Skip to main content

Advertisement

SpringerLink
Log in

Urinary concentration of cytokines in children with acute pyelonephritis

  • Original Article
  • Published:
European Journal of Pediatrics Aims and scope Submit manuscript

Abstract

Urinary tract infection (UTI) is a common bacterial infection among infants and children. Predicting which children with upper UTI will develop long-term sequelae remains difficult. We aimed at evaluating the predictive value of urine concentrations of interleukin-6 (UIL-6) and interleukin-8 (UIL-8) in subsequent renal scarring. In the current observational prospective study, urine samples for UIL-6 and UIL-8 were obtained from two groups: 31 children with first episode of febrile UTI and 22 febrile children of other origin. UIL-6 and UIL-8 were increased in children with febrile UTI, compared to children with fever of other origin [median and range (picograms per milliliter): (1) UIL-6, 74.46 (0–168) vs. 10.51 (0–47.50), respectively, p = 0.0001; (2) UIL-8, 2,660.38 (0–13,801) vs. 0, respectively, p = 0.0001]. Renal scarring was found in 5/31 (16 %) children with acute pyelonephritis. Initial median UIL-8 values were significantly higher in children with later renal scarring than in those without renal scarring [median and range (picograms per milliliter): 6,163 (2,021–13,801) vs. 1,490.5 (0–5,737), respectively, p = 0.018]. In conclusion, UIL-8 might serve as a predictive biomarker for renal scarring after an acute episode of pyelonephritis. Since UIL-8 emerges as a renal-specific diagnostic and prognostic marker, it may be suitable as a selective screening tool for children with febrile UTI.

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. Agace W, Hedges S, Andersson U, Andersson J, Ceska M, Svanborg C (1993) Selective cytokine production by epithelial cells following exposure to Escherichia coli. Infect Immun 61:602–609

    PubMed  CAS  Google Scholar 

  2. Baggiolini M, Walz A, Kunkel SL (1989) Neutrophil-activating peptide-1/interleukin 8, a novel cytokine that activates neutrophils. J Clin Invest 84:1045–1049

    Article  PubMed  CAS  Google Scholar 

  3. Benador D, Benador N, Slosman D, Mermillod B, Girardin E (1994) Are younger children at highest risk of renal sequelae after pyelonephritis? Lancet 349:17–19

    Article  Google Scholar 

  4. Benson M, Jodal U, Andreasson A, Karlsson A, Rydberg J, Svanborg C (1994) Interleukin 6 response to urinary tract infection in childhood. Pediatr Infect Dis J 13:612–616

    Article  PubMed  CAS  Google Scholar 

  5. Bitsori M, Karatzi M, Dimitriou H, Christakou E, Savvidou A, Galanakis E (2003) Urine IL-8 concentrations in infectious and non-infectious urinary tract conditions. Pediatr Nephrol 26:2003–2007

    Article  Google Scholar 

  6. Coulthard MG, Lambert HJ, Keir MJ (1997) Occurrence of renal scars in children after their first referral for urinary tract infection. BMJ 11:918–919

    Article  Google Scholar 

  7. Coulthard MG, Lambert HJ, Keir MJ (2009) Do systemic symptoms predict the risk of kidney scarring after urinary tract infection? Arch Dis Child 94:278–281

    Article  PubMed  CAS  Google Scholar 

  8. Dick PT, Feldman W (1994) Routine diagnostic imaging for childhood urinary tract infections: a systematic overview. J Pediatr 128:15–22

    Google Scholar 

  9. Ehsanipour F, Gharouni M, Rafati AH, Ardalan M, Bodaghi N, Otoukesh H (2012) Risk factors of renal scars in children with acute pyelonephritis. Braz J Infect Dis 16:15–18

    Article  PubMed  Google Scholar 

  10. Frendéus B, Godaly G, Hang L, Karpman D, Lundstedt AC, Svanborg C (2000) Interleukin 8 receptor deficiency confers susceptibility to acute experimental pyelonephritis and may have a human counterpart. J Exp Med 192:881–890

    Article  PubMed  Google Scholar 

  11. Fünfstück R, Franke S, Hellberg M, Ott U, Knöfel B, Straube E, Sommer M, Hacker J (2001) Secretion of cytokines by uroepithelial cells stimulated by Escherichia coli and Citrobacter spp. Int J Antimicrob Agents 17:253–258

