Skip to main content

Advertisement

Log in

Identification of new urinary risk markers for urinary stones using a logistic model and multinomial logit model

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

Abstract

Background

Risk assessment for urinary stones has been mainly based on urinary biochemistry. We attempted to identify the risk factors for urinary stones by statistically analyzing urinary biochemical and inflammation-related factors.

Methods

Male participants (age, 20–79 years) who visited Nagoya City University Hospital were divided into three groups: a control group (n = 48) with no history of stones and two stone groups with calcium oxalate stone experience (first-time group, n = 22; recurring group, n = 40). Using 25-µL spot urine samples, we determined the concentrations of 18 candidate urinary proteins, using multiplex analysis on a MagPix® system.

Results

In univariate logistic regression models classifying the control and first-time groups, interleukin (IL)-1a and IL-4 were independent factors, with significantly high areas under the receiver operating characteristic curve (1.00 and 0.87, respectively, P < 0.01 for both). The multivariate models with IL-4 and granulocyte–macrophage colony-stimulating factor (GM-CSF) showed higher areas under the receiver operating characteristic curve (0.93) compared to that for the univariate model with IL-4. In the classification of control, first-time, and recurrence groups, accuracy was the highest for the multinomial logit model with IL-4, GM-CSF, IL-1b, IL-10, and urinary magnesium (concordance rate 82.6%).

Conclusions

IL-4, IL-1a, GM-CSF, IL-1b, and IL-10 were identified as urinary inflammation-related factors that could accurately distinguish control individuals from patients with urinary stones. Thus, the combined analysis of urinary biochemical data could provide an index that more clearly evaluates the risk of urinary stone formation.

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

Access this article

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

Instant access to the full article PDF.

Fig. 1

Similar content being viewed by others

References

  1. Scales CD Jr., Smith AC, Hanley JM, Saigal CS. Urologic diseases in America Project. Prevalence of kidney stones in the United States. Eur Urol. 2012;62:160–5.

    Article  PubMed  PubMed Central  Google Scholar 

  2. Yasui T, Iguchi M, Suzuki S, Kohri K. Prevalence and epidemiological characteristics of urolithiasis in Japan: national trends between 1965 and 2005. Urology. 2008;71:209–13.

    Article  PubMed  Google Scholar 

  3. Zeng G, Mai Z, Xia S, Wang Z, Zhang K, Wang L, et al. Prevalence of kidney stones in China: an ultrasonography based cross-sectional study. BJU Int. 2017;120:109–16.

    Article  PubMed  Google Scholar 

  4. Okada A, Nomura S, Higashibata Y, Hirose M, Gao B, Yoshimura M, et al. Successful formation of calcium oxalate crystal deposition in mouse kidney by intraabdominal glyoxylate injection. Urol Res. 2007;35:89–99.

    Article  CAS  PubMed  Google Scholar 

  5. Okada A, Yasui T, Hamamoto S, Hirose M, Kubota Y, Itoh Y, et al. Genome-wide analysis of genes related to kidney stone formation and elimination in the calcium oxalate nephrolithiasis model mouse: detection of stone-preventive factors and involvement of macrophage activity. J Bone Miner Res. 2009;24:908–24.

    Article  CAS  PubMed  Google Scholar 

  6. Okada A, Yasui T, Fujii Y, Niimi K, Hamamoto S, Hirose M, et al. Renal macrophage migration and crystal phagocytosis via inflammatory-related gene expression during kidney stone formation and elimination in mice: detection by association analysis of stone-related gene expression and microstructural observation. J Bone Miner Res. 2010;25:2701–11.

    Article  CAS  PubMed  Google Scholar 

  7. Ichikawa J, Okada A, Taguchi K, Fujii Y, Zuo L, Niimi K, et al. Increased crystal-cell interaction in vitro under co-culture of renal tubular cells and adipocytes by in vitro co-culture paracrine systems simulating metabolic syndrome. Urolithiasis. 2014;42:17–28.

    Article  CAS  PubMed  Google Scholar 

  8. Zuo L, Tozawa K, Okada A, Yasui T, Taguchi K, Ito Y, et al. A paracrine mechanism involving renal tubular cells, adipocytes and macrophages promotes kidney stone formation in a simulated metabolic syndrome environment. J Urol. 2014;191:1906–12.

    Article  CAS  PubMed  Google Scholar 

  9. Cao Q, Wang Y, Wang XM, Lu J, Lee VW, Ye Q, et al. Renal F4/80+ CD11c+ mononuclear phagocytes display phenotypic and functional characteristics of macrophages in health and in adriamycin nephropathy. J Am Soc Nephrol. 2015;26:349–63.

