Blood pressure and glomerular filtration rate in obese adolescents

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INTRODUCTION
Hypertension (HT) has long been known as a health problem. In adolescents, hypertension is also a problem because adolescents who experience hypertension can continue into adulthood and have a high risk of morbidity and mortality. 1 The risk factors for HT include obesity, family history of HT, change in dietary habits, decreased physical activity, and increasing stress. 1 Obesity is a disorder characterized by excessive accumulation of body fat tissue, increasing in prevalence and is a health problem throughout the world. 2, 3 The majority of obesity in children and adolescents has increased in various countries, including Indonesia. 3, 4 Obesity in children and adolescents is estimated to increase the risk of hypertension 3-5 times, and there is a positive relationship between obesity in children with hypertension as reported in various countries. [2][3][4][5] There is clear evidence of an association between being overweight and an increased risk of kidney disease in adults. 5 The same relationship is also seen in children and adolescents who are obese, although there are still conflicts about glomerular filtration rate (GFR) in children with obese and non-obese. Obesity is a risk factor for the development and progression of kidney disease, which can still be modified. 4,5 Efforts to prevent obesity and treat obese children and adolescents have a considerable impact on the incidence, development, and comorbidities of kidney disease. The present study was conducted to prove the difference in blood pressure and kidney function in adolescents with obese and non-obese.

METHODS
A cross-sectional study was conducted among high school children in Denpasar aged 15-17 years from October 2019 until April 2020. Eligible subjects were enrolled by consecutive sampling and agreed to participate in the study. Exclusion criteria were subjects with Diabetes Mellitus (DM) and didn't come when taking the blood serum. The final sample included 4 high schools in Denpasar, representing 4 districts in Denpasar. Written informed consent was obtained from the parents of all the participating children.
Height percentile and body mass index (BMI) percentile were determined by using Centres for Disease Control (CDC) growth charts (2-20 years, CDC and Prevention growth charts, USA): obesity was defined as BMI≥95 th percentile, and non-obese was BMI<95 th percentile for age and gender. 6 The diagnosis and classification of hypertension were based on 'The 4th Report on Diagnosis, Evaluation and Treatment of High Blood pressure (BP) in

Blood pressure and glomerular filtration rate in obese adolescents
Gusti Ayu Putu Sri Satya Mahayani 1* , I Made Arimbawa 1 , Ida Bagus Subanada 1 , I Wayan Dharma Artana 1 , I Nyoman Budi Hartawan 1 , I Ketut Suarta 1 Background: Obesity in children has the potential to increase the risk of morbidity and even death in the future. One of the diseases that are at risk due to obesity is hypertension and also impaired kidney function. Glomerular filtration rate differences in obese and normal-weight children are somehow contradictory. This study aims to prove the difference in blood pressure and kidney function in adolescents with obese and non-obese. Methods: A cross-sectional study was conducted among high school children in Denpasar. Subjects were classified as obese and non-obese. The Mann-Whitney test was used to assess the mean difference of blood pressure, whereas the Independent t-test was used to determine the mean difference of GFR. Multivariate analysis was performed with logistic regression and ANCOVA. Data were analyzed using SPSS version 20 for Windows. Results: A total of 68 subjects with obese and 52 subjects with non-obese were included in this study. Systolic and diastolic blood pressure in the obese group was higher than in a non-obese group, with the mean difference in systolic and diastolic blood pressure was 29 mmHg (P<0.001) and 18 mmHg (P=0.002), respectively. Obesity increases the risk of hypertension 9.78 times (95% CI: 1.86-51.39; P=0.007), and obese adolescents have an average GFR of 11.51 lower than non-obese (95% CI: 17.32 -(-5.69); P<0.001). Conclusion: Hypertension is higher in obese adolescents than non-obese, while glomerular filtration rate is lower than non-obese adolescents.
Children and Adolescents, 2004: hypertension (HT) in this study was defined from prehypertension and above (BP levels ≥90 th percentile). 7 Blood pressure was measured separately three times during one    8 Salt intake is the total amount of salt sourced from the food consumed by the subject. The description of salt intake is obtained from food recall 3x24 hours since it was used as a sample. Family history is a record of health information covering three generations of families, including relatives, parents, aunts and uncles, and grandparents, regarding the history of hypertension and DM. All the data is recorded using a questionnaire that was completed by the subjects. Data were entered into a computer program. The Mann-Whitney test was used to assess the mean difference of blood pressure, whereas the Independent t-test was used to evaluate the mean difference of GFR. Multivariate analysis was performed with logistic regression and ANCOVA. Data were analyzed using SPSS version 20 for Windows.

RESULTS
Total subjects obtained amounted to 120, consisting of 68 obese and 52 were non-obese. The distribution of boys and girls in the obese group is greater than the non-obese group (Table 1), with the largest population being 16 years. Family history (HT or DM) was higher in the obese group by 23 (71.9%) with a median salt consumption of 4.02 (2.8-5.8) grams/day (Table 1). Most obese groups are present a familial history (71.9%) of hypertension (Table 3).
Hypertension in the obese group was more significant than the non-obese group (Table 2), with a prevalence ratio of 3.97 (95% CI: 1.6-9.6; P<0.001). Glomerular filtration rate in the obese and non-obese groups are shown in Table 3. Table  3 shows the mean GFR value in the obese group is lower than the non-obese group with a mean difference of 12.62 ml/min/1.73 m 2 (95% CI: -18.56 -(-6.68); P<0.001).
Systolic and diastolic blood pressure in the obese group was higher than in a non-obese group, with the mean difference in systolic and diastolic blood pressure was 29 mmHg (P<0.001) and 18 mmHg (P=0.002), respectively (Table 4).
Multivariate analysis was performed to determine the pure relationship between obesity to blood pressure and GFR after calculating confounding variables, namely age, sex, family history, and salt intake (

