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Journal of Nephrology

, Volume 27, Issue 5, pp 467–475 | Cite as

Calibration and precision of serum creatinine and plasma cystatin C measurement: impact on the estimation of glomerular filtration rate

  • Pierre DelanayeEmail author
  • Etienne Cavalier
  • Jean-Paul Cristol
  • Joris R. Delanghe
Review

Abstract

Serum creatinine (SCr) is the main variable for estimating glomerular filtration rate (GFR). Due to inter-assay differences, the prevalence of chronic kidney disease (CKD) varies according to the assay used, and calibration standardization is necessary. For SCr, isotope dilution mass spectrometry (IDMS) is the gold standard. Systematic differences are observed between Jaffe and enzymatic methods. Manufacturers subtract 0.30 mg/dl from Jaffe results to match enzymatic results (‘compensated Jaffe method’). The analytical performance of enzymatic methods is superior to that of Jaffe methods. In the original Modification of Diet in Renal Disease (MDRD) equation, SCr was measured by a Jaffe Beckman assay, which was later recalibrated. A limitation of this equation was an underestimation of GFR in the high range. The Chronic Kidney Disease Epidemiology (CKD-EPI) consortium proposed an equation using calibrated and IDMS traceable SCr. The gain in performance was due to improving the bias whereas the precision was comparable. The CKD-EPI equation performs better at high GFR levels (GFR >60 ml/min/1.73 m2). Analytical limitations have led to the recommendation to give a grade (>60 ml/min/1.73 m2) rather than an absolute value with the MDRD equation. By using both enzymatic and calibrated methods, this cutoff-grade could be increased to 90 ml/min/1.73 m2 (with MDRD) and 120 ml/min/1.73 m2 (with CKD-EPI). The superiority of the CKD-EPI equation over MDRD is analytical, but the precision gain is limited. IDMS traceable enzymatic methods have been used in the development of the Lund–Malmö (in CKD populations) and Berlin Initiative Study equations (in the elderly). The analytical errors for cystatin C are grossly comparable to issues found with SCr. Standardization is available since 2011. A reference method for cystatin C is still lacking. Equations based on standardized cystatin C or cystatin C and creatinine have been proposed. The better performance of these equations (especially the combined CKD-EPI equation) has been demonstrated.

Keywords

Calibration Creatinine Cystatin C Glomerular filtration rate 

Notes

Conflict of interest

The authors declare that there is no conflict of interest.

