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Evaluation of a new immunoassay for cystatin C, based on a double monoclonal principle, in men with normal and impaired renal function.

Ristiniemi N, Savage C, Bruun L, Pettersson K, Lilja H, Christensson A - Nephrol. Dial. Transplant. (2011)

Bottom Line: The study enrolled 170 men without known CKD (Group A) and 104 men with CKD (Group B).Concordance correlation coefficients and the 95% limits of agreement were used to estimate the agreement of reciprocal cystatin C and reciprocal creatinine with iohexol clearance.Median iohexol clearance (mL/min/1.73 m(2)) was 81 [interquartile range (IQR) 70, 92] in Group A and 23 (IQR 16, 34) in Group B.

View Article: PubMed Central - PubMed

Affiliation: Department of Biotechnology, University of Turku, Turku, Finland.

ABSTRACT

Background: Elevated cystatin C in blood reflects impaired glomerular filtration rate (GFR), but current cystatin C assays, based on polyclonal antibodies and immunoturbidimetric or nephelometric detection, have several limitations. We evaluated a new immunoassay based on monoclonal antibodies in samples from patients with and without chronic kidney disease (CKD).

Methods: The study enrolled 170 men without known CKD (Group A) and 104 men with CKD (Group B). All patients were assessed with iohexol clearance, plasma creatinine and plasma cystatin C by a conventional particle-enhanced immunoturbidimetric assay (PETIA) and by the new double monoclonal assay. In Group A, three serial blood draws were performed at median intervals of 4 h and 12 days between samples, to also allow assessments of the variability in cystatin C values with the new assay. Concordance correlation coefficients and the 95% limits of agreement were used to estimate the agreement of reciprocal cystatin C and reciprocal creatinine with iohexol clearance.

Results: Median iohexol clearance (mL/min/1.73 m(2)) was 81 [interquartile range (IQR) 70, 92] in Group A and 23 (IQR 16, 34) in Group B. The concordance correlation with GFR for the new cystatin C assay compared to the established assay was similar in Group A (0.441 versus 0.465) but higher in Group B (0.680 versus 0.593). Cystatin C measured by both assays exhibited closer agreement with GFR than creatinine. The agreement between the two cystatin C assays was high, with concordance correlations of 0.815 in Group A and 0.935 in Group B. Compared to the conventional assay, the new assay tended to yield lower values of cystatin C at the low end of the range in Group A. The new cystatin C assay exhibited small intraindividual variability across serial samples (coefficient of variation ≤ 6%).

Conclusions: In this first clinical evaluation, the new cystatin C assay performed similarly to the established PETIA in patients with normal GFR and better in patients with CKD. The new assay may offer an alternative to current commercial assays to detect and monitor impaired kidney function.

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Related in: MedlinePlus

Calibration plot of 1/cystatin C values from the conventional assay as compared to iohexol clearance (gold standard). The black line represents perfect agreement. Patients with CKD (Group B) are represented by solid circles; patients without diagnosis of kidney disease (Group A) are represented by hollow circles.
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fig1: Calibration plot of 1/cystatin C values from the conventional assay as compared to iohexol clearance (gold standard). The black line represents perfect agreement. Patients with CKD (Group B) are represented by solid circles; patients without diagnosis of kidney disease (Group A) are represented by hollow circles.

Mentions: Table 2 summarizes the concordance correlation coefficients and limits of agreement for 1/cystatin C and 1/creatinine compared to iohexol clearance. Overall, the agreement between cystatin C and the true GFR was higher in patients with renal disease (Group B) than in those with normal renal function (Group A). When the two cystatin C assays were compared with iohexol clearance in Group A, the conventional assay had a slightly higher concordance correlation than the new assay, whereas in Group B, the new assay had the higher concordance correlation. Both cystatin C assays tended to overestimate true GFR in both cohorts (Figures 1 and 2, Table 2), but both cystatin C assays exhibited better agreement with iohexol clearance than did creatinine in Group A and B (Figures 1–3). The lowest concordance correlation was shown between 1/creatinine and iohexol clearance. However, at low levels of renal function (GFR < 30), creatinine appeared to have better agreement with GFR (Figure 3).


Evaluation of a new immunoassay for cystatin C, based on a double monoclonal principle, in men with normal and impaired renal function.

