Acute tubulointerstitial nephritis induced by checkpoint inhibitors versus classical acute tubulointerstitial nephritis: are they the same disease?

Abstract

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.

Immune-related adverse kidney events by immune checkpoint inhibitors; a narrative review on current studies

“…Patients diagnosed with ICPI-related AIN revealed a lower plasma creatinine level accompanied by higher urinary leucocyte counts compared with the classical AIN. The serum creatinine decrement was also lower in cases of ICPI administered patients compared to non-ICPI-related ones (26).…”

Adverse Renal Effects of Anticancer Immunotherapy: A Review

“…Some investigators concluded that tubulointerstitial nephritis caused by ICIs presents some differences from the classical ATIN caused by other drugs. Draibe et al compared 13 patients with renal injury after taking ICIs with 34 patients with tubulonephritis related to other drugs and suggested that patients with ATIN related to ICIs had lower serum creatinine levels at the time of diagnosis (3.8 ± 1.0 vs 6.0 ± 4.1 mg/dL, p<0.01), and time from starting the treatment with the responsible drug to the diagnosis was longer in this group (197 ± 185 vs 114 ± 352 days, p<0.01) [65]. This suggests a milder course of kidney damage caused by ICIs.…”

Chronic Kidney Disease and Cancer: Inter-Relationships and Mechanisms

“…Injecting anti-PD1 or anti-PD-L1 antibodies not only blocked PD-1 receptor, but also triggerred T cell proliferation and cytotoxic injury of the kidney ( Dumoulin et al, 2020 ). Compared with classic acute tubulointerstitial nephritis patients, ICI-related interstitial nephritis showed similar renal histological manifestations, but there were potential differences in the development of pathological mechanisms, such as longer incubation period, lighter acute renal injury, and slower improvement of creatinine, etc ( Draibe et al, 2021 ). Retrospective cohort study showed the incidence of CKD in 2,563 cancer patients treated with ICI for more than 1 year was approximately 6.34/100 person-years, indicating that CKD events were common in ICI therapy ( Chute et al, 2022 ).…”