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CHECKPOINT-INHIBITOR TOXICITY

Kidney immune-related adverse events

Acute tubulointerstitial nephritis dominates; glomerular lesions and electrolyte disturbances are increasingly reported.

The atlas covers kidney irAEs in depth elsewhere; this card is the organ-indexed view of the same content. Educational reference, not medical advice.

Anchored on the ASCO and ESMO chapters for this organ. Every source is named beside the position it supports, and labelled with what kind of source it is.

At a glance

ICI-associated acute tubulointerstitial nephritis

Also called: ICI-AKI · ICI-AIN · checkpoint inhibitor nephritis · immune checkpoint nephritis

The dominant kidney irAE: steroid-responsive interstitial nephritis presenting weeks to months into therapy, often with a concomitant AIN-inducing drug on board.

uncommonseriousonset: month 3 onward

Reported frequency

  • 2-5% — any-grade ICI-AKI incidence

    of patients treated with ICIs · ICI-treated oncology patients, as synthesized in a nephrology review — a summary assertion with no denominator, which is why it is carried at review weight beside the pooled figure below

    narrative review · 36168055

  • 1.4% (95% CI 1.0-2.1%), incidence rate 4.3 per 100 patient-years (95% CI 2.3-6.3) — pooled one-year incidence of ICI-associated AKI

    of 10,726 participants across 16 studies · Systematic review and meta-analysis. Materially lower than the 2-5% carried above, which is a review's summary assertion with no denominator — both are shown rather than reconciled

    pooled meta-analysis · 41026215

Onset

Median 14 weeks from ICI initiation, IQR 6-37 weeks — the interquartile range alone spans early-weeks to late-months presentation, so a late AKI does not argue against the diagnosis.

Presentation

  • · Subnephrotic proteinuria in most patients
  • · Pyuria in approximately half
  • · Rise in serum creatinine, frequently while an AIN-inducing co-medication is in use

Differential

  • · Alternative causes of AKI — prerenal, obstructive, and other nephrotoxic exposures — which every anchor guideline requires be excluded first
  • · AIN attributable to a concomitant drug rather than the ICI: 69% of patients in the multicenter cohort were concurrently receiving a potential tubulointerstitial-nephritis-causing medication

Work-up

  • Serum creatinine trend against baseline · All patients

    Establishes the CTCAE grade that indexes every management step below.

  • Urinalysis with microscopy and urine protein-to-creatinine ratio · All patients

    Subnephrotic proteinuria and pyuria are the reported urinary phenotype.

    31896554

  • Review of concomitant AIN-inducing medications (PPIs, NSAIDs) · All patients

    Stopping them is part of the intervention, not only the differential. In the multicentre cohort 69% were concurrently receiving a potential tubulointerstitial-nephritis-causing medication.

    31896554

  • Kidney biopsy · Grade 2+

    Confirms interstitial nephritis versus an alternative lesion and informs treatment. The cited source scopes this to moderate-to-severe disease in words, not to a numeric grade — the grade threshold below is this atlas's reading of that phrase, not a quoted one.

    36168055

Grade ladder

Grade 1

Continue the ICIOutpatient

Grade 1 — creatinine 1.5-2.0x above baseline (CTCAE v5.0, Acute kidney injury).

No corticosteroid at this grade

ESMO permits continuing the ICI with monitoring at stage 1 AKI; the intervention at this rung is exclusion of alternative causes and withdrawal of concomitant nephrotoxins, not immunosuppression.

  • · Exclude alternative etiologies of AKI
  • · Stop concomitant nephrotoxins (PPIs, NSAIDs) where possible

Escalate when: Creatinine rising to grade 2, or failure to improve after nephrotoxin withdrawal.

Grade 2

Hold the ICIOutpatient

Grade 2 — creatinine >2.0-3.0x above baseline (CTCAE v5.0, Acute kidney injury).

Corticosteroid 0.5–1 mg/kg/day (oral)

Taper over 4–6 weeks or longer, starting once: Creatinine improving toward baseline.

