Cystatin C for Glomerular Filtration Rate Estimation: Coming of Age

[摘要] Assessment of glomerular filtration rate (GFR)4 is essential for clinical practice. GFR is difficult to measure [measured GFR (mGFR)]; instead it is estimated [estimated GFR (eGFR)] by use of the serum concentration of endogenous filtration markers. However, all endogenous filtration markers are affected by factors other than GFR (non-GFR determinants), including generation, renal tubular reabsorption and secretion, and extrarenal elimination. Creatinine, a 113-Da breakdown product of muscle metabolism, was first identified in 1847 and proposed as a filtration marker in 1926 (1, 2). Creatinine-based eGFR (eGFRcr) is computed from serum creatinine concentration in combination with age, sex, and race as surrogates for creatinine generation by muscle. Cystatin C, a 13 300-Da serum protein produced by virtually all nucleated cells, was first identified in 1979 and proposed as a filtration marker in 1985 (3–5). Cystatin C is less influenced by muscle mass than creatinine and has often been proposed to be more accurate than creatinine for estimation of measured GFR in subgroups of the population, including vegetarians and those with muscle wasting, chronic disease, or limb amputation. The non-GFR determinants of cystatin C are not well known, and cystatin C–based eGFR (eGFRcys) is not more accurate for routine GFR estimation than eGFRcr. eGFR based on the combination of creatinine and cystatin C (eGFRcr-cys) is more accurate than either alone, reflecting the lesser influence of non-GFR determinants of either marker when both are used (6). eGFRcys is also more accurate in predicting prognosis than either eGFRcr-cys or eGFRcr, possibly reflecting opposite influences of non-GFR determinants of the markers (for example, muscle wasting leading to lower serum creatinine and inflammation leading to higher serum cystatin C) (7).Standardized reference materials are available for both creatinine and cystatin C, and estimating equations have been developed for use with standardized …

[学科分类] 过敏症与临床免疫学