Ipilimumab

Acute Interstitial Nephritis — representative incidence ~2% (1–2% range across studies).

Clinically significant kidney injury from ipilimumab monotherapy is uncommon; renal immune-related adverse events are reported in roughly 1-2% of patients on single-agent checkpoint blockade. The dominant driver of elevated incidence is combination therapy: in real-world ICI cohorts any-cause AKI reaches about 16-17%, but only a minority is true immune-mediated nephritis. The combination of ipilimumab plus nivolumab carries a substantially higher and more severe AKI risk than either single agent. In a pooled analysis of biopsy-proven ICI-related acute tubulointerstitial nephritis, all patients on dual ICI blockade developed stage 3 AKI versus about half on a single agent, and complete renal recovery was less likely with dual blockade.

Source: Single-center cohort: 16.5% (51/309) developed AKI, ~2% biopsy/clinically attributed to ICI nephritis (Meraz-Munoz et al., J Immunother Cancer 2020, PMID 32601079); dual-blockade severity from pooled biopsy analysis (Esposito et al., Front Oncol 2023, PMID 37936605).

Reported injury signatures: Acute Interstitial Nephritis, Chronic Interstitial Nephropathy, Glomerular Injury / Proteinuria, Thrombotic Microangiopathy, Prerenal / Hemodynamic AKI.

1. Acute Interstitial NephritisPrimary~3.5%Acute interstitial nephritis (often granulomatous) is the dominant ipilimumab renal lesion; ICI-attributable AKI pooled ~3.5% (overall AKI during ICI therapy ~16%), and ipilimumab is the highest-risk single agent (adjusted OR 2.18) — biopsy series show AIN as the leading pattern.
2. Glomerular Injury / ProteinuriaSecondarySecond most common (but uncommon) ICI kidney lesion after AIN; biopsy-confirmed cases include membranous nephropathy and minimal-change/podocytopathy.
3. Thrombotic MicroangiopathyRareCase-level thrombotic microangiopathy documented in ICI kidney-biopsy cohorts (2 of 12 biopsy-attributed lesions).
4. Prerenal / Hemodynamic AKIRare
5. Chronic Interstitial NephropathyRare

Variable / unpredictable — Delayed and variable onset, typically weeks to several months (median ~3 months/91 days), though combination therapy can trigger nephritis after one or two doses or even after discontinuation.

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 ipilimumab + nivolumab therapy (strongest risk for incidence and severity)
• Concurrent or prior extrarenal immune-related adverse events
• Pre-existing hypertension
• Concomitant nephritis-associated drugs (PPIs, NSAIDs, antibiotics)
• RAAS inhibitor or diuretic use (predisposes to prerenal AKI)
• Pre-existing chronic kidney disease
• Higher cumulative checkpoint-inhibitor exposure

• Review and minimize concomitant AIN-associated drugs (PPIs, NSAIDs) before and during treatment
• Maintain euvolemia; reassess RAAS inhibitors and diuretics

• Urinalysis for proteinuria, pyuria, and hematuria
• Surveillance for concurrent immune-related adverse events (skin, GI, hepatic, thyroid, pituitary)
• Quantify proteinuria (urine protein:creatinine ratio) if glomerular involvement suspected
• Electrolytes including potassium and magnesium
• Trend creatinine after any drug hold or steroid course to confirm recovery

• CheckMate 067 (NCT01844505): phase 3 nivolumab + ipilimumab vs nivolumab vs ipilimumab in advanced melanoma; established the combination but with markedly higher grade 3-4 immune-related toxicity
• CheckMate 214 (NCT02231749): nivolumab + ipilimumab vs sunitinib in advanced renal cell carcinoma
• CheckMate 9LA / CheckMate 743: ipilimumab + nivolumab combinations in NSCLC and pleural mesothelioma

• Ipilimumab monotherapy rarely hurts the kidney; the renal risk surges when it is paired with nivolumab - dual blockade drives both higher incidence and more stage 3/dialysis-requiring AKI.
• The CTLA-4 nephritis lesion leans granulomatous, a histologic tilt distinct from the more purely lymphocytic AIN of PD-1 monotherapy.
• ICI nephritis is a delayed, slow-burn diagnosis (median ~3 months) - it does not behave like classic days-after-drug allergic AIN.
• An extrarenal immune-related adverse event (rash, colitis, hepatitis, thyroiditis) often precedes the creatinine rise - treat it as a renal early-warning sign.
• Co-prescribed PPIs and NSAIDs are frequent cofactors; checkpoint blockade can unmask T-cell reactivity to them, so review and stop them when nephritis is suspected.
• Most AKI on these agents is still prerenal/hemodynamic, not drug-immune - reserve high-dose steroids for genuine immune nephritis and consider biopsy when uncertain.

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