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

George J Schwartz, Michael F Schneider, Paula S Maier, Marva Moxey-Mims, Vikas R Dharnidharka, Bradley A Warady, Susan L Furth, Alvaro Muñoz, George J Schwartz, Michael F Schneider, Paula S Maier, Marva Moxey-Mims, Vikas R Dharnidharka, Bradley A Warady, Susan L Furth, Alvaro Muñoz

Abstract

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.

Figures

Figure 1
Figure 1
Box-percentile plots of cystatin C measured using the DAKO turbidimetric method vs. the Siemens Healthcare nephelometric method.
Figure 2
Figure 2
Univariate analysis of log(iGFR) vs. log(1.8/(cystatin C [Siemens Healthcare]) in N=965 person-visits.
Figure 3
Figure 3
Univariate analysis of log(iGFR) vs. log(ht/Scr) in N=965 person-visits.
Figure 4
Figure 4
Three box-percentile plots illustrating ht/Scr-based and nephelometric cystatin C-based eGFR vs. iGFR in N=965 person-visits.

References

    1. Dharnidharka VR, Kwon C, Stevens G. Serum cystatin C is superior to serum creatinine as a marker of kidney function: a meta-analysis. Am J Kidney Dis. 2002;40:221–226.
    1. Ylinen EA, Ala-Houhala M, Harmoinen APT, Knip M. Cystatin C as a marker for glomerular filtration rate in pediatric patients. Pediatr Nephrol. 1999;13:506–509.
    1. Stickle D, Cole B, Hock K, et al. Correlation of plasma concentrations of cystatin C and creatinine to inulin clearance in a pediatric population. Clinical Chemistry. 1998;44:1334–1338.
    1. Filler G, Lepage N. Should the Schwartz formula for estimation of GFR be replaced by cystatin C formula? Pediatr Nephrol. 2003;18:981–985.
    1. Finney H, Newman DJ, Thakkar H, et al. Reference ranges for plasma cystatin C and creatinine measurements in premature infants, neonates, and older children. Arch Dis Childh. 2000;82:71–75.
    1. Bökenkamp A, Domanetzki M, Zinck R, et al. Reference values for cystatin C serum concentrations in children. Pediatr Nephrol. 1998;12:125–129.
    1. Grubb A. Diagnostic value of analysis of cystatin C and protein HC in biological fluids. Clin Nephrol. 1992;38:S20–S27.
    1. Tenstad O, Roald AB, Grubb A, Aukland K. Renal handling of radiolabelled human cystatin C in the rat. Scand J Clin Lab Invest. 1996;56:409–414.
    1. Keevil BG, Kilpatrick ES, Nichols SP, Maylor PW. Biological variation of cystatin C: implications for the assessment of glomerular filtration rate. Clin Chem. 1998;44:1535–1539.
    1. Hills LP, Tiffany TO. Comparison of turbidimetric and light-scattering measurements of immunoglobulins by use of a centrifugal analyzer with absorbance and fluorescence/light-scattering optics. Clin Chem. 1980;26:1459–1466.
    1. Flodin M, Hansson LO, Larsson A. Variations in assay protocol for the Dako cystatin C method may change patient results by 50% without changing the results for controls. Clin Chem Lab Med. 2006;44:1481–1485.
    1. Finney H, Newman DJ, Gruber W, et al. Initial evaluation of cystatin C measurement by particle-enhanced immunonephelometry on the Behring nephelometer systems (BNA, BN II) Clin Chem. 1997;43:1016–1022.
    1. Dworkin LD. Serum cystatin C as a marker of glomerular filtration rate. Current Opinion in Nephrology and Hypertension. 2001;10:551–553.
    1. Coll E, Botey A, Alvarez L, et al. Serum cystatin C as a new marker for noninvasive estimation of glomerular filtration rate and as a marker for early renal impairment. Am J Kid Dis. 2000;36:29–34.
    1. Christensson A, Ekberg J, Grubb A, et al. Serum cystatin C is a more sensitive and more accurate marker of glomerular filtration rate than enzymatic measurements of creatinine in renal transplantation. Nephron Physiol. 2003;94:19–27.
    1. Filler G, Priem F, Lepage N, et al. β-Trace protein, cystatin C, β2-microglobulin, and creatinine compared for detecting impaired glomerular filtration rates in children. Clinical Chemistry. 2002;48:729–736.
    1. Filler G, Priem F, Vollmer I, et al. Diagnostic sensitivity of serum cystatin for impaired glomerular filtration rate. Pediatr Nephrol. 1999;13:501–505.
    1. Schwartz GJ, Munoz A, Schneider MF, et al. New equations to estimate GFR in children with CKD. J Am Soc Nephrol. 2009;20:629–637.
    1. Schwartz GJ, Kwong T, Erway B, et al. Validation of creatinine assays utilizing HPLC and IDMS traceable standards in sera of children. Pediatr Nephrol. 2009;24:113–119.
    1. Grubb A, Blirup-Jensen S, Lindstrom V, et al. First certified reference material for cystatin C in human serum ERM-DA471/IFCC. Clin Chem Lab Med. 2010;48:1619–1621.
    1. Zappitelli M, Parvex P, Joseph L, et al. Derivation and validation of cystatin C-based prediction equations for GFR in children. Am J Kidney Dis. 2006;48:221–230.
    1. Hoek FJ, Kemperman FA, Krediet RT. A comparison between cystatin C, plasma creatinine and the Cockcroft and Gault formula for the estimation of glomerular filtration rate. Nephrol Dial Transplant. 2003;18:2024–2031.
