Immune Checkpoint Inhibitors

Acute Interstitial Nephritis — representative incidence ~3% (2–5% range across studies).

ICI-associated AKI ~2–5% (higher with combination therapy); ~93% of biopsies show interstitial nephritis.

Source: Cortazar et al., JASN 2020

Reported injury signatures: Acute Interstitial Nephritis, Glomerular Injury / Proteinuria, Electrolyte Disturbance.

1. Acute Interstitial NephritisPrimary
2. Glomerular Injury / ProteinuriaSecondary
3. Electrolyte DisturbanceSecondary

Delayed (>6 weeks / cumulative) — Delayed — a median of about 14 weeks after starting therapy.

Rechallenge: Case-by-case — In the multicenter ICI-AKI cohort ~22% were rechallenged and ~23% of those developed recurrent AKI — feasible but an individualized, co-managed decision.

• Combination ICI therapy
• Lower baseline eGFR
• Concurrent PPI / AIN-associated drugs

• Review and avoid concurrent AIN-causing drugs

• Check serum creatinine before every infusion — ICI-AIN often presents as an asymptomatic creatinine rise weeks to months into therapy, classically later than skin/GI/thyroid irritis
• Screen urinalysis for new pyuria/sterile leukocyturia and sub-nephrotic proteinuria; eosinophiluria is insensitive and should not be relied on
• Review the concurrent med list at each visit for PPIs, NSAIDs, and antibiotics — these are strongly associated with ICI-AIN and are potential confounding AIN triggers to stop
• Track for concurrent extra-renal immune-related adverse events (colitis, hepatitis, thyroiditis, dermatitis), which frequently co-occur and support an immune-mediated etiology
• Monitor creatinine response within days to 1-2 weeks of starting corticosteroids; failure to improve should prompt biopsy reconsideration and steroid escalation

• CheckMate 067 (nivolumab +/- ipilimumab in melanoma) — defined the higher immune-related toxicity burden of combination CTLA-4/PD-1 blockade, including nephritis, versus monotherapy
• KEYNOTE-189 / KEYNOTE-407 (pembrolizumab-chemotherapy in NSCLC) — registrational combination trials in which AKI/nephritis was more frequent with the ICI-plus-platinum-pemetrexed arms, highlighting combination nephrotoxicity
• Cortazar et al., Kidney Int 2016 — first multicenter clinicopathologic series of ICI-associated AKI establishing acute interstitial nephritis as the dominant lesion and steroid responsiveness
• Cortazar et al., J Am Soc Nephrol 2020 — large multicenter ICI-AKI cohort defining risk factors (PPI use, combination ICI, lower baseline eGFR) and that most patients recover renal function with steroids

• AIN is by far the dominant ICI renal lesion; glomerular lesions (minimal change, pauci-immune/ANCA GN, podocytopathies) and electrolyte disorders occur but are much less common
• Onset is characteristically delayed — typically weeks to several months after starting therapy, later than most other irAEs — so a 'late' creatinine bump should still trigger an ICI-AIN workup
• Concomitant PPIs are a reproducible risk factor and a frequent companion AIN trigger; deprescribing an unnecessary PPI is both diagnostic and therapeutic
• Most patients have at least partial renal recovery with prompt corticosteroids, and many can be successfully rechallenged with the ICI, though recurrence risk is real and is higher when nephritis was severe
• Combination anti-CTLA-4 plus anti-PD-1 carries a higher nephritis rate than PD-1/PD-L1 monotherapy; baseline lower eGFR also raises risk

Each recommendation below is this atlas's faithful summary of the source, not a quotation from it — follow the PubMed link for the wording the society published. Summaries may be superseded; consult the current full text and individualize to the patient.

