Clinicopathological Features of Kidney Injury Related to Immune Checkpoint Inhibitors: A Systematic Review
Abstract
1. Introduction
2. Materials and Methods
2.1. Search Strategy and Selection Criteria
2.2. Data Extraction and Quality Assessment
2.3. Statistical Analyses
3. Results
3.1. Clinical Characteristics of Patients with ICI-Kidney IRAEs
3.2. Treatment and Outcome of Patients with ICI-Kidney IRAEs
3.3. Pooled Individual Analysis of Patients with ICI-Associated Kidney IRAEs
3.4. Immunohistochemical Staining of Biopsied Kidney Tissues
4. Discussion
5. Conclusions
Supplementary Materials
Author Contributions
Funding
Data Availability Statement
Acknowledgments
Conflicts of Interest
References
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Total (n = 384) | Cohort (n = 163) | Case (n = 221) | |
---|---|---|---|
Age (year) | 67 (59.73) | NA | 67 (59.73) |
Male [n/N(%)] | 261/384 (68.0) | 108/163 (66.3) | 153/221 (69.2) |
Hypertension [n/N(%)] | 151/305 (49.5) | 75/148 (50.7) | 76/157 (48.4) |
Diabetics [n/N(%)] | 44/307 (14.3) | 17/148 (11.5) | 27/159 (17.0) |
CKD [n/N(%)] | 60/219 (27.4) | 19/60 (31.7) | 41/159 (25.8) |
CHD [n/N(%)] | 20/222 (9.0) | 5/63 (7.9) | 15/159 (9.4) |
Tumor type | |||
Melanoma [n/N(%)] | 150/384 (39.0) | 63/163 (38.7) e | 87/221 (39.4) |
Lung cancer [n/N(%)] | 110/384 (28.6) | 54/163 (33.1) e | 56/221 (25.3) |
Renal cancer [n/N(%)] | 29/324 (9.0) | 8/103 (7.8) | 21/221 (9.5) |
Hematologic cancer a [n/N(%)] | 13/324 (4.0) | 2/103 (1.9) | 11/221 (5.0) |
Others b [n/N(%)] | 57/324 (17.6) | 11/103 (10.7) | 46/221 (20.8) |
ICI type | |||
PD-1/PD-L1 [n/N(%)] | 281/372 (75.5) | 129/163 (79.1) | 152/209 (72.8) |
CTLA-4 [n/N(%)] | 22/372 (5.9) | 6/163 (3.7) | 16/209 (7.7) |
Combination c [n/N(%)] | 69/372 (18.5) | 28/163 (17.2) | 41/209 (19.6) |
Other treatment | |||
Only ICI [n/N(%)] | 249/282 (88.3) | 94/102 (92.1) | 155/180 (86.1) |
ICI+ targeted therapy [n/N(%)] | 8/282 (2.8) | 1/102 (1.0) | 7/180 (3.9) |
ICI+ chemotherapy [n/N(%)] | 20/282 (7.1) | 5/102 (4.9) | 15/180 (8.3) |
ICI+VEGF [n/N(%)] | 5/282 (1.8) | 2/102 (2.0) | 3/180 (1.7) |
Interval time (d) | 105 (59,210) | NA | 105 (59,210) |
PPI [n/N(%)] | 123/272 (45.2) | 71/137 (51.8) | 52/135 (38.5) |
NSAIDs [n/N(%)] | 36/213 (16.9) | 9/78 (11.5) | 27/135 (20.0) |
Baseline SCr (mg/dl) | 1.0 (0.8,1.2) | NA | 1.0 (0.8,1.2) |
Peak SCr (mg/dl) | 3.9 (2.5,5.9) | NA | 3.9 (2.5,5.9) |
AKD [n/N(%)] | 363/384 (94.5) | 162/163 (99.4) | 201/221 (91.0) |
AKD grade | |||
1 grade [n/N(%)] | 25/179 (14.0) | NA | 25/179 (14.0) |
