Anti-GD2 antibody
Dinutuximab
Unituxin · DIN
Anti-GD2 antibody · approved 2015 · 7 references
Anti-GD2 antibody for high-risk neuroblastoma whose capillary-leak syndrome, hypertension and severe pain are the renal-relevant signals.
- Signature injury
- Prerenal / Hemodynamic AKI
- Severity
- Moderate
- Reversibility
- Reversible
- Onset
- Infusion-associated and acute — pain, capillary leak and blood-pressure swings occur during/around each infusion.
Signature kidney injury & incidence
Prerenal / Hemodynamic AKI.
Severe neuropathic pain is near-universal, and capillary-leak syndrome and hypertension are common, sometimes severe, infusion-associated toxicities (driven partly by concurrent IL-2). The resulting fluid shifts and prerenal AKI are managed proactively but not separately quantified.
Source: Yu et al., N Engl J Med 2010 (ANBL0032)
Reported injury signatures: Prerenal / Hemodynamic AKI, Hypertension, Thrombotic Microangiopathy.
Renal toxicity profile
- Prerenal / Hemodynamic AKIPrimary~4%Grade 3-4 capillary-leak syndrome in 4% on dinutuximab beta alone (up to ~15% when combined with IL-2); hypotension among the most frequently reported ADRs
- HypertensionSecondary
- Thrombotic MicroangiopathyRareA single biopsy-confirmed case of dinutuximab-associated atypical HUS (uncontrolled hypertension with renal dysfunction, treated with eculizumab then ravulizumab) — a case report, not a rate
Onset timing & rechallenge
Acute (~1–7 days) — Infusion-associated and acute — capillary leak and blood-pressure swings occur during/around each infusion.
Mechanism of kidney injury
Clinical presentation
Management
Risk factors
- Concurrent IL-2 (amplifies capillary leak)
- Pre-existing renal or cardiac compromise
- Inadequate pre-hydration or premedication
- High infusion rate
Prevention
- Pre-hydration and careful fluid management around infusions
- Premedication (analgesia/opioids, antihistamines, antipyretics) and slow infusion
- Dose interruption/rate reduction for severe capillary leak or hemodynamic instability
Renal dose adjustment
Dialyzability & ESKD dosing
Differential diagnosis
Monitoring
- Blood pressure and volume status continuously during infusions
- Pain assessment and analgesic titration
- Signs of capillary leak (edema, weight gain, hypotension)
Key trials & series
- ANBL0032 (Yu, NEJM 2010) — registrational trial defining capillary leak, hypertension and severe pain
Clinical pearls
- Capillary-leak syndrome with hypotension and intravascular depletion is the renal mechanism — support circulating volume.
- Severe neuropathic pain is on-target (GD2 on nerves) and near-universal — pre-emptive opioids are standard.
- Co-administered IL-2 amplifies the capillary leak and hemodynamic swings.
- Blood pressure can swing both ways during infusions; monitor continuously.
Anticancer mechanism
Note
Guidelines & consensus
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
References
7 peer-reviewed references. Citation metadata via PubMed / NLM.
- 1.Anti-GD2 antibody with GM-CSF, interleukin-2, and isotretinoin for neuroblastoma.Yu AL et al. · N Engl J Med · 2010 · PMID 20879881
- 2.Long-Term Follow-up of a Phase III Study of ch14.18 (Dinutuximab) + Cytokine Immunotherapy in Children with High-Risk Neuroblastoma: COG Study ANBL0032.Yu AL et al. · Clin Cancer Res · 2021 · PMID 33504555
- 3.Interleukin 2 with anti-GD2 antibody ch14.18/CHO (dinutuximab beta) in patients with high-risk neuroblastoma (HR-NBL1/SIOPEN): a multicentre, randomised, phase 3 trial.Ladenstein R et al. · Lancet Oncol · 2018 · PMID 30442501
- 4.Anti-GD2 mAbs and next-generation mAb-based agents for cancer therapy.Perez Horta Z et al. · Immunotherapy · 2016 · PMID 27485082
- 5.Mechanisms, Characteristics, and Treatment of Neuropathic Pain and Peripheral Neuropathy Associated with Dinutuximab in Neuroblastoma Patients.Mastrangelo S et al. · Int J Mol Sci · 2021 · PMID 34884452
- 6.Strategies to manage the adverse effects of immunotherapy with dinutuximab beta in neuroblastoma: an Italian experience and literature review.Amoroso L et al. · Support Care Cancer · 2025 · PMID 39907793
- 7.Case Report of Dinutuximab-induced Atypical Hemolytic Uremic Syndrome.Huang L, et al. · J Pediatr Hematol Oncol · 2025 · PMID 39530431