Pediatric Nephrology

, Volume 21, Issue 4, pp 533–537 | Cite as

Serum cystatin C levels in children with sickle cell disease

  • Ofelia AlvarezEmail author
  • Gaston Zilleruelo
  • Dale Wright
  • Brenda Montane
  • Gabriela Lopez-Mitnik
Original Article


Patients with sickle cell disease (SCD) may develop kidney dysfunction from childhood. The purpose of this study was to examine the value of serum cystatin C as a marker for glomerular filtration rate (GFR) in children with SCD, as compared to serum creatinine and creatinine clearance (CrCl). Twenty children (ages 9–21, ten males) with SCD with and without albuminuria were studied. The mean serum cystatin for the whole group was 0.89 mg/l (0.5–1.7 mg/l). Mean serum cystatin C was significantly different among the children with proteinuria (n=4), microalbuminuria (n=5), and without albuminuria (n=11) (1.25 mg/l, 0.84 mg/l, and 0.78 mg/l, respectively). The mean GFR derived from serum cystatin was significantly different among these subgroups, becoming abnormal in the proteinuric cohort (63 ml/min per 1.73 m2), in contrast to 94 for the microalbuminuric, and 103 for the normal subgroups. Serum creatinine (mean: 0.58 mg/dl, range: 0.3–1.1) did not change significantly with the level of albuminuria. Mean CrCl remained normal to increased within the subgroups, (133 ml/min per 1.73 m2 for those with proteinuria, 144 for those with microalbuminuria, and 163 for the normal subgroup). We conclude that serum cystatin C correlates with the level of albuminuria and may be a reliable method to measure renal function in SCD.


Children Glomerular filtration rate Hemoglobinopathy Microalbuminuria Proteinuria 



We would like to thank ARUP Laboratories for the cystatin C analysis and Dr. Astrid Mack and the Sickle Cell Disease Association of America, Miami-Dade County Chapter, for providing economic support for this study.