No step size or interval is carried: the source guideline states a total window and a response marker, and does not specify a cadence.

  • · Exclude alternative causes before attributing the event to the ICI
  • · Stop concomitant AIN-inducing medications

Sources differ here

Grade definition

  • MD Anderson Cancer Center, Department of Clinical Effectiveness V3 (institutional, approved 06/2026) (institutional protocol) — Grade 2 (G2): creatinine > 1.5-3 times above the baseline. A patient at 1.8x baseline is grade 1 by CTCAE and grade 2 here — and grade 2 is where the ICI is held and corticosteroids start.
  • CTCAE v5.0 (standard grading vocabulary) — Grade 2 — creatinine >2.0-3.0x above baseline. CTCAE v5.0 'Acute kidney injury', which is the vocabulary this entry's ladder is written in and which no cited guideline chapter reproduces.

Taper

  • ASCO 2021 (society guideline) — tapered over 4-6 weeks once creatinine improves
  • MD Anderson Cancer Center, Department of Clinical Effectiveness V3 (institutional, approved 06/2026) (institutional protocol) — Once SCr starts to improve, start taper over 2-4 weeks.

Escalate when: No creatinine improvement on steroids, or progression to grade 3.

Grade 3

Hold — consider permanent discontinuationConsider admission

Grade 3 — creatinine >3.0x baseline or >4.0 mg/dL (CTCAE v5.0, Acute kidney injury).

Corticosteroid 1–2 mg/kg/day (oral)

Taper over 4–6 weeks or longer, starting once: Creatinine improving toward baseline.

No step size or interval is carried: the source guideline states a total window and a response marker, and does not specify a cadence.

Second line

  • Infliximab, added to glucocorticoids — Steroid-refractory or relapsed disease. In a 55-patient comparative series the advantage was tied to timing — infliximab started within 30 days of steroids shortened time to renal response — and it did not translate into a progression-free survival difference. An earlier 10-patient series had two patients with no improvement at all.Contraindicated in hepatic impairment, heart failure, and tuberculosis exposure; screen for latent TB and hepatitis B before the first dose.
  • Mycophenolate mofetil — Glucocorticoid-refractory disease, and — in the one reported case where steroids were contraindicated by concurrent ICI-induced diabetes — as first-line therapy instead of them. The evidence here is two single case reports, not a series: it establishes that the drug has been used successfully in this indication, and nothing about how often it works.
  • · Nephrology involvement
  • · Stop concomitant AIN-inducing medications

Escalate when: Steroid-refractory disease or progression to dialysis requirement.

Grade 4

Discontinue permanentlyAdmit

Grade 4 — life-threatening renal impairment, including dialysis requirement. The anchor guideline treats grade 3-4 as one dosing band but separates the discontinuation decision, which is why this rung repeats the grade 3 dose and diverges on ICI action.

Corticosteroid 1–2 mg/kg/day (oral)

Taper over 4–6 weeks or longer, starting once: Creatinine improving toward baseline.

No step size or interval is carried: the source guideline states a total window and a response marker, and does not specify a cadence.

Second line

  • Infliximab, added to glucocorticoids — Steroid-refractory or relapsed disease. In a 55-patient comparative series the advantage was tied to timing — infliximab started within 30 days of steroids shortened time to renal response — and it did not translate into a progression-free survival difference. An earlier 10-patient series had two patients with no improvement at all.Contraindicated in hepatic impairment, heart failure, and tuberculosis exposure; screen for latent TB and hepatitis B before the first dose.
  • Mycophenolate mofetil — Glucocorticoid-refractory disease, and — in the one reported case where steroids were contraindicated by concurrent ICI-induced diabetes — as first-line therapy instead of them. The evidence here is two single case reports, not a series: it establishes that the drug has been used successfully in this indication, and nothing about how often it works.
  • · Nephrology involvement
  • · Renal replacement therapy where indicated
  • · Pooled analysis found no additional benefit from combining intravenous with oral steroids (OR 0.928, P = 0.863), which is why no pulse regimen is carried on this rung

Escalate when: Already the top rung — failure to recover carries the prognostic weight below.

