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THE RELATIONSHIP BETWEEN BODY MASS INDEX AND ESTIMATED GLOMERULAR FILTRATION RATE

INTRODUCTION: The increasing prevalence of chronic kidney disease (CKD) is a major health problem. The prevalence of obesity has also been rapidly increasing worldwide. Few studies have examined the relationship between excess body weight and CKD risk. Aim: To evaluate the possible contribution of increased body mass index (BMI) to impaired renal function in the general population sample. METHODS: The study involved 500 participants older than 30 years (228 men, 272 women, age blood pressure anthropometric measures were performed on each participant. Estimated glomerular filtration rate was calculated using the abbreviated equation from MDRD study ( ) and CKD was defined as eGFR less than 60 ml/min/1.73m2. Statistical analysis was performed using SPSS 19.0 software (IBM, Somers, New York, USA). RESULTS: The mean BMI was 25.09±3.54 kg/m2with 0.6% in underweight (BMI 18.5 kg/m2), 17.6% in lower normal (BMI 18.5 to 21.9 kg/m2), 33.2% in upper normal (BMI 22.0 to 24.9 kg/m2) and 48.6% in overweight or obese (BMI 25.0 kg/m2) body mass category. The mean eGFR was 100.33±30.78 ml/min/1.73m2 with 112±8.62 in underweight, 116.94±3.8 in lower normal, 102.37±2.39 in upper normal and 92.78±1.72 in overweight or obese category. Estimated GFR values decreased significantly with increasing BMI specially in those in upper normal compared to lower normal (p 0.001) and overweight and obese compared to lower normal body mass category (p 0.001). Compared with participants with lower normal body mass, the nonadjusted odds ratio (OR) for mildly or moderately reduced renal function (eGFR 90 ml/min/1.73m2) was 2.54 (95% CI 1.41-4.56) for upper normal and 3.26 (95% CI 1.88-5.70) for overweight and obese participants. After adjusting for potential confounding variables (age, sex, diabetes mellitus, hypertension, hypercholesterolemia, hypertriglyceridemia and smoking status) OR for mildly or moderately reduced renal function was 2.23 (95% CI 1.21-4.10) for upper normal 2.65 (95% CI 1.44-4.87) for overweight or obese participants compared to those in lower normal body mass category. CONCLUSION: Estimated GFR values decreased significantly with increasing BMI specially in those in upper normal compared to lower normal (p 0.001) and overweight and obese compared to lower normal body mass category (p 0.001). This study showed that increasing BMI is strongly associated with decreasing eGFR in the general population. The underlying mechanism behind this association remains to be investigated through prospective populationbased studies.


INTRODUCTION
Chronic kidney disease (CKD) is a global health problem and represents a big economic burden for health systems. Global prevalence of CKD lies between 11 and 13% with the third stadium having the largest share. All CKC stadiums are related to the increased risk for cardiovascular morbidity, early death and/or poorer quality of life 1 .
The prevalence of obesity has also been rapidly increasing worldwide so much that obesity acquired the proportions of a global epidemic of chronic noncommunicable disease of the 21st century. The prevalence of obesity (body mass index 2 ) almost doubled in the period between 1980 and 2008. In 1980 5% of men and 8% of women were obese while in 2008 it was 10% of men and 14% of women which makes more than half a billion people 2 . If this secular trend continues it is estimated that by 2030 38% of adult world population will be overweight while 20% will be obese 3 .
Overweight and obesity have adverse metabolic effects on blood pressure, leading to Obesity is a big risk factor for the development of a renal disease. It increases the for CKD such as diabetes and hypertension and has a direct impact on the development of CKD and terminal renal insufficiency 5 .
Purpose of the study is examination of possible contribution of increased body mass index (BMI) to the impaired renal function in the general population sample.The hypothesis that the increased BMI is associated with glomerular filtration rate decrease was tested. According to our knowledge, this is the first study which examined the correlation between body mass index and glomerular filtration rate in these regions in the population sample in primary health care.

