Kidney Function in Obesity—Challenges in Indexing and Estimation

Abstract

As the prevalence of obesity continues to increase worldwide, an increasing number of people are at risk for kidney disease. Thus, there is a critical need to understand how best to assess kidney function in this population, and several challenges exist. The convention of indexing glomerular filtration rate (GFR) to body surface area (BSA) attempts to normalize exposure to metabolic wastes across populations of differing body size. In obese individuals, this convention results in a significantly lower indexed GFR than unindexed GFR, which has practical implications for drug dosing. Recent data suggest that "unindexing" estimated GFR (multiplying by BSA/1.73 m) for drug dosing may be acceptable, but pharmocokinetic data to support this practice are lacking. Beyond indexing, biomarkers commonly used for estimating GFR may induce bias. Creatinine is influenced by muscle mass, whereas cystatin C correlates with fat mass, both independent of kidney function. Further research is needed to evaluate the performance of estimating equations and other filtration markers in obesity, and determine whether unindexed GFR might better predict optimal drug dosing and clinical outcomes in patients whose BSA is very different than the conventional normalized value of 1.73 m.

Cystatin C: A Primer for Pharmacists

“…Rather, the increase in GFR observed in obese individuals reflects compensatory hyperfiltration in the nephrons that do exist. This hyperfiltration in obese patients can become maladaptive and is largely unaccounted for in existing eGFR equations [43].…”

“…This means that independent of underlying kidney function, the biomarker may be elevated and consequently lead to an underestimated GFR. Another aspect of using eGFR for drug dosing in obesity is whether or not to index the eGFR to body surface area (BSA) [43]. In the validated CKD-EPI eGFR cysC or eGFR creatinine-cysC equations, kidney function is expressed in milliliters per minute per BSA (mL/min/1.73 m 2 ) [44].…”

“…In the validated CKD-EPI eGFR cysC or eGFR creatinine-cysC equations, kidney function is expressed in milliliters per minute per BSA (mL/min/1.73 m 2 ) [44]. Historically, a BSA of 1.73 m 2 was the mean value for an average 25-year-old American male, but recent data suggest that it is closer to 2.05 m 2 [43,45]. Studies have questioned the appropriateness of the BSA correction value of 1.73 m 2 and which BSA estimation strategy should be used [43,44,[46][47][48][49].…”

“…Historically, a BSA of 1.73 m 2 was the mean value for an average 25-year-old American male, but recent data suggest that it is closer to 2.05 m 2 [43,45]. Studies have questioned the appropriateness of the BSA correction value of 1.73 m 2 and which BSA estimation strategy should be used [43,44,[46][47][48][49]. Take the example of a 126.7 kilogram patient, who has a calculated BSA between 2.41 and 2.56 m 2 , depending on the BSA equation used [43].…”

“…Studies have questioned the appropriateness of the BSA correction value of 1.73 m 2 and which BSA estimation strategy should be used [43,44,[46][47][48][49]. Take the example of a 126.7 kilogram patient, who has a calculated BSA between 2.41 and 2.56 m 2 , depending on the BSA equation used [43]. The eGFR for this obese patient might be approximately 70 mL/min, but if an indexed eGFR value were used instead, the value would be 47-50 mL/min/1.73 m 2 .…”