria (14). A high prevalence of hypercalciuria also has been reported in patients with untreated essential hypertension (15). Because serum calcium concentration was within the normal range and not associated with BMI, systemic disorders such as primary hyperparathyreoidism as cause for the higher calcium excretion can be excluded.
In the current data, urinary oxalate excretion was positively correlated with BMI only in women. Among obese women (BMI ≥ 30 kg/m2), oxalate excretion was 39% higher compared with normal-weight women (BMI 18.5 to 24.9 kg/m2). In a recent study of 476 patients (286 men and 190 women) with idiopathic renal calcium stone disease, urinary oxalate excretion was also significantly related to BMI (16). The relationship between BMI and urinary oxalate excretion may be more likely due to increased endogenous production or intestinal absorption of oxalate. Intestinal oxalic acid absorption is dependent on dietary intake (17) and the presence of other nutritional factors, such as calcium (18), ascorbic acid (18), fat (19), or dietary fiber (20), which are suggested to influence enteric oxalate concentration and absorption rate. Moreover, the percentage of intestinal oxalate absorption was shown to be significantly higher in stone formers compared with healthy subjects (21). Although we do not have information regarding dietary intake for our subjects, a higher intake of chocolate, a foodstuff rich in oxalate, could be the reason for the higher urinary oxalate excretion in overweight women. Previous studies revealed a significant increase in urinary oxalate excretion after ingestion of chocolate (17, 22, 23).
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 but was higher in men than in women.
The role of urine volume as a major risk factor in calcium oxalate stone formation is well recognized. In a prospective randomized study of high water intake in 199 first time calcium stone formers and 101 controls, results demonstrated that subjects in the intervention group had significantly higher urine volumes, a 50% lower recurrence rate, and a longer interval for recurrence during a 5-year follow-up (24). Due to the dilutional effect and the reduction in supersaturation ratios, a high fluid intake is the most important measure in the treatment of urinary stones. There is consensus that a daily intake of fluid should be at a level that results in at least 2.0 to 2.5 L of urine output (25). Depending on the degree of physical activity and surrounding temperature, it is necessary to drink 2.5 to 3.0 L, evenly distributed over the day. Based on these results, a weight-related and not consistent fluid intake should be recommended to stone formers to ensure an adequate urinary dilution with increasing BMI.
The present data demonstrate that overweight and obesity are strongly associated with an elevated risk of stone formation in both genders due to an increased excretion of urinary promoters but not inhibitors of calcium oxalate stone formation. Moreover, the increased incidence of hypertension and the elevated number of stone episodes in patients with increasing BMI resulted in a slightly impaired renal function as indicated by an increased serum creatinine level. The essential findings of this study are a higher risk of calcium oxalate stone formation, median number of stone episodes, and frequency of diet-related diseases in overweight and obese men vs. women, indicating that overweight and obese men are more prone to stone formation than women.
In conclusion, the data suggest that overweight, obesity-related food pattern and nonadjusted drinking habits are related to increased risk of calcium oxalate stone formation and other metabolic disorders. The data support evidence on the significance of dietary modification to prevention of overweight and related diseases. Therefore, weight reduction along with a sufficient fluid intake should be the first line treatment in every overweight or obese stone former.