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Drug-induced tubulointerstitial nephritis and uveitis syndrome in a nationwide surveillance

Eye volume 39, pages 2036–2041 (2025)Cite this article

Subjects

Abstract

Purpose

To investigate primary suspect drugs and identify a potential association between medication use and Tubulointerstitial Nephritis and Uveitis (TINU).

Methods

A retrospective pharmacovigilance study was conducted using the Food and Drug Administration (FDA) Adverse Events Database (FAERS) from Q1 2004 to Q2 2024, focusing on patient demographics and statistical signal detection. A qualitative analysis assessed patient demographics. To ascertain if these reports yielded statistically significant signals, we used the proportional reporting ratio (PRR), chi-squared with Yates’ correction (χ2), reporting odds ratio (ROR), empirical Bayes geometric mean (EBGM), and information component (IC).

Results

One hundred twenty-six adverse reports for TINU were identified, along with 37 primary suspect drugs from the FAERS database. The mean age of patients was 30.05 ± 20.88 years. Most reports were of female patients (n = 67, 53%). Of the 37 primary suspect drugs, lamotrigine (n = 35, 27%) and diclofenac (n = 15, 12%) were the most frequently reported suspect drugs. The signal detection analysis also identified positive signals and potential causality for both drugs. Lamotrigine demonstrated the strongest positive signal (PRR = 90.09, χ2 = 3001.58, ROR 95% CI: 124.35 [84.20-183.66], EBGM [EBGM05]: 70.98 [50.21], IC [IC05]: 5.32 [4.83]), followed by diclofenac (PRR = 24.21, χ2 = 312.49, ROR 95% CI: 27.35 [15.95-46.90], EBGM [EBGM05]: 4.11 [2.47], IC [IC05]: 3.79 [2.99]).

Conclusion

Our study identified 37 primary suspect drugs associated with TINU, with lamotrigine and diclofenac showing the strongest statistical signals. Lamotrigine demonstrated the highest association, suggesting a potential drug-related risk for developing TINU, particularly in younger patients and females. Further research is warranted to explore causality and underlying mechanisms in these associations.

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Data availability

The datasets generated for the statistical analysis and signal detection analysis are available from the corresponding author upon reasonable request.

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Authors and Affiliations

  1. Department of Rural Medicine, University of New England, Armidale, NSW, Australia

    Ayesh Ali & David G. Downes

  2. Department of Ophthalmology, Benha University, Benha, Egypt

    Taher K. Eleiwa

  3. Department of Ophthalmology, Magrabi Eye and Dental Hospital, Al-Ahsaa, Kingdom of Saudi Arabia

    Taher K. Eleiwa

  4. Department of Ophthalmology, University of California Irvine, Irvine, CA, USA

    Amr K. Hassan

  5. Department of Ophthalmology, Harvey and Bernice Jones Eye Institute, University of Arkansas for Medical Sciences, Little Rock, AR, USA

    Reem H. ElSheikh, Muhammad Z. Chauhan, Paul H. Phillips & Abdelrahman M. Elhusseiny

  6. Department of Neuroscience, Reproductive and Odontostomatological Sciences, University of Naples Federico II, Naples, Italy

    Lucia Ambrosio

  7. Department of Public Health, University of Naples Federico II, Naples, Italy

    Lucia Ambrosio

  8. Department of Ophthalmology, Boston Children’s Hospital, Harvard Medical School, Boston, MA, USA

    Bharti R. Nihalani & Abdelrahman M. Elhusseiny

Authors
  1. Ayesh Ali
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Contributions

AME was responsible for designing the review protocol. AA conducted the statistical analysis and signal detection analysis, created tables and figures, and updated the reference list. AA and DGD were responsible for writing the manuscript. TKE and AKH helped in writing the manuscript. RHE reviewed the related literature. MZC reviewed the statistical analysis. LA, BRN, PHP reviewed and edited the manuscript. All authors reviewed the final manuscript.

Corresponding author

Correspondence to Abdelrahman M. Elhusseiny.

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Competing interests

BRN is a member of the Eye I editorial board. No other conflicts.

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Ali, A., Downes, D.G., Eleiwa, T.K. et al. Drug-induced tubulointerstitial nephritis and uveitis syndrome in a nationwide surveillance. Eye 39, 2036–2041 (2025). https://doi.org/10.1038/s41433-025-03808-z

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