Rechallenge

individualized

Roughly a quarter of rechallenged patients in the multicenter cohort developed recurrent ICI-associated AKI, and a single-center series records both uneventful rechallenges and one recurrence with a fatal extra-renal event. The decision turns on recovery, severity and whether an effective alternative therapy exists.

  • 23% — recurrent ICI-associated AKI after rechallenge

    of patients rechallenged with an ICI after ICI-associated AKI · Multicenter cohort of 138 patients with ICI-associated AKI, 22% of whom were rechallenged

    cohort · 31896554

  • · Kidney function recovered, and the degree of recovery explicitly weighed
  • · Co-management with nephrology
  • · Concomitant AIN-inducing drugs stopped and kept off

Deliberately not carried

  • gradeThreePlus — No cited source in this repo reports the grade 3+ share of ICI-AKI as a separate figure. Omitted rather than derived from the recovery distribution, which measures something else.
  • mortality — The multicenter cohort reports that failure to achieve kidney recovery was independently associated with higher mortality, but states no case-fatality rate. A rate would have to be invented, so none is carried.
  • agentClassSkew — Combination ICI therapy was reported as an independent risk factor for developing ICI-AKI, but that is a risk-factor association rather than a measured class-stratified incidence, so it is not entered as a skew framing.
  • secondLine — mycophenolate dose — Mycophenolate is carried as an agent on the evidence of two single case reports, but NO dose is encoded. The only schedule available is an institutional protocol's (500 mg every 12 hours titrated over 2 weeks to 1 g every 12 hours, maximum 3 months), and an institutional protocol may not set a number alone. There is no society position on a renal mycophenolate dose to place beside it, so it cannot even be carried as a divergence — a divergence needs two voices. This row previously asserted that no second-line agent at all was supported here, which became false once the infliximab and mycophenolate evidence was verified.
  • ladder[].gradeDefinition — The bands are CTCAE v5.0 'Acute kidney injury' as named, not a quotation from any cited guideline — no anchor chapter carried here reproduces the CTCAE table, and CTCAE is not a PubMed record. Named explicitly because the previous strings were unsourced prose: grade 1 read 'creatinine rise above baseline without meeting grade 2 criteria', which graded a 1.2x rise as grade 1 and routed it to a rung that continues the ICI, when CTCAE puts 1.2x below grade 1 entirely.
  • ladder[].steroid.taper step cadence — The ASCO recommendation gives a total window and a response marker — tapered over 4-6 weeks once creatinine improves — and no step size or interval. Earlier drafts carried 25% every 1-2 weeks, which came from the beta taper planner's illustrative 'e.g. by ~25% every 1-2 weeks' rather than from the cited recommendation. Nulled rather than re-attributed: no anchor guideline states a cadence for any organ.