MATERIAL AND METHOD
The study was conducted as an observational analytical cross sectional study. The study involved participants older than 30 years who visited their general practitioner in Health Center . Data collection was completed a month after the sample of 500 participants was formed. Blood samples, blood pressure and anthropometric measures were performed on each participant. Laboratory measurements involved determining of glucose, urea, creatinine, total cholesterol and triglyceride concentrations and were performed on each of the participants. Blood pressure was measured on the left upper arm in a sitting position. Body mass and height were measured in the office and BMI was calculated as the quotient of body mass expressed in kilograms and square height expressed in meters. Based on the BMI values, the participants were classified into the categories shown in Table 1 6 . Participants stated whether they were non-smokers, former or active smokers. Glomerular filtration rate was determined using the shortened formula from 7 .
Stadiums of renal insufficiency were given in the table 2 8 . CKD is defined as GFR less than 60 ml/min/1.73m 2 . SPSS 19.0 software (IBM, Somers, New York, USA) was used to create the database and analyze it. For testing of correlation between body mass index and glomerular filtration ratewith adjusting in relation to the associated variable logistical regression was used. The level of significance was 0.05.

RESULTS
The study involved 500 participants, 228 (45.6%) men and 272 (54.4%) women. BMI mean value was 25.09±3,54 kg/m 2 with 0.6% participants in the category of malnourished (ITM 18.5 kg/m 2 ), 17.6% in the group of body mass in the range of lower normal (BMI 18.5 up to 21.9 kg/m 2 ), 33.2% in the group with upper normal body mass (BMI from 22.0 to 24.9 kg/m 2 ) and 48.6% in the group of overweight or obese (ITM 25.0 kg/m 2  Most studies showed existence of a higher risk for CKD in participants with the BMI which is equal to or greater than 25 kg/m 2 while results of our study show increased risk for mild and moderately impaired renal function in the group of participants with upper normal body mass (BMI 22.0 to 24.9 kg/m 2 ) as well as in the category of overweight and obese (BMI kg/m 2 ) compared to the participants from the category of lower normal body mass.
The exact mechanism of contribution of obesity to the development or worsening of CKD www.tmg.org.rs is still insufficiently known. In support of the claim that obesity itself is not responsible for the development of CKD is the fact that most obese people never develop CKD and as many as 25% of obese people do not have metabolic disorders 19 . However, the frequency of so-called glomerulopathy associated with obesity (obesity-related glomerulopathy) which in the observational studies was proven to affect the development of CKD increased by 10 times in the period from 1986 to the year 2000 20 . Adipose tissue has its endocrine function through the production of adiponectin 21 , leptin 22 , resistin 23 and numerous other mediators which leads to oxidative stress 24 , inflammation 25 , insulin resistance 26 , RAAS activation 27 and impaired fat metabolism 28 . The effect of the above on the kidneys is reflected through ectopic fat accumulation and increased fat deposition in the renal sinuses 29 , development of glomerular hypertension as well as hyperfiltration with consequent damage to the glomerular basement membrane and increased permeability resulting in glomerulomegaly and focal segmental glomerulosclerosis 20 .
Obesity is also associated with increased risk for nephrolithiasis. Higher body weight is associated with lower urine pH 30 and increased oxalate excretion 31 , uric acid, sodium and phosphate 32 . A diet with a lot of proteins and salt decreases urine pHand citrate concentration, which contributes to the formation of stone. Also, through effects on tubular Na-H transporter and ammoniogenesis, insulin residence may contribute to urinary acidity favouring nephrolithiasis 33 .
Apart from obesity having a direct impact to kidneys in pathophysiology of CKD, traditional risk factors such as diabetes mellitus, arterial hypertension and chronic vascular diseases proven to be more frequent in obese persons play a major role here.

CONCLUSION
Estimated GFR values decreased significantly with increasing BMI specially in those in upper normal compared to lower normal (p 0.001) and overweight and obese compared to lower normal weight category (p 0.001). This study showed that increasing BMI is strongly associated with decreasing eGFR in the general population. The underlying mechanism behind this association remains to be investigated through prospective populationbased studies.