Skip to main content
SpringerLink
Log in

Characterizing ceftriaxone-induced urolithiasis and its associated acute kidney injury: an animal study and Chinese clinical systematic review

  • Urology - Original Paper
  • Published:
International Urology and Nephrology Aims and scope Submit manuscript

Abstract

Objective

To investigate the pathophysiological process of ceftriaxone-induced urolithiasis and its associated acute kidney injury (AKI) based on an animal study and summarize the main clinical characteristics based on a Chinese clinical systematic review.

Materials and methods

Male Sprague–Dawley rats were randomly divided into five groups of six each according to different treatments including control; ceftriaxone; ceftriaxone with calcium; calcium; and ceftriaxone, calcium with citrate, respectively. The 24-h urine volume, serum creatinine (Scr) and blood urea nitrogen (BUN) were measured; kidney histological examination and stone analysis were performed. Systematic searches of the Chinese Knowledge Database were conducted for reports on ceftriaxone-induced urolithiasis and AKI. The eligibility of each full-text publication was accessed, and qualified data were extracted and reviewed.

Results

Kidney stones and a significantly low 24-h urine volume with increased high Scr and BUN levels were found in the group that received ceftriaxone combined with calcium. Citrate was able to inhibit these biochemical changes and stone formations. A total of 161 qualified patients were included in the Chinese clinical systematic review: The proportion of ceftriaxone-induced urolithiasis was 21.1, 19.3, 19.3, 39.1 and 1.2 % for ages <3, 3–6, 7–17, 18–60 and >60 years. 72.7 % developed acute kidney injury eventually.

Conclusion

Ceftriaxone-induced urolithiasis was associated with a high risk of AKI. The pathophysiological process may be related to urinary obstruction and crystalline nephropathy. Citrate was able to inhibit stone formation and prevent further kidney injury.

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
Fig. 5
Fig. 6

Similar content being viewed by others

References

  1. Araz N, Okan V, Demirci M et al (2007) Pseudolithiasis due to ceftriaxone treatment for meningitis in children: report of 8 cases. The Tohoku Journal of Experimental Medicine 211(3):285–290

    Article  CAS  PubMed  Google Scholar 

  2. Schmutz HR, Detampel P, Bühler T et al (2011) In vitro assessment of the formation of ceftriaxone–calcium precipitates in human plasma. J Pharm Sci 100(6):2300–2310

    Article  CAS  PubMed  Google Scholar 

  3. Cochat P, Cochat N, Jouvenet M, Floret D, Wright C, Martin X, Vallon JJ, David L (1990) Ceftriaxone-associated nephrolithiasis. Nephrol Dial Transplant 5(11):974–976

    Article  CAS  PubMed  Google Scholar 

  4. Daudon M, Jungers P (2004) Drug-induced renal calculi. Drugs 64(3):245–275

    Article  PubMed  Google Scholar 

  5. Tang X, Lieske JC (2014) Acute and chronic kidney injury in nephrolithiasis. Curr Opin Nephrol Hypertens 23(4):385–390

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  6. de Moor RA, Egberts AC, Schröder CH (1999) Ceftriaxone-associated nephrolithiasis and biliary pseudolithiasis. Eur J Pediatr 158(12):975–977

    Article  PubMed  Google Scholar 

  7. Grasberger H, Otto B, Loeschke K (2000) Ceftriaxone-associated nephrolithiasis. Ann Pharmacother 34(9):1076–1077

    Article  CAS  PubMed  Google Scholar 

  8. Prince JS, Senac MO Jr (2003) Ceftriaxone-associated nephrolithiasis and biliary pseudolithiasis in a child. Pediatr Radiol 33(9):648–651

    Article  PubMed  Google Scholar 

  9. Cochat P, Cochat N, Jouvenet M, Floret D, Wright C, Martin X, Vallon JJ, David L (1990) Ceftriaxone-associated nephrolithiasis. Nephrol Dial Transplant 5(11):974–976

    Article  CAS  PubMed  Google Scholar 

  10. Avci Z, Koktener A, Uras N, Catal F, Karadag A, Tekin O, Degirmencioglu H, Baskin E (2004) Nephrolithiasis associated with ceftriaxone therapy: a prospective study in 51 children. Arch Dis Child 89(11):1069–1072

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  11. Mohkam M, Karimi A, Gharib A, Daneshmand H, Khatami A, Ghojevand N, Sharifian M (2007) Ceftriaxone associated nephrolithiasis: a prospective study in 284 children. Pediatr Nephrol 22(5):690–694

    Article  PubMed  Google Scholar 

  12. Klesel N, Limbert M, Seeger K, Seibert G, Winkler I, Schrinner E (1984) Cefodizime, an aminothiazolylcephalosporin. II. Comparative studies on the pharmacokinetic behavior in laboratory animals. J Antibiot (Tokyo) 37(8):901–909

    Article  CAS  Google Scholar 

  13. Stoeckel K (1981) Pharmacokinetics of Rocephin, a highly active new cephalosporin with an exceptionally long biological half-life. Chemotherapy 27(Suppl 1):42–46

    Article  CAS  PubMed  Google Scholar 

  14. Matsui H, Komiya M, Ikeda C, Tachibana A (1984) Comparative pharmacokinetics of YM-13115, ceftriaxone, and ceftazidime in rats, dogs, and rhesus monkeys. Antimicrob Agents Chemother 26(2):204–207