  1. 1.
    Pham PT, Pham C, Wilkinson AH, Lew SQ (2000) Renal abnormalities in sickle cell disease. Kidney Int 57:1–8CrossRefPubMedGoogle Scholar
  2. 2.
    Osarogiagbon UR, Choong S, Belcher JD, Vercelotti GM, Paller MS, Hebbel RP (2000) Reperfusion injury pathophysiology in sickle transgenic mice. Blood 96:314–320PubMedGoogle Scholar
  3. 3.
    Ataga KI, Orringer EP (2000) Renal abnormalities in sickle cell disease. Am J Hematol 63:205–211CrossRefPubMedGoogle Scholar
  4. 4.
    Sklar AH, Campbell H, Caruana RJ, Lightfoot BO, Gaier JG, Milner P (1990) A population study of renal function in sickle cell anemia. Int J Artif Organs 13:231–236PubMedGoogle Scholar
  5. 5.
    Falk RJ, Scheinman J, Phillips G, Orringer E, Johnson A, Jennette JC (1992) Prevalence and pathologic features of sickle cell nephropathy and response to inhibition of angiotensin-converting enzyme. N Engl J Med 326:910–915PubMedCrossRefGoogle Scholar
  6. 6.
    Platt OS, Brambilla DJ, Rosse WF, Milner PF, Castro O, Steinberg MH, Klug PP (1994) Mortality in sickle cell disease. Life expectancy and risk factors in early death. N Engl J Med 330:1639–1644CrossRefPubMedGoogle Scholar
  7. 7.
    Remuzzi G, Bertani T (1998) Pathophysiology of progressive nephropathies. N Engl J Med 339:1448–1456CrossRefPubMedGoogle Scholar
  8. 8.
    Guasch A, Cua M, Mitch WE (1996) Early detection and course of glomerular injury in patients with sickle cell anemia. Kidney Int 49:786–791PubMedCrossRefGoogle Scholar
  9. 9.
    Weber JA, Van Zanten AP (1991) Interferences in current methods for measurements of creatinine. Clin Chem 37:695–700PubMedGoogle Scholar
  10. 10.
    Swaminathan R, Major P, Snieder H, Spector T (2000) Serum creatinine and fat-free mass (lean body mass). Clin Chem 46:1695–1696PubMedGoogle Scholar
  11. 11.
    Filler G, Bokenkamp A, Hoffman W, Le Bricon T, Martinez-Bru C, Grubb A (2005) Cystatin C as a marker of GFR-history, indications, and future research. Clin Biochem 38:1–8CrossRefPubMedGoogle Scholar
  12. 12.
    Bokenkamp A, Domanetzki M, Zinck R, Schumann G, Byrd D, Brodehl J (1998) Cystatin C—a new marker of glomerular filtration rate in children independent of height and age. Pediatrics 101:875–881CrossRefPubMedGoogle Scholar
  13. 13.
    Newman D, Thakkar H, Edwards RG, Wilkie M, White T, Grubb AO, Price CP (1995) Serum cystatin C measured by automated immunoassay: a more sensitive marker of changes in GFR than serum creatinine. Kidney Int 47:312–318PubMedCrossRefGoogle Scholar
  14. 14.
    Tenstad O, Roald AB, Grubb A, Aukland K (1996) Renal handling of radiolabeled human cystatin C in the rat. Scand J Clin Lab Invest 56:409–414PubMedCrossRefGoogle Scholar
  15. 15.
    Newman D (2002) Cystatin C. Ann Clin Biochem 39(pt 2):89–104CrossRefPubMedGoogle Scholar
  16. 16.
    Finney H, Newman DJ, Thakkar H, Fell JME, Price CP (2000) Reference ranges for plasma cystatin C and creatinine measurements in premature infants, neonates, and older children. Arch Dis Child 82:71–75CrossRefPubMedGoogle Scholar
  17. 17.
    Finney H, Newman DJ, Gruber W, Merle P, Price CP (1997) Initial evaluation of cystatin C measurement by particle-enhanced immunonephelometry on the Behring nephelometer systems (BNA, BN II). Clin Chem 43:1016–1022PubMedGoogle Scholar
  18. 18.
    Schwartz GJ, Haycock GB, Edelmann CM Jr, Spitzer A (1976) A simple estimate of glomerular filtration rate in children derived from body length and plasma creatinine. Pediatrics 58:259–263PubMedGoogle Scholar
  19. 19.
    Cockcroft D, Gault M (1976) Prediction of creatinine clearance from serum creatinine. Nephron 16:31–41PubMedCrossRefGoogle Scholar
  20. 20.
    Hoek FJ, Kemperman FAW, Krediet RT (2003) A comparison between cystatin C, plasma creatinine, and the Cockcroft and Gault formula for the estimation of glomerular filtration rate. Nephrol Dial Transplant 18:2024–2031CrossRefPubMedGoogle Scholar
  21. 21.
    Filler G, Foster J, Acker A, Lepage N, Akbari A, Ehrich JHH (2005) The Cockcroft-Gault formula should not be used in children. Kidney Int 67:2321–2324CrossRefPubMedGoogle Scholar
  22. 22.
    Simonsen O, Grubb A, Thysell H (1985) The blood serum concentration of cystatin C (gamma-trace) as a measure of the glomerular filtration rate. Scand J Clin Lab Invest 45:97–101PubMedCrossRefGoogle Scholar
  23. 23.
    Kyhse-Andersen J, Schmidt C, Nordin G, Andersson B, Nilsson-Ehle P, Lindstrom V, Grubb A (1994) Serum cystatin C, determined by a rapid, automated particle-enhanced turbidometric method, is a better marker than serum creatinine for glomerular filtration rate. Clin Chem 40:1921–1926PubMedGoogle Scholar
