Urolithiasis and sleeve gastrectomy: a prospective assessment of urinary biochemical variables

ABSTRACT Introduction: to evaluate urinary biochemical alterations related to urolithogenesis processes after sleeve gastrectomy (SG). Materials and methods : prospective study with 32 individuals without previous diagnosis of urolithiasis who underwent SG. A 24-h urine test was collected seven days prior to surgery and at 6-month follow-up. The studied variables were urine volume, urinary pH, oxalate, calcium, citrate, and magnesium and calcium oxalate super saturation (CaOx SS). Results: patients were mainly women (81.2%), with mean age of 40.6 years. Mean pre- and postoperative BMI were 47.1 ± 8.3 Kg/m2 and 35.5 ± 6.1 Kg/m2, respectively (p<0.001). Urine volume was significantly lower at the postoperative evaluation in absolute values (2,242.50 ± 798.26 mL x 1,240.94 ± 352.39 mL, p<0.001) and adjusted to body weight (18.58 ± 6.92 mL/kg x 13.92 ± 4.65 mL/kg, p<0.001). CaOx SS increased significantly after SG (0.11 ± 0.10 x 0.24 ± 0.18, p<0.001). Moreover, uric acid levels were significantly lower at the postoperative evaluation (482.34 ± 195.80 mg x 434.75 ± 158.38 mg, p=0.027). Urinary pH, oxalate, calcium, citrate, and magnesium did not present significant variations between the pre- and postoperative periods. Conclusion: SG may lead to important alterations in the urinary profile. However, it occurs in a much milder way than that of RYGB.


INTRODUCTION
T he association between obesity and the risk of urinary lithiasis has been extensively reported. The mechanisms underlying this relation are multifactorial 1,2 .
Studies on the urinary biochemistry of patients with obesity have shown alterations that predispose to the formation of urinary stones, including hypercalciuria, hypocitraturia, hyperoxaluria, hyperuricosuria, and acid pH 3 .
Ironically, patients who undergo surgical treatment for obesity, specifically using procedures with a malabsorptive component, have also an increased risk of urinary lithiasis 4 . This situation occurs mainly due to hyperoxaluria, hypocitraturia, and reduction of urine volume, which leads to an increase in calcium oxalate super saturation (CaOx SS), facilitating the precipitation process [4][5][6] .
Most published articles on the relation between bariatric surgery and urinary lithiasis analyzed patients who underwent Roux-en-Y gastric bypass (RYGB), a procedure with a malabsorptive component responsible for all of the abovementioned urinary biochemical alterations, which increases the risk of urinary stones after surgery 4,7 . However, there is a lack of data in the literature regarding urinary lithiasis in patients undergoing nonmalabsorptive procedures, especially sleeve gastrectomy (SG). Only a few prospective studies have been published and the results are sometimes conflicting 5,7 .
Therefore, this study aims to prospectively evaluate urinary biochemical alterations related to urolithogenesis processes after SG and determine whether this procedure increases or not the risk of formation of urinary stones.

Study design
We recruited patients who underwent laparoscopic SG in our Institution between July 2018 and December 2019. We included patients from both sexes, aged between 18 and 65, with formal indication for bariatric surgery (BMI between 30 and 34.9kg/m 2 associated with a severe comorbidity, or BMI between 35 and 40kg/m 2 associated with any comorbidity, or BMI > 40 kg/m 2 regardless of comorbidities). Patients with previous diagnosis of urinary lithiasis (regardless of treatment), preoperative glomerular filtration rate < 60mL/min/1.73 m 2 (calculated using the MDRD equation) 8 , and use of medications that interfered with the urinary metabolism (diuretics, probenecid, angiotensin-converting-enzyme inhibitors, and angiotensin II receptor blockers) were excluded from the study. Patients with inadequate urine collection were also excluded (see "Technical procedures" below).

Technical procedures
All included patients underwent an abdominal ultrasonography as a screening method for the diagnosis of urinary lithiasis. Those patients who did not present urolithiasis in the ultrasound were evaluated through a 24-h urine collection test at two different moments: seven days prior to surgery and at the 6-month postoperative follow-up. To collect the 24-h urine for testing, patients were instructed to discard the first sample in the morning and collect all subsequent samples, including the first sample in the following morning. Urine samples were stored in a refrigerator (2-8ºC) before sending them to the laboratory for analysis. This occurred, in all cases, right after the collection of the last sample.
To estimate the reliability of the collected samples, 24-h urinary creatinine was measured. The normal 24-h urinary creatinine excretion is 955-2,936mg (or 13-29 mg/kg) for men and 601-1,689mg (or 9-26mg/ kg) for women 9 . Levels of urinary creatinine in a 24-h sample below these normal ranges means inadequate urine collection, and thus, the sample was excluded from the analysis.
The same laboratory analyzed all samples. The quantitative variables were 24-h urine volume, 24-h urine volume adjusted to body weight, urine pH, 24-h levels of urinary oxalate, calcium, citrate, magnesium, uric acid, and calcium oxalate SS, calculated by the Tiselius index 10 .

Statistical analysis
As part of data analysis, a database was created using Microsoft Excel. It was then exported to SPSS 13.0, in which the analysis was performed. The Kolmogorov-Smirnov test was applied to assess the normality of quantitative variables. To analyze paired samples, the Student T-test was used in situations that had a normal distribution. When the hypothesis of normality of distribution was refuted, the Wilcoxon test was applied. All conclusions considered a significance level of 95%.

DISCUSSION
The onset of urolithiasis in patients undergoing bariatric surgery generally occurs one to two years after the procedure. The mean interval is 1.5-3.6 years between surgery and diagnosis [11][12][13][14]  The mechanism related to a malabsorptive surgery leading to hyperoxaluria is that the unabsorbed fatty acids bind calcium in the intestines, preventing the formation of gut calcium oxalate, which facilitates the absorption of the unbound oxalate 23,24 . Low urinary pH is a common feature in patients with obesity. Generally, it is attributed to insulin resistance 28