Cystatin limitations

Serum creatinine is ubiquitously used as an indicator for GFR despite the knowledge that a substantial proportion of patients with reduced GFR display serum creatinine levels within the normal range and that even a 50% reduction of GFR not infrequently is associated with a normal concentration of serum creatinine (L8, P5, S3). The usefulness of serum creatinine as a marker for GFR is limited by, inter alia, the influence of an individual s muscle mass on the production rate of creatinine (H8, P5, S5), by the tubular secretion and reabsorption of creatinine, by the dietary intake of creatine and creatinine, and by analytical difficulties (P5). These significant limitations in the use of serum creatinine as an indicator for GFR has made it of interest to search for better indicators for GFR. Several recent studies have compared the use of serum cystatin C and creatinine as markers for GFR as determined by golden standard procedures based upon determinations of the... 

Combined use of serum cystatin C and creatinine produces the best possible information on GFR in situations where more accurate, but invasive and more expensive, clearance determinations cannot be performed for biomedical or economic reasons. If both serum cystatin C and creatinine are within the relevant reference limits, the risk of missing a decrease in GFR will be minimal. 

Grubb A. Diagnostic value of analysis of cystatin C and protein HC in biological fluids. Clin Nephrol 1992 38(Suppl 1) S20-S27. Tencer J,Thysell H, Grubb A. Analysis of proteinuria Reference limits for urine excretion of albumin, protein HC, immunoglobin G, k- and 1-chain immunoreactrivity, orosomucoid and al-antitrypsin. Scand J Clin Lab invest 1996 56 691-700. 

Cystatin C has been measured by immunodiffusion or rocket electroimmunoassay, but the methods are too insensitive, and any form of labeled immunometric assay is too cumbersome and time consuming for the response time required. The most practical approaches described are to use a latex particle-enhanced turbidimetric or nephelometric immunoassay. An intraassay precision of less than 3% can be expected at the upper limit of the reference interval ( 1.00mg/L), with less than 4% for the between-day value. Further, cystatin C measurement appears unaffected by the spectral interferences affecting creatinine assays. ... 

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. 

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