Background The incidence of acute tubulointerstitial nephritis (ATIN) related to drugs has dramatically increased over recent years. A new subtype of ATIN, apparently different from classical drug-related ATIN, has emerged that has been related to the administration of immune checkpoint inhibitors (ICIs). We investigated these differences between ICI-related ATIN (ICI ATIN) and non-ICI-related ATIN in terms of clinical features, response to treatment with steroids and the evolution of kidney function. Methods A total of 47 patients diagnosed with ATIN from two centres were recruited. Of these, 13 patients presented with ATIN during ICI treatment and 34 were diagnosed with ATIN attributed to other drugs. The main demographic, clinical and analytical variables such as gender, age and current medication were recorded. The type of malignancy, oncological treatment, ICI dose and presence of extrarenal immune-related adverse events were also reviewed. Renal biopsy diagnosis, time to drug withdrawal and ATIN-specific treatment, as well as laboratory data during follow-up, were also studied. Results Patients diagnosed with ICI ATIN presented with lower creatinine (ICI ATIN 3.8 ± 1.03  versus classical ATIN 5.98 ± 4.15 mg/dL, P = 0.007) at diagnosis and higher urinary leucocyte counts (ICI ATIN 263.2 ± 418.04 versus classical ATIN 133.55 ± 284.62, P = 0.048) compared with patients with non-ICI-related ATIN. Time from initiation of the culprit drug to ATIN diagnosis was longer in patients with ICI ATIN than in those with classical ATIN (197.07 ± 184.99 versus 114.4 ± 352.16 days, P = 0.006). In addition, during follow-up, the slope of decreasing creatinine over time was lower for ICI ATIN compared with non-ICI-related ATIN. Conclusions In this study, we analysed differences between ICI ATIN and classical ATIN. We found that patients with ICI ATIN presented with a larger latency period after culprit drug initiation, milder acute kidney injury and slower creatinine amelioration compared with those with classical ATIN. These results may, in part, be ascribed to potential differences in the pathological mechanisms involved in ATIN development, suggesting that ICI and classical ATIN may be different diseases with similar renal histologies.

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Background and Aims The incidence of acute tubulointerstitial nephritis (ATIN) related to drugs has dramatically increased during the past years. A new subtype of ATIN apparently different from classical drug related ATIN has emerged, which has been related to the administration of immune check point inhibitors (ICI). We herein investigated these differences between ICI related ATIN and non-ICI related ATIN, in terms of clinical features, response to treatment with steroids, and the kidney function evolution. Method A total of 47 patients diagnosed with acute tubulointerstitial nephritis (ATIN) from two centers were recruited. Of these, 13 patients presented with ATIN during the treatment with ICI, and 34 patients were diagnosed with ATIN attributed to other drugs. The main demographical, clinical and analytical variables such as gender, age, and current medication were recorded. The type of malignancy, oncological treatment, dose of ICI, and presence of extra-renal immune-related adverse-events were also reviewed. Renal biopsy diagnostic, time to drug withdrawal and ATIN specific treatment, as well as laboratory data during the follow-up were also studied. Results Patients diagnosed with ICI related ATIN presented with lower creatinine (ICI ATIN 3.8±1.03mg/dl vs. classical ATIN 5.98±4.15, p=0.007) at diagnostic and higher urinary leukocyte count (ICI ATIN 263.2±418.04 vs. classical ATIN 133.55±284.62, p=0.048) as compared to patients with non-ICI related ATIN. Time elapsed from the initiation of the culprit drug to the ATIN diagnostic was longer in ICI ATIN compared to classical ATIN (197.07±184.99 vs 114.4±352.16 days, p=0.006). In addition, during follow-up, the slope of decreasing creatinine over time was lower in ICI related ATIN compared to non-ICI related patients. Conclusion In this study we analyzed the differences between ICI ATIN and the classical ATIN. We found that ICI ATIN patients presented a larger latency period after offending drug initiation, milder acute kidney injury, and slower creatinine amelioration as compared to the classical ATIN. These results may be in part ascribed to potential differences in the pathological mechanisms in ATIN development, suggesting that ICI ATIN and the classical ATIN may be different disease with similar renal histology.