Skip to main content

Advertisement

SpringerLink
Log in

Urinary biomarkers in the early detection and follow-up of tubular injury in childhood urolithiasis

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

Abstract

Background

To investigate relationships among urinary biomarkers [kidney injury molecule-1 (KIM-1), N-acetyl-β-glucosaminidase (NAG)], neutrophil gelatinase-associated lipocalin (NGAL) levels and renal tubular injury in childhood urolithiasis.

Methods

Seventy children [36 girls, mean age: 7.3 ± 5.0 years (0.5–18.2)] with urolithiasis/microlithiasis and 42 controls [18 girls, mean age: 8.5 ± 3.8 years (0.9–16.2)] were included in this multicenter, controlled, prospective cohort study. Patients were evaluated three times in 6-month intervals (0, 6 and 12th months). Anthropometric data, urinary symptoms, family history and diagnostic studies were recorded. Urine samples were analyzed for metabolic risk factors (urinary calcium, uric acid, oxalate, citrate, cystine, magnesium, and creatinine excretion), and the urinary KIM-1, NAG, and NGAL levels were measured.

Results

Stones were mostly located in the upper urinary system (82.9%), and six patients (8.6%) had hydronephrosis. Thirty patients (42.9%) had several metabolic risk factors, and the most common metabolic risk factor was hypocitraturia (22.9%). Urinary KIM-1/Cr, NAG/Cr and NGAL/Cr ratios were not significantly different between patients and controls. Furthermore, no significant changes in their excretion were shown during follow-up. Notably, the urinary KIM-1/Cr, NAG/Cr, and NGAL/Cr levels were significantly higher in children under 2 years of age (p = 0.011, p = 0.006, and 0.015, respectively). NAG/Cr and NGAL/Cr ratios were significantly increased in patients with hydronephrosis (n = 6, p = 0.031 and 0.023, respectively).

Conclusions

The results of this study suggest that none of the aforementioned urinary biomarkers (KIM-1, NAG and NGAL levels) may be useful for the early detection and/or follow-up of renal tubular injury and/or dysfunction in childhood urolithiasis.

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

Access this article

Log in via an institution

Subscribe and save

Springer+ Basic
$34.99 /Month
  • Get 10 units per month
  • Download Article/Chapter or eBook
  • 1 Unit = 1 Article or 1 Chapter
  • Cancel anytime
Subscribe now

Buy Now

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

Instant access to the full article PDF.

Institutional subscriptions

Similar content being viewed by others

References

  1. Pearle MS, Antonelli JA, Lotan Y. Urinary lithiasis: etiology, epidemology, and pathogenesis. In: Wein AJ, editor. Campbell–Walsh urology. 17th ed. Philadelphia: Elsevier; 2016. p. 1170–99.

    Google Scholar 

  2. Edvardsson V, Elidottir H, Indridason OS, Palsson R. High incidence of kidney stones in Icelandic children. Pediatr Nephrol. 2005;20(7):940–4.

    Article  PubMed  Google Scholar 

  3. Sas DJ, Hulsey TC, Shatat IF, Orak JK. Increasing incidence of kidney stones in children evaluated in the emergency department. J Pediatr. 2010;157(1):132–7.

    Article  PubMed  Google Scholar 

  4. Celiksoy MH, Yilmaz A, Aydogan G, Kiyak A, Topal E, Sander S. Metabolic disorders in Turkish children with urolithiasis. Urology. 2015;85(4):909–13.

    Article  PubMed  Google Scholar 

  5. Elmaci AM, Ece A, Akin F. Clinical characteristics and metabolic abnormalities in preschool-age children with urolithiasis in southeast Anatolia. J Pediatr Urol. 2014;10(3):495–9.

    Article  CAS  PubMed  Google Scholar 

  6. Bastug F, Dusunsel R. Pediatric urolithiasis: causative factors, diagnosis and medical management. Nat Rev Urol. 2012;9(3):138–46.

    Article  CAS  PubMed  Google Scholar 

  7. Alpay H, Ozen A, Gokce I, Biyikli N. Clinical and metabolic features of urolithiasis and microlithiasis in children. Pediatr Nephrol. 2009;24(11):2203–9.

    Article  PubMed  Google Scholar 

  8. Bilge I, Yilmaz A, Kayiran SM, Emre S, Kadioglu A, Yekeler E, et al. Clinical importance of renal calyceal microlithiasis in children. Pediatr Int. 2013;55(6):731–6.