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  15. Akl KF, Masri AT, Hjazeen MM (2011) Acute urine retention induced by ceftriaxone. Saudi J Kidney Dis Transpl 22(6):1226–1228

    PubMed  Google Scholar 

  16. Guan N, Fan Q, Ding J, Zhao Y, Lu J, Ai Y, Xu G, Zhu S, Yao C, Jiang L, Miao J, Zhang H, Zhao D, Liu X, Yao Y (2009) Melamine-contaminated powdered formula and urolithiasis in young children. N Engl J Med 360(11):1067–1074

    Article  CAS  PubMed  Google Scholar 

  17. Lozanovski VJ, Gucev Z, Avramoski VJ, Kirovski I, Makreski P, Tasic V (2011) Ceftriaxone associated urolithiasis in a child with hypercalciuria. Hippokratia 15(2):181–183

    CAS  PubMed  PubMed Central  Google Scholar 

  18. Chutipongtanate S, Thongboonkerd V (2011) Ceftriaxone crystallization and its potential role in kidney stone formation. Biochem Biophys Res Commun 406(3):396–402

    Article  CAS  PubMed  Google Scholar 

  19. Karliczek SB, Döring S, Vogt S et al (1996) Ceftriaxone-associated nephrolithiasis. Two case reports. Monatsschr Kinderheilkd 144:702–706

    Google Scholar 

  20. Li ZL, Li HL, Chen HW, Li HC, Zhang P, Wang ZM, Chong T (2013) Anuria and abdominal pain induced by ceftriaxone-associated ureterolithiasis in adults. Int Urol Nephrol 45(1):73–76

    Article  CAS  PubMed  Google Scholar 

  21. Li N, Zhou X, Yuan J, Chen G, Jiang H, Zhang W (2014) Ceftriaxone and acute renal failure in children. Pediatrics 133(4):e917–e922

    Article  PubMed  Google Scholar 

  22. Shen X, Liu W, Fang X et al (2014) Acute kidney injury caused by ceftriaxone-induced urolithiasis in children: a single-institutional experience in diagnosis, treatment and follow-up. Int Urol Nephrol 46(10):1909–1914

    Article  CAS  PubMed  Google Scholar 

  23. Mason J, Olbricht C, Takabatake T et al (1977) The early phase of experimental acute renal failure. Pflügers Arch 370(2):155–163

    Article  CAS  PubMed  Google Scholar 

  24. Markowitz GS, Perazella MA (2005) Drug-induced renal failure: a focus on tubulointerstitial disease. Clin Chim Acta 351(1):31–47

    Article  CAS  PubMed  Google Scholar 

  25. Lin WC, Lai MT, Chen HY, Ho CY, Man KM, Shen JL, Lee YJ, Tsai FJ, Chen YH, Chen WC (2012) Protective effect of Flos carthami extract against ethylene glycol-induced urolithiasis in rats. Urol Res 40(6):655–661

    Article  PubMed  Google Scholar 

Download references

Author information

Authors and Affiliations

  1. Medical School of Nanjing University, 22#, Hankou Road, Nanjing, China

    Yifan Zhang, Leqing Zhou, Qiang Wang, Liming Zhang & Xizhao Sun

  2. Nanjing Drum Tower Hospital, Affiliated Hospital of Nanjing University Medical School, 321#, Zhongshan Road, Nanjing, China

    Benxiang Ning & Huaijun Zhu

  3. Jiangsu Province Hospital of TCM, Affiliated Hospital of Nanjing University of TCM, 155#, Hanzhong Road, Nanjing, China

    Xiaoming Cong

Authors
  1. Yifan Zhang
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Benxiang Ning
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. Huaijun Zhu
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. Xiaoming Cong
    View author publications

    You can also search for this author in PubMed Google Scholar

  5. Leqing Zhou
    View author publications

    You can also search for this author in PubMed Google Scholar

  6. Qiang Wang
    View author publications

    You can also search for this author in PubMed Google Scholar

  7. Liming Zhang
    View author publications

    You can also search for this author in PubMed Google Scholar

  8. Xizhao Sun
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to Xizhao Sun.

Ethics declarations

Conflict of interest

All the authors declare that they have no conflict of interest and there has been no significant financial support for this work that could have influenced its outcome. The manuscript has been read and approved by all named authors and there are no other persons who satisfied the criteria for authorship but are not listed. The order of authors listed in the manuscript has been approved by all of the authors.

Ethical approval

All applicable international, national and/or institutional guidelines for the care and use of animals were followed. All procedures performed in studies involving human participants were in accordance with the ethical standards of the institutional and/or national research committee and with the 1964 Helsinki Declaration and its later amendments or comparable ethical standards.

Rights and permissions

Reprints and permissions

About this article

Check for updates. Verify currency and authenticity via CrossMark

Cite this article

Zhang, Y., Ning, B., Zhu, H. et al. Characterizing ceftriaxone-induced urolithiasis and its associated acute kidney injury: an animal study and Chinese clinical systematic review. Int Urol Nephrol 48, 1061–1069 (2016). https://doi.org/10.1007/s11255-016-1273-4

Download citation

  • Received:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s11255-016-1273-4

Keywords

Search

Navigation