    Article  PubMed  Google Scholar 

  12. Gokce I, Alpay H, Biyikli N, Unluguzel G, Dede F, Topuzoglu A (2010) Urinarylevels of interleukin-6 and interleukin-8 in patients with vesicoureteral reflux and renalparenchymal scar. Pediatr Nephrol 25:905–912

    Article  PubMed  Google Scholar 

  13. Hang L, Frendéus B, Godaly G, Svanborg C (2000) Interleukin-8 receptor knockout mice have subepithelial neutrophil entrapment and renal scarring following acute pyelonephritis. J Infect Dis 182:1738–1748

    Article  PubMed  CAS  Google Scholar 

  14. Hewitt IK, Zucchetta P, Rigon L, Maschio F, Molinari PP, Tomasi L, Toffolo A, Pavanello L, Crivellaro C, Bellato S, Montini G (2008) Early treatment of acute pyelonephritis in children fails to reduce renal scarring: data from the Italian Renal Infection Study Trials. Pediatrics 122:486–490

    Article  PubMed  Google Scholar 

  15. Huang YY, Chen MJ, Chiu NT, Chou HH, Lin KY, Chiou YY (2011) Adjunctive oral methylprednisolone in pediatric acute pyelonephritis alleviates renal scarring. Pediatrics 128:e496–e504

    Article  PubMed  Google Scholar 

  16. Jakobsson B, Berg U, Svensson L (1994) Renal scarring after acute pyelonephritis. Arch Dis Child 70:111–115

    Article  PubMed  CAS  Google Scholar 

  17. Jantausch BA, O’Donnell R, Wiedermann BL (2000) Urinary interleukin-6 and interleukin-8 in children with urinary tract infection. Pediatr Nephrol 15:236–240

    Article  PubMed  CAS  Google Scholar 

  18. Krzemień G, Roszkowska-Blaim M, Kostro I, Szmigielska A, Karpińska M, Sieniawska M, Bartłomiejczyk I, Paczek L, Toth K (2004) Urinary levels of interleukin-6 and interleukin-8 in children with urinary tract infections to age 2. Med Sci Monit 10:CR593–CR597

    PubMed  Google Scholar 

  19. Lee JH, Kim MK, Park SE (2012) Is a routine voiding cystourethrogram necessary in children after the first febrile urinary tract infection? Acta Paediatr 101:105–109

    Article  Google Scholar 

  20. Lee MD, Lin CC, Huang FY, Tsai TC, Huang CT, Tsai JD (2009) Screening young children with a first febrile urinary tract infection for high-grade vesicoureteral reflux with renal ultrasound scanning and technetium-99 m-labeled dimercaptosuccinic acid scanning. J Pediatr 154:797–802

    Article  PubMed  Google Scholar 

  21. Lee YJ, Lee JH, Park YS (2012) Risk factors for renal scar formation in infants with first episode of acute pyelonephritis: a prospective clinical study. J Urol 187:1032–1036

    Article  PubMed  Google Scholar 

  22. Lin KY, Chiu NT, Chen MJ, Lai CH, Huang JJ, Wang YT, Chiou YY (2003) Acute pyelonephritis and sequelae of renal scar in pediatric first febrile urinary tract infection. Pediatr Nephrol 18:362–365

    PubMed  Google Scholar 

  23. Mantadakis E, Vouloumanou EK, Georgantzi GG, Tsalkidis A, Chatzimichael A, Falagas ME (2011) Acute Tc-99 m DMSA scan for identifying dilating vesicoureteral reflux in children: a meta-analysis. Pediatrics 128:e169–e179

    Article  PubMed  Google Scholar 

  24. Misao S, Tetsuro M, Osamu M, Koichi T, Joichi K (1998) Urinary concentration of cytokines in patient with pyelonephritis and cystitis. J Infect Chemother 4:24–27

    Article  Google Scholar 

  25. Pecile P, Miorin E, Romanello C, Vidal E, Contardo M, Valent F, Tenore A (2009) Age-related renal parenchymal lesions in children with first febrile urinary tract infections. Pediatrics 124:23–29

