Skip to main content
SpringerLink
Log in

Cystatin C in children on chronic hemodialysis

  • Original Article
  • Published:
Pediatric Nephrology Aims and scope Submit manuscript

Abstract

Background

Cystatin C (CyC) concentration has been suggested as a marker of middle-molecule accumulation, hemodialysis (HD) adequacy and for estimating residual renal function (RRF), but it has not been studied in pediatric HD. High CyC is associated with increased cardiovascular disease (CVD). We investigated CyC kinetics and the effect of RRF on CyC in a pediatric HD population.

Methods

A total of 21 HD sessions and 20 interdialytic periods were analyzed in seven patients, age 5–19 years, of whom four were anuric (A) and three were non-anuric (NA). CyC was measured before (preHD) and after (postHD) three standard HD sessions in 1 week and prior to the first session of the following week.

Results

We found no difference (p = 0.67) in CyC concentration between preHD CyC (9.85 ± 2.15 mg/l; A vs. NA, p = 0.37) and postHD CyC (10.04 ± 2.83 mg/l; A vs NA, p = 0.28). The weekly average preHD CyC median concentration was 10.14 mg/l (A vs. NA, p = 0.87) and correlated with age (r = 0.808, p = 0.03) and height measurement (r = 0.799, p = 0.03), but not with RRF, single-pool Kt/V, ultrafiltration, HD duration or blood liters processed.

Conclusions

Cystatin C is very elevated in children on HD. It does not rise between HD sessions, is not removed by standard HD and remains at steady state; therefore, elimination is extrarenal. Low RRF does not affect CyC elimination. CyC increases with age and height. If a high CyC concentration can be proven to have a causative role in the development of CVD, routine intensified HD regimens in children may be indicated for its removal.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Log in via an institution

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Institutional subscriptions

Fig. 1

Similar content being viewed by others

References

  1. Sharma AP, Kathiravelu A, Nadarajah R, Yasin A, Filler G (2009) Body mass does not have a clinically relevant effect on cystatin C eGFR in children. Nephrol Dial Transplant 24:470–474

    Article  PubMed  CAS  Google Scholar 

  2. Huang SH, Filler G, Yasin A, Lindsay RM (2011) Cystatin C reduction ratio depends on normalized blood liters processed and fluid removal during hemodialysis. Clin J Am Soc Nephrol 6:319–325

    Article  PubMed  CAS  Google Scholar 

  3. Zaffanello M, Franchini M, Fanos V (2007) Is serum Cystatin-C a suitable marker of renal function in children? Ann Clin Lab Sci 37:233–240

    PubMed  CAS  Google Scholar 

  4. Tenstad O, Roald AB, Grubb A, Aukland K (1996) Renal handling of radiolabelled human cystatin C in the rat. Scand J Clin Lab Invest 56:409–414

    Article  PubMed  CAS  Google Scholar 

  5. Bacchetta J, Cochat P, Rognant N, Ranchin B, Hadj-Aissa A, Dubourg L (2011) Which creatinine and cystatin C equations can be reliably used in children? Clin J Am Soc Nephrol 6:552–560

    Article  PubMed  CAS  Google Scholar 

  6. Inker LA, Schmid CH, Tighiouart H, Eckfeldt JH, Feldman HI, Greene T, Kusek JW, Manzi J, Van Lente F, Zhang YL, Coresh J, Levey AS, Investigators CKD-EPI (2012) Estimating glomerular filtration rate from serum creatinine and cystatin C. N Engl J Med 367:20–29

    Article  PubMed  CAS  Google Scholar 

  7. Sjöström 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 65:111–124

    Article  PubMed  Google Scholar 

  8. Sjöström PA, Jones IL, Tidman MA (2009) Cystatin C as a filtration marker: haemodialysis patients expose its strengths and limitations. Scand J Clin Lab Invest 69:65–72

    Article  PubMed  Google Scholar 

  9. Andersen TB, Jødal L, Boegsted M, Erlandsen EJ, Morsing A, Frøkiær J, Brøchner-Mortensen J (2011) GFR prediction from Cystatin C and Creatinine in children: effect of including body cell mass. Am J Kidney Dis 59:50–57

    Article  PubMed  Google Scholar 

  10. Sharma AP, Yasin A, Garg AX, Filler G (2011) Diagnostic accuracy of Cystatin C–based eGFR equations at different GFR levels in children. Clin J Am Soc Nephrol 6:1599–1608

    Article  PubMed  CAS  Google Scholar 

  11. Patel PC, Ayers CR, Murphy SA, Peshock R, Khera A, de Lemos JA, Balko JA, Gupta S, Mammen PP, Drazner MH, Markham DW (2009) Association of cystatin C with left ventricular structure and function: the Dallas Heart Study. Circ Heart Fail 2:98–104

    Article  PubMed  CAS  Google Scholar 

  12. Codoñer-Franch P, Ballester-Asensio E, Martínez-Pons L, Vallecillo-Hernández J, Navarro-Ruíz A, Valle-Pérez R (2011) Cystatin C, cardiometabolic risk, and body composition in severely obese children. Pediatr Nephrol 26:301–307