References

  1. 1.
    KDIGO (2012) Clinical practice guideline for the evaluation and management of chronic kidney disease. Kidney Int Suppl 2013(3):1–150Google Scholar
  2. 2.
    Delanghe JR, Speeckaert MM (2011) Creatinine determination according to Jaffe—what does it stand for? NDT plus 4:83–86CrossRefGoogle Scholar
  3. 3.
    Folin O (1905) Approximately complete analyses of thirty “normal” urines. Am J Physiol 13:45–65Google Scholar
  4. 4.
    Gaebler OH (1930) Further studies of blood creatinine. J Biol Chem 89:451–466Google Scholar
  5. 5.
    Blijenberg BG, Brouwer HJ, Kuller TJ, Leeneman R, van Leeuwen CJ (1994) Improvements in creatinine methodology: a critical assessment. Eur J Clin Chem Clin Biochem 32:529–537PubMedGoogle Scholar
  6. 6.
    Cook JG (1975) Factors influencing the assay of creatinine. Ann Clin Biochem 12:219–232PubMedCrossRefGoogle Scholar
  7. 7.
    Perrone RD, Madias NE, Levey AS (1992) Serum creatinine as an index of renal function: new insights into old concepts. Clin Chem 38:1933–1953PubMedGoogle Scholar
  8. 8.
    Spencer K (1986) Analytical reviews in clinical biochemistry: the estimation of creatinine. Ann Clin Biochem 23(Pt 1):1–25PubMedCrossRefGoogle Scholar
  9. 9.
    Cobbaert CM, Baadenhuijsen H, Weykamp CW (2009) Prime time for enzymatic creatinine methods in pediatrics. Clin Chem 55:549–558PubMedCrossRefGoogle Scholar
  10. 10.
    Myers GL, Miller WG, Coresh J et al (2006) Recommendations for improving serum creatinine measurement: a report from the laboratory working group of the national kidney disease education program. Clin Chem 52:5–18PubMedCrossRefGoogle Scholar
  11. 11.
    Greenberg N, Roberts WL, Bachmann LM et al (2012) Specificity characteristics of 7 commercial creatinine measurement procedures by enzymatic and Jaffe method principles. Clin Chem 58:391–401PubMedCrossRefGoogle Scholar
  12. 12.
    Arant BS Jr, Edelmann CM Jr, Spitzer A (1972) The congruence of creatinine and inulin clearances in children: use of the Technicon AutoAnalyzer. J Pediatr 81:559–561PubMedCrossRefGoogle Scholar
  13. 13.
    Fabiny DL, Ertingshausen G (1971) Automated reaction-rate method for determination of serum creatinine with the CentrifiChem. Clin Chem 17:696–700PubMedGoogle Scholar
  14. 14.
    Delanghe J (2002) Standardization of creatinine determination and its consequences for the clinician. Acta Clin Belg 57:172–175PubMedCrossRefGoogle Scholar
  15. 15.
    Miller BF, Dubos R (1937) Determination by a specific enzymatic method of the creatinine content of blood and urine from normal and nephritic individuals. J Biol Chem 121:457–464Google Scholar
  16. 16.
    Fossati P, Prencipe L, Berti G (1983) Enzymic creatinine assay: a new colorimetric method based on hydrogen peroxide measurement. Clin Chem 29:1494–1496PubMedGoogle Scholar
  17. 17.
    McLean MH, Gallwas J, Hendrixson M (1973) Evaluation of an automated creatininase creatinine procedure. Clin Chem 19:623–625PubMedGoogle Scholar
  18. 18.
    Stevens LA, Manzi J, Levey AS et al (2007) Impact of creatinine calibration on performance of GFR estimating equations in a pooled individual patient database. Am J Kidney Dis 50:21–35PubMedCrossRefGoogle Scholar
  19. 19.
    Delanaye P, Mariat C (2013) The applicability of eGFR equations to different populations. Nat Rev Nephrol 9:513–522PubMedCrossRefGoogle Scholar
  20. 20.
    Delanaye P, Cavalier E, Krzesinski JM, Chapelle JP (2006) Why the MDRD equation should not be used in patients with normal renal function (and normal creatinine values)? Clin Nephrol 66:147–148PubMedCrossRefGoogle Scholar
  21. 21.
    Delanaye P, Cohen EP (2008) Formula-based estimates of the GFR: equations variable and uncertain. Nephron Clin Pract 110:c48–c53PubMedCrossRefGoogle Scholar
  22. 22.
    Klee GG, Schryver PG, Saenger AK, Larson TS (2007) Effects of analytic variations in creatinine measurements on the classification of renal disease using estimated glomerular filtration rate (eGFR). Clin Chem Lab Med 45:737–741PubMedCrossRefGoogle Scholar
