Table 3.
Summary of clinical characteristics of patients with immune checkpoint inhibitor–associated AKI
| Reference | n | Centers, n | Drugs Received | AKI Criteria | Time to AKI, wka | Concomitant ATIN Medications, n (%) | Combined Therapyb, n (%) | Concomitant or Prior Extrarenal irAEs, n (%) | Pyuria or WBC Casts, n (%) | Biopsy, n (%) | ATIN, n (%) |
| Shirali et al. (16) | 6 | 1 | Nivo, n=3; Pembro, n=2; Ipi and Nivo, n=1 | Biopsy-proven ATIN | 40 | PPIs, n= 33 (83);NSAIDs, n=2 (33) | 1 (17) | 3 (50)c | 5 (83) | 6 (100) | 6 (100) |
| Cortazar et al. (15) | 13 | 7 | Ipi, n=6; Nivo, n=1; Pembro, n=2; Ipi and Nivo, n=4 | Biopsy-proven AKI | 13 | PPIs, n=6 (46);NSAIDs, n=1(8) | 4 (31) | 8 (62)d | 8 (62) | 13 (100) | 12 (92) |
| Izzedine et al. (17) | 12 | 1 | Pembro, n=12 | Biopsy-proven AKI | 36 | 0 | 0e | NR | 4 (33) | 12 (100) | 4 (33) |
| Mamlouk et al. (28) | 16 | 1 | Nivo, n=6; Pembro, n=6; Atezo, n=1; Treme, n=1; Ipi and Nivo, n=2 | Biopsy-proven AKI; AKIN criteria | 14 | PPIs, n=9 (56)NSAIDs, n=3 (19) | 13 (81) | 9 (56)f | 7 (44) | 16 (100) | 14 (88) |
| Seethapathy et al. (20) | 30 | 1 | Ipi, n=12; Nivo, n=9; Pembro, n=7; Durva, n=1; Ipi and Nivo, n=1; | SCr ≥1.5× baseline for ≥3 d; expert adjudicated | 15 | PPIs, n=23 (77);NSAIDs, n=13 (43) | 3 (10) | 26 (87)g | 13 (43) | 1 (3) | 1 (100) |
| Cortazar et al. (21) | 138 | 18 | Nivo, n=40; Pembro, n=47; Durva and pembro, n=1; Ipi, n=4; Atezo, n=5; Ipi and nivo, n=32; Ipi and pembro, n=6; Other combination tx, n=3 | SCr ≥2× baseline or need for RRT | 14 | PPIs, n=75 (54)NSAIDs, n=30 (22) | 28 (20) | 59 (43)h | 76 (55) | 60 (43) | 56 (93) |
| Totali | 215 | Nivo, n=59; Pembro, n=76; Atezo, n=6; Durva, n=1; Ipi, n=22; Treme, n=1; Any combination tx, n=50 | — | 16 | PPIs, n=146 (68)NSAIDs, n=49 (23) | 49 (23) | 105 (49) | 113 (53) | 108 (61) | 93 (91) |
ATIN, acute tubulointerstitial nephritis; irAEs, immune-related adverse events; WBC, white blood cell; nivo, nivolumab; pembro, pembrolizumab; ipi, ipilimumab; PPI, proton pump inhibitor; NSAID, nonsteroidal anti-inflammatory drug; NR, not recorded; atezo, atezolizumab; treme, tremelimumab; AKIN, Acute Kidney Injury Network (70); durva, durvalumab; SCr, serum creatinine; tx, treatment.
From immune checkpoint inhibitor initiation, mean or median.
This refers to combination therapy with a cytotoxic T lymphocyte–associated protein 4 inhibitor and a programmed cell death protein 1 (PD-1)/PD-ligand 1 inhibitor.
Two patients with hypophysitis; one patient with concomitant rash.
Seven patients had an irAE preceding AKI onset, one had one concomitantly.
All patients were treated with pembrolizumab, although one patient had received ipilimumab in the past.
Five irAEs before diagnosis; three at the time of diagnosis; one after the diagnosis.
Concurrent irAEs; thyroiditis most common, occurring in 13 patients.
Concurrent or prior irAE; rash most common.
Weighted average, based on number of patients in each study.