Cystatin C-based equation without race or sex improves accuracy of GFR estimation

1. In this cross-sectional study, serum cystatin C levels were similar in both Black and White patients at the same measured glomerular filtration rate (GFR). 

2. A cystatin C-based equation had better accuracy in estimating GFR when compared to serum creatinine equations.

Evidence Rating Level: 1 (Excellent)

Study Rundown: GFR is used as a marker of renal function as well as a parameter to determine disease severity in conditions like chronic kidney disease. Historically, estimated GFR is determined with equations based on measurements of serum creatinine, taking into account sociodemographic variables such as race. There is a gap in the knowledge as to the value of using cystatin C to estimate renal function. In the present cross-sectional study, serum creatinine was higher at the same measured GFR in Black patients compared to White patients, while serum cystatin C levels were similar. Cystatin C levels were higher in men than women and relatively stable between the ages of 18 to 50. A rescaling factor for cystatin C without the inclusion of sex was developed. European kidney function consortium (EKFC) estimating equations performed better than the chronic kidney disease epidemiology collaboration (CKD-EPI) equation counterparts. EFKC estimating equations had similar or less bias, a lower interquartile range, and a higher P10 (percentage of patients with an estimated GFR that was within 10% of their measured GFR) compared to CKD-EPI equations. The EKFC equations were also more accurate than full-age-spectrum, Lund-Malmo revised, and CAPA equations across five different populations. The strength of this study lies in its diverse global study population and validated tools for measuring GFR. Conversely, it is limited in that children were not included to verify the age-related accuracy of the equations used.

Click to read the study in NEJM

Relevant Reading: Estimating glomerular filtration rate from serum creatinine and cystatin C

In-Depth [cross-sectional study]: The aim of this cross-sectional study was to compare the EKFC eGFR creatinine equation and a cystatin C-based equation for accuracy in estimating renal function while examining the role of race- and sex-specific scaling factors in the equation. Patient data were obtained from multiple centers in Europe, the United States, and Africa. To develop the rescaling factor for cystatin C levels, differences between Black and White patients were matched on age, sex, body mass index, and measured GFR. Measured GFR was obtained through either plasma clearance or urinary clearance. In total, 577 Black patients were matched to 577 White patients from the same hospital. Serum creatinine levels were higher at the same GFR in the Black patients than in the White patients. However, serum cystatin C levels were similar at the same measured GFR. The cystatin C rescaling factor was calculated with a large cohort of White patients from Sweden, which showed that cystatin C levels were relatively constant with age, but higher in men than women. The specific rescaling factor for cystatin C was defined as 0.86 mg per liter for men and 0.79 mg per liter for women until 50 years of age, after which 0.005 x (age-50) was added to individuals who are 50 years old or older. The EKFC eGFRcr-cys without sex equation had the least median bias for the EKFC cohort of 7,727 White patients (0.37 ml/min/1.73 m2; 95% Confidence Interval [CI], 0.14 to 0.66), United States cohort of 1093 White patients (0.97 ml/min/1.73 m2; 95% CI, 0.01 to 2.12), and African cohort of 508 Black patients (0.42 ml/min/1.73 m2; 95% CI, -1.03 to 1.51). In summary, Cystatin-C-based equations may improve the estimation of GFR.

Image: PD

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