• ASON (2025) — Diagnosis and management of immune checkpoint inhibitor-associated nephrotoxicity: a position statement from the American Society of Onco-nephrologyICI-AKI most commonly presents as acute interstitial nephritis; nephrology consultation and kidney biopsy should be considered for stage 2 or higher AKI or suspected glomerular disease, but where biopsy is not feasible, prompt empiric corticosteroids (prednisone ~1 mg/kg/day) should be started for clinically suspected ICI-AKI since early steroids improve renal recovery, with cautious individualized consideration of ICI rechallenge after recovery.Kidney Int · PMID 39455026
• ASCO (2021) — Management of Immune-Related Adverse Events in Patients Treated With Immune Checkpoint Inhibitor Therapy: ASCO Guideline UpdateFor grade 2 or higher ICI-related nephritis/AKI, hold the ICI, exclude alternative causes, and initiate corticosteroids (prednisone 0.5-1 mg/kg/day for grade 2, 1-2 mg/kg/day for grade 3-4) tapered over 4-6 weeks once creatinine improves; permanently discontinue for grade 4 toxicity.J Clin Oncol · PMID 34724392
• ESMO (2022) — Management of toxicities from immunotherapy: ESMO Clinical Practice Guideline for diagnosis, treatment and follow-upFor ICI-related AKI, exclude alternative etiologies and stop concomitant nephrotoxins (PPIs, NSAIDs); ESMO permits continuing the ICI for stage 1 AKI with monitoring, but recommends withholding the ICI and starting corticosteroids for stage 2 or higher nephritis, escalating immunosuppression for steroid-refractory disease.Ann Oncol · PMID 36270461
• SITC (2021) — Society for Immunotherapy of Cancer (SITC) clinical practice guideline on immune checkpoint inhibitor-related adverse eventsGrade ICI-related AKI by CTCAE; for persistent grade 2 or higher renal toxicity, discontinue the ICI, exclude other causes, and treat with corticosteroids with a taper begun once creatinine improves toward grade 1, considering kidney biopsy and additional immunosuppression for refractory cases.J Immunother Cancer · PMID 34172516
• IC-OS (2026) — Immune Checkpoint Inhibitor-Associated Cardiovascular Toxic Effects: International Cardio-Oncology Society Position StatementConcerns for myocarditis continue to dominate the spectrum of CV toxic effects in patients receiving ICI therapy. Recommendations for management vary according to severity. Multidisciplinary collaborations remain key for managing acute toxic effects and future cancer treatment decisions, including ICI rechallenge.JAMA Oncol · PMID 41231466
• EULAR (2021) — EULAR points to consider for the diagnosis and management of rheumatic immune-related adverse events due to cancer immunotherapy with checkpoint inhibitorsOncologists should be encouraged to consult rheumatologists promptly for assessment when rheumatic musculoskeletal and systemic signs or symptoms are suspected due to immunotherapy, and rheumatologists should provide facilitated access for such patients.Ann Rheum Dis · PMID 32327425
• ASCO (2018) — Management of Immune-Related Adverse Events in Patients Treated With Immune Checkpoint Inhibitor Therapy: American Society of Clinical Oncology Clinical Practice GuidelineWithhold the checkpoint inhibitor and start corticosteroids for grade 2 or higher immune-related renal toxicity after excluding other causes of AKI, with steroid taper as renal function recovers and permanent discontinuation for severe (grade 4) events.J Clin Oncol · PMID 29442540
• PUMCH Expert Panel (2020) — Clinical recommendations on diagnosis and treatment of immune checkpoint inhibitor-induced renal immune-related adverse eventsScreen and monitor with serum creatinine, urinalysis/sediment, and 24-hour urine protein; strongly recommend kidney biopsy to confirm ICI-related ATIN and exclude other AKI causes, withdraw nephrotoxins (PPIs, NSAIDs), and initiate corticosteroids when a grade 2 or higher renal irAE is highly suspected, with multidisciplinary decisions on ICI withdrawal and rechallenge.Thorac Cancer · PMID 32232975
• ADQI (2026) — Immune Checkpoint Inhibitor-Associated Acute Kidney Injury: A Report from the 34th Acute Disease Quality Initiative (ADQI) Consensus ConferenceAKI occurs in up to 20% of ICI-treated patients with ICI-AKI accounting for roughly 2-5% of cases, and acute tubulointerstitial nephritis dominates (80-90% of biopsies); no clinical feature reliably separates ICI-AKI from other causes, so kidney biopsy remains the diagnostic gold standard and emerging biomarkers are not yet ready for routine use. Early glucocorticoid initiation (within 3 days of diagnosis) is associated with higher rates of kidney recovery, and recurrent ICI-AKI occurs in fewer than 20% of rechallenged patients, supporting cautious rechallenge in selected patients with individualized multidisciplinary decisions for transplant recipients and other high-risk groups.J Am Soc Nephrol · PMID 42536415
• ADQI (2026) — The nephrotoxic effects of anti-cancer therapies: consensus report of the 34th Acute Disease Quality Initiative workgroupProvides expert-based statements (modified Delphi) on preventing and managing cisplatin/platinum-associated AKI, including isotonic IV hydration, attention to volume status and concomitant nephrotoxins, and incorporates evidence that IV magnesium supplementation may reduce cisplatin-associated AKI; emphasizes risk stratification and standardized AKI definitions.Nat Rev Nephrol · PMID 41361704