    Article  CAS  PubMed  Google Scholar 

  10. Nelson PJ, Rees AJ, Griffin MD, Hughes J, Kurts C, Duffield J. The renal mononuclear phagocytic system. J Am Soc Nephrol. 2012;23:194–203.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  11. Lee S, Huen S, Nishio H, Nishio S, Lee HK, Choi BS, et al. Distinct macrophage phenotypes contribute to kidney injury and repair. J Am Soc Nephrol. 2011;22:317–26.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  12. Cao Q, Wang C, Zheng D, Wang Y, Lee VW, Wang YM, et al. IL-25 induces M2 macrophages and reduces renal injury in proteinuric kidney disease. J Am Soc Nephrol. 2011;22:1229–39.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  13. Nikolic-Paterson DJ, Wang S, Lan HY. Macrophages promote renal fibrosis through direct and indirect mechanisms. Kidney Int Suppl 2011. 2014;4:34–8.

    CAS  PubMed  Google Scholar 

  14. Taguchi K, Okada A, Kitamura H, Yasui T, Naiki T, Hamamoto S, et al. Colony-stimulating factor-1 signaling suppresses renal crystal formation. J Am Soc Nephrol. 2014;25:1680–97.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  15. Taguchi K, Okada A, Hamamoto S, Iwatsuki S, Naiki T, Ando R, et al. Proinflammatory and metabolic changes facilitate renal crystal deposition in an obese mouse model of metabolic syndrome. J Urol. 2015;194:1787–96.

    Article  CAS  PubMed  Google Scholar 

  16. Taguchi K, Okada A, Hamamoto S, Unno R, Moritoki Y, Ando R, et al. M1/M2-macrophage phenotypes regulate renal calcium oxalate crystal development. Sci Rep. 2016;6:35167.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  17. Okada A, Hamamoto S, Taguchi K, Unno R, Sugino T, et al. Kidney stone formers have more renal parenchymal crystals than non-stone formers, particularly in the papilla region. BMC Urol. 2018;18:19.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  18. Taguchi K, Hamamoto S, Okada A, Unno R, Kamisawa H, Naiki T, et al. Genome-wide gene expression profiling of Randall’s plaques in calcium oxalate stone formers. J Am Soc Nephrol. 2017;28:333–47.

    Article  CAS  PubMed  Google Scholar 

  19. Lukens JR, Gross JM, Kanneganti TD. IL-1 family cytokines trigger sterile inflammatory disease. Front Immunol. 2012;3:315.

    Article  PubMed  PubMed Central  Google Scholar 

  20. Boswell RN, Yard BA, Schrama E, van Es LA, Daha MR, van der Woude FJ. Interleukin 6 production by human proximal tubular epithelial cells in vitro: analysis of the effects of interleukin-1 alpha (IL-1 alpha) and other cytokines. Nephrol Dial Transplant. 1994;9:599–606.

    Article  CAS  PubMed  Google Scholar 

  21. Weisinger JR, Alonzo E, Bellorín-Font E, Blasini AM, Rodriguez MA, Paz-Martínez V, et al. Possible role of cytokines on the bone mineral loss in idiopathic hypercalciuria. Kidney Int. 1996;49:244–50.

    Article  CAS  PubMed  Google Scholar 

  22. Okumura N, Tsujihata M, Momohara C, Yoshioka I, Suto K, Nonomura N, et al. Diversity in protein profiles of individual calcium oxalate kidney stones. PLoS One. 2013;8:e68624.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  23. Yanagimachi MD, Niwa A, Tanaka T, Honda-Ozaki F, Nishimoto S, Murata Y, et al. Robust and highly-efficient differentiation of functional monocytic cells from human pluripotent stem cells under serum- and feeder cell-free conditions. PLoS One. 2013;8:e59243.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

Download references

Acknowledgements

We thank N. Kasuga and M. Noda for administrative assistance. This work was supported in part by Grants-in-Aid for Scientific Research from the Ministry of Education, Culture, Sports, Science, and Technology, Japan (Grant nos. 15H04976, 15K10627, 16K11054, 16K15692, and 16K20153), Takeda Science Foundation, and Japanese Society on Urolithiasis Research.

Author information

Authors and Affiliations

Authors

Corresponding author

Correspondence to Atsushi Okada.

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 and/or national research committee at which the studies were conducted (IRB approval number 878) 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.

Additional information

Publisher’s Note

Springer Nature remains neutral with regard to jurisdictional claims in published maps and institutional affiliations.

About this article

Check for updates. Verify currency and authenticity via CrossMark

Cite this article

Okada, A., Ando, R., Taguchi, K. et al. Identification of new urinary risk markers for urinary stones using a logistic model and multinomial logit model. Clin Exp Nephrol 23, 710–716 (2019). https://doi.org/10.1007/s10157-019-01693-x

Download citation

  • Received:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s10157-019-01693-x

Keywords

Navigation