Value of Cystatin C Based Equations for Assessment of Glomerular filtration rate In Relation To Renal Pathology

Abstract

Kidney function typically is measured by GFR. In clinical practice, it is most frequently estimated using endogenous surrogate markers. Serum creatinine remains the most widely used endogenous marker. Serum cystatin C is a relatively new endogenous marker that offers the advantage of a constant production by all nucleated body cells and its almost entire catabolism at the proximal tubule .In clinical studies, serum cystatin C has been found to be a good marker for predicting GFR.

The concentration of serum Cystatin C is mainly determined by glomerular filtration, which makes Cystatin C an endogenous marker of glomerular filtration rate. As with creatinine, cystatin C can be incorporated into a formula to estimate the glomerular filtration rate (GFR).

Cystatin C was found to be an effective marker for glomerular filtration rate in patients with cirrhosis following liver transplantation .Cystatin C has been found more useful for detecting early renal impairment in both type 1 and type 2 diabetic patients . Moreover Cystatin C was also found to be associated with mild kidney dysfunction with increased risk for cardiovascular events, peripheral arterial disease and heart failure.Serum cystatin C level alone provides GFR estimates that are nearly as accurate as serum creatinine level adjusted for age, sex, and race, thus providing an alternative GFR estimate that is not linked to muscle mass.Serum cystatin C levels may not be altered by inflammation, fever or other agents and so cystatin C was considered as a superior marker for GFR than creatinine.

Despite this, cystatin C has not been introduced into clinical laboratory practice and remains very much a research tool. As there are several limitations to the use of cystatin C where high glucocorticoid doses increase cystatin C plasmatic concentrations .Besides, cystatin C levels fall in hypothyroidism andserum cystatin C concentrations may be influenced by underlying malignancy.

Other limitations of Cystatin C use include: lack of uniformity and standardisation of available commercial assay formats may be contributing to this limitation,another factor is the contradicting results in the literature although the majority of studies have showed superiority or at least equal performance of cystatin C in comparison with serum creatinine for detection of renal impairment ,another disadvantage is the different reference ranges published for different age groups plus the high Cost and turnaround time of cystatin C measurements which limits its use. This study was conducted on 20 CKD patients classified according to renal biopsy into mild tubular affection and moderate to severe tubular affection to assess the value of Cystatin C based equations in the assessment of glomerular filtration rate in relation to renal pathology where it was established that estimated GFR by Cystatin C underestimated measured GFR. Despite the fact that univariate analysis showed that in mild degree of tubular affection cystatin based equationscorrelated with the measured GFR by Iohexol clearance, especially CKD EPI Cystatin,the multivariateanalysis established thatthere was no independent association between the estimated GFRby cystatin based equations and Iohexol clearance. Also cystatin C based equations showed a high level of bias with a non statistically significant trend towards higher bias with Stevens equation whereas Grubb equations showed least bias. It is clear that although cystatin based equations have shown a good level of correlation with measured GFR they are still considered inaccurate and cannot yet be established as an equivalent to measured GFR or as a gold standard for GFRestimation.