{"doi":"10.34067/kid.0000132020","title":"Kidney Biopsy Should Be Performed to Document the Cause of Immune Checkpoint Inhibitor–Associated Acute Kidney Injury: CON","abstract":"Immune checkpoint inhibitors (ICPis) have revolutionized the treatment of cancers by engaging the patient’s own immune system against the tumor (1–3). Checkpoint pathways are innate mechanisms to put the brakes on immune activation. Approved agents target checkpoint pathways mediated by cytotoxic T lymphocyte–associated antigen 4 (CTLA4), programmed cell death protein 1 (PD-1), and programmed death ligand 1 (PDL-1) (1,4–7). Releasing the breaks on the immune system enhances destruction of tumor cells, but can lead to immune-related adverse effects (8,9), including renal toxicity (1,2,10–13). The incidence of renal toxicity with ICPis ranges from 1% to 5% (12). This risk is higher in patients that are on combination therapy with both anti-CTLA4 and anti–PD-1/PD-L1 with an odds ratio of 3.88 (95% CI, 2.21 to 6.81) (14). Further, a lower baseline GFR before therapy increases risk of kidney injury with an odds ratio of 1.99 (95% CI, 1.43 to 2.76) for every 30 ml/min per 1.73 m2 decline (14). The time to prevent kidney injury starts at the time of ICPi initiation. Based on a recent multicenter review of 138 patients, risk of ICPi-associated AKI (ICPi-AKI) was higher with concomitant use of proton pump inhibitors (PPIs) with an odds ratio of 2.85 (95% CI, 1.81 to 4.48) (14). Cortazar et al. describe that 70% of patients with ICPi-AKI were on potential acute interstitial nephritis (AIN)–causing medications including PPIs (15,16), nonsteroidal anti-inflammatory drugs (NSAIDs) (17), and antibiotics (18) where PPI was present on >50% of patients’ medication lists. Baseline use of PPIs was also associated with ICPi-AKI in a large study by Seethapathy et al. (1), particularly 2.5 months after being on ICPi. Appropriate counseling to stop or substitute these medications should be given before ICPi initiation and these medications should certainly be discontinued in patients with ICPi-AKI. In patients that develop ICPi-AKI, the most common pathologic finding identified to date is AIN (10–12,19). In 2016, Shirali et al. (11) reviewed six patients on PD-L1 inhibitor therapy and all six patients had AIN on kidney biopsy. Notably, all patients were also receiving either PPIs or NSAIDs. Similarly, Cortazar et al. (12) describe 13 patients on ICPis where AIN was present in 12 of the 13 (92%) patients, and Mamlouk et al. (10) describe 16 patients on ICPis with AIN identified in 14 of the 16 (86%) patients. These case series emphasize that it is reasonable to assume that AIN is the cause for ICPi-AKI in the majority of cases. Finally, in a recent multicenter study of AKI in this setting, 60 patients underwent a kidney biopsy and 93% of samples were consistent with AIN (14). Glomerular disease is less common in ICPi-AKI and, in the majority of glomerular cases reported, patients had nephrotic range proteinuria of >3 g/g (10,13). Izzedine et al. (13) reported two cases with minimal change disease: one with 3.5 g/g and the other with 6 g/g. Mamlouk et al. (10) identified two cases of IgA nephropathy: one with 7.7 g/g and the other with no protein and IgA as part of the pathology interpretation with a comment that no pathologic indication of active disease present. Of note, the latter patient also had interstitial inflammation on the biopsy report (10). The same case series also identified one case of membranous nephropathy with 9.7 g/g (10). Acute tubular necrosis (ATN) is another finding reported after biopsy in patients with ICPi-AKI (13,19). Izzedine et al. (13) report ATN in five out of 12 cases and highlight that without kidney biopsy patients would have been inappropriately treated with steroids. However, investigation into these cases suggests other reasons for ATN on kidney biopsy. As an example, two of five patients underwent prior platinum therapy which is nephrotoxic and known to cause ATN (20,21). Further, the majority of these patients had more cardiovascular risk factors and marked histologic vascular lesions on kidney biopsy (13). It wo","journal":"Kidney360","year":2020,"id":83944,"datarank":0.0,"base_score":0.0,"endowment":0.0,"self_citation_contribution":0.0,"citation_network_contribution":0.0,"self_endowment_contribution":0.0,"citer_contribution":0.0,"corpus_percentile":null,"corpus_rank":null,"citation_count":10,"citer_count":0,"citers_with_citation_signal":0,"citers_with_endowment":0,"datacite_reuse_total":0,"is_dataset":false,"is_dataset_confidence":0.9568,"is_data_producer":false,"deposit_databanks":null,"is_oa":true,"file_count":0,"downloads":0,"has_version_chain":false,"published_date":"2020-01-01","fair_score":null,"fair_percentile":null,"algorithm_id":"datarank_citation_only_1hop_v6","ranking_scope":"data_only","authors":[{"id":411549,"name":"Ilya Glezerman","orcid":"0000-0002-2212-9097","position":1,"is_corresponding":false},{"id":280698,"name":"Victoria Gutgarts","orcid":"0000-0002-8789-9172","position":0,"is_corresponding":true}],"reference_count":25,"raw_metadata":null,"created_at":"2026-07-18T21:54:50.827092Z","pmid":"35368625","pmcid":null,"fwci":null,"citation_percentile":null,"influential_citations":0,"oa_status":null,"license":null,"views":0,"total_file_size_bytes":0,"version_count":0,"fair_f":null,"fair_a":null,"fair_i":null,"fair_r":null,"fair_zscore":null,"fair_rationale":null,"fair_model":null,"fair_agent_version":null,"fair_fulltext_source":null,"fair_has_llm":null,"fair_computed_at":null,"clinical_trials":[],"software_tools":[],"db_accessions":[],"linked_datasets":[],"topics":[]}