Abnormal Kidney Function as a Cause and a Consequence of Obesity Hypertension

Abstract

1. Obesity is the most common nutritional disorder in the US and is a major cause of human essential hypertension. Although the precise mechanisms by which obesity raises blood pressure (BP) are not fully understood, there is clear evidence that abnormal kidney function plays a key role in obesity hypertension. 2. Obesity increases tubular reabsorption and this shifts pressure natriuresis towards higher BP. The increased tubular reabsorption is not directly related to hyperinsulinaemia, but is closely linked to activation of the sympathetic and renin-angiotensin systems, and possible changes in intrarenal physical forces caused by medullary compression due to accumulation of adipose tissue around the kidney and increased extracellular matrix within the kidney. 3. Obesity is also associated with marked renal vasodilation and increased glomerular filtration rate, which are compensatory responses that help overcome the increased tubular reabsorption and maintain sodium balance. However, chronic renal vasodilation causes increased hydrostatic pressure and wall stress in the glomeruli which, along with increased lipids and glucose intolerance, may cause glomerulosclerosis and loss of nephron function in obese subjects. Because obesity is a primary cause of essential hypertension as well as type II diabetes, there is good reason to believe that obesity may also be the most frequent cause of end-stage renal disease. 4. Future research is needed to determine the mechanisms by which excess weight gain activates the neurohumoral systems and alters renal structure and function. Because of the high prevalence of obesity in most industrialized countries, unravelling these mechanisms will likely provide a better understanding of the pathophysiology of human essential hypertension and chronic renal failure.

Adult growth hormone treatment reduces hypertension and obesity induced by an adverse prenatal environment

“…We have observed significant reductions in glomeruli number in UN offspring (authors' unpublished observations) and this supports recent work by others showing that an adverse fetal environment can give rise to a reduction in nephron number (Hinchliffe et al 1992, Merlet-Benichou et al 1997. It is possible that the decrease in renal fat mass following GH treatment in the present study directly lowered blood pressure via a reduction in medullary compression as proposed by Hall et al (1998). More recently, an adipose-derived reninangiotensin system has been described with angiotensinogen overproduction by adipose tissue resulting in elevated angiotensin II levels in the progression to obesity-related hypertension.…”

Ultrasonography for the Evaluation of Visceral Fat and Cardiovascular Risk

“…29,30 In our study, a positive correlation was found between measurements of visceral fat and systolic BP determined by ambulatory BP monitoring, although a significant difference in BP levels between visceral and nonvisceral obese patients could not be shown, possibly because both groups had patients under antihypertensive therapy. The weak but significant correlation between intra-abdominal fat and serum sodium might reflect the increased salt reabsorption associated with visceral obesity 31 and insulin resistance. 32 Higher heart rate among nonvisceral obese patients was not previously described.…”

<b>The Relationship Between Obesity and Transforming Growth Factor Beta on Renal Damage in Essential Hypertension</b>

“…Obesity leads to glomerulosclerosis via renal vasodilatation and increases in glomerular filtration and hydrostatic pressure. 8,9) Porreca and coworkers have reported that TGF-β1 levels are independently associated with obesity in hypertensive patients. 10) The aim of this study was to evaluate the effect of obesity on renal functions and the possible relationship between TGF-β1 and obesity in hypertensive patients.…”