    Article  PubMed  Google Scholar 

  9. Lieske JC, Toback FG. Renal cell-urinary crystal interactions. Curr Opin Nephrol Hypertens. 2000;9(4):349–55.

    Article  CAS  PubMed  Google Scholar 

  10. Balasar M, Piskin MM, Topcu C, Demir LS, Gurbilek M, Kandemir A, et al. Urinary kidney injury molecule-1 levels in renal stone patients. World J Urol. 2016;. doi:10.1007/s00345-016-1765-y.

    PubMed  Google Scholar 

  11. Daggulli M, Utangac MM, Dede O, Bodakci MN, Hatipoglu NK, Penbegul N, et al. Potential biomarkers for the early detection of acute kidney injury after percutaneous nephrolithotripsy. Ren Fail. 2016;38(1):151–6.

    Article  CAS  PubMed  Google Scholar 

  12. Han WK, Bailly V, Abichandani R, Thadhani R, Bonventre JV. Kidney injury molecule-1 (KIM-1): a novel biomarker for human renal proximal tubule injury. Kidney Int. 2002;62(1):237–44.

    Article  CAS  PubMed  Google Scholar 

  13. Ichimura T, Hung CC, Yang SA, Stevens JL, Bonventre JV. Kidney injury molecule-1: a tissue and urinary biomarker for nephrotoxicant-induced renal injury. Am J Physiol Renal Physiol. 2004;286(3):F552–63.

    Article  CAS  PubMed  Google Scholar 

  14. Kuehn EW, Park KM, Somlo S, Bonventre JV. Kidney injury molecule-1 expression in murine polycystic kidney disease. Am J Physiol Renal Physiol. 2002;283(6):F1326–36.

    Article  CAS  PubMed  Google Scholar 

  15. Liangos O, Perianayagam MC, Vaidya VS, Han WK, Wald R, Tighiouart H, et al. Urinary N-acetyl-beta-(d)-glucosaminidase activity and kidney injury molecule-1 level are associated with adverse outcomes in acute renal failure. J Am Soc Nephrol. 2007;18(3):904–12.

    Article  CAS  PubMed  Google Scholar 

  16. Nepal M, Bock GH, Sehic AM, Schultz MF, Zhang PL. Kidney injury molecule-1 expression identifies proximal tubular injury in urate nephropathy. Ann Clin Lab Sci. 2008;38(3):210–4.

    PubMed  Google Scholar 

  17. Sikora P, Glatz S, Beck BB, Stapenhorst L, Zajaczkowska M, Hesse A, et al. Urinary NAG in children with urolithiasis, nephrocalcinosis, or risk of urolithiasis. Pediatr Nephrol. 2003;18(10):996–9.

    Article  PubMed  Google Scholar 

  18. Winter P, Ganter K, Heimbach D, Hesse A. N-acetyl-beta-d-glucosaminidase excretion in calcium oxalate stone patients and its relation to the risk of stone formation. Scand J Urol Nephrol. 1996;30(6):439–43.

    Article  CAS  PubMed  Google Scholar 

  19. Yilmaz A, Sevketoglu E, Gedikbasi A, Karyagar S, Kiyak A, Mulazimoglu M, et al. Early prediction of urinary tract infection with urinary neutrophil gelatinase associated lipocalin. Pediatr Nephrol. 2009;24(12):2387–92.

    Article  PubMed  Google Scholar 

  20. Zhu W, Liu M, Wang GC, Che JP, Xu YF, Peng B, et al. Urinary neutrophil gelatinase-associated lipocalin, a biomarker for systemic inflammatory response syndrome in patients with nephrolithiasis. J Surg Res. 2014;187(1):237–43.

    Article  CAS  PubMed  Google Scholar 

  21. Jobs K, Straz-Zebrowska E, Placzynska M, Zdanowski R, Kalicki B, Lewicki S, et al. Interleukin-18 and NGAL in assessment of ESWL treatment safety in children with urolithiasis. Cent Eur J Immunol. 2014;39(3):384–91.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  22. Hoppe B, Leuman E, Milliner DS. Urolithiasis and nephrocalcinosis in childhood. In: Geary DF, editor. Comprehensive pediatric nephrology. 1st ed. Philadelphia: Mosby; 2008. p. 499–526.

    Chapter  Google Scholar 

  23. Vaidya VS, Ramirez V, Ichimura T, Bobadilla NA, Bonventre JV. Urinary kidney injury molecule-1: a sensitive quantitative biomarker for early detection of kidney tubular injury. Am J Physiol Renal Physiol. 2006;290(2):F517–29.

