Cystatin C: current position and future prospects

Séronie-Vivien, Sophie; Delanaye, Pierre; Piéroni, Laurence; Mariat, Christophe; Froissart, Marc; Cristol, Jean‐Paul

doi:10.1515/cclm.2008.336

Cited by 160 publications

(152 citation statements)

References 254 publications

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“…This confirms the independence of cystatin C from age-and sex-associated conditions (14,16,36) and may thus make it the preferred laboratory variable to be included in a GFR-estimating equation in an elderly population where reduction in muscle mass is common. Advantages of cystatin C to identify a moderate decline in renal function in elderly persons have been described (44).…”

Section: Discussionsupporting

confidence: 60%

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Two Novel Equations to Estimate Kidney Function in Persons Aged 70 Years or Older

Schaeffner¹,

Ebert²,

Delanaye³

et al. 2012

Ann Intern Med

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496

410

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Background: In older adults, current equations to estimate glomerular filtration rate (GFR) are not validated and may misclassify elderly persons in terms of their stage of chronic kidney disease. Objective: To derive the Berlin Initiative Study (BIS) equation, a novel estimator of GFR in elderly participants. Design: Cross-sectional. Data were split for analysis into 2 sets for equation development and internal validation. Setting: Random community-based population of a large insurance company. Participants: 610 participants aged 70 years or older (mean age, 78.5 years). Intervention: lohexol plasma clearance measurement as gold standard. Measurements: GFR, measured as the plasma clearance of the endogenous marker iohexol, to compare performance of existing equations of estimated GFR with measured GFR of the gold standard; estimation of measured GFR from standardized creatinine and cystatin C levels, sex, and age in the learning sample; and comparison of the BIS equations (BIS1: creatinine-based; BIS2: creatinine-and cystatin C-based) with other estimating equations and determination of bias, precision, and accuracy in the validation sample. Results:The new BIS2 equation yielded the smallest bias followed by the creatinine-based BIS1 and CockcroftGault equations. All other equations considerably overestimated GFR. The BIS equations confirmed a high prevalence of persons older than 70 years with a GFR less than 60 mL/min per 1.73 m 2 (BIS1, 50.4%; BIS2, 47.4%; measured GFR, 47.9%). The total misclassification rate for this criterion was smallest for the BIS2 equation (11.6%), followed by the cystatin C equation 2 (15.1%) proposed by the Chronic Kidney Disease Epidemiology Collaboration. Among the creatinine-based equations, BIS1 had the smallest misclassification rate (17.2%), followed by the Chronic Kidney Disease Epidemiology Collaboration equation (20.4%). Limitation: There was no validation by an external data set. Conclusion: The BIS2 equation should be used to estimate GFR in persons aged 70 years or older with normal or mild to moderately reduced kidney function. If cystatin C is not available, the BIS1 equation is an acceptable alternative. Primary Funding Source: Kuratorium für Dialyse und Nierentransplatation (KfH) Foundation of Preventive Medicine.

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Section: Discussionsupporting

confidence: 60%

“…All cystatin C samples were frozen at -80 °C and analyzed within 4 days in December 2011. Cystatin C is stable at -80 °C (36).…”

Section: Other Blood Measuresmentioning

confidence: 99%

Two Novel Equations to Estimate Kidney Function in Persons Aged 70 Years or Older

Schaeffner¹,

Ebert²,

Delanaye³

et al. 2012

Ann Intern Med

Self Cite

496

410

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“…Fourth, we excluded patients with CKD stage 4 to 5, which could potentially explain the lower rate of CKD in our cohort. Fifth, SCysC may be influenced by a number of nonrenal factors, including large doses of corticosteroids, thyroid dysfunction, systemic inflammation, neoplasia, age, type of assay used, and even to some extent by muscle mass (28).…”

