title: Evaluation of a new immunoassay for cystatin C, based on a double monoclonal principle, in men with normal and impaired renal function.
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.
authors.affiliation: Department of Biotechnology, University of Turku, Turku, Finland.
authors.forename: Noora
authors.initials: N
authors.lastname: Ristiniemi
authors.forename: Caroline
authors.initials: C
authors.lastname: Savage
authors.forename: Laila
authors.initials: L
authors.lastname: Bruun
authors.forename: Kim
authors.initials: K
authors.lastname: Pettersson
authors.forename: Hans
authors.initials: H
authors.lastname: Lilja
authors.forename: Anders
authors.initials: A
authors.lastname: Christensson
mesh_terms: D000368:Aged; D000911:Antibodies, Monoclonal; D016022:Case-Control Studies; D003404:Creatinine / Q000097:blood; D055316:Cystatin C / Q000032:analysis / Q000097:blood*; D005919:Glomerular Filtration Rate; D006801:Humans; D007118:Immunoassay / Q000379:methods*; D007472:Iohexol / Q000493:pharmacokinetics; D008297:Male; D008875:Middle Aged; D012016:Reference Values; D051436:Renal Insufficiency, Chronic / Q000097:blood* / Q000175:diagnosis; D015203:Reproducibility of Results; D012680:Sensitivity and Specificity; D012720:Severity of Illness Index
chemical_list: D000911:Antibodies, Monoclonal; D055316:Cystatin C; D007472:Iohexol; D003404:Creatinine