    Article  CAS  PubMed  Google Scholar 

  24. Dance N, Price RG, Robinson D, Stirling JL. Beta-galactosidase, beta-glucosidase and N-acetyl-beta-glucosaminidase in human kidney. Clin Chim Acta. 1969;24(2):189–97.

    Article  CAS  PubMed  Google Scholar 

  25. Bagshaw SM, Bennett M, Haase M, Haase-Fielitz A, Egi M, Morimatsu H, et al. Plasma and urine neutrophil gelatinase-associated lipocalin in septic versus non-septic acute kidney injury in critical illness. Intensive Care Med. 2010;36(3):452–61.

    Article  CAS  PubMed  Google Scholar 

  26. Kardakos IS, Volanis DI, Kalikaki A, Tzortzis VP, Serafetinides EN, Melekos MD, et al. Evaluation of neutrophil gelatinase-associated lipocalin, interleukin-18, and cystatin C as molecular markers before and after unilateral shock wave lithotripsy. Urology. 2014;84(4):783–8.

    Article  PubMed  Google Scholar 

  27. Matos V, van Melle G, Boulat O, Markert M, Bachmann C, Guignard JP. Urinary phosphate/creatinine, calcium/creatinine, and magnesium/creatinine ratios in a healthy pediatric population. J Pediatr. 1997;131(2):252–7.

    Article  CAS  PubMed  Google Scholar 

  28. http://ltd.aruplab.com/Tests/Pub/0081106. Accessed 11 Mar 2017.

  29. Walther PC, Lamm D, Kaplan GW. Pediatric urolithiases: a ten-year review. Pediatrics. 1980;65(6):1068–72.

    CAS  PubMed  Google Scholar 

  30. Milliner DS, Murphy ME. Urolithiasis in pediatric patients. Mayo Clin Proc. 1993;68(3):241–8.

    Article  CAS  PubMed  Google Scholar 

  31. Dursun I, Poyrazoglu HM, Dusunsel R, Gunduz Z, Gurgoze MK, Demirci D, et al. Pediatric urolithiasis: an 8-year experience of single centre. Int Urol Nephrol. 2008;40(1):3–9.

    Article  PubMed  Google Scholar 

  32. Coward RJ, Peters CJ, Duffy PG, Corry D, Kellett MJ, Choong S, et al. Epidemiology of paediatric renal stone disease in the UK. Arch Dis Child. 2003;88(11):962–5.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  33. Tefekli A, Esen T, Ziylan O, Erol B, Armagan A, Ander H, et al. Metabolic risk factors in pediatric and adult calcium oxalate urinary stone formers: is there any difference? Urol Int. 2003;70(4):273–7.

    Article  CAS  PubMed  Google Scholar 

  34. VanDervoort K, Wiesen J, Frank R, Vento S, Crosby V, Chandra M, et al. Urolithiasis in pediatric patients: a single center study of incidence, clinical presentation and outcome. J Urol. 2007;177(6):2300–5.

    Article  PubMed  Google Scholar 

  35. Kok DJ, Iestra JA, Doorenbos CJ, Papapoulos SE. The effects of dietary excesses in animal protein and in sodium on the composition and the crystallization kinetics of calcium oxalate monohydrate in urines of healthy men. J Clin Endocrinol Metab. 1990;71(4):861–7.

    Article  CAS  PubMed  Google Scholar 

  36. Hess B, Michel R, Takkinen R, Ackermann D, Jaeger P. Risk factors for low urinary citrate in calcium nephrolithiasis: low vegetable fibre intake and low urine volume to be added to the list. Nephrol Dial Transplant. 1994;9(6):642–9.

    Article  CAS  PubMed  Google Scholar 

  37. McKay CP. Renal stone disease. Pediatr Rev. 2010;31(5):179–88.

    Article  PubMed  Google Scholar 

  38. Waanders F, van Timmeren MM, Stegeman CA, Bakker SJ, van Goor H. Kidney injury molecule-1 in renal disease. J Pathol. 2010;220(1):7–16.

    Article  CAS  PubMed  Google Scholar 

  39. Ichimura T, Bonventre JV, Bailly V, Wei H, Hession CA, Cate RL, et al. Kidney injury molecule-1 (KIM-1), a putative epithelial cell adhesion molecule containing a novel immunoglobulin domain, is up-regulated in renal cells after injury. J Biol Chem. 1998;273(7):4135–42.

