Immune checkpoint inhibitor nephrotoxicity: what do we know and what should we do?

The Use of Immune Checkpoint Inhibitors in Oncology and the Occurrence of AKI: Where Do We Stand?

“…In the tumor microenvironment, cancer cells can evade the immunosurveillance by changing their surface antigens, thus avoiding the detection and destruction by host lymphocytes. A central mechanism of tumor-induced immune suppression is the increased expression of ligands able to bind inhibitory T cell receptors ( 2 , 3 , 5 ). These ligands are known as immune checkpoints and act in physiological conditions to prevent the development of autoimmunity at multiple steps during the immunological response.…”

“…An emerging complication of ICIs administration is kidney damage, which includes acute kidney injury (AKI) – possibly evolving towards chronic kidney disease (CKD), proteinuria, and electrolyte abnormalities ( 5 ).…”

“…the immune checkpoints themselves), referred to as immune-related adverse events (irAEs) characterized by clinical manifestations that closely resemble autoimmunity disorders ( 3 , 4 ). Given the extrarenal clearance of ICIs, the contribution of these agents to kidney toxicity has been neglected and underestimated for several years ( 5 ). This was further complicated by the fact too often, renal toxicities from anticancer agents in general, are reported, within oncology clinical trials, just as “creatinine increase”, or similar definitions, without any further pathogenic insight.…”

Kidney Biopsy Should Be Performed to Document the Cause of Immune Checkpoint Inhibitor–Associated Acute Kidney Injury: Commentary

“…Although the ICPIs have greatly improved cancer therapy, immune-related adverse drug effects complicate their course (6,7). Extrarenal complications occur relatively commonly; however, drug nephrotoxicity is also observed (7)(8)(9). In review articles containing published biopsy-proven cases, acute tubulointerstitial nephritis (ATIN) is most common (51 of 90; 57%), whereas acute tubular injury (ATI; n513), various glomerulopathies (n520), and other kidney lesions (n56) have also been described (7)(8)(9)(10).…”

“…These include AKI from ischemic and/or nephrotoxic tubular injury, various drug-or cancer-related glomerular injuries, crystalline nephropathy, paraneoplastic kidney damage, and urinary obstruction. As such, patients with cancer who develop AKI during ICPI therapy should be carefully evaluated to correctly diagnose the kidney lesion and guide appropriate management (8)(9)(10).…”