Skip to main content
SpringerLink
Log in

Urinary neopterin: an immune activation marker in mesangial proliferative glomerulonephritis

  • Original Article
  • Published:
Clinical and Experimental Nephrology Aims and scope Submit manuscript

Abstract

Background

To clarify in vivo neopterin expression within the human kidney and its clinical role as a biomarker for immune complex-mediated mesangial proliferative glomerulonephritis (mesPGN) in children.

Methods

We examined neopterin expression within the kidneys of 14 patients with mesPGN and five patients with minimal changes. We also measured the serum and urinary neopterin levels in fourteen patients with mesPGN and sixteen age-matched healthy controls and correlated the histological findings and clinical features.

Results

Neopterin expression was observed within the distal tubular epithelial cells. It was induced within the glomerular endothelial cells and infiltrated CD68-positive macrophages in the glomeruli and interstitial areas. Furthermore, urinary neopterin levels were significantly elevated and positively correlated with histopathological findings and the degree of proteinuria.

Conclusions

These findings indicate that increased urinary neopterin may reflect macrophage activation and active inflammation within the kidney in immune complex-mediated glomerulonephritis. Neopterin may thus represent a useful biomarker of immune complex-mediated glomerulonephritis in the clinical setting.

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
Fig. 2
Fig. 3
Fig. 4

Similar content being viewed by others

References

  1. Nagata M. Immune mediated glomerular injury. In: Avner ED, Harmon WE, Niaudet P, Yoshikawa N, editors. Pediatric nephrology. 6th ed. Berlin: Springer; 2009. p. 703–41.

    Chapter  Google Scholar 

  2. Striker GE, Mannik M, Tung MY. Role of marrow-derived monocytes and mesangial cells in removal of immune complexes from renal glomeruli. J Exp Med. 1979;149:127–36.

    Article  CAS  PubMed  Google Scholar 

  3. Nathan CF, Murray HW, Cohn ZA. The macrophage as an effector cell. N Engl J Med. 1980;303:622–6.

    Article  CAS  PubMed  Google Scholar 

  4. Nath KA. Tubulointerstitial changes as a major determinant in the progression of renal damage. Am J Kidney Dis. 1992;20:1–17.

    Article  CAS  PubMed  Google Scholar 

  5. Ricardo SD, Goor H, Eddy AA. Macrophage diversity in renal injury and repair. J Clin Invest. 2008;118:3522–30.

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  6. Lange-Sperandio B, Fulda S, Vandewalle A, Chevalier RL. Macrophages induce apoptosis in proximal tubule cells. Pediatr Nephrol. 2003;18:335–41.

    PubMed  Google Scholar 

  7. Murr C, Widner B, Wirleitner B, Fuchs D. Neopterin as a marker for immune system activation. Curr Drug Metab. 2002;3:175–87.

    Article  CAS  PubMed  Google Scholar 

  8. Andert SE, Griesmacher A, Zuckermann A, Müller MM. Neopterin release from human endothelial cells is triggered by interferon-gamma. Clin Exp Immunol. 1992;88:555–8.

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  9. Moutabarrik A, Takahara S, Nakanishi I, Kokado Y, Takano Y, Kameoka H, et al. Interferon-gamma stimulates neopterin release from cultured kidney epithelial cells. Scand J Immunol. 1994;39:27–30.

    Article  CAS  PubMed  Google Scholar 

  10. Plüss C, Werner ER, Blau N, Wachter H, Pfeilschifter J. Interleukin 1 beta and cAMP trigger the expression of GTP cyclohydrolase I in rat renal mesangial cells. Biochem J. 1996;318:665–71.

    PubMed Central  PubMed  Google Scholar 

  11. Coppo R, Amore A. Henoch–Schonlein purpura. In: Avner ED, Harmon WE, Niaudet P, Yoshikawa N, editors. Pediatric nephrology. 6th ed. Berlin: Springer; 2009. p. 1111–26.

