الفهرس 
Association between obesity and kidney functionsOnly 14 pages are availabe for public view
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Abstract
This work was designed to throw more light on the impact of obesity on renal functions and the renal contribution in obesity-induced hypertension, and to probe, as well, the effect of telmisartan treatment and renosympathectomy in correction of hypertension associated with obesity.
The study was performed on 80 female albino rats, which were allocated into the following groups:
group I: Control rats (n=20): Rats in this group received the control diet formula, described by Abood (1999). Seven rats of these non-obese control rats were given distilled water, the solvent for telmisartan, by gavage in an amount equivalent to that in which telmisartan is dissolved, for 2 weeks, and six rats were exposed to the same surgical manipulation adopted for the bilateral renal sympathectomy operation, except for performance of the sympathectomy.
group II: Obese rats (n=20): Rats in this group were fed high fat diet formula (butter rich diet, having fat content 16-17%), described by Woods et al (2003), till the BMI and Lee index reached the level indicative of obesity, and for 2 weeks after.
group III: Obese telmisartan-treated rats (n= 20): Rats in this group were fed the high fat diet formula till the BMI and Lee index reached the level indicative of obesity. Then, in addition to the high fat diet, telmisartan was given orally once per day, by gavage, in a dose of 3mg/kg/day, for 2 weeks (Nakagami et al, 2010).
group IV: Obese sympathectomized rats (n=20): Rats in this group were fed high fat diet formula until they became obese, and were then subjected to bilateral renal sympathectomy as described by Nagaoka and Kakihana (1982). They were fed high fat diet formula for another 2 weeks.
All rats were subjected to the following:
1-Assessment of obesity indices: Body Mass Index (BMI) and Lee index.
2-Measurement of arterial blood pressure.
3-Determination of glomerular filtration rate (GFR) by creatinine clearance which required:
a- Estimation of plasma and urine creatinine concentration.
b- Assessment of 24-hour urine volume.
4-Assessment of 24-hour sodium excretion in urine by flame photometry.
5- Determination of fasting blood glucose.
6- Hormonal assay for plasma insulin and leptin.
7- Determination of homeostasis model assessment of insulin resistance (HOMA-IR).
The encountered results revealed that ingestion of high fat diet resulted in obesity. The percent change in body weight (BW) body mass index (BMI) and Lee index (LI) were all significantly increased in the obese rats.
Obese rats showed a significant increase in systolic blood pressure (SBP), diastolic blood pressure (DBP) and mean blood pressure (MAP) compared to the control rats.
Pronounced renal damage was also apparent in the obese rats, as revealed by the significant decrease in the final glomerular filtration rate compared to the control rat. As regards sodium and water excretion, the present findings revealed that the obese rats were in a state of sodium retention and water retention, as evidenced by the significant reduction in 24-hour sodium excretion and urinary volume compared to the control rats.
Furthermore, the obese rats showed elevated fasting blood glucose level, plasma insulin level and HOMA-IR, indicating impaired glucose tolerance and insulin resistance, associated with approximately 2.5 fold increase in plasma leptin level compared to the control rats.
Following telmisartan treatment, rats showed non-significant change in the percent change in BW, BMI and LI compared to the untreated obese rats, though all blood pressure values were significantly decreased compared to either their pretreatment values or the untreated obese rats.
The final glomerular filtration rate was non-significantly changed from both the initial value and the matching value in the untreated obese rats though significantly reduced compared to the control rats.
Obese telmisartan-treated rats also showed a non-significant increase in the final 24-hour urinary sodium excretion and the final 24-hour urinary volume compared to the non-treated obese rats, but still lower than its value in control rats as well as to the initial value encountered for this group.
As regards glucose homeostasis, obese telmisartan-treated rats showed a concomitant significant decrease in the fasting blood glucose level, plasma insulin level and HOMA-IR compared to the untreated obese rats. However, leptin level was non-significantly changed compared to the untreated obese rats.
Renal sympathectomy, on the other hand, resulted in non-significant changes in the percent change in BW, BMI and LI compared to the untreated obese rats, though all blood pressure values were significantly decreased compared to either their pretreatment values or the values encountered in the untreated obese rats.
The final glomerular filtration rate was non-significantly changed from both the initial value and matching value in the untreated obese rats, though significantly reduced compared to the control rats.
Obese sympathectomized also rats showed a significant increase in the final 24-hour urinary sodium excretion and the final 24-hour urinary volume compared to the untreated obese rats, though still not reaching values in the control rats.
As regards glucose homeostasis, in the obese sympathectomized rats, both the plasma insulin level and HOMA-IR were significantly reduced compared to the untreated obese rats. While the fasting blood glucose and leptin levels were non-significantly changed compared to the untreated obese rats.
The heart rate values and plasma creatinine values were, however, non-significantly different in all the studied groups.
In conclusion, obesity and the associated cardio-vascular and metabolic abnormalities might cause changes in the renal function, which might progress to renal injury.
The role of enhanced sympathetic nerve activity in obesity-associated hypertension have been characterized. Hyperleptinemia and hyperinsulinemia could play a role in this sympatho-activation.
from a clinical viewpoint, the achieved results suggest that telmisartan therapy may confer greater arterial blood pressure reductions in obesity associated hypertension, while minimizing the concomitant metabolic disturbances; namely hyperinsulinemia and insulin resistance. In addition, telmisartan halted the affiliated progressive renal dysfunction.
Bilateral renal sympathetic denervation promises not only antihypertensive efficacy, but also, relative improvement in glucose homeostasis and excretory renal functions.