Stone disease affects 7%-15% of the population and is a disease observed more often in men than in women (1.8/1). Genetic and environmental factors are the main causes of this disease. Factors like diabetes mellitus (DM), obesity, bariatric surgeries, small intestine surgeries, vitamin C supplements, nutritional habits, and excessively warm climate and working in warm environments for long durations are blamed for the etiology of this disease. Some of these factors affect urine pH, while some affect urinary metabolites.‌^[1]

Obesity has become a continuously increasing epidemic problem in the present day, especially in developed countries.^[2] Studies in recent times have reported that more than 30% of Americans are obese. Obesity is simultaneously a metabolic syndrome causing many morbid, mortal, and chronic diseases led by type 2 DM, heart diseases, hypertension, pregnancy complications, and sleep apnea. Based on epidemiological studies, urinary system stone disease may be added to the morbidities due to obesity. While recent epidemiological studies reported increasing prevalence of obesity^[3], the prevalence of kidney stone disease was also reported to increase^[4]. This association leads to the conclusion that these diseases share a common pathophysiology. However, to date, very little is known about the pathophysiological relationship between obesity and stone disease. Some studies reported that obesity and being overweight lowered urine pH and increased uric acid, calcium, oxalate, and phosphate in urine.^[5]

In this study, we aimed to see whether there was a negative effect of weight on stone disease by assessing 24-hour urine analysis in stone patients in our region.

Aune et al.^[6] found that stone formation increased 1.4 times in overweight patients, while it increased by 2-3 times in obese and severely obese patients. A study by Akarken et al.^[7] found that metabolic syndrome components like obesity, hyperlipidemia, and hypertension, along with the ratio of visceral fat tissue to subcutaneous fat tissue, were important factors for kidney stone formation. Deng et al.^[8] found that the risks for hypertension and DM were higher in overweight and obese patients compared to people with a standard weight, and this situation increased the tendency to ward off urinary system stone disease. Taylor et al.^[9] reported a connection between BMI and waist circumference measurements with increased kidney stone formation. Sorensen et al.^[10] found that the risk of stone formation increased as BMI increased. Lama et al.^[11] reported that in kidneys containing calcium oxalate stones, perirenal fat volume was higher than in patients without stones and the increase in abdominal visceral fat tissue was associated with uric acid and calcium oxalate stone formation, while the ratio of visceral fat tissue to subcutaneous fat tissue was positively correlated with renal stone formation. In fact, obesity in the pediatric age group was reported to increase stone formation risk without observing any change in lithogenic amounts in urine.

In this study, we found that increasing BMI showed a positive correlation with the increase of lithogenic factors such as urinary pH, uric acid, calcium, oxalate and phosphate, but inhibitory factors such as citrate and magnesium did not change. In fact, in multivariate analysis, BMI was the only factor predicting recurrent stone formation. Siener et al.^[4] reported that weight and obesity increased lithogenic factors without changing stone inhibitors in urine for formation of calcium oxalate stones and that people who were overweight had a higher risk of calcium oxalate saturation compared to patients with normal weight.

Abdominal obesity is reported to make urinary pH more acidic as a result of increasing the net acid load in urine by reducing reabsorption of H+ ions and ammonium secretion from proximal renal tubules causing insulin resistance.‌^[12] Zanette et al.^[13] reported that patients with hypercalciuria and hyperuricosuria had high endogenous organic acid levels, which caused urine pH to fall. Additionally, high protein intake in overweight stone patients is known to increase urine acidity. Because of the decrease in urine pH, tubular uric acid crystal saturation is easier, increasing uric acid stone formation, a long-known fact. Additionally, as BMI increases, urinary uric acid amounts elevate in both sexes.^[14] A national database study assessing 5942 patients with a variety of urinary stones reported that excessively overweight men and women had higher serum and urinary uric acid levels compared to overweight men and women.‌^[3] For this reason, the elevated urinary uric acid level in patients with high BMI in our study is considered to be due to both consumption/nutrition and body mass weight. In this study, we also found a weak positive correlation between uric acid and stone volume. In other words, as the amount of uric acid in the urine increased, the stone size also increased. There are studies in the literature reporting that factors such as age, UTI, recurrence, serum calcium, serum phosphate, and urine albumin correlate directly with stone size.^{[15, 16]} However, we could not find an article that studies the connection between urinary lithogenic factors and stone volume. Since the causes of stone formation are multifactorial, we think that this positive correlation should be considered in studies with larger series in order to make a decision and make recommendations.

