Measuring the Glomerular Filtration Rate in Obese Individuals without Overt Kidney Disease

Abstract

Background: Identifying methods to accurately measure the glomerular filtration rate (GFR) in obese individuals without kidney overt kidney disease is necessary to understanding the pathophysiology and natural history of obesity-related kidney disease. Methods: Using a cross-sectional design, iohexol clearance and disposition was measured, an optimal sampling schedule was identified, and the reliability of GFR-estimating methods was described in 29 obese individuals with normal serum creatinine levels. Iohexol disposition was measured using population pharmacokinetics. The agreement with GFR-estimating equations was assessed by intraclass coefficients. Results: Mean age was 44 ± 10 years, body mass index 45 ± 10, creatinine 0.7 ± 0.2 mg/dl (62 ± 18 µmol/l) , and cystatin C 0.83 ± 0.18 mg/dl (8.3 ± 1.8 mg/l). Iohexol disposition fit a two-compartment model and 5 sampling windows were identified over a 4-hour period to optimize model accuracy and minimize blood draws. Precision was not compromised with this sampling design. Neither creatinine nor cystatin C were linearly correlated with the measured GFR though cystatin C was independent of body composition. Agreement was fair to poor between the measured GFR and GFR-estimating equations. Conclusion: This study offers a rigorous method to study obesity-related kidney disease and improve upon suboptimal GFR-estimating methods.

How Measuring Glomerular Filtration Rate? Comparison of Reference Methods

“…The details of these comparison studies were published three years after (see clinical data) (Olsson et al, 1983). In the same study, the authors confirm that iohexol is distributed through the extracellular volume, which will be confirmed by other authors (including in CKD patients and in obese subjects) (Friedman et al, 2010;Nossen et al, 1995;Edelson et al, 1984;Back et al, 1988b;Olsson et al, 1983). Iohexol has not effect per se on GFR (Olofsson et al, 1996).…”

Accuracy of GFR Estimation in Obese Patients

“…Most studies relate that formulas are not validated in obese population. Although these equations were established in populations that are not obese, average BMI for the CKD-EPI formula was 28 kg/m 2 (16)(17)(18)(19). This population was overweight but not obese.…”

Comparative Effects of Low-Carbohydrate High-Protein Versus Low-Fat Diets on the Kidney

“…Moreover, the already high prevalence of glomerular hyperfiltration observed in obese individuals (23,27,29,36,37) could at least in theory increase the susceptibility to diet-associated hyperfiltration-related kidney damage. However, the assumption that prolonged glomerular hyperfiltration leads to kidney damage has never been definitely proven and remains controversial (38,39).…”

“…Important questions remain about the potential adverse renal effects of such diets from prolonged elevations in the GFR (i.e., glomerular hyperfiltration) (16,17); increased proteinuria (18)(19)(20)(21)(22); and derangements in electrolyte, acid-base, and bone mineral status (18). Unease over prescribing a lowcarbohydrate high-protein diet takes on special significance in the obese population, where glomerular hyperfiltration, excess proteinuria, and a greater risk for kidney failure and other kidney-related abnormalities already exist (23)(24)(25)(26)(27).…”