Skip to main content
SpringerLink
Log in

KIM-1 expression predicts renal outcomes in IgA nephropathy

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

Abstract

Background

Kidney injury molecule-1 (KIM-1) is a sensitive biomarker for proximal tubular injury. Recently, a few studies have shown that urinary KIM-1 has clinical implications in IgA nephropathy (IgAN). We performed this study to determine whether tissue KIM-1 has clinical implications for predicting long-term outcome and whether urinary KIM-1 is correlated with tissue KIM-1 and kidney injury in IgAN patients.

Methods

We assessed the prognostic prediction capability of tissue KIM-1 expression in 69 adult patients with IgAN retrospectively. Renal biopsies from all patients were scored by a pathologist who was blinded to the clinical data for the pathologic variables. The primary outcome was the composite of a 50 % reduction in eGFR or end-stage renal disease. Tissue KIM-1 expression was assessed semiquantitatively by counting the stained tubules per 100× power field; 0 tubule indicates grade 0; 1–5 tubules, grade 1; 6–10 tubules, grade 2; and more than 10 tubules, grade 3. Comparing urinary KIM-1 and tissue KIM-1 expression, 50 consecutive IgAN patients were prospectively enrolled to measure urinary KIM-1 levels and examine their biopsy specimens by KIM-1 immunohistochemistry.

Results

Univariate analysis showed that tissue KIM-1 expression was associated with the renal outcome in IgAN. Multivariate regression analysis, as the relationship of tissue KIM-1 with prognosis, was consistent. Proteinuria at biopsy and tissue KIM-1 grade 3 were shown to have a prognostic value. The concentration of urinary KIM-1/Cr in patients with IgAN was significantly higher than that in the normal controls.

Conclusion

Tissue KIM-1 expression is an independent predictor of adverse renal outcomes in IgA nephropathy patients.

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

Similar content being viewed by others

References

  1. Alamartine E, Sabatier JC, Guerin C, Berliet JM, Berthoux F. Prognostic factors in mesangial IgA glomerulonephritis: an extensive study with univariate and multivariate analyses. Am J Kidney Dis. 1991;18:12–9.

    PubMed  CAS  Google Scholar 

  2. D’Amico G. Influence of clinical and histological features on actuarial renal survival in adult patients with idiopathic IgA nephropathy, membranous nephropathy, and membranoproliferative glomerulonephritis: survey of the recent literature. Am J Kidney Dis. 1992;20:315–23.

    PubMed  Google Scholar 

  3. Haas M. Histologic subclassification of IgA nephropathy: a clinicopathologic study of 244 cases. Am J Kidney Dis. 1997;29:829–42.

    Article  PubMed  CAS  Google Scholar 

  4. Johnston PA, Brown JS, Braumholtz DA, Davison AM. Clinico-pathological correlations and long-term follow-up of 253 United Kingdom patients with IgA nephropathy. A report from the MRC Glomerulonephritis Registry. Q J Med. 1992;84:619–27.

    PubMed  CAS  Google Scholar 

  5. Bohle A, Mackensen-Haen S, von Gise H, Grund KE, Wehrmann M, Batz C, et al. The consequences of tubulo-interstitial changes for renal function in glomerulopathies. A morphometric and cytological analysis. Pathol Res Pract. 1990;186:135–44.

    Article  PubMed  CAS  Google Scholar 

  6. Roberts IS, Cook HT, Troyanov S, Alpers CE, Amore A, Barratt J, et al. The Oxford classification of IgA nephropathy: pathology definitions, correlations, and reproducibility. Kidney Int. 2009;76:546–56.

    Article  PubMed  Google Scholar 

  7. Cattran DC, Coppo R, Cook HT, Feehally J, Roberts IS, Troyanov S, et al. The Oxford classification of IgA nephropathy: rationale, clinicopathological correlations, and classification. Kidney Int. 2009;76:534–45.

    Article  PubMed  Google Scholar 

  8. Coppo R, Troyanov S, Camilla R, Hogg RJ, Cattran DC, Cook HT, et al. The Oxford IgA nephropathy clinicopathological classification is valid for children as well as adults. Kidney Int. 2010;77:921–7.

    Article  PubMed  CAS  Google Scholar 

  9. Peters HP, Waanders F, Meijer E, van den Brand J, Steenbergen EJ, van Goor H, et al. High urinary excretion of kidney injury molecule-1 is an independent predictor of end-stage renal disease in patients with IgA nephropathy. Nephrol Dial Transpl. 2011;26:3581–8.

