Body Mass Index and Angiotensin-Dependent Control of the Renal Circulation in Healthy Humans

Abstract

Abstract-Obesity is increasingly recognized as a risk factor for renal disease, but the mechanism is unclear. Renal plasma flow response to captopril, as an index of renin-angiotensin system activity, was measured by para-aminohippurate clearance technique in 100 healthy, normotensive subjects in balance on a high-salt diet. Of the 100 subjects, body mass index exceeded 25 in 56 and exceeded 30 in 22. The average vasodilator response to captopril was 27Ϯ7 mL/min per 1.73 m 2 (PϽ0.0001). After adjustment for other predictors of the renal plasma flow response to captopril using a multivariate linear regression model, there was a highly significant relationship between age-and plasma renin activity-adjusted body mass index and the renal plasma flow response to captopril; however, a quadratic model provided a substantially better fit (rϭ0.55; PϽ0.0001; Pϭ0.03 versus linear correlation). The strong association between increasing body mass index and angiotensin-dependent control of the renal circulation suggests that this may be a mechanism by which obesity contributes to renal disease. Weight loss should be considered in the overweight or obese patient for renal protection. Ն30) 1 and each year, an estimated 300 000 US adults die prematurely of obesity-related causes. 2 Obesity is an independent risk factor for the development of kidney disease. [3][4][5][6] There is little doubt that excess weight gain is a major cause of hypertension and type 2 diabetes, which, together, account for Ͼ70% of end-stage renal disease in the United States. 7 Moreover, evidence also suggests that even in nondiabetic obese patients, there is some degree of renal dysfunction that can lead to more serious injury to the kidneys because metabolic and hemodynamic disturbances worsen with prolonged obesity. 4,6,8,9 The mechanism by which obesity predisposes to kidney damage is unclear, but animal studies suggest an important role for the renin-angiotensin system (RAS). 9 -11 Because animal studies typically involve rapid weight gain from overfeeding, and obesity in humans represents a much more gradual weight gain over years, it has not been clear to what extent these observations in animal models apply to humans. Two observations from our laboratory brought this potential relationship to our attention. Hopkins et al observed that obesity was associated with a blunted renovascular response to angiotensin II (Ang II) infusion, a finding consistent with increased intrarenal Ang II production. 12 Price et al later reported that BMI accounted for Ϸ50% of the renal plasma flow (RPF) response to irbesartan in type 2 diabetic subjects. 13 Because activation of the RAS is associated with progression of kidney disease, 14 these observations raised the question of whether obesity is associated with activation of the intrarenal RAS. We hypothesized that a positive relationship existed between BMI and activation of the intrarenal RAS. We thus examined renal hemodynamic function at baseline and in response to the angiotensin-converting enzyme (ACE) inhibit...

Effects of weight loss on renal function in overweight Japanese men

“…48 The decrease in GFR and arterial pressure after WL is comparable with this hypothesis. Chagnac et al, 15 however, reported that obesity-related glomerular hyperfiltration was improved after WL in morbidly obese subjects as assessed using insulin and p-aminohippuric acid clearance.…”

“…46,47 Such reduction in RAS is important for renal protection. 48,49 A recent study by our group in Caucasian subjects demonstrated that exercise, but not calorie restriction, contributed more to improvements in renal function and suppression of plasma renin activity. 30 In the present study, we did not measure RAS parameters, and hence cannot unequivocally assess the contributions of the RAS on renal function improvement.…”

Low-Density Lipoprotein (LDL) Cholesterol is Cross-Sectionally Associated with Preclinical Chronic Kidney Disease (CKD) in Japanese Men

“…Renal damage can be caused by each component of MetS, such as low HDL cholesterol (22), high triglyceride levels (10,11), and inflammatory cytokines. Insulin resistance may cause dyslipidemia, salt retention, autonomic dysfunction, and renal hemodynamic change (23). However, few studies have examined the relationship between LDL cholesterol, which is also an important established risk factor of cardiovascular disease, and CKD (10,11 (9).…”

Age is a determinant of acute hemodynamic responses to hyperglycemia and angiotensin II in humans with uncomplicated type 1 diabetes mellitus

“…Between group differences in renal hemodynamic responses to hyperglycemia and ANG II were determined by repeated measures ANOVA. We controlled for baseline between group differences in hemodynamic parameters by entering these factors into a multivariate stepwise regression analysis, and we controlled for the effects of gender and body mass index (BMI) on renal function by including these factors in the statistical model (21,(27)(28)(29). In the primary analysis, we included the entire 66 member cohort and did not correct for differences in diabetes duration.…”