Naxitamab

Prerenal / Hemodynamic AKI.

Frank acute kidney injury is not a systematically reported endpoint for naxitamab and no validated AKI incidence figure exists; the renal-relevant risk is hemodynamic rather than a direct nephrotoxic lesion. The closest quantitative anchor comes from the pivotal single-arm phase 2 Trial 201 (NCT03363373), where naxitamab-related grade 3 adverse events were dominated by hypotension in 58% and pain in 54% of patients — the infusion-reaction physiology that can transiently compromise renal perfusion. Pharmacovigilance corroborates the signal: in an FDA Adverse Event Reporting System analysis of anti-GD2 antibodies, hypotension, hypertension, urticaria, and capillary-leakage syndrome were among the most frequent and strongest naxitamab-associated signals. Because these figures describe hemodynamic events (not measured creatinine-defined AKI), the numeric AKI rate is left unquantified.

Source: 39952926

Reported injury signatures: Prerenal / Hemodynamic AKI, Hypertension.

1. Prerenal / Hemodynamic AKIPrimary
2. HypertensionSecondary

Hyperacute (<24 h) — Infusion-locked — hypotension/hypertension and the infusion-reaction complex begin within minutes to a few hours of starting the infusion, most pronounced during the early cycles.

• Early treatment cycles (infusion reactions and blood-pressure lability are most severe in the first 1-3 cycles)
• The high naxitamab dose itself (~270 mg/m2 per cycle, roughly 2.5x the dose of dinutuximab/dinutuximab beta)
• Pre-existing volume depletion from concurrent vomiting, diarrhea, or poor intake
• Rapid infusion rate or inadequate premedication
• Concomitant nephrotoxins or agents affecting renal perfusion (e.g., NSAIDs, ACE inhibitors/ARBs, diuretics)
• Underlying cardiac, renal, or hemodynamic compromise
• Prior severe infusion reactions to an anti-GD2 antibody

• Protocolized premedication before every infusion (antihistamines, antipyretics, analgesia including opioids +/- ketamine, and corticosteroids per protocol) to blunt the infusion reaction
• Start at a slow infusion rate with stepwise escalation as tolerated
• Ensure adequate hydration and correct volume depletion before infusing
• Continuous blood-pressure and cardiorespiratory monitoring during and after the infusion, with IV fluids, vasopressors, and resuscitation equipment immediately available
• Educate patients/caregivers on premedication and post-infusion monitoring; treat in a setting equipped for rapid intervention
• Review and, where possible, hold agents that impair renal perfusion (NSAIDs, RAAS blockers, diuretics) around infusion days

• Continuous blood pressure and heart rate during the infusion and through the post-infusion observation window (capture both hypotensive and hypertensive swings)
• Cardiorespiratory/oxygen saturation monitoring for the broader infusion-reaction complex
• Fluid balance, body weight, and edema (screen for capillary leak)
• Serum creatinine and electrolytes around each cycle, with closer checks after any significant hypotensive episode
• Serum albumin if capillary-leak syndrome is suspected
• Symptom review for pain, urticaria, bronchospasm to gauge premedication adequacy

• Trial 201 (NCT03363373) — pivotal single-arm, multicenter phase 2 of naxitamab + GM-CSF in relapsed/refractory high-risk neuroblastoma in bone/bone marrow; supported U.S. accelerated approval and defined the safety profile (grade 3 hypotension 58%, pain 54%)
• Study 201/12750 outpatient AE-management experience — protocolized algorithms for infusion-related hypotension and bronchospasm
• HITS regimen study (irinotecan, temozolomide, naxitamab + GM-CSF) — chemo-immunotherapy for primary refractory disease, with pain and hypertension noted as expected naxitamab toxicities

• The kidney is a bystander: naxitamab has no intrinsic tubular/glomerular lesion — renal injury, when it occurs, is prerenal/hemodynamic from infusion-reaction blood-pressure swings and capillary leak.
• Expect blood-pressure lability in BOTH directions — hypotension is the dominant grade 3 event, but on-treatment hypertension is also an expected naxitamab toxicity.
• Naxitamab is dosed roughly 2.5x higher (~270 mg/m2/cycle) than dinutuximab/dinutuximab beta, yet hemodynamic events concentrate in the first few cycles and are largely outpatient-manageable.
• Overt capillary-leak syndrome and PRES are uncommon with the short (30-90 minute) outpatient infusions used for naxitamab.
• Rate reduction, an IV fluid bolus, or a half-dose for the day rescues most hypotensive episodes; full dosing usually resumes at the next infusion.
• Not renally cleared and not dialyzable — there is no creatinine-based dose adjustment; manage the hemodynamics, not a clearance number.

• 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 (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