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Immunotherapy can occasionally inflame the kidneys. It usually causes no symptoms and is found when the creatinine on a routine blood test rises. Other causes are looked for first, some medicines may be stopped, immunotherapy is paused, and steroids are given if the immunotherapy is the cause. Some people can later restart.
Acute kidney injury is common on checkpoint inhibitors (up to 20% in observational data) but only about 2 to 5% is caused by the checkpoint inhibitor (ADQI 2026). Tubulointerstitial nephritis is the commonest lesion (80 to 90% of biopsies); glomerular disease is rarer. Pooled-trial incidence is about 2% on PD-(L)1 inhibitors or ipilimumab and 5% on the combination (SITC 2021).
SITC 2021: urinalysis and spot urine protein to creatinine ratio (a normal urinalysis does not exclude nephritis); stop drugs known to cause interstitial nephritis, including NSAIDs and proton pump inhibitors; hold the checkpoint inhibitor at KDIGO stage 1 while reversible causes are treated, restarting if the injury resolves; at stage 2 or 3 or significant proteinuria, withhold and refer urgently to nephrology; strongly consider biopsy. Glucocorticoids are first-line (LE: 3); infliximab or mycophenolate for steroid-refractory nephritis (LE: 4).
ADQI 2026 (abstract): no clinical feature reliably separates ICI-AKI from other causes and biopsy remains the gold standard; starting glucocorticoids within 3 days of diagnosis is associated with more kidney recovery; recurrence after rechallenge is under 20%, and the panel supports cautious rechallenge in selected patients.
Why: The urine helps separate nephritis from glomerular disease, though a normal result does not rule nephritis out.
“Patients with possible ICI-related AKI should have a urinalysis and quantification of proteinuria with a spot urine protein:Cr ratio. It should be noted that normal urinalysis does not exclude TIN.”
Why: These drugs cause the same kidney inflammation and may be the real culprit.
“In cases of potential ICI-related AKI, concomitant medications known to cause TIN (eg, NSAIDs, proton pump inhibitors, and some antibiotics) should be discontinued.”
Why: Most kidney injury in people on immunotherapy has another cause that can be fixed.
“In patients with stage I AKI (Cr increase of >0.3 mg/dL or 1.5–1.9 times baseline), the ICI should be held while the patient undergoes evaluation and treatment of reversible causes (eg, hypovolemia). ICI therapy can be restarted if the AKI resolves.”
Why: Larger falls in kidney function need specialist assessment and often a biopsy.
“Patients with stage II or III AKI (Cr ≥2 times baseline) and/or significant (grade ≥2) proteinuria should have ICIs temporarily withheld and undergo expedited evaluation by a nephrologist.”
Why: No blood or urine test reliably proves the immunotherapy is the cause; a biopsy does.
“Given the lack of specific clinical features for ICI-related AKI, renal biopsy should be strongly considered when feasible, particularly when a plausible alternative etiology for AKI exists or urine studies are suggestive of glomerular disease.”
Why: Most cases respond to steroids, and recovery is better when they start within 3 days of diagnosis.
“The first-line treatment for ICI-related TIN is glucocorticoids”
Why: Earlier steroids were associated with more kidney recovery.
“Early glucocorticoid initiation (within 3 days of ICI-AKI diagnosis versus >3 days after diagnosis) is associated with higher rates of kidney recovery, although optimal dosing and duration remain uncertain.”
Acute Disease Quality Initiative, Journal of the American Society of Nephrology 2026
Why: A second immunosuppressant can rescue kidneys that do not respond to steroids.
“Patients with interstitial nephritis that does not respond to glucocorticoid therapy may receive infliximab or mycophenolate mofetil”
Why: The kidney injury comes back in fewer than 1 in 5 people who restart.
“Recurrent ICI-AKI occurs in fewer than 20% of patients undergoing ICI rechallenge.”
Acute Disease Quality Initiative, Journal of the American Society of Nephrology 2026
How care is usually carried out, read from the guidelines and standards cited. Your own team's protocol and their judgement come first; this page is for understanding it, not for doing it yourself.
SITC 2021 (full text) gives the stepwise protocol: urine studies, stop drugs that cause interstitial nephritis, hold at KDIGO stage 1 and refer at stage 2 or 3, strongly consider biopsy, glucocorticoids first-line (LE: 3), infliximab or mycophenolate if refractory (LE: 4). The ADQI 2026 consensus, the most recent and the only nephrology-led statement, agrees and adds from its abstract that steroids started within 3 days are associated with more recovery, that biopsy is the diagnostic gold standard, and that cautious rechallenge is reasonable in selected patients because recurrence is under 20%. Neither sets a steroid dose or duration with confidence: ADQI says the optimal dosing and duration remain uncertain.
SITC, Journal for ImmunoTherapy of Cancer 2021 · Acute Disease Quality Initiative, Journal of the American Society of Nephrology 2026 · ASCO, Journal of Clinical Oncology 2021 · ESMO, Annals of Oncology 2022
Where it differs: Stages the kidney injury with KDIGO creatinine and urine output criteria, which use both a rise above baseline and absolute thresholds, rather than the CTCAE grade; SITC notes that most trials use CTCAE, which may underestimate kidney injury.
Evidence: Expert consensus.
Where it differs: Allows treatment only after extensive counselling about the high probability of rejection and dialysis dependence, particularly with PD-(L)1 antibodies.
Evidence: LE: 4.
| Recommendation | Grade, as printed | Source |
|---|---|---|
| Glucocorticoids first-line for immune-related interstitial nephritis | LE: 3 | SITC, Journal for ImmunoTherapy of Cancer 2021 |
| Infliximab or mycophenolate mofetil for steroid-refractory interstitial nephritis | LE: 4 | SITC, Journal for ImmunoTherapy of Cancer 2021 |
| Checkpoint inhibitors in kidney transplant recipients only after counselling on rejection risk “Patients with renal allografts may receive ICIs, but only after extensive counseling on the associated risks and high probability of rejection and subsequent dialysis dependence” | LE: 4 | SITC, Journal for ImmunoTherapy of Cancer 2021 |
| Cautious rechallenge in selected patients “these consensus statements provide a framework for diagnosis and management, support cautious ICI rechallenge in selected patients, and identify priorities for future research.” | consensus statement (modified Delphi) | Acute Disease Quality Initiative, Journal of the American Society of Nephrology 2026 |
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Shares Baseline tests and monitoring before and during checkpoint inhibitor treatment, ASCO 2021 guideline: how to recognise and manage the immune-related side effects of checkpoint inhibitors, Society for Immunotherapy of Cancer, Avelumab and the tags protocol, irae.
Shares ASCO 2021 guideline: how to recognise and manage the immune-related side effects of checkpoint inhibitors, Society for Immunotherapy of Cancer, Avelumab, Tremelimumab and the tags protocol, irae.
Shares ASCO 2021 guideline: how to recognise and manage the immune-related side effects of checkpoint inhibitors, Society for Immunotherapy of Cancer, Avelumab, Tremelimumab and the tags protocol, irae.
Shares Baseline tests and monitoring before and during checkpoint inhibitor treatment, ASCO 2021 guideline: how to recognise and manage the immune-related side effects of checkpoint inhibitors, Society for Immunotherapy of Cancer, Avelumab and the tags protocol, irae.
Shares Baseline tests and monitoring before and during checkpoint inhibitor treatment, ASCO 2021 guideline: how to recognise and manage the immune-related side effects of checkpoint inhibitors, Society for Immunotherapy of Cancer, Avelumab and the tags protocol, irae.