  23. 23.
    Panteghini M, Myers GL, Miller WG, Greenberg N (2006) The importance of metrological traceability on the validity of creatinine measurement as an index of renal function. Clin Chem Lab Med 44:1287–1292PubMedCrossRefGoogle Scholar
  24. 24.
    Panteghini M (2008) Enzymatic assays for creatinine: time for action. Scand J Clin Lab Invest Suppl 241:84–88PubMedCrossRefGoogle Scholar
  25. 25.
    Coresh J, Astor BC, McQuillan G et al (2002) Calibration and random variation of the serum creatinine assay as critical elements of using equations to estimate glomerular filtration rate. Am J Kidney Dis 39:920–929PubMedCrossRefGoogle Scholar
  26. 26.
    Chan MH, Ng KF, Szeto CC et al (2004) Effect of a compensated Jaffe creatinine method on the estimation of glomerular filtration rate. Ann Clin Biochem 41:482–484PubMedCrossRefGoogle Scholar
  27. 27.
    Coresh J, Eknoyan G, Levey AS (2002) Estimating the prevalence of low glomerular filtration rate requires attention to the creatinine assay calibration. J Am Soc Nephrol 13:2811–2812PubMedCrossRefGoogle Scholar
  28. 28.
    Murthy K, Stevens LA, Stark PC, Levey AS (2005) Variation in the serum creatinine assay calibration: a practical application to glomerular filtration rate estimation. Kidney Int 68:1884–1887PubMedCrossRefGoogle Scholar
  29. 29.
    McKillop DJ, Cairns B, Duly E, Van DM, Ryan M (2006) The effect of serum creatinine method choice on estimated glomerular filtration rate determined by the abbreviated MDRD formula. Ann Clin Biochem 43:220–222PubMedCrossRefGoogle Scholar
  30. 30.
    Van Biesen W, Vanholder R, Veys N et al (2005) The importance of standardization of creatinine in the implementation of guidelines and recommendations for CKD: implications for CKD management programmes. Nephrol Dial Transplant 21:77–83PubMedCrossRefGoogle Scholar
  31. 31.
    Selvin E, Manzi J, Stevens LA et al (2007) Calibration of serum creatinine in the National Health and Nutrition Examination Surveys (NHANES) 1988–1994, 1999–2004. Am J Kidney Dis 50:918–926PubMedCrossRefGoogle Scholar
  32. 32.
    Wade WE, Spruill WJ (2007) New serum creatinine assay standardization: implications for drug dosing. Ann Pharmacother 41:475–480PubMedCrossRefGoogle Scholar
  33. 33.
    Joffe M, Hsu CY, Feldman HI, Weir M, Landis JR, Hamm LL (2010) Variability of creatinine measurements in clinical laboratories: results from the CRIC study. Am J Nephrol 31:426–434PubMedPubMedCentralCrossRefGoogle Scholar
  34. 34.
    Thienpont LM, Van Landuyt KG, Stöckl D, De Leenheer AP (1995) Candidate reference method for determining serum creatinine by isocratic HPLC: validation with isotope dilution gas chromatography-mass spectrometry and application for accuracy assessment of routine test kits. Clin Chem 41:995–1003PubMedGoogle Scholar
  35. 35.
    Stöckl D, Reinauer H (1993) Candidate reference methods for determining target values for cholesterol, creatinine, uric acid, and glucose in external quality assessment and internal accuracy control. I. Method setup. Clin Chem 39:993–1000PubMedGoogle Scholar
  36. 36.
    Dodder NG, Tai SS, Sniegoski LT, Zhang NF, Welch MJ (2007) Certification of creatinine in a human serum reference material by GC–MS and LC–MS. Clin Chem 53:1694–1699PubMedCrossRefGoogle Scholar
  37. 37.
    Delanghe JR, Cobbaert C, Galteau MM et al (2008) Trueness verification of actual creatinine assays in the European market demonstrates a disappointing variability that needs substantial improvement. An international study in the framework of the EC4 creatinine standardization working group. Clin Chem Lab Med 46:1319–1325PubMedCrossRefGoogle Scholar
  38. 38.
    Pieroni L, Delanaye P, Boutten A et al (2011) A multicentric evaluation of IDMS-traceable creatinine enzymatic assays. Clin Chim Acta 412:2070–2075PubMedCrossRefGoogle Scholar
  39. 39.
