Cystatin C as a Marker of Renal Function in Critically III Patients at Risk for or with Acute Renal Failure

  • A. A. N. M. Royakkers
  • M. J. Schultz
  • P. E. Spronk


Acute renal failure is a common complication of critical illness [1, 2]. Of all intensive care unit (ICU) admissions, 15–20% develop acute renal failure and 4–6% require some form of renal replacement therapy [3]. Causes of acute renal failure include direct renal toxicity due to medication or radiocontrast agents, hypovolemic hypotension, and shock. Acute renal failure frequently accompanies sepsis — its incidence varies from 20% in patients with moderate sepsis to >50% in patients with septic shock [2, 4]. Acute renal failure carries a high mortality rate, in particular in patients with sepsis — in patients with acute renal failure alone mortality is 45 %; in patients with acute renal failure and sepsis, mortality is reported to be as high as 70% [4]. The most frequently used form of renal replacement therapy is continuous venovenous hemofiltration (CVVH), an expensive and laborious treatment. CVVH, however, permits efficient control of fluid balance and azotemia in ICU patients with acute renal failure [5].


Glomerular Filtration Rate Acute Renal Failure Renal Replacement Therapy Intensive Care Unit Patient Continuous Renal Replacement Therapy 


Unable to display preview. Download preview PDF.

Unable to display preview. Download preview PDF.