    Article  PubMed  Google Scholar 

  26. Peters C, Rushton HG (2010) Vesicoureteral reflux associated renal damage: congenital reflux nephropathy and acquired renal scarring. J Urol 184:265–273

    Article  PubMed  Google Scholar 

  27. Pohl HG, Rushton HG, Park JS, Chandra R, Majd M (1999) Adjunctive oral corticosteroids reduce renal scarring: the piglet model of reflux and acute experimental pyelonephritis. J Urol 162:815–820

    Article  PubMed  CAS  Google Scholar 

  28. Preda I, Jodal U, Sixt R, Stokland E, Hansson S (2007) Normal dimercaptosuccinic acid scintigraphy makes voiding cystourethrography unnecessary after urinary tract infection. J Pediatr 151:581–584

    Article  PubMed  Google Scholar 

  29. Ragnarsdóttir B, Svanborg C (2012) Susceptibility to acute pyelonephritis or asymptomatic bacteriuria: host–pathogen interaction in urinary tract infections. Pediatr Nephrol 27:2017–2029

    Article  PubMed  Google Scholar 

  30. Sheu JN, Chen MC, Lue KH, Cheng SL, Lee IC, Chen SM, Tsay GJ (2006) Serum and urine levels of interleukin-6 and interleukin-8 in children with acute pyelonephritis. Cytokine 36:276–282

    Article  PubMed  CAS  Google Scholar 

  31. Sheu JN, Chen SM, Meng MH, Lue KH (2009) The role of serum and urine interleukin-8 on acute pyelonephritis and subsequent renal scarring in children. Pediatr Infect Dis J28:885–890

    Google Scholar 

  32. Siomou E, Giapros V, Fotopoulos A, Aasioti M, Papadopoulou F, Serbis A, Siamopoulou A, Andronikou S (2009) Implications of 99mTc-DMSA scintigraphy performed during urinary tract infection in neonates. Pediatrics 124:881–887

    Article  PubMed  Google Scholar 

  33. Stokland E, Hellström M, Jacobsson B, Jodal U, Sixt R (1996) Renal damage one year after first urinary tract infection: role of dimercaptosuccinic acid scintigraphy. J Pediatr 129:815–820

    Article  PubMed  CAS  Google Scholar 

  34. Tramma D, Hatzistylianou M, Gerasimou G, Lafazanis V (2012) Interleukin-6 and interleukin-8 levels in the urine of children with renal scarring. Pediatr Nephrol 27:1525–1530

    Article  PubMed  Google Scholar 

  35. Tsai JD, Huang CT, Lin PY, Chang JH, Lee MD, Huang FY, Shih BF, Hung HY, Hsu CH, Kao HA, Lin CC (2012) Screening high-grade vesicoureteral reflux in young infants with a febrile urinary tract infection. Pediatr Nephrol 27:955–963

    Article  PubMed  Google Scholar 

Download references

Conflict of interest

None declared.

Author information

Authors and Affiliations

  1. Pediatrics Department, Hillel Yaffe Medical Center, Hadera, P.O.B. 169, 38100, Israel

    Yakubov Renata, Hassan Jassar, Amit Hochberg & Adi Klein-Kremer

  2. Laboratory of Clinical Immunology and Tissue Typing, Rambam Health Care Campus, Haifa, Israel

    Rina Katz

  3. The Ruth and Bruce Rappaport Faculty of Medicine, Technion–Israel Institute of Technology, Haifa, Israel

    Rony-Reuven Nir

Authors
  1. Yakubov Renata
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Hassan Jassar
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. Rina Katz
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. Amit Hochberg
    View author publications

    You can also search for this author in PubMed Google Scholar

  5. Rony-Reuven Nir
    View author publications

    You can also search for this author in PubMed Google Scholar

  6. Adi Klein-Kremer
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to Adi Klein-Kremer.

Rights and permissions

Reprints and permissions

About this article

Cite this article

Renata, Y., Jassar, H., Katz, R. et al. Urinary concentration of cytokines in children with acute pyelonephritis. Eur J Pediatr 172, 769–774 (2013). https://doi.org/10.1007/s00431-012-1914-2

Download citation

  • Received:

  • Revised:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s00431-012-1914-2

Keywords

Search

Navigation