    Kytzia HJ (2008) How to implement traceability of creatinine results: a manufacturer’s experience. Scand J Clin Lab Invest Suppl 241:64–66PubMedCrossRefGoogle Scholar
  40. 40.
    Mazzachi BC, Peake MJ, Ehrhardt V (2000) Reference range and method comparison studies for enzymatic and Jaffe creatinine assays in plasma and serum and early morning urine. Clin Lab 46:53–55PubMedGoogle Scholar
  41. 41.
    Lawson N, Lang T, Broughton A, Prinsloo P, Turner C, Marenah C (2002) Creatinine assays: time for action? Ann Clin Biochem 39:599–602PubMedCrossRefGoogle Scholar
  42. 42.
    Miller WG, Myers GL, Ashwood ER et al (2005) Creatinine measurement: state of the art in accuracy and interlaboratory harmonization. Arch Pathol Lab Med 129:297–304PubMedGoogle Scholar
  43. 43.
    Séronie-Vivien S, Galteau MM, Carlier MC et al (2005) Impact of standardized calibration on the inter-assay variation of 14 automated assays for the measurement of creatinine in human serum. Clin Chem Lab Med 43:1227–1233PubMedCrossRefGoogle Scholar
  44. 44.
    Vickery S, Stevens PE, Dalton RN, Van Lente F, Lamb EJ (2006) Does the ID-MS traceable MDRD equation work and is it suitable for use with compensated Jaffe and enzymatic creatinine assays? Nephrol Dial Transplant 21:2439–2445PubMedCrossRefGoogle Scholar
  45. 45.
    Boutten A, Bargnoux AS, Carlier MC et al (2013) Enzymatic but not compensated Jaffe methods reach the desirable specifications of NKDEP at normal levels of creatinine. Results of the French multicentric evaluation. Clin Chim Acta 419:132–135PubMedCrossRefGoogle Scholar
  46. 46.
    Liu Y, Xu GB (2010) Trueness investigation of routine creatinine assays on nine homogeneous systems in Beijing demonstrates an encouraging outcome that meets clinical requirements. Chin Med J (Engl) 123:2364–2369Google Scholar
  47. 47.
    Carobene A, Ceriotti F, Infusino I, Frusciante E, Panteghini M (2013) Evaluation of the impact of standardization process on the quality of serum creatinine determination in Italian laboratories. Clin Chim Acta 427C:100–106Google Scholar
  48. 48.
    Cheuiche AV, Soares AA, Camargo EG, Weinert LS, Camargo JL, Silveiro SP (2013) Comparison between IDMS-traceable Jaffe and enzymatic creatinine assays for estimation of glomerular filtration rate by the CKD-EPI equation in healthy and diabetic subjects. Clin Biochem 46:1423–1429PubMedCrossRefGoogle Scholar
  49. 49.
    Kuster N, Cristol JP, Cavalier E et al (2013) Enzymatic creatinine assays allow estimation of glomerular filtration rate in stages 1 and 2 chronic kidney disease using CKD-EPI equation. Clin Chim Acta 428C:89–95Google Scholar
  50. 50.
    Delanaye P, Pottel H, Botev R (2013) Con: Should we abandon the use of the MDRD equation in favour of the CKD-EPI equation? Nephrol Dial Transplant 28:1396–1403PubMedCrossRefGoogle Scholar
  51. 51.
    Levey AS, Bosch JP, Lewis JB, Greene T, Rogers N, Roth D (1999) A more accurate method to estimate glomerular filtration rate from serum creatinine: a new prediction equation. Modification of Diet in Renal Disease Study Group. Ann Intern Med 130:461–470PubMedCrossRefGoogle Scholar
  52. 52.
    Levey AS, Coresh J, Greene T et al (2006) Using standardized serum creatinine values in the modification of diet in renal disease study equation for estimating glomerular filtration rate. Ann Intern Med 145:247–254PubMedCrossRefGoogle Scholar
  53. 53.
    Levey AS, Coresh J, Greene T et al (2007) Expressing the modification of diet in renal disease study equation for estimating glomerular filtration rate with standardized serum creatinine values. Clin Chem 53:766–772PubMedCrossRefGoogle Scholar
  54. 54.
    Froissart M, Rossert J, Jacquot C, Paillard M, Houillier P (2005) Predictive performance of the modification of diet in renal disease and Cockcroft–Gault equations for estimating renal function. J Am Soc Nephrol 16:763–773PubMedCrossRefGoogle Scholar
  55. 55.
