METABOLIC SYNDROME TRAITS IN UROLITHIASIS PATIENTS

Objective: To explore the relation of MetS and urolithiasis in our center. Material & Methods: This is a prospective study of all patients diagnosed with urolithiasis in Kardinah Hospital, Tegal, from April to June 2018, who were screened for metabolic syndrome criteria. The data was collected from the medical record and analyzed with SPSS ver. 23. Results: We included 71 cases of urinary tract stone in our center. 8.4% of the patients didn't undergo definitive therapy for stones caused by patients' preferences or the surgery being postponed with various reasons. The patient's mean age is 54.7 ± 2 11.24, with a male to female ratio 2.4:1. The average BMI is 20.9 ± 2.3 kg/m . Most of the stones are found in kidney (38.0%) and bladder (26.8%). The average blood pressure is 127.2 ± 7.96 mmHg for systolic pressure and 81.6 ± 5.77 mmHg for diastolic pressure. The average values of lipid profile include total cholesterol, highand low-density lipoprotein, and triglyceride were 177.0 ± 35.92, 52.0 (27-96), 107.3 ± 37.58 and 131 (50-406), respectively. The mean of patient's blood glucose level is 122 mg/dL, and the highest level is 203 mg/dL. Conclusion: Not all of the MetS traits found in our patients in Kardinah Hospital. The HDL level is the only variable that shown abnormal level and it could be included into one of the MetS criteria of diagnosis. Thus, this observational study needs further research to confirm the correlation between urolithiasis and MetS, and also the underlying mechanism.


INTRODUCTION
Metabolic syndrome (MetS) is a cluster of commonly co-occurring metabolic risk factors associated with cardiovascular disease and type 2 diabetes mellitus, including elevated blood pressure, atherogenic dyslipidemia, insulin resistance, and syndrome varies by definition used, ethnic 2 background, age, sex, and socioeconomic status. This appears to increase worldwide, likely due to 1 increasing obesity and sedentary lifestyles. In Europe, the prevalence of the metabolic syndrome is 3 41% in men and 38% in women.
In Indonesia, the prevalence of MetS is 4 28.4%. MetS influences the acidity in urine, which the oretically influence the formation of uric acid, 5 calcium and oxalate stone. The previous study showed that metabolic syndrome was associated with other chronic diseases, such as renal failure, prostatic disorder, and stone formation, especially kidney 6 stone. Another study also recommends patients with urolithiasis should be screened for metabolic syndrome. However, this recommendation remains controversial in the case of different demographic 7 data of the patients. In our center, there is no previous study that examined the profile of MetS with urolithiasis.

OBJECTIVE
This study aims to explore the relation of MetS and urolithiasis in our center.

MATERIAL & METHODS
This study was conducted using prospective study. All patients diagnosed with urolithiasis in Kardinah Hospital, Tegal, from April to June 2018, were screened for metabolic syndrome criteria. We will determine demographic data as well. Then, data was analyzed descriptively with SPSS ver. 23.0.

RESULTS
We included 71 cases of urinary tract stone in our center. Not all of the patients underwent definitive therapy for stones caused by patients' preferences or the surgery being postponed with various reasons (n = 6, 8.4%). The results are were presented in the following tables.

