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ORIGINAL CONTRIBUTIONS

Received: May 27^th 2014

Accepted: January 30^th 2015

Obesity as a risk factor for metabolic disorders in adults with urolithiasis

Martha Medina-Escobedo,^a Rogelio Alcocer-Dzul,^a José López-López,^a Jorge Salha-Villanueva^a

^aUnidad de Investigación en Enfermedades Renales, Hospital General “Dr. Agustín O´Horán”, Servicios de Salud de Yucatán, Mérida, Yucatán, México

Communication with: Martha Medina-Escobedo

Telephone: (999) 930 3320, extensión 45652

Email: marthamedinaescobedo@hotmail.com

Background: Yucatán ranks first in the prevalence of urinary calculi (UL), and above the national average of obesity (OB). The aim of the study was to determine whether there is an association between obesity and metabolic disorders (MD) in patients with UL.

Methods: In a case-control design, 197 patients were studied with and without UL. Weight and height were measured; urine calcium, phosphate, magnesium, uric acid, oxalates, citrates and sodium were quantified.

Results: 197 subjects, 62 men and 135 women were studied; 114 subjects with UL and 83 without UL. Hyperuricosuria was more frequent in obese patients without UL. Hypocitraturia was the most frequent MD in patients both with and without OB, with and without UL. There was a positive trend towards a greater number of MD as weight increased. Urinary sodium excretion in patients with OB was significant.

Conclusions: Obesity is a risk factor for MD in patients with UL. Strategies must be implemented to spread awareness on the influence of obesity on UL, and how it can be modified by diet.

Keywords: Obesity, Urolithiasis, Metabolic diseases.

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Introduction

The 2006 Encuesta Nacional de Salud y Nutrición (ENSANUT) defines obesity as the result of an imbalance between energy intake and expenditure.¹ A positive energy balance maintained over time will result in the accumulation of fat, which is considered the central feature of obesity.² It is also known that there are several genetic factors that predispose to weight gain.³ 

The 2012 ENSANUT in Mexico reports that 73% of women and 69.4% of adult men were overweight/obese,⁴ for Yucatan, the values ​​of overweight and obesity in adults were 82% for women and 78.6% for men, in both cases higher than the national average.⁵

Obesity is associated with increased risk of some metabolic and cardiovascular diseases, and some cancers.⁶

Moreover, urolithiasis (UL) is defined as the presence of stones in the kidney, ureter, bladder and/or urethra; it is the result of one or more disorders in urinary composition that favor the crystallization of urine.^7,8 It is a multifactorial disease that may involve intrinsic factors such as genetics, race, age, and sex, plus extrinsic factors such as geography, climate, diet, and factors of occupational activity, etc.^9-13

Internationally, UL prevalence described varies significantly by geographic location, ranging from 8 to 19% in men and from 3 to 5% in women; an increase has been seen over time in its prevalence and incidence in countries like Germany, USA, and Iran.¹⁴

In Mexico, there have been few epidemiological studies about UL. A national survey conducted by the Instituto Mexicano del Seguro Social (IMSS) reported a mean UL prevalence of 2.4/10,000 inhabitants; it also reports that Yucatan ranks first with the highest frequency (5.8/10,000 inhabitants). Another work in open population in Yucatan reports a prevalence of 550/10,000 inhabitants.^15,16 

UL is due to an imbalance between the amount of inhibitors (citrate, magnesium) and promoters (calcium, uric acid, phosphates, oxalates) of crystallization in urine;^17,18 various disorders of the chemical composition of urine can create a favorable environment for the formation of kidney stones;⁸ this occurs when the concentration of promoters such as calcium oxalate, calcium phosphate, uric acid, and cystine is high enough, in combination with a low urine volume.^19,20

Furthermore, an inverse relationship is reported between excess weight and urine pH, i.e., the greater the degree of obesity, the more acidic the urine, increasing the risk of developing UL; this, coupled with inadequate food habits and diets rich in purines, oxalates, phosphates, and proteins, alter the pH of the urine and thereby favor the formation of uric acid or calcium phosphate, depending on the pH value present.^17,18,21

It is known that an increase in urinary sodium excretion is a promoting factor of the increase in urinary calcium excretion, thereby increasing the probability of UL formation; the increase in urinary sodium excretion is associated with increased salt intake in the diet.²²

The aim of this study was to determine whether there is an association between obesity and metabolic abnormalities in patients with urolithiasis.

Methods

With prior approval by the Research and Ethics Committee of the Hospital General “Dr. Agustín O´Horán,” the investigation studied adults included consecutively and non-probabilistically, with a case-control design. Cases were patients with UL, and controls were those without UL. UL diagnosis was confirmed by the presence of a stone greater than 0.5 cm in ultrasound and/or x-ray; subjects with a history of a stone expelled within ≤ 7 days previous to study inclusion were classified with UL. Controls were healthy subjects with no history of chronic illness or acute illness within ≤ 7 days prior to study inclusion, who did not take medications or vitamin supplements.

After signing a letter of informed consent where the aim of the research project was explained, both cases and controls had blood and urine sampled. The values ​​of blood chemistry and blood count were determined as part of an initial assessment; subjects with alterations in the normal range were discarded. Controls with alterations in the urinalysis (proteinuria, hematuria) or ultrasound and/or x-ray (cysts, urinary tract malformations) were eliminated.