    Levey AS, Stevens LA, Schmid CH et al (2009) A new equation to estimate glomerular filtration rate. Ann Intern Med 150:604–612PubMedPubMedCentralCrossRefGoogle Scholar
  56. 56.
    Inker LA, Levey AS (2013) Pro: Estimating GFR using the chronic kidney disease epidemiology collaboration (CKD-EPI) 2009 creatinine equation: the time for change is now. Nephrol Dial Transplant 28:1390–1396PubMedCrossRefGoogle Scholar
  57. 57.
    Earley A, Miskulin D, Lamb EJ, Levey AS, Uhlig K (2012) Estimating equations for glomerular filtration rate in the era of creatinine standardization: a systematic review. Ann Intern Med 156:785–795PubMedCrossRefGoogle Scholar
  58. 58.
    Gaspari F, Ruggenenti P, Porrini E et al (2013) The GFR and GFR decline cannot be accurately estimated in type 2 diabetics. Kidney Int 84:164–173PubMedCrossRefGoogle Scholar
  59. 59.
    Hallan SI, Matsushita K, Sang Y et al (2012) Age and association of kidney measures with mortality and end-stage renal disease. JAMA 308:2349–2360PubMedPubMedCentralCrossRefGoogle Scholar
  60. 60.
    Matsushita K, Selvin E, Bash LD, Astor BC, Coresh J (2010) Risk implications of the new CKD Epidemiology Collaboration (CKD-EPI) equation compared with the MDRD Study equation for estimated GFR: the Atherosclerosis Risk in Communities (ARIC) Study. Am J Kidney Dis 55:648–659PubMedPubMedCentralCrossRefGoogle Scholar
  61. 61.
    Komenda P, Beaulieu M, Seccombe D, Levin A (2008) Regional implementation of creatinine measurement standardization. J Am Soc Nephrol 19:164–169PubMedPubMedCentralCrossRefGoogle Scholar
  62. 62.
    Inker LA, Schmid CH, Tighiouart H et al (2012) Estimating glomerular filtration rate from serum creatinine and cystatin C. N Engl J Med 367:20–29PubMedCrossRefGoogle Scholar
  63. 63.
    Björk J, Grubb A, Sterner G, Nyman U (2011) Revised equations for estimating glomerular filtration rate based on the Lund–Malmö Study cohort. Scand J Clin Lab Invest 71:232–239PubMedCrossRefGoogle Scholar
  64. 64.
    Schaeffner ES, Ebert N, Delanaye P et al (2012) Two novel equations to estimate kidney function in persons aged 70 years or older. Ann Intern Med 157:471–481PubMedCrossRefGoogle Scholar
  65. 65.
    Koppe L, Klich A, Dubourg L, Ecochard R, Hadj-Aissa A (2013) Performance of creatinine-based equations compared in older patients. J Nephrol 26:716–723PubMedCrossRefGoogle Scholar
  66. 66.
    Séronie-Vivien S, Delanaye P, Pieroni L, Mariat C, Froissart M, Cristol JP (2008) Cystatin C: current position and future prospects. Clin Chem Lab Med 46:1664–1686PubMedGoogle Scholar
  67. 67.
    Donadio C, Kanaki A, Caprio F, Donadio E, Tognotti D, Olivieri L (2012) Prediction of glomerular filtration rate from serum concentration of cystatin C: comparison of two analytical methods. Nephrol Dial Transplant 27:2826–2838PubMedCrossRefGoogle Scholar
  68. 68.
    Delanaye P, Cavalier E, Krzesinski JM, Mariat C (2008) Cystatin C-based equations: don’t repeat the same errors with analytical considerations. Nephrol Dial Transplant 23:1065–1066PubMedCrossRefGoogle Scholar
  69. 69.
    Delanaye P, Pieroni L, Abshoff C et al (2008) Analytical study of three cystatin C assays and their impact on cystatin C-based GFR-prediction equations. Clin Chim Acta 398:118–124PubMedCrossRefGoogle Scholar
  70. 70.
    Larsson A, Hansson LO, Flodin M, Katz R, Shlipak MG (2011) Calibration of the Siemens cystatin C immunoassay has changed over time. Clin Chem 57:777–778PubMedCrossRefGoogle Scholar
  71. 71.
    Voskoboev NV, Larson TS, Rule AD, Lieske JC (2011) Importance of cystatin C assay standardization. Clin Chem 57:1209–1211PubMedCrossRefGoogle Scholar
  72. 72.
    White CA, Rule AD, Collier CP et al (2011) The impact of interlaboratory differences in cystatin C assay measurement on glomerular filtration rate estimation. Clin J Am Soc Nephrol 6:2150–2156PubMedPubMedCentralCrossRefGoogle Scholar
  73. 73.