DISCUSSION
This study included adolescents as research subjects because the prevalence of adolescents with obesity has increased, including in Indonesia. National and Bali Province Riskesdas data in 2013 showed that the highest majority of obese adolescents was 13 to 15 years. Denpasar regency was one of the cities with the highest prevalence of obese adolescents in Bali Province. 9 This study found a more significant proportion of obesity than non-obese in both boys (63.5% vs. 36.5%) and girls (51.5% vs. 48.5%). A previous study by Malik M and Bakir A also found a high prevalence of obesity in both boys and girls by 20.2% and 22.9%. 10 The high prevalence of obesity in both boys and girls adolescents was also reported in a previous study by Rutkowski B et al. and Kumar P et al. 1,11 This increased prevalence of obesity is associated with an increased time spent in sedentary activities and decreased levels of physical activity, related cardiovascular risk factors, including HT and insulin resistance. 1 Adolescents who come from families with a history of hypertension have a greater risk of suffering from hypertension than families without a history of hypertension. 4 Adrogue HJ and Madias NE, regarding the pathogenesis of potassium and sodium in hypertension, mentioned hereditary factors affecting primary hypertension through several genes involved in vascular regulation and sodium reabsorption by the kidneys. 12 In this study, a greater family history of hypertension or DM was found in the obese group (71.9%) than non-obese (28.1%).
Predisposing factors for primary hypertension are quite a lot, namely race, sex, family/ genetic history, and influencing factors such as salt consumption, stress, and obesity. Obesity is often associated with primary hypertension and is found in almost 50% of cases. 13 Feld LG and Corey H found around 85-95% in adolescents with primary hypertension. 14 Adolescents with primary hypertension are mostly asymptomatic and are often detected only at a routine examination.
In this study, the incidence of hypertension in obese adolescents 3.97 times compared to nonobese adolescents, with systolic and diastolic blood pressure, was higher in the obese group rather than a non-obese group with a mean difference for systolic and diastolic blood pressure was 29 mmHg (P<0.001) and 18 mmHg (P=0.002) respectively. A meta-analysis study conducted by Rosner B et al. also found that children with BMI> P90 had a 2.5-3.7 times higher chance of hypertension than children who had normal weight. 15 Research conducted in Minahasa by Kembuan IY et al. found that obese subjects were 3.4 times more likely to develop hypertension. 16 Multivariate analysis showed that obesity increased the risk of hypertension by 9.78 times. Obesity is known to affect the occurrence of hypertension with various pathways. The hypothesis is most likely to explain hypertension in obesity if hypertension is associated with a complex interaction between sodium retention, activation of the sympathetic nervous system, the renin-angiotensin-aldosterone system (RAAS), and insulin resistance. 13 Obesity also causes decreased arterial compliance, decreased distensibility, and decreased endothelial function that plays a role in hypertension occurrence. 17 Multivariate analysis also found male sex results reduced the risk of hypertension by 88% (OR= 0.12; 95%CI: 0.03-0.52; P=0.004), and also adolescents who consume high salt have a 33 times risk of hypertension compared to normal salt consumption. This result is in line with the previous study by Malik M and Bakir A, who also mention that hypertension in girls (5-17 years) is higher than in boys with research conducted in urban areas. 10 Current social and cultural factors are said to play a role, namely more women and especially teenage girls tend to spend most of their time at home. They usually have less time to exercise and spend more time socializing by involving food in these activities. Different results  3 Multivariate analysis showed that the obese group had an average GFR of 11.51 lower than the nonobese group (CI 95% -17, 32 to -5.69), P <0.001). Obesity is associated with various risk factors, including hyperinsulinemia, hypertension, glucose metabolism and hyperlipidemia, RAAS activation, oxidative stress, and pro-inflammatory cytokines. Among these risk factors, decreased insulin sensitivity is an essential factor in the relationship between obesity and metabolic complications, leading to chronic kidney disease (CKD). Different results were found by Koulouridis E et al. which showed a higher GFR in obese children reflecting the stage of hyperfiltration. 20 In contrast, Goknar N et al., and Cindik N et al. found no difference in GFR between obese and non-obese children. 21, 22 The study also showed that gender and salt intake influenced the decrease in GFR, with women having an average GFR of 10.77 times lower than men and high salt intake increasing the likelihood of a GFR decrease of 9.85 times. Some studies mention the reduction in GFR is more quickly seen in women. It was explained that women might have a higher GFR than men in young adults due to greater body surface area, which can cause a faster rate of GFR reduction similar to that seen in renal pathology related to hyperfiltration. Second, as a woman's age increases, the impact of estrogen on hemodynamics and kidney structure decreases due to a gradual decrease in estrogen levels even before the menopause. 23 High salt intake has a damaging effect on glomerular hemodynamics, induces hyperfiltration and increases glomerular filtration fraction and pressure. A decrease in proteinuria is consistently observed in patients with restricted salt consumption, regardless of blood pressure changes. [24][25][26] This study's limitation is that this study has not been able to fully control the confounding factors because stress factors and physical activity have not been included in the questionnaire. The method used in this study was a cross-sectional method so that the assessment of blood pressure and GFR in this study does not consider the duration of obesity.

CONCLUSION
Hypertension is higher in obese adolescents than non-obese, while glomerular filtration rate is lower than non-obese adolescents. There was a statistically significant difference between hypertension, GFR, and blood pressure based on nutritional status. In addition, obesity increases the risk of hypertension 9.78 times and obese adolescents have an average GFR of 11.51 lower than non-obese significantly.