Metabolic and Hormonal Determinants of Glomerular Filtration Rate and Renal Hemodynamics in Severely Obese Individuals

Abstract

Objective: Renal function is often compromised in severe obesity. A true measurement of glomerular filtration rate (GFR) is unusual, and how estimation formulae (EstForm) perform in such individuals is unclear. We characterized renal function and hemodynamics in severely obese individuals, assessing the reliability of EstForm. Methods: We measured GFR (mGFR) by iohexol plasma clearance, renal plasma flow (RPF) by ¹²³I-ortho-iodo-hippurate, basal and stimulated vascular renal indices, endothelium-dependent and -independent vasodilation using flow-mediated dilation (FMD) as well as metabolic and hormonal profile in morbid, otherwise healthy, obese subjects. Results: Compared with mGFR, the better performing EstForm was CKD-EPI (5.3 ml/min/1.73 m² bias by Bland-Altman analysis). mGFR was directly related with RPF, total and incremental glucose AUC, and inversely with PTH and h8 cortisol. Patients with mGFR below the median shown significantly higher PTH and lower vitamin D3. Basal or dynamic renal resistive index, FMD, pulse wave velocity were not related with mGFR. In an adjusted regression model, renal diameter and plasma flow remained related with mGFR (R² = 0.67), accounting for 15% and 21% of mGFR variance, respectively. Conclusions: CKD-EPI formula should be preferred in morbid obesity; glucose increments during oral glucose tolerance test correlate with hyperfiltration; RPF and diameter are independent determinants of mGFR; slightly high PTH values, frequent in obesity, might influence mGFR.

Estimated Glomerular Filtration Rate Bias in Participants with Severe Obesity Regardless of Deindexation

“…Previous reports comparing CKD‐EPI and MDRD for GFR estimation in subjects with obesity have shown discrepant results . In the present study, which included a larger cohort of participants with obesity, we confirmed that CKD‐EPI outperformed MDRD, which is in line with a previous report from our team and the recent publication from Vitolo et al in 50 patients with severe obesity. Accuracy 30% was better for patients with BMI between 35 and 39 compared with those with BMI ≥ 40, which is also in agreement with previous studies .…”

Relationship Between the Estimated Glomerular Filtration Rate and Visceral Fat Thickness Based on Ultrasound in Patients With Obesity Who Have Normal Renal Function Without Hypertension or Diabetes

“…As far as the potential mechanism, the RAAS plays an important role. Increased angiotensin (atrial natriuretic factor II) alters renal hemodynamics by dilating small arteries, leading to glomerular enlargement and focal glomerulosclerosis . At the same time, RAAS activation affects hypertension, dyslipidemia, and insulin resistance .…”

“…Second, in addition to hemodynamic effects, these pathophysiologic pathways also alter the glomerular basement membrane components, leading to podocyte apoptosis . Third, inflammatory cytokines such as C‐reactive protein, tumor necrosis factor α, interleukin 6, and angiotensin II) produced by visceral adipose tissue further exacerbate oxidative stress and nitrosation emergencies . Adipose tissue can also produce higher concentrations of leptin, which affects endothelial cells by paracrine mechanisms, ultimately leading to glomerular sclerosis .…”

Renal Resistive Index Predicts Post–Bariatric Surgery Renal Outcome in Nondiabetic Individuals with Severe Obesity

“…Recent findings show that bariatric surgery may stabilize, or even improve, renal function, given that glomerular filtration rate (GFR) has been reported to decrease in subjects with obesity hyperfiltering at baseline , to increase in patients with CKD , or to remain stable in individuals with normal renal function . Nevertheless, most of these outcomes have been based on 24‐hour creatinine clearance or estimated GFR (eGFR) according to different formulas, although a certain degree of inaccuracy was demonstrated for many of them when compared, for example, with iohexol plasma clearance . The effect of bariatric surgery on renal hemodynamics, measured by gold standard techniques (inulin , chromium‐EDTA , or iohexol clearance ), is still unclear.…”

“…Furthermore, measured GFR (mGFR) is dependent on renal hyperperfusion, evaluated as RPF, which may in turn be influenced by systemic hemodynamics . Indeed, bariatric surgery is able to improve subclinical atherosclerosis, arterial stiffness, and endothelial dysfunction characterizing obesity ; this positive effect on systemic vascular function might be beneficial for renal vasculature too, potentially favoring the restoration of a normal filtration rate after bariatric surgery.…”