Advertisement
American Journal of Kidney Diseases

Serum cystatin C as a new marker for noninvasive estimation of glomerular filtration rate and as a marker for early renal impairment

      Abstract

      Cystatin C is a nonglycosylated basic protein produced at a constant rate by all investigated nucleated cells. It is freely filtered by the renal glomeruli and primarily catabolized in the tubuli (not secreted or reabsorbed as an intact molecule). Because serum cystatin C concentration is independent of age, sex, and muscle mass, it has been postulated to be an improved marker of glomerular filtration rate (GFR) compared with serum creatinine level. We compared serum cystatin C level with other markers of GFR, such as serum creatinine level and creatinine clearance, and analyzed their variations based on iothalamate labeled with iodine 125 (125I-iothalamate) clearance (125I-ICl), used as the gold standard for GFR. The concentrations of the two different markers of GFR in patients with impaired renal function were classified according to 125I-ICl. Twenty individuals with normal renal function (125I-ICl, 128 ± 23 mL/min/1.73 m2) were used as the control group. Serum cystatin C level showed a greater sensitivity (93.4%) than serum creatinine level (86.8%). Also, serum cystatin C showed the greatest proportion of increased values in patients with impaired renal function (100%) compared with serum creatinine level (92.15%). Serum cystatin C levels started to increase to greater than normal values when GFR was 88 mL/min/1.73 m2, whereas serum creatinine level began to increase when GFR was 75 mL/min/1.73 m2. These data suggest that measurement of serum cystatin C may be useful to estimate GFR, especially to detect mild reductions in GFR, and therefore may be important in the detection of early renal insufficiency in a variety of renal diseases for which early treatment is critical.

      Keywords

      To read this article in full you will need to make a payment

      Purchase one-time access:

      Academic & Personal: 24 hour online accessCorporate R&D Professionals: 24 hour online access
      One-time access price info
      • For academic or personal research use, select 'Academic and Personal'
      • For corporate R&D use, select 'Corporate R&D Professionals'

      Subscribe:

      Subscribe to American Journal of Kidney Diseases
      Already a print subscriber? Claim online access
      Already an online subscriber? Sign in
      Institutional Access: Sign in to ScienceDirect

      References

        • Doolan PD
        • Alpen EL
        • Theil GB
        A clinical appraisal of the plasma concentration and endogenous clearance of creatinine.
        Am J Med. 1962; 32: 65-79
        • Chasis H
        • Smith WH
        The excretion of urea in normal man and in subjects with glomerulonephritis.
        J Clin Invest. 1938; 17: 347-358
        • Shils ME
        Renal disease and the metabolic effects of tetracycline.
        Ann Intern Med. 1963; 58: 389-408
        • Young DS
        Effects of Drugs on Clinical Laboratory Tests.
        ed 3. American Association of Clinical Chemistry Press,, Washington, DC1990
        • Fitch CD
        • Sinton DW
        A study of creatine metabolism in diseases causing muscle wasting.
        J Clin Invest. 1964; 43: 444-452
        • James GD
        • Sealey JE
        • Alderman M
        A longitudinal study of urinary creatinine and creatinine clearance in normal subjects: Race, sex and age differences.
        Am J Hypertens. 1988; 1: 124-131
        • Saah Aj
        • Koch TR
        • Drusano GL
        Cefoxitin falsely elevates creatinine levels.
        JAMA. 1982; 247: 205-206
        • Pergande M
        • Jung K
        Sandwich enzyme immunoassay for cystatin C in serum with commercially available antibodies.
        Clin Chem. 1993; 39: 1885-1890
        • Kylse Andersen J
        • Schmidt C
        • Nordin G
        • Andersson B
        • Nilsson-Ehle P
        • Lindstrom L
        • Grubb A
        Serum cystatin C, determined by a rapid automated particle-enhanced turbidimetric method, is a better marker than serum creatinine for glomerular filtration rate.
        Clin Chem. 1994; 40: 1921-1926
        • Newman DJ
        • Thakkar H
        • Edwards RG
        • Wilkie M
        • White T
        • Grubb A
        • Price CP
        Serum cystatin C measured by automated immunoassay: A more sensitive marker of changes in GFR than serum creatinine.
        Kidney Int. 1995; 47: 312-318
        • Simonsen O
        • Grubb A
        • Thysell H
        The blood serum concentration of cystatin C (γ-trace) as a measure of glomerular filtration rate.
        Scand J.Clin Lab Invest. 1985; 45: 97-101
        • Sapirstein LA
        • Vidt DG
        • Mandel MJ
        • Hanusek G
        Volumes of distribution and clearances of intravenously injected creatinine in the dog.
        Am J Physiol. 1955; 181: 330-336
        • Blaufox MD
        Compartment analysis of the radiorenogram and kinetics of I131-hippuran.
        Prog Nucl Med. 1972; 2: 107-124
        • Du Bois D
        • Du Bois EF
        A formula to estimate the approximate surface area if height and weight are known.
        Arch Intern Med. 1916; 17: 863-871
        • Carrie BJ
        • Golbetz HV
        • Michaels AS
        • Myers BD
        Creatinine: An inadequate filtration marker in glomerular diseases.
        Am J Med. 1980; 69: 177-182
        • Fuller NJ
        • Elia M
        Factors influencing the production of creatinine: Implications for the determination and interpretation of urinary creatinine and creatine in man.
        Clin Chim Acta. 1988; 175: 199-210
        • Hilbrands LB
        • Artz MA
        • Wetzels JFM
        Cimetidine improves the reliability of creatinine as a marker of glomerular filtration rate.
        Lancet. 1992; 340: 1326-1329
        • Nilsson-Ehle P
        • Grubb A
        New markers for the determination of GFR: Iohexol clearance and cystatin C serum concentration.
        Kidney Int. 1994; 46: S17-S19