Section: Discussionmentioning

confidence: 99%

Cystatin C as a Marker of Acute Kidney Injury in the Emergency Department

Soto

Coelho

Rodrigues

et al. 2010

Clinical Journal of the American Society of Nephrology

104

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Background and objectives: The diagnosis of acute kidney injury (AKI) is usually based on changes in serum creatinine, which is a poor marker of early renal dysfunction. The discriminative and predictive abilities of serum and urinary cystatin C were examined for the prediction of AKI.Design, setting, participants, & measurements: In this prospective cohort study, serum and urinary cystatin C were serially measured in a heterogeneous group of patients (n ‫؍‬ 616) presenting to a tertiary care emergency department. The primary outcome was AKI, classified according to RIFLE and AKIN criteria. The secondary outcome was an adjudication based on clinical criteria to AKI, prerenal azotemia, chronic kidney disease (CKD), and normal kidney function.Results: Patients were adjudicated to have AKI in 21.1%, prerenal azotemia in 25.8%, CKD in 2.4%, and normal kidney function in 50.7%. For the diagnosis of AKI, the discriminatory ability of urinary creatinine and cystatin C was marginal. Both serum cystatin C and serum creatinine (at presentation and 6 hours later) showed high discriminatory ability for the diagnosis of AKI. However, only serum cystatin C attained a significant early predictive power (Hosmer-Lemeshow P value > 0.05). Serum cystatin C could differentiate between AKI and prerenal azotemia, but not between AKI and CKD.Conclusions: Serum cystatin C is an early, predictive biomarker of AKI, which outperforms serum creatinine in the heterogeneous emergency department setting. However, neither biomarker discriminated between AKI and CKD. Additional biomarkers continue to be needed for improved specificity in the diagnosis of community-acquired AKI.

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“…It is possible that some of the observed interlaboratory differences could be explained by this factor (20). It is also possible that sample stability was affected during freezing and shipping, although evidence, to date, does not suggest that this is a significant issue (24).…”

Section: Discussionmentioning

confidence: 99%

The Impact of Interlaboratory Differences in Cystatin C Assay Measurement on Glomerular Filtration Rate Estimation

White¹,

Rule²,

Collier³

et al. 2011

Clinical Journal of the American Society of Nephrology

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SummaryBackground and objectives Cystatin C (CysC) is a promising marker of GFR. Several equations have been derived to estimate GFR from its serum concentration. Heterogeneity in the performance of these equations exists in validation studies even when the same CysC assay from the same manufacturer is utilized. This study was designed to examine the differences in CysC and GFR estimation (eGFR) using Siemens' nephelometric immunoassay and the Mayo Clinic equation. The ability of the eGFRs to predict measured GFR was also examined.Design, setting, participants, & measurements Ninety-seven split samples were sent to laboratories at Children's Hospital of Eastern Ontario (CHEO) in Ottawa, Canada, and at the Mayo Clinic in Rochester, Minnesota. ResultsThe mean CHEO CysC was 0.17 mg/L (10%) lower than the mean Mayo Clinic CysC. Using the Mayo Clinic equation, the mean eGFR difference was 7.2 ml/min per 1.73 m 2 (15%). Approximately 36% of the results agreed within 10%, while 13% were discordant by greater than 30%. Larger absolute differences in mean eGFR between the two laboratories were found in the subgroup with CysC less than 1.41 mg/L as compared with the subgroup greater than 1.41 mg/L (9.5 versus 5.0 ml/min per 1.73 m 2 ). Correction of CHEO values to the Mayo Clinic did not improve GFR estimation. Conclusions Significant differences in CysC measurement exist between laboratories using the same assay by the same manufacturer and these lead to clinically relevant differences in GFR estimation. This interlaboratory variability needs to be recognized when interpreting and comparing CysC and eGFR results.

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Cystatin C: current position and future prospects

Cited by 160 publications

References 254 publications

Two Novel Equations to Estimate Kidney Function in Persons Aged 70 Years or Older

Two Novel Equations to Estimate Kidney Function in Persons Aged 70 Years or Older

Cystatin C as a Marker of Acute Kidney Injury in the Emergency Department

The Impact of Interlaboratory Differences in Cystatin C Assay Measurement on Glomerular Filtration Rate Estimation

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