2 grade [n/N(%)] | 31/179 (17.3) | NA | 31/179 (17.3) |
3 grade [n/N(%)] | 146/242 (60.3) | 23/63 (36.5) f | 123/179 (68.7) |
Only proteinuria [n/N(%)] | 21/384 (5.5) | 1/163 (0.6) | 20/221 (9.0) |
Extrarenal IRAE [n/N(%)] | 117/340 (34.4) | 53/134 (39.6) | 64/206 (31.1) |
Skin [n/N(%)] | 36/340 (10.0) | 14/134 (10.4) g | 22/206 (10.7) |
Gastrointestinal [n/N(%)] | 30/284 (10.6) | 9/78 (11.5) | 21/206 (10.2) |
Endocrine [n/N(%)] | 22/284 (6.5) | 5/78 (6.4) | 17/206 (8.3) |
Pneumonitis [n/N(%)] | 10/340 (2.9) | 3/134 (2.2) g | 7/206 (3.4) |
Others d [n/N(%)] | 31/284 (4.6) | 1/78 (1.3) | 12/206 (5.8) |
Total (n = 384) | Cohort (n = 163) | Case (n = 221) | |
---|---|---|---|
ATIN/AIN [n/N(%)] | 277 (72.3) | 134 | 143 a |
ATIN [n/N(%)] | 191 (49.9) | 121 | 70 |
AIN [n/N(%)] | 86 (22.5) | 13 | 73 |
Total ATN [n/N(%)] | 29 (7.6) | 18 | 11 |
ATN alone [n/N(%)] | 23 (6.0) | 17 | 6 |
ATN with glomerular injury [n/N(%)] | 6 (1.6) | 1 | 5 |
Glomerular injury [n/N(%)] | 54 (14.1) | 8 | 46 b |
Podocyte injury [n/N(%)] | 23 (6.0) | 4 | 19 |
FSGS [n/N(%)] | 8 (2.1) | 1 | 7 |
MCD [n/N(%)] | 15 (3.9) | 3 | 12 |
IgA nephropathy [n/N(%)] | 8 (2.1) | 0 | 8 |
MN [n/N(%)] | 11 (2.9) | 1 | 10 |
GN [n/N(%)] | 15 (3.9) | 3 | 12 |
Crescent GN [n/N(%)] | 2 (0.5) | 0 | 2 |
C3 GN [n/N(%)] | 3 (0.8) | 1 | 2 |
Immune-mediated GN [n/N(%)] | 5 (1.3) | 0 | 5 |
Unclassed GN [n/N(%)] | 5 (1.3) | 2 | 3 |
Systematic disease [n/N(%)] | 42 (10.9) | 3 | 39 c |
Vasculitis/ANCA vasculitis [n/N(%)] | 18 (4.7) | 2 | 16 |
Anti-GBM disease [n/N(%)] | 4 (1.0) | 1 | 3 |
TMA [n/N(%)] | 8 (2.1) | 0 | 8 |
AA amyloidosis [n/N(%)] | 5 (1.3) | 0 | 5 |
Renal graft rejection [n/N(%)] | 7 (1.8) | 0 | 7 |
Lupus nephritis [n/N(%)] | 1 (0.3) | 0 | 1 |
Total (n = 384) | Cohort (n = 163) | Case (n = 221) | |
---|---|---|---|
Corticosteroid [n/N(%)] | 342/384 (89.1) | 138/163 (84.7) | 204/221 (92.3) |
Intravenous corticosteroid [n/N(%)] | 76/289 (26.3) | 18/88 (20.5) | 58/201 (28.9) |
Dose (mg/d) | 500 (225,1000) | NA | 500 (225–1000) |
Pulse steroid therapy [n/N(%)] | 31/43 (72.1) | NA | 31/43 (72.1) |
Dose (mg/d) | 701 ± 262 | NA | 701 ± 262 |
Oral corticosteroid (mg/kg/d) | 1.0 (0.8,1.0) | NA | 1.0 (0.8–1.0) |
Low-dose (<0.5 mg/kg/d) | 18/136 (13.2) | NA | 18/136 (13.2) |
Moderate-dose (0.5–1.0 mg/kg/d) | 99/136 (72.8) | NA | 99/136 (72.8) |
High-dose (>1.0 mg/kg/d) | 19/136 (14.0) | NA | 19/136 (14.0) |
Immunosuppressants [n/N(%)] | 49/351 (14.0) | 7/148 (4.7) | 42/203 (20.7) a |
Infliximab [n/N(%)] | 12/351 (3.4) | NA | 12/203 (5.6) |