    Li J, Dunn W, Breaud A, Elliott D, Sokoll LJ, Clarke W (2010) Analytical performance of 4 automated assays for measurement of cystatin C. Clin Chem 56:1336–1339PubMedCrossRefGoogle Scholar
  74. 74.
    Shlipak MG, Weekley CC, Li Y, Hansson LO, Larsson A, Whooley M (2011) Comparison of cardiovascular prognosis by 3 serum cystatin C methods in the Heart and Soul Study. Clin Chem 57:737–745PubMedCrossRefGoogle Scholar
  75. 75.
    Delanaye P, Ebert N (2012) Assessment of kidney function: estimating GFR in children. Nat Rev Nephrol 8:503–504PubMedCrossRefGoogle Scholar
  76. 76.
    Schwartz GJ, Schneider MF, Maier PS et al (2012) Improved equations estimating GFR in children with chronic kidney disease using an immunonephelometric determination of cystatin C. Kidney Int 82:445–453PubMedPubMedCentralCrossRefGoogle Scholar
  77. 77.
    Grubb A, Blirup-Jensen S, Lindstrom V, Schmidt C, Althaus H, Zegers I (2010) First certified reference material for cystatin C in human serum ERM-DA471/IFCC. Clin Chem Lab Med 48:1619–1621PubMedCrossRefGoogle Scholar
  78. 78.
    Blirup-Jensen S, Grubb A, Lindstrom V, Schmidt C, Althaus H (2008) Standardization of Cystatin C: development of primary and secondary reference preparations. Scand J Clin Lab Invest Suppl 241:67–70PubMedCrossRefGoogle Scholar
  79. 79.
    Delanaye P, Cavalier E (2013) Staging chronic kidney disease and estimating glomerular filtration rate: an opinion paper about the new international recommendations. Clin Chem Lab Med 51:1911–1917PubMedCrossRefGoogle Scholar
  80. 80.
    Masson I, Maillard N, Tack I et al (2013) GFR estimation using standardized cystatin C in kidney transplant recipients. Am J Kidney Dis 61:279–284PubMedCrossRefGoogle Scholar
  81. 81.
    Mindikoglu AL, Dowling TC, Weir MR, Seliger SL, Christenson RH, Magder LS (2013) Performance of chronic kidney disease epidemiology collaboration creatinine-cystatin C equation for estimating kidney function in cirrhosis. Hepatology 59:1532–1542PubMedCrossRefGoogle Scholar
  82. 82.
    Obiols J, Bargnoux AS, Kuster N et al (2013) Validation of a new standardized cystatin C turbidimetric assay: evaluation of the three novel CKD-EPI equations in hypertensive patients. Clin Biochem 46:1542–1547PubMedCrossRefGoogle Scholar
  83. 83.
    Maahs DM, Jalal D, McFann K, Rewers M, Snell-Bergeon JK (2011) Systematic shifts in cystatin C between 2006 and 2010. Clin J Am Soc Nephrol 6:1952–1955PubMedPubMedCentralCrossRefGoogle Scholar
  84. 84.
    Delanghe JR (2009) How to estimate GFR in children. Nephrol Dial Transplant 24:714–716PubMedCrossRefGoogle Scholar
  85. 85.
    Speeckaert MM, Wuyts B, Stove V, Walle JV, Delanghe JR (2012) Compensating for the influence of total serum protein in the Schwartz formula. Clin Chem Lab Med 50:1597–1600PubMedCrossRefGoogle Scholar
  86. 86.
    Kuster N, Bargnoux AS, Pageaux GP, Cristol JP (2012) Limitations of compensated Jaffe creatinine assays in cirrhotic patients. Clin Biochem 45:320–325PubMedCrossRefGoogle Scholar
  87. 87.
    Schwartz GJ, Munoz A, Schneider MF et al (2009) New equations to estimate GFR in children with CKD. J Am Soc Nephrol 20:629–637PubMedPubMedCentralCrossRefGoogle Scholar
  88. 88.
    Schwartz GJ, Kwong T, Erway B et al (2009) Validation of creatinine assays utilizing HPLC and IDMS traceable standards in sera of children. Pediatr Nephrol 24:113–119PubMedPubMedCentralCrossRefGoogle Scholar

Copyright information

© Italian Society of Nephrology 2014

Authors and Affiliations

  • Pierre Delanaye
    • 1
    Email author
  • Etienne Cavalier
    • 2
  • Jean-Paul Cristol
    • 3
  • Joris R. Delanghe
    • 4
  1. 1.Department of Nephrology-Dialysis-TransplantationUniversity of LiègeLiègeBelgium
  2. 2.Department of Clinical ChemistryUniversity of LiègeLiègeBelgium
  3. 3.Department of BiochemistryUniversity of Montpellier 1MontpellierFrance
  4. 4.Department of Laboratory MedicineGhent University HospitalGhentBelgium

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