Cystatin C-Creatinine Based Glomerular Filtration Rate Equation in Obese Chronic Kidney Disease Patients: Impact of Deindexation and Gender

Abstract

Background: Cystatin C is considered an alternative to creatinine to estimate glomerular filtration rate (GFR). However, studies have reported that increased adiposity is associated with a higher level of circulating cystatin C questioning the performance of estimation of GFR using cystatin C in obese subjects. Methods: We prospectively included 166 obese stages 1-5 chronic kidney disease (CKD) patients between 2013 and 2015. GFR was measured with a reference method without (measured GFR [mGFR]) and with adjustment to body surface area (mGFRr) and estimated (eGFR) or de-indexed eGFR using the Chronic Kidney Disease and Epidemiology (CKD-EPI) equation using creatinine (CKD-EPI_creat), cystatin (CKD-EPI_cyst) and the combination of cystatin and creatinine (CKD-EPI_cyst-creat). Results: The biases between mGFR and de-indexed CKD-EPI_cyst-creat were significantly lower than de-indexed CKD-EPI_creat (p = 0.001). Accuracies were significantly better with de-indexed CKD-EPI_cyst-creat compared to CKD-EPI_creat and CKD-EPI_cyst, respectively (p = 0.04 and 0.03). Bland and Altman plot showed a great dispersion of all formulae when patients had a GFR >60 ml/min. Interestingly, there is a gender difference; biases, precisions and accuracies of de-indexed CKD-EPI_cyst-creat were significantly lower in obese women. These results may be related to a difference in the change of body composition during obesity in men versus women and in fact only waist circumference (WC) was positively and significantly correlated with cystatin C (p < 0.0001) whereas body mass index (BMI; p = 0.3) was not; bias for CKD-EPI_cyst-creat was related with WC. Conclusion: Cystatin C-creatinine-based GFR equations outperform creatinine-based formula in obese CKD patients especially those with BMI ≥35 and in obese women.

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

“…Fotheringham et al found a different relation between biases and BMI for men compared with women. Moreover, our team recently showed better accuracy for women compared with men when using creatinine and cystatine C with the deindexed CKD‐EPIcreat‐cyst formula . These results may highlight the difference in body composition between men and women for both lean and fat mass.…”

The Enlarging Effect of Obesity on Estimating Kidney Function: Blaming Serum Creatinine Versus Indexation and Methodology

“…Given the inherent limitation of serum creatinine and the issues related to estimating the GFR based on serum creatinine (whether via MDRD or CKD‐EPI) , other kidney filtration markers, such as serum cystatin C, are of great interest here (Table ). Indeed, the same group of investigators recently examined 166 patients with obesity and CKD stages 1 to 5, comparing CKD‐EPI equations that use cystatin C, creatinine, or their combination, and found that using cystatin C alone or in combination with creatinine was less biased, especially when eGFR was deindexed. Therefore, it can be argued that the use of serum creatinine in any eGFR formula tends to overestimate the GFR in obesity and that serum cystatin C concentration measurement should be added as a more reliable filtration marker.…”

Establishing the presence or absence of chronic kidney disease: Uses and limitations of formulas estimating the glomerular filtration rate

“…Sarcopenia in subjects with neuromuscular disease is the source of systematic overestimation of GFR by creatinine-based eGFR formulas. Studies have found differences between various eGFR formulas in obese subjects[ 119 - 122 ]. One large study concluded that cystatin-based eGFR formulas are deficient in detecting CKD stage 3 or 4 in obese subjects[ 119 ].…”

“…One large study concluded that cystatin-based eGFR formulas are deficient in detecting CKD stage 3 or 4 in obese subjects[ 119 ]. In contrast, two smaller studies concluded that creatinine-based equations produce higher eGFR values than cystatin-based formulas and may lead to underestimation of the presence and degree of CKD[ 120 , 122 ]. The finding that sarcopenia is highly prevalent in CKD patients leading to underestimation of the degree of obesity in this patient group[ 121 ] provides an explanation for the discrepancies between cystatin-based and creatinine-based eGFR in obese subjects with CKD.…”