Background/Aims: Identifying the best method to estimate the glomerular filtration rate (GFR) in bariatric surgery patients has important implications for the clinical care of obese patients and research into the impact of obesity and weight reduction on kidney health. We therefore performed such an analysis in patients before and after surgical weight loss. Methods: Fasting measured GFR (mGFR) by plasma iohexol clearance before and after bariatric surgery was obtained in 36 severely obese individuals. Estimated GFR was calculated using the Modification of Diet in Renal Disease equation, the Chronic Kidney Disease Epidemiology Collaboration (CKD-EPI) equation using serum creatinine only, the CKD-EPI equation using serum cystatin C only and a recently derived equation that uses both serum creatinine and cystatin C (CKD-EPI_creat-cystC) and then compared to mGFR. Results: Participants were primarily middle-aged white females with a mean baseline body mass index of 46 ± 9, serum creatinine of 0.81 ± 0.24 mg/dl and mGFR of 117 ± 40 ml/min. mGFR had a stronger linear relationship with inverse cystatin C before (r = 0.28, p = 0.09) and after (r = 0.38, p = 0.02) surgery compared to the inverse of creatinine (before: r = 0.26, p = 0.13; after: r = 0.11, p = 0.51). mGFR fell by 17 ± 35 ml/min (p = 0.007) following surgery. The CKD-EPI_creat-cystC was unquestionably the best overall performing estimating equation before and after surgery, revealing very little bias and a capacity to estimate mGFR within 30% of its true value over 80% of the time. This was true whether or not mGFR was indexed for body surface area. Conclusions: In severely obese bariatric surgery patients with normal kidney function, cystatin C is more strongly associated with mGFR than is serum creatinine. The CKD-EPI_creat-cystC equation best predicted mGFR both before and after surgery.

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.

Obesity is associated with glomerular hyperfiltration and increased urinary protein excretion, as well as structural and functional changes that lead to kidney disease and failure. Dietary protein mimics obesity's effects on the glomerular filtration rate (GFR) and proteinuria and, in certain circumstances, may have the potential to adversely affect kidney function. Here we tested the hypothesis that dietary protein independently explains elevations in the GFR and proteinuria found in obese persons with a normal serum creatinine. Seventeen patients were randomized in a double-blind, crossover fashion for 1-week periods to high (140 g/day) and low (50 g/day) protein diets with a 1-week washout interval separating these periods. High protein consumption was associated with a very modest but significant increase in the GFR of 5 ± 6 ml/min. Hence, while dietary protein does modulate kidney parameters, it is unlikely to fully account for the elevations in GFR and proteinuria found in obesity.