    Article  PubMed  Google Scholar 

  13. Ix JH, Shlipak MG, Chertow GM, Whooley MA (2007) 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 115:173–179

    Article  PubMed  CAS  Google Scholar 

  14. Menon V, Shlipak MG, Wang X, Coresh J, Greene T, Stevens L, Kusek JW, Beck GJ, Collins AJ, Levey AS, Sarnak MJ (2007) Cystatin C as a risk factor for outcomes in chronic kidney disease. Ann Intern Med 147:19–27

    PubMed  Google Scholar 

  15. Shin MJ, Song SH, Kwak IS, Lee SB, Lee DW, Seong EY, Kim IY, Rhee H, Lee N (2012) Serum cystatin C as a predictor for cardiovascular events in end-stage renal disease patients at the initiation of dialysis. Clin Exp Nephrol 16:456–463

    Article  PubMed  CAS  Google Scholar 

  16. Imai A, Komatsu S, Ohara T, Kamata T, Yoshida J, Miyaji K, Shimizu Y, Takewa M, Hirayama A, Deshpande GA, Takahashi O, Kodama K (2011) Serum cystatin C is associated with early stage coronary atherosclerotic plaque morphology on multidetector computed tomography. Atherosclerosis 218:350–355

    Article  PubMed  CAS  Google Scholar 

  17. Taglieri N, Koenig W, Kaski JC (2009) Cystatin C and cardiovascular risk. Clin Chem 55:1932–1943

    Article  PubMed  CAS  Google Scholar 

  18. Al-Malki N, Heidenheim PA, Filler G, Yasin A, Lindsay RM (2009) Cystatin C levels in functionally anephric patients undergoing dialysis: the effect of different methods and intensities. Clin J Am Soc Nephrol 4:1606–1610

    Article  PubMed  CAS  Google Scholar 

  19. Park JS, Kim GH, Kang CM, Lee CH (2010) Application of Cystatin C reduction ratio to high-flux Hemodialysis as an alternative indicator of the clearance of middle molecules. Korean J Intern Med 25:77–81

    Article  PubMed  CAS  Google Scholar 

  20. Krieter DH, Hackl A, Rodriguez A, Chenine L, Moragues HL, Lemke HD, Wanner C, Canaud B (2010) Protein-bound uraemic toxin removal in haemodialysis and post-dilution haemodiafiltration. Nephrol Dial Transplant 25:212–218

    Article  PubMed  CAS  Google Scholar 

  21. Lindstrom V, Grubb A, Hegbrant MA, Christensson A (2008) Different elimination patterns of b-trace protein, b2-microglobulin and cystatin C in haemodialysis, haemodiafiltration and haemofiltration. Scand J Clin Lab Invest 68:685–691

    Article  PubMed  Google Scholar 

  22. Hoek FJ, Korevaar JC, Dekker FW, Boeschoten EW, Krediet RT (2007) Estimation of residual glomerular filtration rate in dialysis patients from the plasma cystatin C level. Nephrol Dial Transplant 22:1633–1638

    Article  PubMed  CAS  Google Scholar 

  23. Kim SJ, Sohn YB, Park SW, Jin DK, Paik KH (2011) Serum Cystatin C for estimation of residual renal function in children on peritoneal dialysis. Pediatr Nephrol 26:433–440

    Article  PubMed  Google Scholar 

  24. Filler G, Huang SS, Lindsay RM (2011) Residual renal function assessment with cystatin C. Pediatr Nephrol 26:333–335

    Article  PubMed  Google Scholar 

  25. Goldstein SL, Currier H, Watters L, Hempe JM, Sheth RD, Silverstein D (2003) Acute and chronic inflammation in pediatric patients receiving hemodialysis. J Pediatr 143:653–657

    Article  PubMed  CAS  Google Scholar 

  26. Grubb A, Björk J, Nyman U, Pollak J, Bengzon J, Ostner G, Lindström V (2011) Cystatin C, a marker for successful aging and glomerular filtration rate, is not influenced by inflammation. Scand J Clin Lab Invest 71:145–149

    PubMed  CAS  Google Scholar 

  27. Özden TA, Tekerek H, Bafl F, Darendeliler F (2010) Effect of hypo-and euthyroid status on serum cystatin C levels. J Clin Res Ped Endo 2:155–158

    Article  Google Scholar 

  28. Manetti L, Pardini E, Genovesi M, Campomori A, Grasso L, Morselli LL, Lupi I, Pellegrini G, Bartalena L, Bogazzi F, Martino E (2005) Thyroid function differently affects serum cystatin C and creatinine concentrations. J Endocrinol Invest 28:346–349

    PubMed  CAS  Google Scholar 

  29. European best practice guidelines for haemodialysis (part 1) (2002) Measurement of residual renal function in HD. Nephrol Dial Transplant 17:11–15