    Article  CAS  PubMed  Google Scholar 

  40. van Timmeren MM, Bakker SJ, Vaidya VS, Bailly V, Schuurs TA, Damman J, et al. Tubular kidney injury molecule-1 in protein-overload nephropathy. Am J Physiol Renal Physiol. 2006;291(2):F456–64.

    Article  PubMed  Google Scholar 

  41. van Timmeren MM, van den Heuvel MC, Bailly V, Bakker SJ, van Goor H, Stegeman CA. Tubular kidney injury molecule-1 (KIM-1) in human renal disease. J Pathol. 2007;212(2):209–17.

    Article  PubMed  Google Scholar 

  42. Kandur Y, Gonen S, Fidan K, Soylemezoglu O. Evaluation of urinary KIM-1, NGAL, and IL-18 levels in determining early renal injury in pediatric cases with hypercalciuria and/or renal calculi. Clin Nephrol. 2016;86(2):62–9.

    Article  CAS  PubMed  Google Scholar 

  43. Baggio B, Gambaro G, Ossi E, Favaro S, Borsatti A. Increased urinary excretion of renal enzymes in idiopathic calcium oxalate nephrolithiasis. J Urol. 1983;129(6):1161–2.

    Article  CAS  PubMed  Google Scholar 

  44. Mishra J, Ma Q, Prada A, Mitsnefes M, Zahedi K, Yang J, et al. Identification of neutrophil gelatinase-associated lipocalin as a novel early urinary biomarker for ischemic renal injury. J Am Soc Nephrol. 2003;14(10):2534–43.

    Article  CAS  PubMed  Google Scholar 

  45. Vanpee M, Blennow M, Linne T, Herin P, Aperia A. Renal function in very low birth weight infants: normal maturity reached during early childhood. J Pediatr. 1992;121(5):784–8.

    Article  CAS  PubMed  Google Scholar 

Download references

Acknowledgements

We thank the patients and their families taking part in this study. Proofreading was performed by American Journal Experts (Certificate Verification Key: 9A3B-B552-136B-C6A6-7B52).

Author information

Authors and Affiliations

  1. Division of Pediatric Nephrology, Department of Pediatrics, Koç University Hospital, Davutpaşa cad no: 4 Topkapı, 34010, Istanbul, Turkey

    Mehmet Taşdemir

  2. Department of Pediatrics, Ministry of Health, Bağcılar Training and Research Hospital, Merkez mah, Mimar Sinan cad, 6. sok, Bağcılar, Istanbul, Turkey

    Dilara Fuçucuoğlu, Meltem Erol & Özgül Yiğit

  3. Department of Biochemistry, Ministry of Health, Bağcılar Training and Research Hospital, Merkez mah, Mimar Sinan cad, 6. sok, Bağcılar, Istanbul, Turkey

    Suat Hayri Küçük

  4. Division of Pediatric Nephrology, Department of Pediatrics, School of Medicine, Koc University, Davutpaşa cad no: 4 Topkapı, 34010, Istanbul, Turkey

    Ilmay Bilge

Authors
  1. Mehmet Taşdemir
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Dilara Fuçucuoğlu
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. Suat Hayri Küçük
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. Meltem Erol
    View author publications

    You can also search for this author in PubMed Google Scholar

  5. Özgül Yiğit
    View author publications

    You can also search for this author in PubMed Google Scholar

  6. Ilmay Bilge
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to Mehmet Taşdemir.

Ethics declarations

Conflict of interest

The authors have declared that no conflict of interest exists.

Ethical approval

All procedures performed in studies involving human participants were in accordance with the ethical standards of the institutional research committee at which the studies were conducted (Ministry of Health Bağcılar Training and Research Hospital, date 22/04/2014, and no: 04) and with the 1964 Helsinki declaration and its later amendments or comparable ethical standards.

Informed consent

Informed consent was obtained from all individual participants included in the study.

About this article

Check for updates. Verify currency and authenticity via CrossMark

Cite this article

Taşdemir, M., Fuçucuoğlu, D., Küçük, S.H. et al. Urinary biomarkers in the early detection and follow-up of tubular injury in childhood urolithiasis. Clin Exp Nephrol 22, 133–141 (2018). https://doi.org/10.1007/s10157-017-1436-3

Download citation

  • Received:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s10157-017-1436-3

Keywords

Search

Navigation