Weight was obtained by body composition analyzer (model TBF-300A Tanita), as well as height (height rod Seca). After measurement, the subjects were classified into 3 groups according to Body Mass Index (BMI) (normal, overweight, and obese) according to NOM-043-SSA2-2012; for purposes of this research overweight subjects were excluded; lacking criteria for levels of obesity in patients with short stature, it was decided to determine this in three levels of severity, according to parameters similar to those of subjects with normal stature, using BMI to classify obesity grade I ≥ 25, obesity grade II 25 to 29.9, and obesity grade III ≥ 30.

24-hour urine determined calcium, phosphate, magnesium, uric acid, oxalates, citrates, and sodium. Any of the following results in a 24-hour urine sample was considered metabolic disorder: a) hypercalciuria, when urinary calcium was ​​above 300 mg/24 h in males and 250 mg/24 h in women; b) hyperuricosuria, when urinary uric acid was above 750 mg/24 h; c) hyperphosphaturia, when urinary phosphate was above 1300 mg/24 h; d) hypomagnesiuria, when urinary magnesium was less than 17 mg/24 h; e) hyperoxaluria, when urinary oxalate was above 45 mg/24 h, and f) hypocitraturia, when urinary citrate excretion was ​​below 320 mg/24 h. Each group was further divided into weight subgroups of normal or obese.

Student’s t test was used to compare independent samples of general characteristics and the averages of excretion of different analytes in the study subjects. Chi-squared test was performed to compare frequencies of MD between cases and controls, with a confidence interval of 95%; p-value < 0.05 was considered significant.

The project was funded by the Servicios de Salud de Yucatán and the Fundación Mexicana para la Salud Capítulo Peninsular A.C.

Results

197 subjects were included in the study. The population consisted of 62 men (31.5%) and 135 women (68.5%). One hundred and four (57.9%) had UL and 83 (42.13%) did not have UL.

When analyzing the general variables of subjects with UL and comparing them to subjects without UL (Table I), there was significant difference in height (p = 0.013), BMI (p = 0.009) and average urinary citrate (p = 0.019).

Significant difference was observed in the frequency of hypocitraturia both in patients with obesity (OR: 2.97; 95% CI 1.36-6.51, p = 0.008) and in patients with normal weight (OR: 3.72; 95% CI 1.38-10.03, p = 0.01) (Table II).

In 54 patients (27.4%) no MD was observed; 105 (53.3%) had at least one MD, and 38 (19.3%) had more than one MD. When comparing the number of MDs with diagnosis of normal BMI versus obesity, a positive trend was noted for a greater number of MDs with greater weight (Table III).

In analyzing other changes that may influence the formation of urinary stones, significant difference was found in the number of patients with urinary sodium excretion ≥ 100 mEq/L in patients with obesity (OR = 2.12, CI 95% 1.12-3.99, p = 0.009).

Discussion

UL is an increasingly common disease in the adult population. There is information associating obesity with MD and UL; this study assessed adults with and without UL from the metabolic point of view.

There was predominance of males among patients with UL, with a ratio of 2.07:1; this observation may be justified by women's interest in participating in the study, as it does not reflect the relationship that could be found in the general population, as evidenced by a previous report done in open population of Yucatan, which mentions that 6% of men had UL, compared with 5.5% of women.15 The prevalence of UL in males (1.4:1) has also been reported by other authors.⁸

This study detected MD in most subjects with UL, but with results lower than those noted by Sesin et al. and Del Valle. Presenting one MD was the most common, similar to that reported by Del Valle, but contrary to Sesin’s findings, whose study more often found two associated MDs;^8,23 ​​also, different from that reported by Sesin, it was found that in patients with UL and OB, the most frequent MD was hyperuricosuria (13.3%), unlike the present study that found higher frequency of hypocitraturia (57%).²³

Hypocitraturia frequency in the population with UL was higher than that reported in other publications, such as Amaro et al. in Brazil;²⁴ this could be due in part to the Ala62Thr polymorphism in the ZNF365 gene, which conditions hypocitraturia, which is found in the population of Yucatan.²⁵ In addition, there are other factors that influence the decreased excretion of citrates in urine, such as high sodium intake and high intake of animal protein,²⁶ both also related to obesity.²⁷ This, coupled with hyperuricosuria and hypocitraturia, increases the probability of UL.

Moreover, it has been reported that obese subjects have significantly higher mean sodium excretion than subjects with normal weight and overweight;²⁸ with respect to this, this study observed that the frequency of people with NaU excretion ≥ 100 mEq/L was higher in the obese. This may be due to more frequent intake of high-sodium foods by people with excess weight. 

The study findings are of particular importance to the population of Yucatan, since OB is a major problem in the state; also, since the conception of OB is based on "beauty" (in Yucatan, obese people are seen to be "beautiful");²⁹ and because genetic and dietary factors predispose to the formation of UL, the problem is aggravated.^5,11,12,28

This study evaluated patients attending only one hospital, so, in case of future research, it is advisable to include a larger number of people from other hospitals, to allow a more accurate representation of what happens in the state.

It is desirable to conduct studies to determine the eating habits that favor the various metabolic disorders observed in the urine of subjects with obesity. In addition, it is appropriate to implement educational strategies that modify the concept of health and disease in the population of Yucatan with respect to obesity, by informing the public about the effect of obesity on the rise in the number of MD, which favors increased risk for stone formation in the urinary tract, and how these can be modified with adherence to good nutrition.

In conclusion, the results show that in the study population mean BMI was higher in patients with UL; also, obesity was more frequent and greater in these same patients. It was observed that, the greater the degree of obesity, the more MD, and the greater the risk of UL. Finally, the number of patients with elevated urinary sodium was greater in patients with obesity, leading to increased risk for stone formation in the urinary tract. For all these reasons it was possible to establish a relationship between obesity and metabolic disorders that promote stone formation in the urinary tract.

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