    Article  CAS  Google Scholar 

  10. Xu PC, Zhang JJ, Chen M, Lv JC, Liu G, Zou WZ, et al. Urinary kidney injury molecule-1 in patients with IgA nephropathy is closely associated with disease severity. Nephrol Dial Transpl. 2011;26:3229–36.

    Article  CAS  Google Scholar 

  11. de Borst MH, van Timmeren MM, Vaidya VS, de Boer RA, van Dalen MB, Kramer AB, et al. Induction of kidney injury molecule-1 in homozygous Ren2 rats is attenuated by blockade of the renin–angiotensin system or p38 MAP kinase. Am J Physiol Renal Physiol. 2007;292:F313–20.

    Article  PubMed  Google Scholar 

  12. 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:F552–63.

    Article  PubMed  CAS  Google Scholar 

  13. 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;273:4135–42.

    Article  PubMed  CAS  Google Scholar 

  14. Katafuchi R, Kiyoshi Y, Oh Y, Uesugi N, Ikeda K, Yanase T, et al. Glomerular score as a prognosticator in IgA nephropathy: its usefulness and limitation. Clin Nephrol. 1998;49:1–8.

    PubMed  CAS  Google Scholar 

  15. Risdon RA, Sloper JC, De Wardener HE. Relationship between renal function and histological changes found in renal-biopsy specimens from patients with persistent glomerular nephritis. Lancet. 1968;2:363–6.

    Article  PubMed  CAS  Google Scholar 

  16. Bartosik LP, Lajoie G, Sugar L, Cattran DC. Predicting progression in IgA nephropathy. Am J Kidney Dis. 2001;38:728–35.

    Article  PubMed  CAS  Google Scholar 

  17. Donadio JV, Bergstralh EJ, Grande JP, Rademcher DM. Proteinuria patterns and their association with subsequent end-stage renal disease in IgA nephropathy. Nephrol Dial Transpl. 2002;17:1197–203.

    Article  CAS  Google Scholar 

  18. Zhang Z, Humphreys BD, Bonventre JV. Shedding of the urinary biomarker kidney injury molecule-1 (KIM-1) is regulated by MAP kinases and juxtamembrane region. J Am Soc Nephrol. 2007;18:2704–14.

    Article  PubMed  CAS  Google Scholar 

  19. Catania JM, Chen G, Parrish AR. Role of matrix metalloproteinases in renal pathophysiologies. Am J Physiol Renal Physiol. 2007;292:F905–11.

    Article  PubMed  CAS  Google Scholar 

Download references

Conflict of interest

The authors have no competing interests.

Author information

Authors and Affiliations

  1. Hyonam Kidney Laboratory, Dae Sa Gwan Ro 59, Hannam-dong Yongsan-gu, Seoul, Korea

    Soon Hyo Kwon, Jin Seok Jeon, Hyunjin Noh & Dong Cheol Han

  2. Department of Internal Medicine, Soon Chun Hyang University Hospital, Seoul, Korea

    Soon Hyo Kwon, Jin Seok Jeon, Hyunjin Noh & Dong Cheol Han

  3. Department of Internal Medicine, Soon Chun Hyang University Hospital, Bucheon, Korea

    Moo Yong Park, Soo Jeong Choi, Jin Kuk Kim & Seung Duk Hwang

  4. Department of Pathology, Soon Chun Hyang University Hospital, Seoul, Korea

    So Young Jin

Authors
  1. Soon Hyo Kwon
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Moo Yong Park
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. Jin Seok Jeon
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. Hyunjin Noh
    View author publications

    You can also search for this author in PubMed Google Scholar

  5. Soo Jeong Choi
    View author publications

    You can also search for this author in PubMed Google Scholar

  6. Jin Kuk Kim
    View author publications

    You can also search for this author in PubMed Google Scholar

  7. Seung Duk Hwang
    View author publications

    You can also search for this author in PubMed Google Scholar

  8. So Young Jin
    View author publications

    You can also search for this author in PubMed Google Scholar

  9. Dong Cheol Han
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to Dong Cheol Han.

About this article

Cite this article

Kwon, S.H., Park, M.Y., Jeon, J.S. et al. KIM-1 expression predicts renal outcomes in IgA nephropathy. Clin Exp Nephrol 17, 359–364 (2013). https://doi.org/10.1007/s10157-012-0707-2

Download citation

  • Received:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s10157-012-0707-2

Keywords

Search

Navigation