Ristiniemi N, Savage C, Bruun L, Pettersson K, Lilja H, Christensson A - Nephrol. Dial. Transplant. (2011)

Calibration plot of 1/cystatin C values from the conventional assay as compared to iohexol clearance (gold standard). The black line represents perfect agreement. Patients with CKD (Group B) are represented by solid circles; patients without diagnosis of kidney disease (Group A) are represented by hollow circles.
© Copyright Policy - creative-commons
Related In: Results  -  Collection

License
Show All Figures
getmorefigures.php?uid=PMC3275784&req=5

fig1: Calibration plot of 1/cystatin C values from the conventional assay as compared to iohexol clearance (gold standard). The black line represents perfect agreement. Patients with CKD (Group B) are represented by solid circles; patients without diagnosis of kidney disease (Group A) are represented by hollow circles.
Mentions: Table 2 summarizes the concordance correlation coefficients and limits of agreement for 1/cystatin C and 1/creatinine compared to iohexol clearance. Overall, the agreement between cystatin C and the true GFR was higher in patients with renal disease (Group B) than in those with normal renal function (Group A). When the two cystatin C assays were compared with iohexol clearance in Group A, the conventional assay had a slightly higher concordance correlation than the new assay, whereas in Group B, the new assay had the higher concordance correlation. Both cystatin C assays tended to overestimate true GFR in both cohorts (Figures 1 and 2, Table 2), but both cystatin C assays exhibited better agreement with iohexol clearance than did creatinine in Group A and B (Figures 1–3). The lowest concordance correlation was shown between 1/creatinine and iohexol clearance. However, at low levels of renal function (GFR < 30), creatinine appeared to have better agreement with GFR (Figure 3).

Bottom Line: The study enrolled 170 men without known CKD (Group A) and 104 men with CKD (Group B).Concordance correlation coefficients and the 95% limits of agreement were used to estimate the agreement of reciprocal cystatin C and reciprocal creatinine with iohexol clearance.Median iohexol clearance (mL/min/1.73 m(2)) was 81 [interquartile range (IQR) 70, 92] in Group A and 23 (IQR 16, 34) in Group B.

View Article: PubMed Central - PubMed

Affiliation: Department of Biotechnology, University of Turku, Turku, Finland.

ABSTRACT

Background: Elevated cystatin C in blood reflects impaired glomerular filtration rate (GFR), but current cystatin C assays, based on polyclonal antibodies and immunoturbidimetric or nephelometric detection, have several limitations. We evaluated a new immunoassay based on monoclonal antibodies in samples from patients with and without chronic kidney disease (CKD).

Methods: The study enrolled 170 men without known CKD (Group A) and 104 men with CKD (Group B). All patients were assessed with iohexol clearance, plasma creatinine and plasma cystatin C by a conventional particle-enhanced immunoturbidimetric assay (PETIA) and by the new double monoclonal assay. In Group A, three serial blood draws were performed at median intervals of 4 h and 12 days between samples, to also allow assessments of the variability in cystatin C values with the new assay. Concordance correlation coefficients and the 95% limits of agreement were used to estimate the agreement of reciprocal cystatin C and reciprocal creatinine with iohexol clearance.

Results: Median iohexol clearance (mL/min/1.73 m(2)) was 81 [interquartile range (IQR) 70, 92] in Group A and 23 (IQR 16, 34) in Group B. The concordance correlation with GFR for the new cystatin C assay compared to the established assay was similar in Group A (0.441 versus 0.465) but higher in Group B (0.680 versus 0.593). Cystatin C measured by both assays exhibited closer agreement with GFR than creatinine. The agreement between the two cystatin C assays was high, with concordance correlations of 0.815 in Group A and 0.935 in Group B. Compared to the conventional assay, the new assay tended to yield lower values of cystatin C at the low end of the range in Group A. The new cystatin C assay exhibited small intraindividual variability across serial samples (coefficient of variation ≤ 6%).

Conclusions: In this first clinical evaluation, the new cystatin C assay performed similarly to the established PETIA in patients with normal GFR and better in patients with CKD. The new assay may offer an alternative to current commercial assays to detect and monitor impaired kidney function.

Show MeSH
Related in: MedlinePlus