Plasma Cystatin

Braun JP, Perxachs A, Pechereau D, de la Farge F (2002) Plasma cystatin C in the dog reference values and variations with renal failure. Comp Clin Pathol 11 44 19 Cockcroft DW, Gault MH (1976) Prediction of creatinine clearance from serum creatinine. Nephron 16 31-41 Corman B, Michel JB(1987) Glomerular filtration, renal blood flow, and solute excretion in conscious aging rats. Am J Physiol 22 R555-R560... 

Loeb WF, Quimby FW (1999) The Clinical Chemistry of Laboratory Animals, 2nd edn. Taylor and Francis, Philadelphia Martin C, Pechereau D, de la Farge F, Braun JP (2002) Plasma cystatin C in the cat current techniques do not allow to use it for the diagnosis of renal failure. Rev Med Vet 153 305-310... 

Serum/Plasma Cystatin C as a Marker for Glomerular Filtration Rate (GFR). 72... 

Finney H, Bates CJ, Price CP. Plasma cystatin C determinations in healthy elderly population. Arch Gerontol Geriatr 1999 29 75-94. 

Braun, J-P, A. Perxachs, D. Pechereau, and F. de La Farge. 2002. Plasma cystatin C in the dog Reference values and variations with renal failure. Comparative Clinical Pathology 11 44-49. 

Serum creatinine is not a good measure of renal function in elderly because muscle mass is reduced and the production of creatinine is thus reduced. Estimation of GFR based on serum creatinine is therefore not accurate enough in the elderly (Baracskay et al. 1997). Creatinine clearance should be used instead. Another possibility is measurement of cystatin C in plasma. The rate of production of cystatin C is relatively constant so it seems to be a more reliable estimation of GFR also in older adults. 

Cystatin C (Formerly Post-y-globulin, y-Trace Protein). Cystatin C is a new parameter in a spinal fluid and serum (plasma), originating from glial elements and belonging to so-called trace proteins. Its increasein CSF is considered to be a marker of tissue destruction. Assessment of cystatin C in serum (plasma) is a marker of renal glomerular filtration. 

Finco et al. 2001) and for the rat using cystatin C (Tenstad et al. 1996). Either urine or plasma clearance methods can be used for the former. For the latter, plasma clearance was used to estimate GFR due to the fact that cystatin C is reabsorbed and degraded by the proximal tubule and does not appear in the urine. 

Estimation of the glomerular filtration rate (GFR) is considered a sensitive index of functional nephron mass (Newman and Price 1999). Point measurements of the plasma levels of several endogenous small molecules (urea, creatinine, 2-(a-mannopyranosyl)-L-tryptophan) or small (less than 66 kDa) proteins (cystatin C (y-trace), prostaglandin D synthase (15-trace protein), ai-microglobulin, p2-microglobulin, and retinol binding protein) have been used to assess GFR in many species. 

The distribution in body fluids of the different cystatins is remarkably different (Fig. 3). For example, while cystatin C is present in appreciable amounts in all investigated body fluids, cystatins S, SN, and SA are virtually confined to saliva, tears, and seminal plasma (Al). Cystatin D is present only in saliva and tear fluid (Al, F3). In some body compartments, e.g., spinal fluid, cystatin C represents more than 90% of the total molar concentration of cysteine protease... 

No investigations have demonstrated that the diagnostic usefulness of the serum level of cystatin C is different from that of the plasma level of cystatin C. The term... 

DNA sequence The nucleotide sequence data are available from the EMBL, GenBank, and DDBJ Nucleotide Sequence Databases under accession number X52255 Half-life About 20 min (experimentally determined for human cystatin C in rat plasma. The similarity in distribution volume and renal clearance between human cystatin C and acknowledged markers of human glomerular filtration, i.e., iohexol and 51 Cr-EDTA, suggests that the substances are eliminated at the same rate in humans with a half-life of approximately 2 h in individuals with normal renal function)... 

Fig. 5. Plasma concentration of intact 125I-cystatin C( ), 51Cr-EDTA ( ) and 131I-aprotinin(Y) relative to the initial plasma concentration after intravenous injection in 12 rats. Error bars show 1 SEM, when larger than the symbols. Aprotinin is a 6.5-kDa microprotein with a pi of 10.5.

Fig. 6. Plasma disappearance of intact 125I-cystatin C in nephrectomized (o) and control ( ) rats. The monoexponential regression line of the plasma concentration, P/Pq, against the time, t, between 60 and 120 min in nephrectomized rats is indicated by a dotted line.

Fig. 7. Renal plasma clearance of 125I-cystatin C (Ccy) compared to that of 51 Cr-EDTA (Cq-—edta) in rats with normal glomerular filtration ( ), and in rats with renal blood flow reduced to 25-50% of control by constricting the aorta above the renal arteries (o). The clearance measurements were completed 2.5-6.0 min after tracer injection. Ccy = 0.944 x Ccr-EDTA f = 0.989.

Harmoinen A, Lehtimaki T, Korpela M, Turjanmaa V, Saha H. Diagnostic accuracies of plasma creatinine, cystatin C, and glomerular filtration rate calculated by the Cockcroft-Gault and Levey (MDRD) formulas. Clin Chem 2003 49 1223-5. 

Plasma Creatinine, Urea (Blood Urea Nitrogen), and Cystatin C... 

These plasma tests are used as indirect measurements of the glomerular filtration rate (GFR) to some extent, these endogenous tests supplement each other despite having different limitations. Plasma creatinine, urea, and cystatin C are normally filtered from the plasma, and they are reabsorbed or secreted by the proximal tubules to a minor extent, which differs between species. Tubular secretion leads to overestimation of GFR and it is higher in laboratory animals than in man. These secretions/reabsorption mechanisms may change as a consequence of major tubular injury. In addition to renal injury, the GFR may be altered by changes of renal hemodynamics or extracellular dehydration. 

In addition to using plasma creatinine (or cystatin C) as an indicator of GFR, several other methods for estimating GFR can be expressed as... 

The GFR can be estimated by clearance measurements of endogenous or exogenous small molecules (urea, creatinine, 2-MPT, inulin, cystatin C, iohexol, or iodixanol). An ideal marker of GFR should be primarily excreted by the kidneys, freely filtered by the glomerulus, and neither secreted nor reabsorbed by the tubule. It should also be supplied to the plasma at a constant rate and exhibit no or minimal protein binding. If these criteria are met, such as for inulin, the GFR is equivalent to the renal/urinary clearance of the substance, as defined earlier in this chapter. 

Cystatin C clearance Plasma or serum Human, dog, rat, mice Affected by inflammation or neoplasia, higher sensitivity than creatinine... 

---