Antibody-drug conjugate (CD33/calicheamicin)
Gemtuzumab ozogamicin
Mylotarg · GO
Antibody-drug conjugate (CD33/calicheamicin) · approved 2017 · 4 references
A CD33/calicheamicin conjugate for AML — renal risk runs through tumor lysis and veno-occlusive disease.
- Signature injury
- Prerenal / Hemodynamic AKI
- Severity
- Moderate
- Reversibility
- Variable
- Onset
- Early — tumor lysis with induction; VOD typically within weeks, notably around hematopoietic stem-cell transplant.
Signature kidney injury & incidence
Prerenal / Hemodynamic AKI.
Direct nephrotoxicity is not a prominent signal. AKI is chiefly secondary to tumor lysis syndrome and to hepatic sinusoidal obstruction syndrome/veno-occlusive disease (VOD), the latter a recognized, sometimes fatal complication that produces hepatorenal-type AKI. Renal-specific incidence is not quantified.
Source: Cortes et al., J Hematol Oncol 2020
Reported injury signatures: Prerenal / Hemodynamic AKI, Electrolyte Disturbance, Crystal / Obstructive Nephropathy.
Renal toxicity profile
- Prerenal / Hemodynamic AKIPrimary
- Electrolyte DisturbanceSecondary
- Crystal / Obstructive NephropathySecondary
Onset timing & rechallenge
Acute (~1–7 days) — Early — tumor lysis with induction (VOD, non-renal, follows within weeks).
Mechanism of kidney injury
Clinical presentation
Management
Risk factors
- High leukemic burden
- Prior or subsequent hematopoietic stem-cell transplant
- Hepatic dysfunction
- Fractionated high cumulative exposure
- Volume depletion
- Pre-existing CKD
Prevention
- Tumor lysis prophylaxis (hydration, allopurinol/rasburicase)
- VOD risk mitigation (fractionated lower dosing, avoid in significant hepatic dysfunction, monitor LFTs and weight)
Renal dose adjustment
Dialyzability & ESKD dosing
Differential diagnosis
Monitoring
- LFTs (especially bilirubin) and daily weight for VOD, before and after transplant
- Tumor lysis labs during induction
- Serum creatinine and volume status, particularly in evolving VOD
Key trials & series
- ALFA-0701 (registrational fractionated dosing)
- Cortes J Hematol Oncol 2020 (adverse-event/VOD management review)
Clinical pearls
- VOD is the dangerous renal pathway: weight gain + bilirubin + hepatomegaly + rising creatinine peri-transplant should trigger early defibrotide consideration.
- Fractionated dosing was adopted partly to reduce VOD risk versus the original single high dose.
- The kidney here is a bystander of liver and tumor - direct calicheamicin tubular toxicity is not the issue.
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
4 peer-reviewed references. Citation metadata via PubMed / NLM.
- 1.Prevention, recognition, and management of adverse events associated with gemtuzumab ozogamicin use in acute myeloid leukemia.Cortes JE et al. · J Hematol Oncol · 2020 · PMID 33059764
- 2.Defibrotide sodium for the treatment of hepatic veno-occlusive disease/sinusoidal obstruction syndrome.Richardson PG et al. · Expert Rev Clin Pharmacol · 2018 · PMID 29301447
- 3.Tumor lysis syndrome in the era of novel and targeted agents in patients with hematologic malignancies: a systematic review.Howard SC et al. · Ann Hematol · 2016 · PMID 26758269
- 4.Anticancer Drug-Induced Acute Kidney Injury.Izzedine H et al. · Kidney Int Rep · 2017 · PMID 29318217