title: Glomerular filtration rate estimation in patients with advanced chronic renal insufficiency based on serum cystatin C levels.
abstract: BACKGROUND
  Cystatin C has an obvious advantage in the recognition of the initial stages of renal impairment. It is questionable whether cystatin C possesses the same benefit in follow-up of pre-dialysis patients. If cystatin C were also a sensitive marker of GFR in pre-dialysis patients, then it could be expected that, for the same degree of a decrease in GFR, the increase in S(cyst) would be higher than in S(cr) because of the significant increase in tubular secretion of creatinine in residual nephrons. The aim of this study was to evaluate whether S(cyst) in patients with GFR <or=40 ml/min/1.73 m(2) provides a more accurate estimate of GFR than S(cr) does.
  
  
  METHODS
  The study was performed in 67 patients (mean age 41.5 +/- 7.6 years) with chronic renal insufficiency (GFR = 19.8 +/- 9.9 ml/min/1.73 m(2)) caused by various chronic renal diseases (predominantly by chronic glomerulonephritis and chronic interstitial nephritis). GFR was measured by inulin clearance under conditions of stabilized plasma concentrations and water loading. Creatinine clearance and serum cystatin C concentration (using immunonephelometry) were measured at the same time. For statistical evaluation, linear regression analysis, receiver-operating characteristic (ROC) curves analysis and the method of Bland and Altman were used.
  
  
  RESULTS
  A significant correlation (r = 0.813, p < 0.001) was demonstrated between 1/S(cyst) and C(in) as well as between 1/S(cr) and C(in) (r = 0.815, p < 0.001). There were no significant differences between the regression coefficients and the intercepts of regression straight lines characterizing these relationships. ROC curves analysis using the cut-off values for C(in) = 20 ml/min/1.73 m(2) and C(in) = 10 ml/min/ 1.73 m(2) did not show significant differences of corresponding AUC values for S(cyst) and S(cr) although there was a trend for superiority of S(cyst) in comparison with S(cr). The multiples of upper reference values of S(cyst) and S(cr) in examined patients did not differ significantly. There was a highly significant linear correlation between C(in) and C(cr) in pre-dialysis patients (r = 0.921, p < 0.001). The regression coefficient of this relation (1.279) was significantly higher than 1.0 (p < 0.001) and the value of intercept (6.50 ml/min/1.73 m(2)) was significantly higher than zero (p < 0.001). The average of C(cr)/C(in) in patients with C(in) <10 ml/min/1.73 m(2) was 2.11 (+/- 0.29) and 1.72 (+/- 0.35) for those with C(in) 10-20 ml/min/1.73 m(2).
  
  
  CONCLUSIONS
  The findings suggest that in patients with advanced chronic renal insufficiency (CRI) for the same decrease in GFR the increase of S(cyst) is not significantly higher than that of S(cr), although the tubular secretion of creatinine is significantly increased. Further studies (especially those focused on nonrenal elimination of cystatin C) are needed to elucidate the lack of difference between changes in S(cyst) and S(cr) in patients with CRI.
authors.affiliation: Department of Nephrology, Institute for Clinical and Experimental Medicine, Prague, Czech Republic. otto.schuck@medicon.cz
authors.forename: Otto
authors.initials: O
authors.lastname: Schück
authors.forename: Vladimir
authors.initials: V
authors.lastname: Teplan
authors.forename: Antonin
authors.initials: A
authors.lastname: Jabor
authors.forename: Milena
authors.initials: M
authors.lastname: Stollova
authors.forename: Jelena
authors.initials: J
authors.lastname: Skibova
mesh_terms: D000293:Adolescent; D000328:Adult; D000368:Aged; D015415:Biomarkers / Q000097:blood; D003404:Creatinine / Q000097:blood / Q000378:metabolism; D055316:Cystatin C; D015891:Cystatins / Q000097:blood*; D005260:Female; D005919:Glomerular Filtration Rate; D006801:Humans; D007676:Kidney Failure, Chronic / Q000097:blood* / Q000503:physiopathology*; D007684:Kidney Tubules / Q000378:metabolism; D008297:Male; D008875:Middle Aged
chemical_list: D015415:Biomarkers; C525030:CST3 protein, human; D055316:Cystatin C; D015891:Cystatins; D003404:Creatinine