Bendamustine
Treanda · Alkylator
Tumor lysis-mediated AKI is the principal risk; TMA is rare.
PRETMALYTE
ModerateOpen →
IL-3 immunotoxin
Tagraxofusp
Elzonris · Tagrax
A CD123-directed diphtheria-toxin fusion whose capillary leak can collapse the circulation and the kidneys.
ModerateIL-3 / CD123-directed immunotoxin · approved 2018
Blastic plasmacytoid dendritic cell neoplasm (BPDCN)
Signature kidney injury
Prerenal / Hemodynamic AKI
Capillary leak syndrome (CLS) is a boxed-warning toxicity occurring in ~19-21% of treated patients (grade >=3 in ~7%, with rare deaths) in the pivotal trial; the resulting hypotension, hypoalbuminemia, and fluid shifts can precipitate prerenal AKI and, with prolonged hypoperfusion, ischemic ATN. Renal-specific AKI incidence is not separately quantified.
Source: Pemmaraju et al., J Clin Oncol 2022
Mechanism of kidney injury
Endothelial injury from the diphtheria-toxin immunotoxin (CD123 is also expressed on endothelium) produces a systemic capillary-leak state: intravascular fluid and albumin extravasate into the interstitium, causing hypoalbuminemia, edema, weight gain, and hypotension. The fall in effective circulating volume drives prerenal azotemia and, when severe or prolonged, ischemic acute tubular necrosis.
Clinical presentation
Weight gain, peripheral and pulmonary edema, hypoalbuminemia (often <3.0 g/dL), hypotension, and rising creatinine, usually in cycle 1. Falling serum albumin and rising weight are the earliest CLS signals; severe cases progress to shock and pulmonary edema.
Onset
Typically during the first treatment cycle, often within days of the first doses; recurrence in later cycles is uncommon with proactive monitoring.
Reversibility
Partially reversible
Anticancer mechanism
Recombinant fusion of interleukin-3 (IL-3) and truncated diphtheria toxin that binds the IL-3 receptor alpha chain (CD123) overexpressed on malignant cells, internalizes, and the diphtheria-toxin payload ADP-ribosylates elongation factor 2 to halt protein synthesis and trigger apoptosis. First approved therapy for blastic plasmacytoid dendritic cell neoplasm (BPDCN).
Management
Treat CLS aggressively: corticosteroids, IV albumin to support oncotic pressure, judicious fluid management, and interruption of tagraxofusp. Support blood pressure and renal perfusion (vasopressors if needed). Most AKI is prerenal and improves with CLS resolution; established ATN requires standard supportive care and occasionally renal replacement therapy.
Risk factors
- Low baseline serum albumin (<3.2 g/dL)
- Pre-existing cardiac or volume-overload states
- First cycle of therapy
- Pre-existing low platelet count / bleeding risk amplifying hemodynamic instability
Prevention
- Require serum albumin >= 3.2 g/dL before the first dose and before each subsequent dose
- Monitor weight, blood pressure, and albumin daily during cycle 1 inpatient observation
- Premedicate (corticosteroids, antihistamines, antipyretics) and give prompt corticosteroids and albumin at the first CLS signs; hold dosing per protocol
Note · Capillary-leak syndrome carries a boxed warning; renal injury is a downstream consequence of endothelial leak and hemodynamic collapse rather than direct tubular toxicity.
Clinical depth
Renal dose adjustment
No established renal dose adjustment (clearance is proteolytic, not renal). Dosing decisions hinge on albumin, weight, and CLS status rather than eGFR.
Dialyzability & ESKD dosing
Large fusion protein cleared by proteolysis; not dialyzable. Hemodialysis/CRRT is used to support AKI/volume overload, not to remove the drug.
Differential diagnosis
Tagraxofusp CLS-driven prerenal AKI/ATN (hypoalbuminemia, weight gain, edema in cycle 1) vs sepsis/neutropenic shock vs cardiogenic edema vs tumor-related fluid overload. Hypoalbuminemia with weight gain and hemoconcentration points to CLS.
Monitoring
- Serum albumin before each dose (hold if <3.2 g/dL)
- Daily weight and blood pressure during cycle 1
- Serum creatinine and electrolytes through each cycle
- Edema, oxygen saturation, and signs of pulmonary edema
Key trials & series
- Pemmaraju phase 1/2 pivotal BPDCN trial (NEJM 2019) and JCO 2022 long-term follow-up
- Pemmaraju & Konopleva Blood Adv 2020 approval review
Clinical pearls
- Albumin is the vital sign for tagraxofusp - do not dose if <3.2 g/dL.
- CLS clusters in cycle 1; intensive monitoring then prevents most severe events.
- The AKI is a hemodynamic consequence of capillary leak, not a direct tubular toxin - fix the circulation and the kidney follows.
Where it strikes
Nephron segments
Vasculature / Endothelium
Glomerular & peritubular capillaries
Proximal Tubule
Bulk reabsorption + drug uptake (OCT2, OATs)
Injury signatures
Prerenal / Hemodynamic AKIAcute Tubular Necrosis
Evidence
6 peer-reviewed references. Citation metadata via PubMed / NLM.
LandmarkLong-Term Benefits of Tagraxofusp for Patients With Blastic Plasmacytoid Dendritic Cell Neoplasm.Pemmaraju N et al. · J Clin Oncol 2022 · PMID 35820082Largest prospective BPDCN trial with long-term follow-up; quantifies CLS at 21% (grade >=3 7%), the driver of hemodynamic/renal compromise.PMIDOptimizing capillary leak syndrome prevention and management in patients receiving tagraxofusp for blastic plasmacytoid dendritic cell neoplasm.Lane AA et al. · Leuk Lymphoma 2025 · PMID 41134616Focused guidance on preventing and managing tagraxofusp CLS: albumin thresholds, monitoring, and early intervention.PMIDApproval of tagraxofusp-erzs for blastic plasmacytoid dendritic cell neoplasm.Pemmaraju N et al. · Blood Adv 2020 · PMID 32841341Drug-development and approval review detailing mechanism and the black-box capillary leak syndrome.PMIDBlastic Plasmacytoid Dendritic Cell Neoplasm.Jain A et al. · J Natl Compr Canc Netw 2023 · PMID 37156483Disease and treatment review emphasizing CLS as a key adverse effect requiring close monitoring.PMIDReversible Myocardial Edema Secondary to Tagraxofusp-Induced Capillary Leak Syndrome.Mouhayar EN et al. · JACC CardioOncol 2021 · PMID 34988487Illustrates the systemic fluid shifts and end-organ edema produced by tagraxofusp capillary leak.PMIDEfficacy of first-line tagraxofusp in blastic plasmacytoid dendritic cell neoplasm with prior or concomitant hematologic malignancy: subgroup analysis of a pivotal trial.Pemmaraju N et al. · Leuk Lymphoma 2025 · PMID 40067964Pivotal-trial subgroup data reinforcing the efficacy/safety profile, including monitored capillary-leak risk.
Related agents
Other agents sharing the same signature kidney injury.