Sources

  • Cortazar FB, et al. (2020) Clinical Features and Outcomes of Immune Checkpoint Inhibitor-Associated AKI: A Multicenter Study.Cited for: Onset window, dominant histology, recovery distribution and rechallenge recurrence in ICI-associated AKI.Supporting text: the PubMed abstract (checkable at the link above)
  • Sprangers B, Leaf DE, Porta C, Soler MJ, Perazella MA (2022) Diagnosis and management of immune checkpoint inhibitor-associated acute kidney injury.Cited for: Incidence of ICI-AKI among ICI-treated patients, steroid responsiveness, and the biopsy threshold.Supporting text: the PubMed abstract (checkable at the link above)
  • Manohar S, et al. (2020) Acute Interstitial Nephritis and Checkpoint Inhibitor Therapy: Single Center Experience of Management and Drug Rechallenge.Cited for: Stopping concomitant AIN-inducing drugs alongside the ICI hold, and small-series rechallenge outcomes.Supporting text: the PubMed abstract (checkable at the link above)
  • Rao Ullur A, Côté G, Pelletier K, Kitchlu A (2023) Immunotherapy in oncology and the kidneys: a clinical review of the evaluation and management of kidney immune-related adverse events.Cited for: AIN as the most frequent kidney irAE, with glomerular and electrolyte phenotypes increasingly reported.Supporting text: the PubMed abstract (checkable at the link above)
  • Schneider BJ, et al. (2021) Management of Immune-Related Adverse Events in Patients Treated With Immune Checkpoint Inhibitor Therapy: ASCO Guideline UpdateParaphrase, not a quotation — this atlas’s condensation of the recommendationCited for: Grade-indexed hold, steroid dose and taper for ICI-related nephritis/AKI. RENAL SCOPE ONLY (D-STEROID).Supporting text: this atlas's condensation
  • Haanen J, et al. (2022) Management of toxicities from immunotherapy: ESMO Clinical Practice Guideline for diagnosis, treatment and follow-upParaphrase, not a quotation — this atlas’s condensation of the recommendationCited for: Excluding alternative causes, stopping concomitant nephrotoxins, and continuing the ICI at stage 1 AKI.Supporting text: this atlas's condensation
  • Herrmann SM, Abudayyeh A, Gupta S, Gudsoorkar P, Klomjit N, Motwani SS, Karam S, et al. (2025) Diagnosis and management of immune checkpoint inhibitor-associated nephrotoxicity: a position statement from the American Society of Onco-nephrology.Cited for: The existence and scope of a subspecialty society consensus statement on ICI nephrotoxicity. Cited for scope only — the per-claim practice points are in the full text, which is not reachable here.Supporting text: the PubMed abstract (checkable at the link above)
  • Youssef N, Habeeb M, Chen H, Alhamal Z, Mamlouk O, Lin H, Page V, et al. (2025) Infliximab for Grade III or IV Immune Checkpoint Inhibitor Nephritis Clinical and Translational Evidence.Cited for: Infliximab added to glucocorticoids in stage III-IV ICI-AIN: comparative design, the timing that mattered, and the limits of what was shown.Supporting text: the PubMed abstract (checkable at the link above)
  • Lin JS, Mamlouk O, Selamet U, Tchakarov A, Glass WF, Sheth RA, Layman RM, et al. (2021) Infliximab for the treatment of patients with checkpoint inhibitor-associated acute tubular interstitial nephritis.Cited for: The earlier, smaller series behind infliximab in CPI-ATIN, including how many patients did not respond.Supporting text: the PubMed abstract (checkable at the link above)
  • Moku P, Bakow B, Muthiah A, Birkenbach M, Austin M (2023) Steroid Refractory Immune Checkpoint Induced Acute Interstitial Nephritis Salvaged by Mycophenolate Mofetil.Cited for: Mycophenolate as salvage in glucocorticoid-refractory ICI-associated acute interstitial nephritis. A single case.Supporting text: the PubMed abstract (checkable at the link above)
  • Jessel S, Austin M, Kluger HM (2021) Mycophenolate as Primary Treatment for Immune Checkpoint Inhibitor Induced Acute Kidney Injury in a Patient with Concurrent Immunotherapy-Associated Diabetes: A Case Report.Cited for: Mycophenolate as FIRST-LINE therapy for ICI-associated AKI in the specific case where corticosteroids are contraindicated. A single case.Supporting text: the PubMed abstract (checkable at the link above)
  • Ho CW, Kang NW, Yeh TH, Chuang MH, Tsai WW, Wang HY, Wu VC, Pan HC, Chen JY (2025) Immune checkpoint inhibitors-associated acute kidney injury: a systematic review and meta-analysis of incidence, kidney recovery, and recurrent risk.Cited for: Pooled incidence of ICI-AKI with a stated denominator, the benefit of corticosteroids on kidney recovery, the absence of added benefit from combining intravenous with oral steroids, and pooled recurrence after rechallenge.Supporting text: the PubMed abstract (checkable at the link above)

Educational use only. Educational synthesis of the published literature — not a treatment protocol, dosing guide, or medical advice. Regimens and agents shown are illustrative of what the literature describes; verify against current guidelines (ASON / KDIGO / ASCO / NCCN) and individualize to the patient. Using this site creates no clinician–patient relationship.

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