Management guidelines for renal irAEs1,2,6
Common renal irAE symptoms
BMS-recommended management guidelines for renal irAEs1,2,6
For suspected irAEs, first exclude other causes
| Grade 1 | Grade 2–3 | Grade 4 | |
|---|---|---|---|
| Definition | Creatinine >ULN and >baseline but ≤1.5× baseline | Creatinine >1.5× to ≤6.0× ULN or
>1.5× baseline |
Creatinine >6.0× ULN |
| Dual NIVO + IPI
or NIVO alone1,6 |
Continue treatment | Grade 2: Withhold treatment
Grade 3 (>3.0–6.0× ULN): Permanently discontinue treatment |
Permanently discontinue treatment |
| Monitoring | Monitor creatinine before treatment and weekly thereafter | Monitor creatinine every 2–3 days | Monitor creatinine daily |
| Consultations | – | Nephrology | |
| Medication | – | 0.5–1 mg/kg/day prednisone equivalents*
If worsening or no improvement: 1–2 mg/kg/day prednisone equivalents |
1–2 mg/kg/day prednisone equivalents** |
| Renal test | – | Consider renal biopsy | |
| Follow-up | If improved to baseline:
Resume routine creatinine monitoring |
If improved to Grade 1:
Taper steroids over ≥1 month before resuming treatment with routine creatinine monitoring* |
If improved to Grade 1:
Taper steroids over ≥1 month** |
| If worsens:
Treat as Grade 2–4 |
If elevations persist >7 days or worsen:
Treat as Grade 3–4 |
– | |
*Consider prophylactic antibiotics for opportunistic infections; **Add prophylactic antibiotics
IPI, ipilimumab; NIVO, nivolumab; ULN, upper limit of normal
International guideline (ASCO, ESMO and NCCN) recommendations for renal irAEs3–5^
^ For detailed guidelines, please refer to original publication
| Grade 1 | Grade 2 | Grade 3 | Grade 4 | |
|---|---|---|---|---|
| Immunotherapy | Continue5
or Consider holding3,4 |
Hold3–5 | Hold4,5
or Permanently discontinue3 |
|
| Monitoring/protein assessment | Weekly creatinine monitoring5 | Repeat creatinine/K+ assessment every 48 hours5 | Repeat creatinine every 24 hours5 | |
| or follow urine protein/creatinine ratio every 3–7 days4 | ||||
| Consultation | Consider nephrology if creatinine remains unchanged over 2 weeks4 | Nephrology consultation3–5 | ||
| Renal work-up | – | Renal ultrasound with or without Doppler if obstruction is suspected5 Consider renal biopsy3–5 before4 or after3 attempting steroids |
||
| Medication | – | Start prednisone or methylprednisolone if other causes are ruled out*
If kidney injury remains Grade >2 after 4–6 weeks of steroids, consider adding additional immunosuppression4:
|
If Grade 3 elevations persist for >3–5 days or worsen, or if Grade 4 elevations persist >2–3 days or worsen, consider additional immunosuppression as Grade 2 or mycophenolate3 | |
| Admission | – | – | Consider inpatient care4
Hospitalisation (Grade 3) or dialysis (Grade 4) indicated3,5 |
|
*Consult steroid and immunosuppression dosing information below for recommendations
FDA, US Food and Drug Administration
Evaluate potential alternative aetiologies and evaluate spot urine protein/creatinine ratio. Consider renal biopsy to confirm diagnosis.4 Reflex kidney biopsy should be discouraged until corticosteroid treatment has been attempted.3 Monitor patients for elevated serum creatinine before every dose3,4 and for AKI.4 Limit or discontinue nephrotoxic medications and dose adjust to creatinine clearance.4 Routine urinalysis is not necessary, except to rule out potential alternative aetiologies such as urinary tract infection, medications, fluid stats3–5 and recent IV contrast.3,4
| ASCO, ESMO, NCCN | |||
|---|---|---|---|
| Grade 1 | Grade 2 | Grade 3 | Grade 4 |
| ASCO & NCCN:
Creatinine 1.5–2.0× above baseline or creatinine increase of ≥0.3 mg/dL ESMO: Creatinine >ULN–1.5x ULN or serum creatinine increase >0.3 mg/dL within 48 hours or 1.5–1.9x baseline |
ASCO & NCCN:
Creatinine 2.0–3.0× above baseline ESMO: Creatinine >1.5–3.0x baseline or >1.5–3.0x ULN or serum creatinine increase to 2–2.9x baseline |
ASCO & NCCN:
Creatinine >3.0× above baseline or >4.0 mg/dL; hospitalisation3 or dialysis4 indicated ESMO: Creatinine >3.0x above baseline or 3.0–6.0x ULN or increase in serum creatinine to 3.0x baseline or to >4.0 mg/dL or initiation of dialysis |
NCCN:
Creatinine >3.0x baseline or >4.0 mg/dL; dialysis indicated ASCO & ESMO: Creatinine >6.0x ULN5 or 6x above baseline3; dialysis indicated3 |
AKI, acute kidney injury; ASCO, American Society of Clinical Oncology; ESMO, European Society for Medical Oncology; IV, intravenous; NCCN, National Comprehensive Cancer Network; ULN, upper limit of normal
| ASCO | ESMO | NCCN | |
|---|---|---|---|
| Grade 2 | Start 0.5–1 mg/kg/day prednisone or equivalent.3–5 For persistent or worsening Grade 2 symptoms beyond a week, start 1–2 mg/kg/day prednisone or methylprednisolone.3,4 If improved to Grade ≤1, taper corticosteroids over at least 4 weeks.3
If no recurrence of chronic renal insufficiency, discuss resumption of ICPI with patient after taking into account the risks and benefits. Resumption of ICPI can be considered once steroids have been successfully tapered to ≤10 mg/d or discontinued.3 If worsening or no improvement, permanently discontinue immunotherapy3,4 |
||
| Grade 3 | Start 1–2 mg/kg/day prednisone or equivalent. Treat until symptoms improve to Grade ≤1 then taper over 4 weeks3 | If worsening, initiate intravenous prednisolone/methylprednisolone 1 mg/kg or pulse dose corticosteroids of 250–500 mg methylprednisolone for 3 days5 | Start 1–2 mg/kg/day prednisone or methylprednisolone4 |
| Grade 4 | |||
ASCO, American Society of Clinical Oncology; ESMO, European Society for Medical Oncology; ICPI, immune checkpoint inhibitor; irAE, immune-related adverse event; NCCN, National Comprehensive Cancer Network
ASCO, American Society of Clinical Oncology; ESMO, European Society for Medical Oncology; irAE, immune-related adverse event; NCCN, National Comprehensive Cancer Network
References:
- OPDIVO® (nivolumab) Product Information, BMS Hong Kong.
- Bristol Myers Squibb. Immune-Related Adverse Reaction (irAR) Management Guide. 1506AU2002148-01. April 2020.
- Schneider BJ, et al. J Clin Oncol 2021;39:4073–4126. Available at: https://ascopubs.org/doi/full/10.1200/JCO.21.01440. Accessed March 2023.
- National Comprehensive Cancer Network. NCCN Clinical Practice Guidelines in Oncology. Management of immunotherapy-Related Toxicities. Version 1.2022. Available: https://www.nccn.org/professionals/physician_gls/pdf/immunotherapy.pdf. Accessed 13 February 2022.
- Haanen J, et al. Ann Oncol 2022;33:1217–1238. Available at: https://www.annalsofoncology.org/article/S0923-7534(22)04187-4/fulltext. Accessed March 2023.
- YERVOY® (ipilimumab) Product Information, BMS Hong Kong.