  1. 1.
    Thadhani R, Pascual M, Bonventre JV (1996) Acute renal failure. N Engl J Med 334:1448–1460PubMedCrossRefGoogle Scholar
  2. 2.
    Larneire N, Van Biesen W, Vanholder R (2005) Acute renal failure. Lancet 365:417–430Google Scholar
  3. 3.
    Block CA, Manning HL (2002) Prevention of acute renal failure in the critically ill. Am Respir Crit Care Med 165:320–324Google Scholar
  4. 4.
    Hoste EA, Lameire NH, Vanholder RC, Benoit DD, Decruyenaere JM, Colardyn FA (2003) Acute renal failure in patients with sepsis in a surgical ICU: predictive factors, incidence, comorbidity, and outcome. J Am Soc Nephrol 14:1022–1030PubMedCrossRefGoogle Scholar
  5. 5.
    Bellomo R, Ronco C (1998) Continuous renal replacement therapy: continuous blood purification in the intensive care unit. Ann Acad Med Singapore 27:426–429PubMedGoogle Scholar
  6. 6.
    Bellomo R, Ronco C, Kellum JA, Mehta RL, Palevsky P (2004) Acute renal failure — definition, outcome measures, animal models, fluid therapy and information technology needs: the Second International Consensus Conference of the Acute Dialysis Quality Initiative (ADQI) Group. Crit Care 8:R204–212PubMedCrossRefGoogle 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.
    Jacobsen FK, Christensen CK, Mogensen CE, Heilskov NS (1980) Evaluation of kidney function after meals. Lancet 1:319PubMedCrossRefGoogle Scholar
  9. 9.
    James GD, Sealey JE, Alderman M, et al (1988) A longitudinal study of urinary creatinine and creatinine clearance in normal subjects. Race, sex, and age differences. Am J Hypertens 1:124–131PubMedGoogle Scholar
  10. 10.
    Levey AS, Berg RL, Gassman JJ, Hall PM, Walker WG (1989) Creatinine filtration, secretion and excretion during progressive renal disease. Modification of Diet in Renal Disease (MDRD) Study Group. Kidney Int Suppl 27:S73–80PubMedGoogle Scholar
  11. 11.
    Newman DJ, Price CP (1999) Renal function and nitrogen metabolites. In: Burtis CA, Ashwood ER (ed) Tietz Textbook of Clinical Chemistry. WB Saunders, Philadelphia, pp 1204–1270Google Scholar
  12. 12.
    Trof RJ, Di Maggio F, Leemreis J, Groeneveld AB (2006) Biomarkers of acute renal injury and renal failure. Shock 26:245–253PubMedCrossRefGoogle Scholar
  13. 13.
    Abrahamson M, Olafsson I, Palsdottir A, et al (1990) Structure and expression of the human cystatin C gene. Biochem J 268:287–294PubMedGoogle Scholar
  14. 14.
    Coll E, Botey A, Alvarez L, et al (2000) Serum cystatin C as a new marker for noninvasive estimation of glomerular filtration rate and as a marker for early renal impairment. Am J Kidney Dis 36:29–34PubMedGoogle Scholar
  15. 15.
    Wulkan R, den Hollander J, Berghout A (2005) Cystatin C: unsuited to use as a marker of kidney function in the intensive care unit. Crit Care 9:531–532PubMedCrossRefGoogle Scholar
  16. 16.
    Dharnidharka VR, Kwon C, Stevens G (2002) Serum cystatin C is superior to serum creatinine as a marker of kidney function: a meta-analysis. Am J Kidney Dis 40:221–226PubMedCrossRefGoogle Scholar
  17. 17.
    Le Bricon T, Thervet E, Benlakehal M, Bousquet 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
  18. 18.
    Sjostrom P, Tidman M, Jones I (2005) Determination of the production rate and non-renal clearance of cystatin C and estimation of the glomerular filtration rate from the serum concentration of cystatin C in humans. Scand J Clin Lab Invest 65:111–124PubMedCrossRefGoogle Scholar
  19. 19.
    den Hollander JG, Wulkan RW, Mantel MJ, Berghout A (2003) Is cystatin C a marker of glomerular filtration rate in thyroid dysfunction? Clin Chem 49:1558–1559CrossRefGoogle Scholar
  20. 20.
    Jayagopal V, Keevil BG, Atkin SL, Jennings PE, Kilpatrick ES (2003) Paradoxical changes in cystatin C and serum creatinine in patients with hypo-and hyperthyroidism. Clin Chem 49:680–681PubMedCrossRefGoogle Scholar
  21. 21.
    Bjarnadottir M, Grubb A, Olafsson I (1995) Promoter-mediated, dexamethasone-induced increase in cystatin C production by HeLa cells. Scand J Clin Lab Invest 55:617–623PubMedGoogle Scholar
  22. 22.
    Cimerman N, Brguljan PM, Krasovec M, Suskovic S, Kos J (2000) Serum cystatin C, a potent inhibitor of cysteine proteinases, is elevated in asthmatic patients. Clin Chim Acta 300:83–95PubMedCrossRefGoogle Scholar
  23. 23.
    Poge U, Gerhardt T, Bokenkamp A, et al (2004) Time course of low molecular weight proteins in the early kidney transplantation period — influence of corticosteroids. Nephrol Dial Transplant 19:2858–2863PubMedCrossRefGoogle Scholar
  24. 24.
    Ahlstrom A, Tallgren M, Peltonen S, Pettila V (2004) Evolution and predictive power of serum cystatin C in acute renal failure. Clin Nephrol 62:344–350PubMedGoogle Scholar
  25. 25.
    Mazul-Sunko B, Zarkovic N, Vrkic N, et al (2004) Proatrial natriuretic peptide (1–98), but not cystatin C, is predictive for occurrence of acute renal insufficiency in critically ill septic patients. Nephron Clin Pract 97:c103–107PubMedCrossRefGoogle Scholar
  26. 26.
    Herget-Rosenthal S, Marggraf G, Husing J, et al (2004) Early detection of acute renal failure by serum cystatin C. Kidney Int 66:1115–1122PubMedCrossRefGoogle Scholar
  27. 27.
    Le Bricon T, Leblanc I, Benlakehal M, Gay-Bellile C, Erlich D, Boudaoud S (2005) Evaluation of renal function in intensive care: plasma cystatin C vs. creatinine and derived glomerular filtration rate estimates. Clin Chem Lab Med 43:953–957PubMedCrossRefGoogle Scholar
  28. 28.
    Delanaye P, Lambermont B, Chapelle JP, Gielen J, Gerard P, Rorive G (2004) Plasmatic cystatin C for the estimation of glomerular filtration rate in intensive care units. Intensive Care Med 30:980–983PubMedCrossRefGoogle Scholar
  29. 29.
    Villa P, Jimenez M, Soriano MC, Manzanares J, Casasnovas P (2005) Serum cystatin C concentration as a marker of acute renal dysfunction in critically ill patients. Crit Care 9: R139–143PubMedCrossRefGoogle Scholar
  30. 30.
    Baas MC, Bouman CS, Hoek F, Krediet RT, Schultz MJ (2006) Cystatin C in critically ill patients treated with continuous venovenous hemofiltration. Hemodial Int 10(Suppl 2): S33–37PubMedCrossRefGoogle Scholar
  31. 31.
    Janowski R, Kozak M, Jankowska E, et al (2001) Human cystatin C, an amyloidogenic protein, dimerizes through three-dimensional domain swapping. Nat Struct Biol 8:316–320.PubMedCrossRefGoogle Scholar

Copyright information

© Springer Science + Business Media Inc. 2007

Authors and Affiliations

  • A. A. N. M. Royakkers
    • 1
  • M. J. Schultz
    • 2
  • P. E. Spronk
    • 2
  1. 1.Department of Intensive CareGooi-Noord HospitalBlaricumNetherlands
  2. 2.Department of Intensive CareAcademic Medical CenterAmsterdamNetherlands

Personalised recommendations