Interleukin-2 (high-dose)

Prerenal / Hemodynamic AKI.

Oliguria / prerenal AKI is very common during therapy at high dose — but reversible.

Source: Belldegrun et al., Ann Intern Med 1987

Reported injury signatures: Prerenal / Hemodynamic AKI, Electrolyte Disturbance, SIADH / Hyponatremia.

1. Prerenal / Hemodynamic AKIPrimary
2. Electrolyte DisturbanceRareHypomagnesemia and hypophosphatemia reported across high-dose IL-2 trials.
3. SIADH / HyponatremiaRareA case report with high-dose bolus IL-2 monotherapy.

Acute (~1–7 days) — Acute AKI during the treatment cycle.

• Pre-existing CKD
• Hypotension
• Concurrent nephrotoxins

• Careful fluid / hemodynamic management

• Daily (often twice-daily) serum creatinine and BUN during each inpatient high-dose IL-2 cycle, with dose-hold thresholds defined in advance (e.g., creatinine >4-4.5 mg/dL or progressive oliguria)
• Strict hourly intake/output and daily weights to track capillary-leak-driven intravascular volume depletion, third-spacing, and oliguria
• Continuous blood pressure/hemodynamic monitoring (frequently ICU/step-down level) to detect the hypotension that drives prerenal azotemia
• Electrolytes including potassium, bicarbonate, magnesium, and phosphate, plus acid-base status, given fluid shifts and pressor/fluid management
• Confirm recovery of creatinine toward baseline before initiating the next cycle, and reassess cumulative renal reserve before re-treatment

• Fyfe 1995 (J Clin Oncol pooled analysis of 255 metastatic RCC patients): established durable responses to high-dose IL-2 and characterized its severe but largely reversible toxicity profile, including hypotension and reversible renal dysfunction from capillary leak
• Atkins 1999 (high-dose IL-2 pooled metastatic melanoma analysis): documented durable complete responses alongside the expected reversible organ toxicities including oliguria/azotemia requiring intensive supportive care
• SELECT trial (prospective high-dose IL-2 in metastatic RCC, Clin Cancer Res): contemporary safety/efficacy series reaffirming that renal and hemodynamic toxicities are manageable and reversible with modern supportive protocols

• Oliguria and a rising creatinine are expected, anticipated, dose-limiting toxicities — they trigger holding doses rather than abandoning therapy, and renal function typically recovers between cycles
• Aggressive crystalloid resuscitation is double-edged: fluids support renal perfusion but worsen pulmonary/peripheral edema from capillary leak, so management balances vasopressors (e.g., low-dose pressors) against volume
• Avoid stacking nephrotoxins — hold NSAIDs, aminoglycosides, and elective iodinated contrast during high-dose IL-2 cycles, since added insults can convert reversible prerenal azotemia into established ATN
• Baseline cardiac, pulmonary, and renal reserve must be adequate before high-dose IL-2; patients with pre-existing CKD or borderline function tolerate the hemodynamic stress poorly and are generally excluded
• High-dose IL-2 trials repeatedly report hypomagnesemia and hypophosphatemia — an electrolyte lesion in its own right, beyond the capillary-leak prerenal picture.
• SIADH is reported with high-dose bolus IL-2 monotherapy, coherent with its water-retentive capillary-leak physiology.

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.

• 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