Abnormal kidney function is an important cause as well as a consequence of obesity. Excess renal sodium reabsorption, probably in the loop of Henle, and a hypertensive shift of pressure natriuresis play a major role in initiating increased blood pressure associated with weight gain. The mechanisms responsible for increased sodium reabsorption and altered pressure natriuresis in obesity include activation of the renin-angiotension and sympathetic nervous systems, and physical compression of the kidneys due to accumulation of intrarenal fat and extracellular matrix. Sympathetic activation may be mediated, in part, by elevated circulating leptin and interactions with neuropeptides in the hypothalamus. Renal remodeling and extracellular matrix proliferation likely involve complex interactions between intrarenal physical forces, neurohumoral factors, and local growth factors and cytokines. Although glomerular hyperfiltration and increased arterial pressure help to compensate for increased renal tubular reabsorption in the early phases of obesity, these changes also increase glomerular capillary wall stress which, along with activation of neurohumoral systems and increased lipids and glucose intolerance, cause glomerular cell proliferation, matrix accumulation, and eventually glomerulosclerosis and loss of nephron function in the early phases of obesity. This creates a slowly developing vicious cycle that requires additional increases in arterial pressure to maintain sodium balance and therefore makes effective antihypertensive therapy more difficult. Because obesity is the main cause of Type 2 diabetes and an important cause of human essential hypertension, it seems likely that obesity is also one of the most important risk factors for end-stage renal disease.
|Original language||English (US)|
|Number of pages||17|
|Journal||Annals of the New York Academy of Sciences|
|State||Published - Jan 1 1999|
ASJC Scopus subject areas
- Biochemistry, Genetics and Molecular Biology(all)
- History and Philosophy of Science