Bendamustine
Treanda · Alkylator
Tumor lysis-mediated AKI is the principal risk; TMA is rare.
PRETMALYTE
ModerateOpen →
Antibody-drug conjugate (CD33/calicheamicin)
Gemtuzumab ozogamicin
Mylotarg · GO
A CD33/calicheamicin conjugate for AML — renal risk runs through tumor lysis and veno-occlusive disease.
ModerateAntibody-drug conjugate · approved 2017
Acute myeloid leukemia
Signature kidney injury
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
Mechanism of kidney injury
Indirect: rapid leukemic-cell lysis causes tumor lysis with crystal nephropathy and electrolyte shifts; calicheamicin-mediated injury to hepatic sinusoidal endothelium produces VOD/SOS with fluid overload, portal hypertension, ascites and hepatorenal-pattern AKI (a functional renal failure of advanced liver injury). Direct tubular toxicity from calicheamicin is not a notable clinical signal.
Clinical presentation
Tumor-lysis labs (hyperuricemia, hyperphosphatemia, hyperkalemia, hypocalcemia) with AKI early in therapy; with VOD, weight gain, painful hepatomegaly, ascites, hyperbilirubinemia and a rising creatinine with low urine sodium (hepatorenal physiology).
Onset
Early — tumor lysis with induction; VOD typically within weeks, notably around hematopoietic stem-cell transplant.
Reversibility
Variable
Anticancer mechanism
Antibody-drug conjugate targeting CD33 and delivering the DNA-damaging enediyne calicheamicin via a hydrolyzable linker. Approved for CD33-positive acute myeloid leukemia.
Management
Tumor-lysis management (hydration, urate-lowering therapy, electrolyte correction); for VOD, supportive care and defibrotide with careful fluid/renal management; supportive AKI care including dialysis if severe.
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/volume monitoring
Note · Renal injury is mediated by tumor lysis and VOD rather than direct tubular toxicity; VOD carries the highest-stakes renal risk.
Clinical depth
Renal dose adjustment
No specific renal dose adjustment; dose decisions are driven by hepatic function and VOD risk, not renal clearance. Calicheamicin is hepatically handled.
Dialyzability & ESKD dosing
Not appreciably dialyzed (large ADC; protein-bound calicheamicin). HD/CRRT in VOD is for fluid/AKI support, not drug removal.
Differential diagnosis
Distinguish tumor lysis AKI (early, electrolyte signature) from VOD-associated hepatorenal AKI (jaundice, weight gain, ascites, low urine sodium) and from sepsis/nephrotoxin ATN in the neutropenic host. VOD carries the highest-stakes renal trajectory.
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.
Where it strikes
Nephron segments
Vasculature / Endothelium
Glomerular & peritubular capillaries
Injury signatures
Prerenal / Hemodynamic AKIElectrolyte Wasting
Beyond the kidney
Class-level context for the major non-renal toxicities of antibody-drug conjugate (cd33/calicheamicin)s.
Hematologic
Cytopenias, thrombosis, TMA
- Myelosuppression (payload-dependent)
Ophthalmic
Keratopathy, uveitis, retinopathy
- Keratopathy (belantamab, mirvetuximab, tisotumab)
Pulmonary
Pneumonitis, ILD, effusions, hypertension
- Interstitial lung disease (deruxtecan ADCs)
Neurologic
Neuropathy, encephalopathy, ICANS, PRES
- Peripheral neuropathy (MMAE payloads)
Evidence
4 peer-reviewed references. Citation metadata via PubMed / NLM.
LandmarkPrevention, recognition, and management of adverse events associated with gemtuzumab ozogamicin use in acute myeloid leukemia.Cortes JE et al. · J Hematol Oncol 2020 · PMID 33059764Authoritative review of tumor lysis and veno-occlusive disease recognition/management with gemtuzumab.PMIDDefibrotide sodium for the treatment of hepatic veno-occlusive disease/sinusoidal obstruction syndrome.Richardson PG et al. · Expert Rev Clin Pharmacol 2018 · PMID 29301447Defibrotide for VOD/SOS with renal/pulmonary dysfunction - directly relevant to the highest-stakes renal pathway.PMIDTumor 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 26758269Frames TLS risk among novel hematologic agents.PMIDAnticancer Drug-Induced Acute Kidney Injury.Izzedine H et al. · Kidney Int Rep 2017 · PMID 29318217Onconephrology reference for tumor-lysis and hemodynamic/hepatorenal AKI mechanisms.
Related agents
Other agents sharing the same signature kidney injury.