Rituximab [n/N(%)] | 15/351 (4.3) | NA | 15/203 (7.4) |
MMF [n/N(%)] | 11/351 (3.1) | NA | 11/203 (5.4) |
Others [n/N(%)] | 7/351 (2.0) | NA | 7/203 (3.5) |
Discontinued ICI [n/N(%)] | 322/336 (95.8) | 139/145 (95.9) | 183/191 (95.8) |
RRT [n/N(%)] | 42/292 (14.4) | 7/90 (7.8) | 35/202 (17.3) |
Disruption of RRT [n/N(%)] | 14/36 (38.9) | 1/2 (50.0) | 13/34 (38.2) |
Recovery SCr level (mg/dl) | 1.5 (1.1,1.8) | NA | 1.5 (1.1,1.8) |
Protein remission [n/N(%)] | 16/20 (80.0) | NA | 16/20 (80.0) |
Renal function recovery | |||
Complete recovery [n/N(%)] | 129/311 (41.5) | 56/143 (39.2) b | 73/168 (43.5) |
Partial recovery [n/N(%)] | 123/287 (42.9) | 59/119 (49.6) | 64/168 (38.1) |
No recovery [n/N(%)] | 48/287 (16.7) | 17/119 (14.3) | 31/168 (18.5) |
Death [n/N(%)] | 36/252 (14.3) | 8/90 (8.9) | 28/162 (17.3) |
Tumor response | |||
DCR [n/N(%)] | 52/93 (55.9) | NA | 52/93 (55.9) |
Complete response [n/N(%)] | 14/93 (15.1) | NA | 14/93 (15.1) |
Partial response [n/N(%)] | 14/93 (15.1) | NA | 14/93 (15.1) |
Stable [n/N(%)] | 24/93 (25.8) | NA | 24/93 (25.8) |
Progression [n/N(%)] | 41/93 (44.1) | NA | 41/93 (44.1) |
Rechallenge [n/N(%)] | 41/190 (21.7) | 18/84 (21.4) | 23/106 (21.7) |
Flare [n/N(%)] | 10/39 (25.6) | 1/18 (5.6) | 9/21 (42.9) |
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Xu, L.-Y.; Zhao, H.-Y.; Yu, X.-J.; Wang, J.-W.; Zheng, X.-Z.; Jiang, L.; Wang, S.-X.; Liu, G.; Yang, L. Clinicopathological Features of Kidney Injury Related to Immune Checkpoint Inhibitors: A Systematic Review. J. Clin. Med. 2023, 12, 1349. https://doi.org/10.3390/jcm12041349
Xu L-Y, Zhao H-Y, Yu X-J, Wang J-W, Zheng X-Z, Jiang L, Wang S-X, Liu G, Yang L. Clinicopathological Features of Kidney Injury Related to Immune Checkpoint Inhibitors: A Systematic Review. Journal of Clinical Medicine. 2023; 12(4):1349. https://doi.org/10.3390/jcm12041349
Chicago/Turabian StyleXu, Ling-Yi, Hai-Ya Zhao, Xiao-Juan Yu, Jin-Wei Wang, Xi-Zi Zheng, Lei Jiang, Su-Xia Wang, Gang Liu, and Li Yang. 2023. "Clinicopathological Features of Kidney Injury Related to Immune Checkpoint Inhibitors: A Systematic Review" Journal of Clinical Medicine 12, no. 4: 1349. https://doi.org/10.3390/jcm12041349
APA StyleXu, L.-Y., Zhao, H.-Y., Yu, X.-J., Wang, J.-W., Zheng, X.-Z., Jiang, L., Wang, S.-X., Liu, G., & Yang, L. (2023). Clinicopathological Features of Kidney Injury Related to Immune Checkpoint Inhibitors: A Systematic Review. Journal of Clinical Medicine, 12(4), 1349. https://doi.org/10.3390/jcm12041349