Immune checkpoint inhibitor-related acute kidney injury: A diagnostic and therapeutic challenge for nephrologists

Table 1 Reported risk factors for immune checkpoint inhibitor-related acute kidney injury

Risk factor	Details/evidence
Type of immunotherapy	Highest incidence with anti-CTLA-4 followed by anti-PD-1 and anti-PD-L1[12-14]
Combination therapy	Increased risk with anti-CTLA-4 and anti-PD-1/anti-PD-L1 combination, however not confirmed in meta-analysis[13-15]
Extrarenal irAEs	Prevalence 62-87% in ICI-related AKI, and most precede the development of AKI[3,11,13,16]; Common: Colitis, thyroiditis, hypophysitis; Others: Dermatitis, hepatitis, pancreatitis, iridocyclitis, lymphadenopathy, neuropathies
Concomitant drugs	NSAIDs, PPIs, various antibiotics, fluindione, ACEIs and diuretics have been shown to increase risk[2,3,13,17]
Pre-existing conditions/factors	CKD and diabetes[2,17]. Older age, male sex, and gynaecological/genitourinary malignancies suggestive but not confirmed in meta-analysis[1,17-20]

CTLA-4: Cytotoxic T lymphocyte-associated antigen 4; PD-1: Programmed cell death receptor 1; PD-L: Programmed cell death ligand 1; irAE: Immune-related adverse event; ICI: Immune checkpoint inhibitor; AKI: Acute kidney injury; NSAID: Non-steroidal anti-inflammatory drug; PPI: Proton pump inhibitor; ACEI: Angiotensin-converting enzyme inhibitor; CKD: Chronic kidney disease.