Renal hemodynamics in overweight and obesity: pathogenetic factors and targets for intervention

Abstract

Weight excess is a risk factor for progressive renal function loss, not only in subjects with renal disease or renal transplant recipients, but also in the general population. Considering the increasing prevalence of obesity worldwide, weight excess may become the main renal risk factor on a population basis, all the more so because the risk is not limited to morbid obesity, but is already apparent in the overweight range. The mechanism of the renal risk is multifactorial. In addition to the role of comorbid conditions such as hypertension and diabetes, current evidence supports a pathogenetic role for renal hemodynamics, specifically glomerular hyperfiltration, and also glomerular hypertension. Weight excess is associated with an elevated glomerular filtration rate and a less pronounced rise in renal plasma flow, resulting in an elevated filtration fraction. This suggests glomerular hypertension due to afferent–efferent dysbalance, which impairs glomerular protection from systemic hypertension. Data in renal transplant recipients support the pathogenetic role of elevated glomerular pressure for long-term renal prognosis. Blockade of the renin–angiotensin–aldosterone system can reverse the renal hemodynamic abnormalities. The obesity-associated renal risk is unfavourably affected by high sodium intake. This may be due to the effects of sodium on blood pressure, which is often sodium-sensitive in obesity, but direct renal effects are also present. Interestingly, sodium restriction ameliorates overweight-associated hyperfiltration in overweight subjects. More focus on weight excess as a renal risk factor is warranted. Preventive measures should focus on weight excess as well as on specific protection against renal damage, by renin–angiotensin–aldosterone system-blockade and moderate sodium restriction.