Measurement of Glomerular Filtration Rate in Obese Patients: Pitfalls and Potential Consequences on Drug Therapy

Abstract

Epidemiological studies have shown that obesity is associated with chronic kidney disease and end stage renal disease. These studies have used creatinine derived equations to estimate glomerular filtration rate (GFR) and have indexed GFR to body surface area (BSA). However, the use of equations using creatinine as a surrogate marker of glomerular filtration and the indexation of GFR for BSA can be questioned in the obese population. First, these equations lack precision when they are compared to gold standard GFR measurements such as inulin clearances; secondly, the indexation of GFR for 1.73 m² of BSA leads to a systematic underestimation of GFR compared to absolute GFR in obese patients who have BSA that usually exceed 1.73 m². Obesity is also associated with pathophysiological changes that can affect the pharmacokinetics of drugs. The effect of obesity on both renal function and drug pharmacokinetics raises the issue of correct drug dosage in obese individuals. This may be particularly relevant for drugs known to have a narrow therapeutic range or excreted by the kidney.

Creatinine‐based equations for the adjustment of drug dosage in an obese population

“…The CG equation has been used for several decades and is still part of the guidance from the FDA and the EMA in pharmacokinetic studies in the setting of renal impairment . Its accuracy for estimating GFR is, however, not optimal in obese patients, as expected by the bias induced by the ABW in the equation . Pharmacologists justify the use of the CG equation by different arguments.…”

Drug Disposition in Obesity: Toward Evidence-Based Dosing

“…In morbidly obese patients who presented with proteinuria, one study reported focal glomerular sclerosis, diabetic nephropathy, or both (42). In addition, estimates of the creatinine clearance from standard formulas tend to be inaccurate in obese patients (43)(44)(45). Even though obesity-associated renal damage may be unpredictable, the available evidence indicates that it is best to use LBW in the Cockroft-Gault formula for estimation of creatinine clearance in obese patients (44,46).…”

Response to Nair et al. The Chronic Kidney Disease Epidemiology Collaboration (CKD‐EPI) formula performs worse than the Modification of Diet in Renal Disease (MDRD) equation in estimating glomerular filtration rate in Type 2 diabetic chronic kidney disease

“…The authors suggest that the poor performance of these equations may be attributed to high obesity rates typically found in patients with Type 2 diabetes. In fact, the use of creatinine‐based equations as a surrogate marker of GFR and the indexation of GFR for body surface area have been questioned in the obese population [3–5]. These equations lack precision when compared with gold standard GFR measurements in this group of patients [3,5].…”

“…In fact, the use of creatinine‐based equations as a surrogate marker of GFR and the indexation of GFR for body surface area have been questioned in the obese population [3–5]. These equations lack precision when compared with gold standard GFR measurements in this group of patients [3,5]. In addition, the indexation of GFR for 1.73 m 2 of body surface area leads to a systematic underestimation of GFR compared with absolute GFR in obese patients who have body surface areas that usually exceed 1.73 m 2 [3].…”

“…These equations lack precision when compared with gold standard GFR measurements in this group of patients [3,5]. In addition, the indexation of GFR for 1.73 m 2 of body surface area leads to a systematic underestimation of GFR compared with absolute GFR in obese patients who have body surface areas that usually exceed 1.73 m 2 [3].…”