Cystatin C:
An index of glomerular filtration rate, especially in patients where serum creatinine may be misleading (eg, very obese, elderly, or malnourished patients)
Assessing renal function in patients suspected of having kidney disease
Monitoring treatment response in patients with kidney disease
Estimated Glomerular Filtration Rate (eGFR):
An index of GFR, especially in patients where serum creatinine may be misleading (eg, very obese, elderly, or malnourished patients); for such patients, use of CKD-EPI cystatin C equation is recommended to estimate GFR
Assessing renal function in patients suspected of having kidney disease
Monitoring treatment response in patients with kidney disease
Cystatin C:
Cystatin C is a low molecular weight (13,250 kD) cysteine proteinase inhibitor that is produced by all nucleated cells and found in body fluids, including serum. Since it is formed at a constant rate and freely filtered by the kidneys, its serum concentration is inversely correlated with the glomerular filtration rate (GFR); that is, high values indicate low GFRs while lower values indicate higher GFRs, similar to creatinine.
The renal handling of cystatin C differs from creatinine. While both are freely filtered by glomeruli, once it is filtered, cystatin C, unlike creatinine, is reabsorbed and metabolized by proximal renal tubules. Thus, under normal conditions, cystatin C does not enter the final excreted urine to any significant degree.
The serum concentration of cystatin C remains unchanged with infections, inflammatory or neoplastic states, and is not affected by body mass, diet, or drugs. Thus, cystatin C may be a more reliable marker of renal function (GFR) than creatinine.
Estimated Glomerular Filtration Rate (GFR):
GFR can be estimated (eGFR) from serum cystatin C utilizing an equation which includes the age and gender of the patient. The CKD-EPI cystatin C equation was developed by Inker et al:(1) and demonstrated good correlation with measured iothalamate clearance in patients with all common causes of kidney disease, including kidney transplant recipients. Cystatin C eGFR may have advantages over creatinine eGFR in certain patient groups in whom muscle mass is abnormally high or low (for example quadriplegics, very elderly, or malnourished individuals). Blood levels of cystatin C also equilibrate more quickly than creatinine, and therefore, serum cystatin C may be more accurate than serum creatinine when kidney function is rapidly changing (for example amongst hospitalized individuals).
CYSTATIN C
Males:
0 days-22 years: no reference values established
23-29 years: 0.60-1.03 mg/L
30-39 years: 0.64-1.12 mg/L
40-49 years: 0.68-1.22 mg/L
50-59 years: 0.72-1.32 mg/L
60-69 years: 0.77-1.42 mg/L
70-79 years: 0.82-1.52 mg/L
>79 years: no reference values established
Females:
0 days-22 years: no reference values established
23-29 years: 0.57-0.90 mg/L
30-39 years: 0.59-0.98 mg/L
40-49 years: 0.62-1.07 mg/L
50-59 years: 0.64-1.17 mg/L
60-69 years: 0.66-1.26 mg/L
70-80 years: 0.68-1.36 mg/L
81-86 years: 0.70-1.45 mg/L
>86 years: no reference values established
eGFR
>60 mL/min/BSA
eGFR will not be calculated for patients under 18 years.
Cystatin C:
Cystatin C inversely correlates with the glomerular filtration rate (GFR), that is elevated levels of cystatin C indicate decreased GFR. Cystatin C may provide more accurate assessment of GFR for very obese, elderly, or malnourished patients than creatinine. Cystatin C equation does not require patient ethnic data, and can be used for those patients with this information unavailable.
Due to immaturity of renal function, cystatin C levels are higher in neonates <3 months of age.(2)
Estimated Glomerular Filtration Rate (eGFR):
Chronic kidney disease (CKD) is defined as the presence of: persistent and usually progressive reduction in GFR (GFR <60 mL/min/1.73 m[2]) and/or albuminuria (>30 mg of urinary albumin per gram of urinary creatinine), regardless of GFR.