  24. 24.
    Fricker M, Wiesli P, Brandle M, Schwegler B, Schmid C (2003) Impact of thyroid dysfunction on serum cystatin C. Kidney Int 63:1944–1947CrossRefPubMedGoogle Scholar
  25. 25.
    Bokenkamp A, van Wijk JAE, Lentze MJ, Stoffel-Wagner B (2002) Effect of corticosteroid therapy on serum cystatin C and β2-microglobulin concentrations. Clin Chem 48:1123–1126PubMedGoogle Scholar
  26. 26.
    Risch I, Herklotz R, Blumberg A, Hueber AR (2001) Effects of glucocorticoid immunosuppression on serum cystatin C concentrations in renal transplant patients. Clin Chem 47:2055–2059PubMedGoogle Scholar
  27. 27.
    Christensson AG, Grubb AO, Nilsson JA, Norrgren K, Sterner G, Sundkvist G (2004) Serum cystatin C advantageous compared with serum creatinine in the detection of mild but not severe diabetic nephropathy. J Intern Med 256:510–518CrossRefPubMedGoogle Scholar
  28. 28.
    Mussap M, Dalla Vestra M, Fioretto P, Saller A, Varagnolo M, Nosadini R, Plebani M (2002) Cystatin C is a more sensitive marker than creatinine for the estimation of GFR in type 2 diabetic patients. Kidney Int 61:1453–1461CrossRefPubMedGoogle Scholar
  29. 29.
    Tomino Y, Suzuki S, Gohda T, Kobayashi M, Horikoshi S, Imai H, Saito T, Kawamura T, Yorioka N, Harada T, Yasumoto Y, Kida H, Kobayashi Y, Endoh M, Sato H, Saito K (2001) Serum cystatin C may predict the prognostic stages of patients with IgA nephropathy prior to renal biopsy. J Clin Lab Anal 15:25–29CrossRefPubMedGoogle Scholar
  30. 30.
    Schuck O, Gottfriedova H, Maly J, Jabor A, Stollova M, Bruzkova I, Skibova J, Ryska M, Spicak J, Trunecka P, Novakova J (2002) Glomerular filtration rate assessments in individuals after orthotopic liver transplantation based on serum cystatin C levels. Liver Transplant 8:594–599CrossRefGoogle Scholar
  31. 31.
    LeBricon T, Thervet E, Benlakehal M, Bouequet B, Legendre C, Erlich D (1999) Changes in plasma cystatin C after renal transplantation and acute rejection in adults. Clin Chem 45:2243–2249PubMedGoogle Scholar
  32. 32.
    Orlando R, Mussap M, Plebani M, Piccoli P, DeMartin S, Floreani M, Padrini R, Palatini P (2002) Diagnostic value of plasma cystatin C as a glomerular filtration marker in decompensated liver cirrhosis. Clin Chem 48:850–858PubMedGoogle Scholar
  33. 33.
    Dharnirharka VR, Kwon G, Stevens G (2002) Serum cystatin C is superior to serum creatinine as a marker of kidney function: a meta-analysis. Am J Kidney Dis 40:221–226CrossRefPubMedGoogle Scholar
  34. 34.
    Alvarez O, Montane B, Lopez G, Wilkinson J, Miller T (2005) Early blood transfusions protect against microalbuminuria in children with sickle cell disease. Pediatr Blood Cancer DOI: 10.1002/pbc.20645Google Scholar
  35. 35.
    Wigfall DR, Ware RE, Burchinal MR, Kinney TR, Foreman JW (2000) Prevalence and clinical correlates of glomerulopathy in children with sickle cell disease. J Pediatr 136:749–753CrossRefPubMedGoogle Scholar
  36. 36.
    Zayas CF, Platt J, Eckman JR, Elsas L, Clark WS, Mitch WE, Guasch A (1996) Prevalence and predictors of glomerular involvement in sickle cell anemia (abstract). J Am Soc Nephrol 7:1401Google Scholar
  37. 37.
    Aoki RY, Saad ST (1990) Microalbuminuria in sickle cell disease. Braz J Med Biol Res 23:1103–1106PubMedGoogle Scholar
  38. 38.
    Powars DR, Elliott-Mills DD, Chan L, Niland J, Hiti AL, Opas LM, Johnson C (1991) Chronic renal failure in sickle cell disease: risk factors, clinical course, and mortality. Ann Intern Med 115:614–620PubMedGoogle Scholar
  39. 39.
    Schmitt F, Martinez F, Brillet G, Giatras I, Choukroun G, Girot R, Bachir D, Galacteros F, Lacour B, Grunfeld JP (1998) Early glomerular dysfunction in patients with sickle cell anemia. Am J Kidney Dis 32:208–221PubMedGoogle Scholar
  40. 40.
    Herrera J, Avila E, Marin C, Rodriguez-Iturbe B (2002) Impaired creatinine secretion after an intravenous creatinine load is an early characteristic of the nephropathy of sickle cell anaemia. Nephrol Dial Transplant 17:602–607CrossRefPubMedGoogle Scholar

Copyright information

© IPNA 2006

Authors and Affiliations

  • Ofelia Alvarez
    • 1
    Email author
  • Gaston Zilleruelo
    • 2
  • Dale Wright
    • 1
  • Brenda Montane
    • 2
  • Gabriela Lopez-Mitnik
    • 3
  1. 1.Division of Pediatric HematologyUniversity of MiamiMiamiUSA
  2. 2.Division of Pediatric NephrologyUniversity of MiamiMiamiUSA
  3. 3.Department of PediatricsUniversity of MiamiMiamiUSA

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