Cystatin C for glomerular filtration rate estimation: coming of age.

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 …

[1]  Anders Larsson,et al.  Generation of a new cystatin C-based estimating equation for glomerular filtration rate by use of 7 assays standardized to the international calibrator. , 2014, Clinical chemistry.

[2]  Josef Coresh,et al.  Cystatin C versus creatinine in determining risk based on kidney function. , 2013, The New England journal of medicine.

[3]  Brenda R. Hemmelgarn,et al.  Notice , 2012, Kidney International Supplements.

[4]  Harold I Feldman,et al.  Estimating glomerular filtration rate from serum creatinine and cystatin C. , 2012, The New England journal of medicine.

[5]  Ingrid Zegers,et al.  First certified reference material for cystatin C in human serum ERM-DA471/IFCC , 2010, Clinical chemistry and laboratory medicine.

[6]  C. Schmid,et al.  A new equation to estimate glomerular filtration rate. , 2009, Annals of internal medicine.

[7]  V. Lindström,et al.  Standardization of Cystatin C: Development of primary and secondary reference preparations , 2008, Scandinavian journal of clinical and laboratory investigation. Supplementum.

[8]  Tom Greene,et al.  Expressing the Modification of Diet in Renal Disease Study equation for estimating glomerular filtration rate with standardized serum creatinine values. , 2007, Clinical chemistry.

[9]  A. Christensson,et al.  Simple cystatin C-based prediction equations for glomerular filtration rate compared with the modification of diet in renal disease prediction equation for adults and the Schwartz and the Counahan-Barratt prediction equations for children. , 2005, Clinical chemistry.

[10]  L. Truedsson,et al.  Serum concentration of cystatin C, factor D and beta 2-microglobulin as a measure of glomerular filtration rate. , 2009, Acta medica Scandinavica.

[11]  H. Thysell,et al.  The blood serum concentration of cystatin C (gamma-trace) as a measure of the glomerular filtration rate. , 1985, Scandinavian journal of clinical and laboratory investigation.

[12]  A. Grubb,et al.  Quantitation of gamma-trace in human biological fluids: indications for production in the central nervous system. , 1979, Scandinavian journal of clinical and laboratory investigation.

[13]  W. G. Walker,et al.  Plasma aldosterone regulation in anephric man. , 1973, Kidney international.

[14]  P. Rehberg,et al.  Studies on Kidney Function: The Rate of Filtration and Reabsorption in the Human Kidney. , 1926, The Biochemical journal.

[15]  J. Liebig.  Kreatin und Kreatinin, Bestandtheile des Harns der Menschen , 1847 .