    1. Flodin M, Larsson A. Performance evaluation of a particle-enhanced turbidimetric cystatin C assay on the Abbott ci8200 analyzer. Clin Biochem. 2009;42:873–876.
    1. Levey AS, Coresh J, Greene T, et al. Using standardized serum creatinine values in the modification of diet in renal disease study equation for estimating glomerular filtration rate. Ann Intern Med. 2006;145:247–254.
    1. Inker LA, Okparavero A. Cystatin C as a marker of glomerular filtration rate: prospects and limitations. Curr Opin Nephrol Hypertens. 2011;20:631–639.
    1. Bouvet Y, Bouissou F, Coulais Y, et al. GFR is better estimated by considering both serum cystatin C and creatinine levels. Pediatr Nephrol. 2006;21:1299–1306.
    1. Schwartz GJ, Work DF. Measurement and estimation of GFR in children and adolescents. Clin J Am Soc Nephrol. 2009;4:1832–1843.
    1. Eriksen BO, Mathisen UD, Melsom T, et al. Cystatin C is not a better estimator of GFR than plasma creatinine in the general population. Kidney Int. 2010;78:1305–1311.
    1. Eriksen BO, Mathisen UD, Melsom T, et al. The Role of Cystatin C in Improving GFR Estimation in the General Population. Am J Kidney Dis. 2011
    1. Stevens LA, Schmid CH, Greene T, et al. Factors other than glomerular filtration rate affect serum cystatin C levels. Kidney Int. 2009;75:652–660.
    1. Knight EL, Verhave JC, Spiegelman D, et al. Factors influencing serum cystatin C levels other than renal function and the impact on renal function measurement. Kidney Int. 2004;65:1416–1421.
    1. Furth SL, Abraham AG, Jerry-Fluker J, et al. Metabolic abnormalities, cardiovascular disease risk factors, and GFR decline in children with chronic kidney disease. Clin J Am Soc Nephrol. 2011;6:2132–2140.
    1. Odlind B, Hällgren R, Sohtell M, Lindström B. Is 125I iothalamate an ideal marker for glomerular filtration? Kidney Int. 1985;27:9–16.
    1. Schwartz GJ, Furth S, Cole S, et al. Glomerular filtration rate via plasma iohexol disappearance: Pilot study for chronic kidney disease in children. Kidney Int. 2006;69:2070–2077.
    1. Gaspari F, Perico N, Ruggenenti P, et al. Plasma clearance of nonradioactive iohexol as a measure of glomerular filtration rate. J Am Soc Nephrol. 1995;6:257–263.
    1. Brown SCW, O’Reilly PH. Iohexol clearance for the determination of glomerular filtration rate in clinical practice: evidence for a new gold standard. J Urol. 1991;146:675–679.
    1. Rahn KH, Heidenreich S, Bruckner D. How to assess glomerular function and damage in humans. J Hypertens. 1999;17:309–317.
    1. Lindblad HG, Berg UB. Comparative evaluation of iohexol and inulin clearance for glomerular filtration rate determinations. Acta Paediatr. 1994;83:418–422.
    1. Berg UB, Back R, Celsi G, et al. Comparison of plasma clearance of iohexol and urinary clearance of inulin for measurement of GFR in children. Am J Kidney Dis. 2011;57:55–61.
    1. Schwartz GJ, Abraham AG, Furth SL, et al. Optimizing iohexol plasma disappearance curves to measure the glomerular filtration rate in children with chronic kidney disease. Kidney Int. 2010;77:65–71.
    1. Ng DK, Schwartz GJ, Jacobson LP, et al. Universal GFR determination based on two time points during plasma iohexol disappearance. Kidney Int. 2011;80:423–430.
    1. Brochner-Mortensen J. A simple method for the determination of glomerular filtration rate. Scand J Clin Lab Invest. 1972;30:271–274.
    1. Grubb A. Non-invasive estimation of glomerular filtration rate (GFR). The Lund model: Simultaneous use of cystatin C- and creatinine-based GFR-prediction equations, clinical data and an internal quality check. Scand J Clin Lab Invest. 2010;70:65–70.
    1. Schwartz GJ, Haycock GB, Edelmann CM, Jr, Spitzer A. A simple estimate of glomerular filtration rate in children derived from body length and plasma creatinine. Pediatrics. 1976;58:259–263.
    1. Schwartz GJ, Brion LP, Spitzer A. The use of plasma creatinine concentration for estimating glomerular filtration rate in infants, children, and adolescents. Pediatr Clin North Am. 1987;34:571–590.
    1. Haycock GB, Schwartz GJ, Wisotsky DH. Geometric method for measuring body surface area: a height-weight formula validated in infants, children, and adults. J Pediatr. 1978;93:62–66.
    1. Erlandsen EJ, Randers E, Kristensen JH. Evaluation of the Dade Behring N Latex Cystatin C assay on the Dade Behring Nephelometer II System. Scand J Clin Lab Invest. 1999;59:1–8.
    1. Ix JH, Shlipak MG, Chertow GM, Whooley MA. Association of cystatin C with mortality, cardiovascular events, and incident heart failure among persons with coronary heart disease: data from the Heart and Soul Study. Circulation. 2007;115:173–179.
    1. Bland JM, Altman DG. Statistical methods for assessing agreement between two methods of clinical measurement. Lancet. 1986;1:307–310.

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