The role of cystatin C in improving GFR estimation in the general population

The equations used to estimate glomerular filtration rate (GFR) based on serum creatinine level are limited by their dependence on muscle mass. Although cystatin C level predicts clinical outcomes better than creatinine level in the general population, its role in estimating GFR in the reference range is unclear. Cystatin C level is not influenced by muscle mass, but by several other non-GFR determinants. We investigated whether regression models using cystatin C level alone or in combination with creatinine level in principle would improve GFR estimation in the general population compared with models using creatinine level alone.

Study of diagnostic accuracy.

A representative sample (n = 1,621; aged 50-62 years) of the general population in Tromsø, Norway, without coronary heart disease, stroke, diabetes mellitus, or kidney disease. Individuals had participated in the Renal Iohexol Clearance Survey (RENIS-T6), part of the sixth Tromsø Study.

Performance of multiple linear and fractional polynomial regression models with plasma creatinine and/or cystatin C levels as independent variables and measured GFR as a dependent variable.

Plasma iohexol clearance.

Creatinine measured with an enzymatic method. Cystatin C measured with a particle-enhanced turbidimetric immunoassay.

In internal validation of models with cystatin C, creatinine, or both levels, percentages of GFR estimates within 10% of measured GFR were 61% (95% CI, 58%-63%), 62% (95% CI, 59%-64%), and 68% (95% CI, 65%-70%), respectively. Models with either cystatin C or creatinine level had very similar precision and ability to detect GFR <90 mL/min/1.73 m(2), whereas models based on both markers performed better.

Only middle-aged individuals of European ancestry were investigated. Lack of standardization between cystatin C assays. No external validation of regression models.

Models based on cystatin C alone are not superior to those based on creatinine, but models based on both markers can improve GFR estimation in the reference range.