According to the National Kidney Foundation Kidney Disease Outcome Quality Initiative (K/DOQI) classification, among patients with CKD, irrespective of diagnosis, the stage of disease should be assigned based on the level of kidney function:
| Stage | Description | GFR mL/min/BSA |
| 1 | Kidney damage with normal or increased GFR | 90 |
| 2 | Kidney damage with mild decrease in GFR | 60-89 |
| 3 | Moderate decrease in GFR | 30-59 |
| 4 | Severe decrease in GFR | 15-29 |
| 5 | Kidney failure | <15 (or dialysis) |
Cystatin C:
Lipemic or frozen specimens, which become turbid after thawing, may interfere with the assay.
Estimated Glomerular Filtration Rate (eGFR):
eGFR is not a precise measure of GFR and can be influenced by nonrenal factors (eg, inflammation).
Supportive Data
In a study to evaluate cystatin C as a measure of renal function in comparison to serum creatinine, 500 patients had cystatin C measured by nephelometry and glomerular filtration rate (GFR) measured by nonradiolabeled iothalamate clearance.(2) In addition, serum creatinine was measured and the patients' medical records reviewed. The correlation of 1/cystatin C with GFR (r=0.90) was significantly superior than 1/creatinine (r=0.82, p<0.05) with GFR. The superior correlation of 1/cystatin C with GFR was observed in the various clinical subgroups of patients studied (ie, subjects with no suspected renal disease, renal transplant patients, recipients of some other transplant, patients with glomerular disease, and patients with non-glomerular renal disease). Using the lower fifth percentile age-adjusted normal values for iothalamate clearance, receiver operator characteristic curves were generated. The area under the curve for 1/cystatin C was significantly greater than for 1/creatinine. These results indicate that cystatin C may be superior to serum creatinine for the assessment of GFR in a wide spectrum of patients-both those with renal disease and those without renal disease. Others have similarly found that cystatin C correlates better than serum creatinine for assessment of GFR.(3)
1. Inker LA, Schmid CH, Tighiouart H, et al: Estimating glomerular filtration rate from serum creatinine and cystatin C. N Engl J Med 2012 Jul;367(1):20-29
2. Buehrig CK, Larson TS, Bergert JH, et al: Cystatin C is superior to serum creatinine for the assessment of renal function. J Am Soc Nephrol 2001;12:194A
3. Grubb AO: Cystatin C - properties and use as a diagnostic marker. Adv Clin Chem 2000;35:63-99
4. Coll E, Botey A, Alvarez L, et al: Serum cystatin C as a new marker for noninvasive estimation of glomerular filtration rate and as a marker for early renal impairment. Am J Kidney Dis 2000 Jul;36(1):29-34
5. Flodin M, Jonsson AS, Hansson LO, et al: Evaluation of Gentian cystatin C reagent on Abbott Ci8200 and calculation of glomerular filtration rate expressed in mL/min/1.73 m(2) from the cystatin C values in mg/L. Scand J Clin Lab Invest 2007;67:560-567
6. Larsson A, Hansson LO, Flodin M, et al: Calibration of the Siemens cystatin C immunoassay has changed over time. Clin Chem 2011;57:777-778
7. Voskoboev NV, Larson TS, Rule AD, Lieske JC: Importance of cystatin C assay standardization. Clin Chem 2011 Aug;57(8):1209-1211
8. Nitsch D, Sandling JK, Byberg L et al: Fetal, developmental, and parental influences on cystatin C in childhood: the Uppsala Family Study. Am J Kidney Dis 2011 Jun;57(6):863-872
9. Voskoboev NV, Larson TS, Rule AD, Lieske JC: Analytic and clinical validation of a standardized cystatin C particle enhanced turbidimetric assay (PETIA) to estimate glomerular filtration rate. Clin Chem Lab Med 2012 Mar;50(9):1591-1596
10. Finney H, Newman DJ, Thakkar H, et al: Reference ranges for the plasma cystatin C and creatinine measurements in premature infants, neonates, and older children. Arch Dis Child 2000 Jan;82(1):71-75