DISCUSSION
The average age of patients come with urolithiasis was 54.7 ± 11.24 years old which slightly [8][9] higher compared to other studies. According to Denstedt et al, stone prevalence increased in all age groups, but the composition of the stone was 10 influenced by the region and age. For example, Taiwanese patients tend to have higher prevalence of calcium stone in young people but tend to have higher prevalence of struvite and uric acid stone in 11 older patients. While in France, the prevalence of 12 uric acid stone increased with age.
In this study, we could also assess the gender profile of urolithiasis patients. Commonly, we use male/female ratios to describe the distribution of gender among urolithiasis patients. The male/female ratio was 2.4, which has no differences with other [12][13] literature.
The differences of urolithiasis cases between male and female might be caused by 14 lifestyle and dietary habits. 2 The average BMI is 20.9 ± 2.3 kg/m , which is within the normal range. This result is different compared to other studies in which the mean BMI of 2 15 patients with urolithiasis was 24.5 ± 7.5 kg/m . BMI is one of many parameters assessed as a risk factor 9 for stone formation. Not only act as a risk factor of stone formation, obesity was also associated with the 16 types of stone formed. Obese patients might have greater risk of stone formation due to increased 8 urinary phosphate excretion. Other mechanism, overweight or obesity was correlated with low urine pH and an increase in uric acid level in urine, thus uric acid stone formation could have happened in 17 acidic urine. However, we referred the stone formation as a multifactorial and complex process, involving metabolic, genetic, and environmental factors. The acidity of urine was not the only factor [18][19] influencing the stone formation.
This study also describes the characteristics of the stone in urolithiasis patients. Most of the stones are found in kidney and bladder. The size of the stones is varied, but the smallest stone found is 5 x 2 mm and the largest is 120 x 90 mm. With various sizes of the stone, the author should decide different approach for the therapy or stone removal procedures. The therapies conducted for these stone cases are extracorporeal shockwave lithotripsy, lithotripsy, open pyelolithotomy, open ureterolithotomy, percutaneous nephrolithotomy, sectio alta, and other therapies to aid releasing the obstruction caused by stone such as nephrostomy or insertion of the double-J stent.
The average blood pressure found in this study is 127.2 ± 7.96 mmHg for systolic pressure and 81.6 ± 5.77 mmHg for diastolic pressure. These values are considered normal according to the Joint t h National Committee's 8 report (JNC 8). Pharmacologic treatment should be initiated at systolic blood pressure (SBP) more than 150 mmHg or diastolic blood pressure (DBP) more than 90 mmHg to lower the blood pressure with goal less 20 than 150 mmHg and 90 mmHg respectively. There are several hypotheses linked urinary tract stone especially nephrolithiasis with abnormal blood pressure, hypertension. A study from Borghi et al. found higher urinary calcium level excretion in hypertensive patients compared to normotensive 21 patients. However, not only urinary calcium linked to hypertension and urolithiasis, but also citrate, 22 oxalate, and uric acid level were connected as well. Stone could also relate to inflammation and oxidative stress which leads to renal vaso- 23 constriction, ischemia, and injury. The prolonged injury would cause a chronic kidney disease with 24 damage at the glomerular and tubulointerstitial site.
Association of stone and hypertension is a reciprocal relationship. Hypertension could be a risk factor for stone formation, as well as urinary tract stone could 25 be a risk factor for hypertension.
The average values of lipid profile include total cholesterol, high-and low-density lipoprotein, and triglyceride were 177.0 ± 35.92, 52.0 (27-96), 107.3 ± 37.58 and 131 (50-406), respectively. This study also shows an increase in HDL level with a normal level of triglyceride. As Masterson et al. stated in their study, dyslipidemia increases the risk of nephrolithiasis, with HDL level less than 45 and 2 6 60 for males and females respectively. Dyslipidemia could be an independent risk factor of kidney stone regardless other aspects of metabolic 27 syndrome such as diabetes mellitus and obesity. Hypertriglyceridemia was known for not only increasing the risk of stone formation but also increasing the risk of recurrence in patients with 28 urolithiasis. The presence of dyslipidemia in particularly children and adolescent was related with calcium oxalate crystallization with hypocitraturia 29 as a predisposing factor.
Another parameter assessed in this study is blood glucose. This study shows that the mean of patient's blood glucose level is 122 mg/dL, and the highest level is 203 mg/dL. For metabolic syndrome classification, it uses fasting blood glucose more than 100 mg/dL as a threshold. However, a c o n s e n s u s f r o m P E R K E N I ( I n d o n e s i a n Endocrinologist Association), states that one of the diagnosis criteria of Diabetes Mellitus is incidental blood plasma glucose level more than 200 mg/dL 30 with classic complaint. Nonetheless, our study shows that most of the patients have normal blood glucose level. Many studies concluded that the severity of Diabetes Mellitus would correlate with the risk of kidney stones. The more severe the 31 disease, the risk would increase. Blood glucose level could be an independent risk factor of kidney 32 stones. Therefore, tighter glycemic control might 33 reduce stone formation in diabetic patients.
If we discuss all of these parameters as one risk factor, we could discuss the metabolic syndrome. Many studies conducted concerning the metabolic profile of urolithiasis patients and their correlation with urolithiasis itself. The dominant aspect in Metabolic Syndrome (MetS) traits could determine the composition of the stone. Kidney 7,34 stone might be the renal manifestation of MetS. The application of this knowledge would be applicable in treating patients since MetS was a 35 modifiable factor. Adequate lifestyle modification and proper treatment could be the prevention of 36 urolithiasis. There would be differences in metabolic profile amongst urolithiasis patient since metabolic syndrome should be considered as a multifactorial systemic disorder needing multidisciplinary approach for the management and 37 prevention.

CONCLUSION
To sum up, not all of the MetS traits found in our patients in Kardinah General Hospital. The HDL level is the only variable that shown abnormal level and it could be included into one of the MetS criteria of diagnosis. Thus, this observational study needs further research to confirm the correlation between urolithiasis and MetS, and also the underlying mechanism.