Kidney Biopsy Should Be Performed to Document the Cause of Immune Checkpoint Inhibitor-Associated Acute Kidney Injury: PRO.

Abstract

Immune checkpoint inhibitors (CPIs) have significantly improved the outcome for patients with cancer by effectively overcoming cancer resistance by allowing the host immune system to recognize and eliminate tumor cells. Immune checkpoints are regulatory receptors and ligands that allow immune-mediated destruction of foreign antigens while at the same time prevent autoimmune host organ injury. CPIs remove these breaks on the immune system and, not unexpectedly, are associated with the development of immune-related adverse events (IRAEs). IRAEs are common with grade 3/4 toxicities developing in approximately 20% of patients. Skin, gastrointestinal tract, and endocrine IRAEs are most frequent; whereas IRAEs affecting the kidney are less common: 1%–2% with monotherapy and 5% with combined immune CPIs (1), although this is likely an underestimate (2). Various types of kidney injury have been described including acute tubulointerstitial nephritis (ATIN), acute tubular injury, glomerular diseases, and thrombotic microangiopathy (3). The 2017 American Society of Clinical Oncology (ASCO) guideline on the treatment of IRAEs describes the expert consensus on the approach of organ-specific events (4). The guidelines recommend that if causes of AKI other than IRAEs have been eliminated, the physician should forego the need for biopsy and proceed with immunosuppressive therapy. According to this guideline, no other urinalysis is indicated but the nephrologist may consider further investigation. As far as kidney IRAEs are concerned, clinical findings and laboratory tests are suboptimal in predicting the precise underlying kidney lesion, making kidney biopsy necessary in the majority of cases to definitely diagnose the precise lesion, to guide therapy, and—possibly—to improve the overall outcome in patients treated with CPIs.