Recalibration of cystatin C using standardized material in Siemens nephelometers.

BACKGROUND: Cystatin C is a key GFR biomarker. Recently, Siemens recalibrated the assay based on certified reference material ERM-DA471/IFCC. The NIH-funded longitudinal chronic kidney disease in children (CKiD) study has > 3000 cystatin C measurements based on a pre-IFCC calibrator provided by Siemens. Since cystatin C values for CKiD are now standardized to IFCC certified reference material, it is important to relate the IFCC-calibrated results to the previous values so that there are no discontinuous results. METHODS: We diluted cystatin C ERM-DA471/IFCC (5.48 mg/L) into buffer and compared results with predicted ones. We then updated the cystatin C application on our BN II nephelometer to provide results based on pre-IFCC and IFCC calibrations of CKiD specimens simultaneously. We assayed 51 previously analyzed sera and 62 fresh additional specimens. RESULTS: The predicted concentrations from the IFCC standard were consistently 17% higher than the measured values using the pre-IFCC calibration (y = 1.1686x). Similarly, the re-run and fresh sample concentrations were 17% higher via the IFCC calibration than by the pre-IFCC calibration (y = 1.168x). There was very high reliability in the measurements using the previous calibration for re-run specimens (0.99) and for 33 pristine specimens using IFCC calibration (0.99). CONCLUSIONS: We confirm the recalibration proposed by Siemens. To convert pre-IFCC results to IFCC-calibrated concentrations, the value is multiplied by 1.17. Conversely, one divides IFCC-calibrated results by 1.17 to estimate GFR via previously published pre-IFCC CKiD eGFR equations. For older adolescents, cystatin C has already been standardized and can be directly applied to the CKD-EPI equations.

Renal Response to a Protein Load in Healthy Young Adults as Determined by Iohexol Infusion Clearance, Cimetidine-Inhibited Creatinine Clearance, and Cystatin C Estimated Glomerular Filtration Rate.

OBJECTIVE: Renal reserve (RR) measures the increase in glomerular filtration rate (GFR) in response to a protein load; lack of RR could indicate subclinical kidney disease but such a test is not routinely used in clinical practice. The purpose of this study was to compare a meat versus liquid protein load in a cystatin C-based (Cys-C) RR test using cimetidine-inhibited creatinine clearance (Cr Cl) and iohexol infusion clearance (Io Cl) for validation. The design was cross-sectional analysis and the setting was a Clinical Research Center. SUBJECTS: Participants (N = 16), mean (standard deviation [SD]) age 22 (2) years, had normal health and blood pressure without proteinuria. INTERVENTION: Participants 1 to 8 received a beef burger (1 g/kg protein) and participants 9 to 16 received a ProCel shake (1-1.5 g/kg protein). MAIN OUTCOME MEASURE: RR defined as the difference in stimulated versus baseline GFR. RESULTS: Baseline GFR (SD) in mL/minute/1.73 m2 averaged 103.0 (15.6) for Cr Cl, 94.8 (7.9) for Io Cl, and 117.0 (6.0) for Cys-C estimated GFR (eGFR). Mean RR (SD) for the burger group (N = 8, mL/minute/1.73 m2) was 16.6 (12.3) for Cr Cl (P = .006); 7.2 (3.7) for Io Cl (P < .001), and 4.9 (2.6) for Cys-C eGFR (P = .001). Mean RR for the shake group (N = 8) was 15.8 (5.8) for Cr Cl (P < .001), 10.1 (7.8) for Io Cl (P = .008), and 2.4 (2.9) for Cys-C eGFR (P = .05). CONCLUSION: Protein loading stimulates Io Cl and Cr Cl after a beef or milk-based protein load. The change in Cys-C eGFR is significant but smaller for the shake and burger group, which may be due to the dilutional effect of water loading or the length of Cys-C half-life in the blood.

Rapid assessment of renal reserve in young adults by cystatin C.

BACKGROUND: The kidney can increase glomerular filtration rate (GFR) in response to a protein load (renal reserve). In a pilot study of healthy young adults we examined renal reserve using changes in serum cystatin C (cysC). METHODS: Glomerular filtration rate was obtained using iohexol single slope plasma disappearance. To stimulate GFR, subjects ingested a beefburger containing 60 grams of protein. CysC was measured by immunonephelometry before and 125-141 minutes after protein loading. RESULTS: All subjects were found to have a normal iohexol plasma disappearance GFR with a mean of 104.6 ± 9.9 mL/min per 1.73 m(2). CysC decreased in each subject after the meat meal. Baseline cysC-based estimated GFR was 98.1 ± 9.1 mL/min per 1.73 m(2) with a mean increase of 12.0 ± 5.2 (p = 0.0003). CONCLUSIONS: Our study showed a consistent decrease in serum cysC and increase in cysC-based estimated GFR following a protein load in young adults. Further studies are needed using renal clearance methods to confirm that cysC accurately determines renal reserve in patients with and without chronic kidney disease.

Improved equations estimating GFR in children with chronic kidney disease using an immunonephelometric determination of cystatin C.

The Chronic Kidney Disease in Children study is a cohort of about 600 children with chronic kidney disease (CKD) in the United States and Canada. The independent variable for our observations was a measurement of glomerular filtration rate(GFR) by iohexol disappearance (iGFR) at the first two visits 1 year apart and during alternate years thereafter. In a previous report, we had developed GFR estimating equations utilizing serum creatinine, blood urea nitrogen, height, gender, and cystatin C measured by an immunoturbidimetric method; however, the correlation coefficient of cystatin C and GFR(0.69) was less robust than expected. Therefore, 495 samples were re-assayed using immunonephelometry. The reciprocal of immunonephelometric cystatin C was as well correlated with iGFR as was height/serum creatinine (both 0.88). We developed a new GFR estimating equation using a random 2/3 of 965 person-visits and applied it to the remaining 1/3 as a validation data set. In the validation dataset, the correlation of the estimated GFR with iGFR was 0.92 with high precision and no bias; 91 and 45% of eGFR values were within 30 and 10% of iGFR, respectively. This equation works well in children with CKD in a range of GFR from 15 to 75 ml/min per 1.73 m2. Further studies are needed to establish the applicability to children of normal stature and muscle mass, and higher GFR.