Predictors of Acute Kidney Injury in Patients Prescribed Immune Checkpoint Inhibitor Therapy and Their Association with Death: A Systematic Review and Meta-Analysis

Immune checkpoint inhibitors (ICIs) are a novel and promising anti-cancer therapy. We conducted this systematic review to precisely quantify the occurrence and development for actue kidney injury(AKI) following ICIs treatment for cancer. We conducted a search of the PubMed, Embase, Web of Science, and Cochrane Library databases. Twenty-nine studies, comprising 24,953 cancer patients who received ICIs were finally eligible. The incidence of AKI was 16.2% (95%CI:12.8%-19.8%); the incidence of immune checkpoint inhibitor-associated acute kidney injury (ICPi-AKI) was 3.1%(95%CI:2.4%-4%); the incidence of non-ICPi-AKI was 11.2%(95%CI:8.4%-14.3%), and the incidence of sustained AKI was 14.9%(95%CI:7.5%-24.3%). Patients who developed AKI (HR = 1.521(95%CI:1.208-1.916)) and ICPi-AKI (HR = 1.407(95%CI:1.059-1.869)) exhibited an elevated risk of all-cause mortality. An increased risk for AKI was observed with preexisting chronic kidney disease (CKD) and combined with other extrarenal immune-related adverse events (irAEs). The use of nonsteroidal anti-inflammatory drugs (NSAIDs), proton pump inhibitor (PPI), diuretic, renin-angiotensin-aldosterone system (RAASi), antibiotics and fluidone was also significantly associated with incident AKI. Combined therapy had a greater impact on renal injury compared to monotherapy. Patients using ipilimumab were more prone to developing AKI, compared to those using nivoluma. CTLA4 (ref'PD-1) was associated with a higher likelihood of sustained AKI. The use of PDL-1(ref='PD-1) was linked to an increased susceptibility to ICPi-AKI. The occurrence of AKI was intricately linked to specific complications, the concomitant use of certain medications, and the specific regimen of ICIs. This deserves our attention.