    Chapter  Google Scholar 

  12. Lhee HY, Kim H, Joo KJ, Jung SS, Lee KB. The clinical significance of serum and urinary neopterin levels in several renal diseases. J Korean Med Sci. 2006;21:678–82.

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  13. Oda K, Arai T, Nagase M. Increased serum and urinary neopterin in nephrotic syndrome indicate cell-mediated immune dysfunction. Am J Kidney Dis. 1999;34:611–7.

    Article  CAS  PubMed  Google Scholar 

  14. Godai K, Uemasu J, Kawasaki H. Clinical significance of serum and urinary neopterins in patients with chronic renal disease. Clin Nephrol. 1991;36:141–6.

    CAS  PubMed  Google Scholar 

  15. Leohirun L, Thuvasethakul P, Sumethkul V, Pholcharoen T, Boonpucknavig V. Urinary neopterin in patients with systemic lupus erythematosus. Clin Chem. 1991;37:47–50.

    CAS  PubMed  Google Scholar 

  16. Andreoli SP, Yum MN, Bergstein JM. IgA nephropathy in children: significance of glomerular basement membrane deposition of IgA. Am J Nephrol. 1986;6:28–33.

    Article  CAS  PubMed  Google Scholar 

  17. Holdsworth SR, Neale TJ, Wilson CB. Abrogation of macrophage-dependent injury in experimental glomerulonephritis in the rabbit. Use of an anti-macrophage serum. J Clin Invest. 1981;68:686–98.

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  18. Ikezumi Y, Hurst LA, Masaki T, Atkins RC, Nikolic-Paterson DJ. Adoptive transfer studies demonstrate that macrophages can induce proteinuria and mesangial cell proliferation. Kidney Int. 2003;63:83–95.

    Article  CAS  PubMed  Google Scholar 

  19. Erwig LP, Kluth DC, Rees AJ. Macrophage heterogeneity in renal inflammation. Nephrol Dial Transplant. 2003;18:1962–5.

    Article  PubMed  Google Scholar 

  20. Shintaku H, Isshiki G. Normal pterin values in urine and serum in neonates. J Inherit Metab Dis. 1982;5:241–2.

    Article  CAS  PubMed  Google Scholar 

Download references

Acknowledgments

We thank Harumi Matsukawa for providing technical assistance.

Conflict of interest

All the authors have declared no competing interest.

Author information

Authors and Affiliations

  1. Department of Pediatrics, Institute of Medical, Pharmaceutical and Health Sciences, School of Medicine, Kanazawa University, 13-1 Takaramachi, Kanazawa, 920-8641, Japan

    Kazuyuki Ueno, Masaki Shimizu, Tadafumi Yokoyama, Sayaka Ishikawa, Yuko Tasaki, Natsumi Inoue, Naotoshi Sugimoto & Akihiro Yachie

  2. Department of Pediatrics, Kanazawa Medical Center, Kanazawa, Japan

    Kazuhide Ohta

Authors
  1. Kazuyuki Ueno
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Masaki Shimizu
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. Tadafumi Yokoyama
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. Sayaka Ishikawa
    View author publications

    You can also search for this author in PubMed Google Scholar

  5. Yuko Tasaki
    View author publications

    You can also search for this author in PubMed Google Scholar

  6. Natsumi Inoue
    View author publications

    You can also search for this author in PubMed Google Scholar

  7. Naotoshi Sugimoto
    View author publications

    You can also search for this author in PubMed Google Scholar

  8. Kazuhide Ohta
    View author publications

    You can also search for this author in PubMed Google Scholar

  9. Akihiro Yachie
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to Masaki Shimizu.

About this article

Check for updates. Verify currency and authenticity via CrossMark

Cite this article

Ueno, K., Shimizu, M., Yokoyama, T. et al. Urinary neopterin: an immune activation marker in mesangial proliferative glomerulonephritis. Clin Exp Nephrol 19, 264–270 (2015). https://doi.org/10.1007/s10157-014-0984-z

Download citation

  • Received:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s10157-014-0984-z

Keywords

Search

Navigation