    Google Scholar 

  30. Gehan E, George SL (1970) Estimation of human body surface area from height and weight. Cancer Chemother Rep 54:225–235

    PubMed  CAS  Google Scholar 

  31. Daugirdas JT (1993) Second generation logarithmic estimates of single-pool variable volume Kt/V: an analysis of error. J Am Soc Nephrol 4:1205–1213

    PubMed  CAS  Google Scholar 

  32. KDOQI Clinical practice guidelines for hemodialysis adequacy (2006) Guideline 3. Methods for postdialysis blood sampling. Am J Kidney Dis 48:S24–S27

    Google Scholar 

  33. Fischbach M, Fothergill H, Zaloszyc A, Menouer S, Terzic J (2011) Intensified daily dialysis: the best chronic dialysis option for children? Semin Dial 24:640–644

    Article  PubMed  Google Scholar 

  34. Fischbach M, Fothergill H, Zaloszyc A, Seuge L (2012) Hemodiafiltration: the addition of convective flow to hemodialysis. Pediatr Nephrol 27:351–356

    Article  PubMed  Google Scholar 

  35. Fischbach M, Hamel G, Koehl C, Geisert J (1989) Beta-2-microglobulin in hemodiafiltered children: long-term efficiency follow-up. Nephron 53:110–114

    Article  PubMed  CAS  Google Scholar 

  36. Bökenkamp A, Domanetzki M, Zinck R, Schumann G, Brodehl J (1998) Reference values for cystatin C serum concentrations in children. Pediatr Nephrol 12:125–129

    Article  PubMed  Google Scholar 

  37. Köttgen A, Selvin E, Stevens LA, Levey AS, Van Lente F, Coresh J (2008) Serum cystatin C in the United States: the Third National Health and Nutrition Examination Survey (NHANES III). Am J Kidney Dis 51:385–394

    Article  PubMed  Google Scholar 

  38. Mitsnefes MM (2012) Cardiovascular disease in children with chronic kidney disease. J Am Soc Nephrol 23:578–585

    Article  PubMed  CAS  Google Scholar 

  39. North American Pediatric Renal Trials and Collaborative Studies (NAPRTCS) (2011) Dialysis patient characteristics. In: NAPRTCS (ed) Annual dialysis report. NAPRTCS, Boston, pp 1–18

  40. Newman DJ (2002) Cystatin C. Ann Clin Biochem 39:89–104

    Article  PubMed  CAS  Google Scholar 

  41. Bökenkamp A, Herget-Rosenthal S, Bökenkamp R (2006) Cystatin C, kidney function and cardiovascular disease. Pediatr Nephrol 21:1223–1230

    Article  PubMed  Google Scholar 

Download references

Acknowledgments

We thank Dr Terrence Stull, Chairman, Department of Pediatrics, OUHSC, for his support.

Author information

Authors and Affiliations

  1. Pediatric Nephrology, Oklahoma University Health Sciences Center, 1200 N. Phillips Ave., Suite 14200, Oklahoma City, OK, 73104, USA

    Olivera Marsenic, Donna R. Wilson, Anne M. Beck, Tiffany J. Swanson, Kathleen Studnicka & Martin A. Turman

  2. Biochemical Genetic Laboratory, Oklahoma University Health Sciences Center, Oklahoma City, OK, USA

    Andrea Wierenga, Tripti Shrivastava, Garfield A. Simon & Dorit Elberg

  3. Department of Biostatistics and Epidemiology, Oklahoma University Health Sciences Center, Oklahoma City, OK, USA

    Michael Anderson

  4. Pediatric Critical Care, Oklahoma University Health Sciences Center, Oklahoma City, OK, USA

    Kevin Couloures

Authors
  1. Olivera Marsenic
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Andrea Wierenga
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. Donna R. Wilson
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. Michael Anderson
    View author publications

    You can also search for this author in PubMed Google Scholar

  5. Tripti Shrivastava
    View author publications

    You can also search for this author in PubMed Google Scholar

  6. Garfield A. Simon
    View author publications

    You can also search for this author in PubMed Google Scholar

  7. Anne M. Beck
    View author publications

    You can also search for this author in PubMed Google Scholar

  8. Tiffany J. Swanson
    View author publications

    You can also search for this author in PubMed Google Scholar

  9. Kathleen Studnicka
    View author publications

    You can also search for this author in PubMed Google Scholar

  10. Dorit Elberg
    View author publications

    You can also search for this author in PubMed Google Scholar

  11. Kevin Couloures
    View author publications

    You can also search for this author in PubMed Google Scholar

  12. Martin A. Turman
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to Olivera Marsenic.

Rights and permissions

Reprints and permissions

About this article

Cite this article

Marsenic, O., Wierenga, A., Wilson, D.R. et al. Cystatin C in children on chronic hemodialysis. Pediatr Nephrol 28, 647–653 (2013). https://doi.org/10.1007/s00467-012-2366-7

Download citation

  • Received:

  • Revised:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s00467-012-2366-7

Keywords

Search

Navigation