• SIRM (2022) — SIRM-SIN-AIOM: appropriateness criteria for evaluation and prevention of renal damage in the patient undergoing contrast medium examinations-consensus statements from Italian College of Radiology (SIRM), Italian College of Nephrology (SIN) and Italian Association of Medical Oncology (AIOM)Recommends eGFR-based renal risk assessment and pre/post-contrast isotonic saline or sodium bicarbonate hydration; advises maintaining a 5-7 day interval between iodinated contrast administration and cisplatin in cancer patients to reduce additive nephrotoxicity.Radiol Med · PMID 35303246
• KDIGO (2020) — KDIGO Controversies Conference on onco-nephrology: understanding kidney impairment and solid-organ malignancies, and managing kidney cancerIdentifies platinum compounds (especially cisplatin) as leading cytotoxic causes of acute tubular injury, AKI, and electrolyte/magnesium wasting; calls for interdisciplinary onco-nephrology care, accurate GFR estimation, and individualized drug dosing in patients with reduced kidney function.Kidney Int · PMID 33126977
• KDIGO (2020) — KDIGO Controversies Conference on onco-nephrology: kidney disease in hematological malignancies and the burden of cancer after kidney transplantationAddresses chemotherapy-associated AKI/CKD in hematologic cancer, GFR estimation and chemotherapy dosing in patients with reduced kidney function, and management priorities and research gaps for onco-nephrology care.Kidney Int · PMID 33276867
• ADDIKD (2025) — Integrating International Consensus Guidelines for Anticancer Drug Dosing in Kidney Dysfunction (ADDIKD) into everyday practiceProvides GRADE-based, drug-specific dose-adjustment recommendations for anticancer agents in kidney dysfunction (illustrated for methotrexate, cisplatin, carboplatin and nivolumab); the recommendations build on Part 1's standardised CKD-EPI eGFR assessment rather than Cockcroft-Gault creatinine clearance.EClinicalMedicine · PMID 40290844
• ADDIKD (2025) — Aligning kidney function assessment in patients with cancer to global practices in internal medicineThree consensus recommendations: assess kidney function by GFR (measured GFR or CKD-EPI eGFR), classify it using KDIGO categories, and use this uniform approach to dose anticancer drugs — moving cancer medicine away from Cockcroft-Gault estimated creatinine clearance.EClinicalMedicine · PMID 40290845
• ADDIKD (2025) — A methodology for determining dosing recommendations for anticancer drugs in patients with reduced kidney functionEstablishes that, where RCT evidence is lacking, anticancer drug dosing recommendations in kidney dysfunction should be derived by critically appraising observational literature via GRADE combined with structured international multidisciplinary consensus voting.EClinicalMedicine · PMID 40290846
• KDIGO (2013) — Diagnosis, evaluation, and management of acute kidney injury: a KDIGO summary (Part 1)Defines/stages AKI by serum creatinine and urine output; emphasizes avoiding nephrotoxins, maintaining euvolemia/perfusion, dose-adjusting drugs to kidney function, and monitoring high-risk patients — the framework applied to nephrotoxic anti-cancer agents.Crit Care · PMID 23394211
• KDIGO (2024) — Executive summary of the KDIGO 2024 Clinical Practice Guideline for the Evaluation and Management of Chronic Kidney Disease: known knowns and known unknownsEvaluate and risk-stratify CKD, manage to delay progression and its complications, and practise explicit medication management and drug stewardship — the framework the atlas's G1–G5 eGFR banding and every renal dose-adjustment recommendation sit inside. Because the guideline excludes dialysis and transplant recipients by its own statement of scope, its recommendations do not carry to those settings, where this atlas's dialyzability and post-transplant guidance rests on other sources.Kidney Int · PMID 38519239
• KDIGO (2021) — Executive summary of the KDIGO 2021 Guideline for the Management of Glomerular DiseasesProvides the staging/treatment framework for drug-associated glomerular lesions (e.g., bisphosphonate- and interferon-related collapsing FSGS, VEGF-inhibitor podocytopathy/proteinuria), including immunosuppression and supportive RAAS-blockade strategies.Kidney Int · PMID 34556300
• KDIGO (2024) — Executive summary of the KDIGO 2024 Clinical Practice Guideline for the Management of ANCA-Associated VasculitisUpdates immunosuppressive induction (rituximab/cyclophosphamide), incorporates avacopan and lower-dose or glucocorticoid-sparing regimens — the management framework for drug- and checkpoint-inhibitor-associated ANCA/pauci-immune glomerulonephritis.Kidney Int · PMID 38388147
• KDIGO (2024) — Executive summary of the KDIGO 2024 Clinical Practice Guideline for the Management of Lupus NephritisUpdates first-line lupus nephritis therapy to combination immunosuppression with the addition of belimumab or a calcineurin inhibitor (voclosporin) — informs management of immune-complex/lupus-like glomerulonephritis encountered with immunotherapy.Kidney Int · PMID 38182299
• KDIGO (2025) — Executive summary of the KDIGO 2025 Clinical Practice Guideline for the Management of Immunoglobulin A Nephropathy (IgAN) and Immunoglobulin A Vasculitis (IgAV)Encourages liberal kidney biopsy and stricter proteinuria control (<0.5 g/d, ideally <0.3 g/d) with RAAS blockers, SGLT2 inhibitors, and targeted-release budesonide — the framework for IgA-dominant glomerular lesions, including those triggered by immune-modulating cancer therapy.Kidney Int · PMID 40975525