Cystatin C: A Reliable Marker

What is Cystatin C? 

Cystatin C

Cystatin C (CysC) is a crucial low molecular weight protein that is produced by all nucleated cells and is found in all biological fluids including plasma (serum), saliva, and urine. The Cystatin C is taken up by the proximal tubes and then metabolized so that it does not return into the bloodstream. As a result, serum Cystatin C closely correlates to glomerular filtration rate (GFR). The normal range of serum Cystatin C is around 0.62-1.15 mg/L (1). An abnormally high level of Cystatin C in your blood may point to renal dysfunction. In addition to renal dysfunction/disease, higher levels of Cystatin C can also point to diabetes, chronic inflammation, obesity, cancer, and hyperthyroidism (5,6).

Cystatin C is a marker for GFR

Glomerular filtration rate (GFR) remains the ideal marker for kidney function & it is commonly assessed by measuring serum markers such as blood urea nitrogen & serum creatinine (4).

Cystatin C and glomerular filtration rateHowever, creatinine is subject to high analytic variability & creatinine levels do not rise until nearly 50% of kidney function is damaged, leading to inaccurate CKD staging. It is important to note that early diagnosis of renal dysfunction is imperative to survive.

New formulas for creatinine and creatinine-cystatin C equations were published by the CKD-EPI journal in November of 2021. According to the NKF-ASN task force, it is recommended to use cystatin c measurement as a confirmatory test because combining filtration markers provides more complete information for clinical decisions (8). In addition, the new equation offers an opportunity for laboratories to standardize the most up-to-date practice & take a step toward lessening racial disparities in healthcare.

Cystatin C is a newer biomarker for GFR & it is not dependent upon age, race, gender, and muscle mass- unlike Creatinine. Creatinine is more prone to biological interference & limitations exist around sensitivity and specificity (10). Recently, the use of a race multiplier in eGFR equations has been under scrutiny for its lack of recognition that race is a social construct rather than a biological one (9). Many institutions dropped it from their eGFR equations, resulting in inconsistency in eGFR estimates. Another example of biological interference, while the eGFR MDRD equation accounts for many intrinsic factors, the magnitude of change in muscle mass can vary among populations and this equation does not account for physiological changes such as illness, inflammation, and sarcopenia (9). This means that the serum concentration of Creatinine can still differ between individuals with the same kidney function. Cystatin C has been shown to be a more reliable biomarker than Creatinine as an indicator of true GFR and to add information about the occurrence of acute kidney injury. The best GFR estimation requires both Cystatin C & Creatinine based equations. The conclusion is that Cystatin C should be used just as often (if not more) as Creatinine in clinical medicine & research.

Our Cystatin C ELISAs

Our direct competitive Cystatin C ELISAs (human, mouse, rat) can provide an avenue for assessing renal dysfunction especially following surgery. Together with Cystatin C, a GFR marker, urinary Cystatin C would be a biomarker of AKI and/or assessing response to therapeutic interventions in experimental and clinical research. Our Cystatin C ELISAs use recombinant (human, mouse, rat) cystatin C as standard and a polyclonal antibody raised against recombinant cystatin C. This antibody does not react with r albumin or r IgG. Native cystatin C samples produced dose-response curves that were colinear with those made with our kit standards. You can feel more confident with your nephrology research by using our accurate, specific, and sensitive assays as a research tool.

Citations

1. Murty, M S N et al. “Serum cystatin C as a marker of renal function in detection of early acute kidney injury.” Indian journal of nephrology vol. 23,3 (2013): 180-3. doi:10.4103/0971-4065.111840

2. National Institute of Diabetes and Digestive and Kidney Diseases. Explaining Your Kidney Test Results: A Tool For Clinical Use. 2014, August.

3. Kar S, Paglialunga S, Islam R. Cystatin C Is a More Reliable Biomarker for Determining eGFR to Support Drug Development Studies. J Clin Pharmacol. 2018 Oct;58(10):1239-1247. doi: 10.1002/jcph.1132. Epub 2018 May 18. PMID: 29775220.

4. Omar F Laterza, Christopher P Price, Mitchell G Scott, Cystatin C: An Improved Estimator of Glomerular Filtration Rate?, Clinical Chemistry, Volume 48, Issue 5, 1 May 2002, Pages 699–707,

5. Muslimovic, Alma et al. “Serum cystatin C – marker of inflammation and cardiovascular morbidity in chronic kidney disease stages 1-4.” Materia socio-medica vol. 27,2 (2015): 75-8. doi:10.5455/msm.2015.27.75-78

6. Muntner, Paul et al. “Overweight, obesity, and elevated serum cystatin C levels in adults in the United States.” The American journal of medicine 121,4 (2008): 341-8. doi:10.1016/j.amjmed.2008.01.003

7. Grubb, Anders. “Cystatin C is Indispensable for Evaluation of Kidney Disease.” EJIFCC vol. 28,4 268-276. 19 Dec. 2017

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