We observed in our study that the increase in BMI showed a positive correlation with the increase in the number of patients with DM. It has also been found that as BMI increases, urine becomes more acidic and uric acid levels become higher. Spiwakov et al.^[17] stated that acidic urine is the most frequently observed abnormality in patients with DM and is responsible for the formation of uric acid stones. Assimos discovered that insulin resistance in type 2 diabetes causes a deficit in the kidneys’ ammonium production, lowering urinary pH.^[18] creating as a result suitable environment for uric acid stones. Nerli et al.^[19] highlighted that there is a strong correlation between type 2 diabetes and uric acid stone formation and that there is a strong association between DM, BMI, and low urinary pH.

Urinary calcium excretion was reported to be higher in overweight and obese males compared to normal weight males.^[4] High urinary uric acid levels may simultaneously lower the solubility of calcium oxalate in urine and cause calcium oxalate stone formation. Additionally, glycosaminoglycans, inhibitors of calcium oxalate crystallization in urine, were reported to be associated with calcium oxalate stone formation in obese people with reduced inhibitory activity. The 6th National Stone Congress in Japan emphasized that kidney stones increased with the reported increase in urinary calcium and uric acid excretion associated with metabolic syndrome. Kohjimoto et al. identified a positive correlation between BMI and urinary calcium excretion.^[12] Insulin reduces calcium absorption in renal tubules in overweight patients and was found to increase urinary excretion of calcium. Additionally, with Dukan-like diets dominated by animal protein, urinary calcium increases, citrate reduces and lithogenic risk is reported to increase.‌^[20] In men, urinary calcium and BMI were associated; as BMI increased, urinary calcium increased, while urinary calcium levels returned to normal when dietary sodium and phosphorus were fixed.

Danilovic et al.^[21] reported a positive relationship between weight and urinary oxalate excretion. When compared with healthy people, those patients who had oxalate stones were shown to have higher oxalate absorption rates.‌^[22] Seiner et al.^[4] predicted that excessive intake of foods rich in chocolate and oxalate, especially in overweight and obese women, may cause high oxalate excretion in urine. In studies conducted in overweight rats, it was found that intestinal and renal tubular oxalate excretion decreased due to the inhibition of the transport pathway by proinflammatory cytokines increasing in the intestinal wall.^{[22, 23]} It has been suggested that the decrease in Oxalobacter formigenes colonization in obese patients reduces the oxalate excretion mechanism.^[22] A study of idiopathic renal calcium stone patients found a clear degree of association between urine oxalate excretion with BMI.^[24] In another study reporting a positive correlation between oxalate excretion with BMI only in women, obese women with BMI >30 kg/m2 had 39% oxalate excretion compared to women with normal weight. Lemann et al.^[25] identified a positive correlation between oxalate excretion in urine and fat-free body mass. Ekeuro et al.^[26] reported higher urine oxalate values in obese stone patients compared to non-obese patients.

Taylor et al.^[9] and Curhan et al.^[27] identified positive correlations between BMI, uric acid and phosphate excretion with multivariate regression analysis. Deng et al.^[8] reported that urine phosphate values were higher in overweight cases compared to normal weight people in multiple regression analysis of 24-hour urine results in individuals without stone disease (p=0.047). Khand et al.^[28] reported a positive correlation between hypocitraturia and phosphaturia in first-time stone patients and considered that high urinary phosphate amount was the main risk factor for calcium urolithiasis. Gyawali et al.^[29] found that people with stone formation had higher urine phosphate level to a clear degree compared to people without stones and this situation was a risk for stone formation in urine. Siener et al.^[4] reported that urinary phosphate excretion was higher in overweight and obese patients with calcium stones.

It has been reported that primary parathyroid hyperplasia causes stone formation in approximately 5% of kidney stone patients. Normally, when blood levels of calcium reach the optimum level, PTH secretion from the parathyroid stops. However, in case of primary hyperplasia, the parathyroid does not listen to the stop command and PTH continues to be released. As serum PTH levels increase, hypercalcemia and hypercalciuria occur. It causes calcium oxalate supersaturation, which causes stone formation in the urine.^[30] However, we did not detect any difference in PTH levels in this study.

The main limitation of our study is that it is retrospective. We could not include serum electrolytes and stone composition data in our study. We also could not investigate diet and nutritional habits in our study. Apart from BMI, we could not investigate the effects of other obesity parameters like visceral obesity, waist circumference measurement, subcutaneous fat rates, and visceral fat/subcutaneous fat ratio on lithogenic factors and stone formation. In the future, it is recommended that prospective multicenter studies encompassing these parameters be performed.

As the BMI index increases, the amount of urinary lithogenic factors increases. On the other hand, there is no change in the amount of inhibitory urinary lithogenic factors. As BMI increases, the risk of recurrent stone formation increases.

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The authors have no funding to report.

The authors have declared that no competing interests exist.