**7. Final Remarks**

To date, there is no reliable, non-invasive test for the diagnosis and monitoring of ATIN. Classical urine studies have shown poor sensitivity and specificity in ATIN diagnosis. Kidney biopsy is the gold standard for the assessment of ATIN, but there are significant drawbacks in the performance of this procedure in certain settings.First, it is contraindicated in certain patients such as those with uncontrolled hypertension or non-corrigible coagulation disorders, and the indication in the case of mononephric, small-sized kidney, or obese patients may be questionable due to the increased risk of serious complications.Second, although infrequent, variable degrees of bleeding may occur during the procedure or the following hours, especially when inflammation is prominent. Third, kidney biopsy requires trained personnel and a sufficient infrastructure that is not generally available in all hospitals, and a shift to specialized units may causedelays in the diagnosis.

Urinary biomarkers are excellent candidates for the evaluation of kidney diseases. Urine sampling has the advantage of being a non-invasive, immediate, and easy-to-performprocedure and can be repeated over time.The infrastructure required for cytokine quantification is relatively simple and frequently ELISA based, thus its use can be widespread.Urinary molecular content is a valuable live, and direct reflection of the inflammatory reactions occurring locally in the kidney tissue.The selection of novel biomarkers based on the pathophysiology of the disease will, over time, permit refinement in the diagnosis of the disease and the follow-up of the immune activity.

Cell-based assayshave an added value because they go beyond the diagnosis of ATIN. They confirm the presence of a DHRagainst aspecific drug in ATIN patients. Genetic biomarkers can help to deepen the knowledge of the pathophysiology of the disease.

Summarizing, novel biomarkers of ATIN are of interest to avoid kidney biopsy and its complications, are based on non-invasive sampling techniques, are low-resource consuming, reflect pathogenic processes ongoing in the kidney tissue, and can help identify the culprit drug in the case of drug-induced ATIN.

**Author Contributions:** L.M.V. performed a literature review of the topic and elaborated the manuscript. J.T. elaborated the manuscript. J.D. and X.F. critically revised the manuscript. All authors have read and agreed to the published version of the manuscript.

**Funding:** This research received no external funding.

**Acknowledgments:** This study has been funded by Instituto de Salud Carlos III through the grant CM19/00107 (co-funded by European Social Fund (ESF investing in your future). We thank CERCA Program /Generalitat de Catalunya for institutional support.

**Conflicts of Interest:** The authors declare no conflict of interest.
