Bendamustine
Treanda · Alkylator
Tumor lysis-mediated AKI is the principal risk; TMA is rare.
PRETMALYTE
ModerateOpen →
Enzyme
Asparaginase
Elspar · ASNase
An enzyme therapy whose rare AKI is downstream of pancreatitis and hemodynamic complications.
MildEnzyme (asparagine depletion) · approved 1978
Acute lymphoblastic leukemiaLymphoblastic lymphoma
Signature kidney injury
Prerenal / Hemodynamic AKI
Direct asparaginase nephrotoxicity is uncommon; classic toxicities are hypersensitivity (up to ~30% with E. coli-derived enzyme), pancreatitis, hepatic dysfunction, hyperammonemia, and coagulopathy/thrombosis. When AKI occurs it is typically secondary to pancreatitis, hemodynamic instability, or thrombotic complications rather than a direct tubular toxin, and is not well quantified.
Source: Hijiya & van der Sluis, Leuk Lymphoma 2016
Mechanism of kidney injury
No characteristic direct renal toxin effect. Severe asparaginase-induced pancreatitis (third-spacing, SIRS, shock) or thrombotic events (the enzyme depletes antithrombin III, fibrinogen, and plasminogen) can compromise renal perfusion, producing prerenal/ischemic injury; coagulopathy may rarely contribute to renal vascular events.
Clinical presentation
When present, AKI accompanies pancreatitis or hemodynamic compromise: rising creatinine, oliguria, and volume disturbance with an otherwise bland renal picture. Watch for abdominal pain (pancreatitis), thrombosis (including cerebral sinus), and encephalopathy (hyperammonemia).
Onset
Linked to intercurrent complications during induction/intensification therapy.
Reversibility
Reversible
Anticancer mechanism
Bacterial enzyme that hydrolyzes circulating asparagine (and some glutamine), starving leukemic lymphoblasts that lack asparagine synthetase and cannot synthesize it. Cornerstone of acute lymphoblastic leukemia (ALL) and lymphoblastic lymphoma regimens.
Management
Treat the underlying complication (pancreatitis, anaphylaxis/shock, thrombosis, hyperammonemia) and support renal perfusion with fluids; prerenal AKI usually reverses with resolution. Discontinue or switch asparaginase formulation for severe toxicity.
Risk factors
- Asparaginase-induced pancreatitis
- Hypersensitivity reactions with hypotension
- Thrombotic complications and acquired coagulopathy (low antithrombin III)
- Hyperammonemia/metabolic stress
Prevention
- Monitor for pancreatitis (amylase/lipase, symptoms) and hypersensitivity reactions
- Supportive hydration and prompt management of complications
- Thrombosis surveillance/prophylaxis and antithrombin repletion per protocol
Note · Rare AKI, predominantly pancreatitis-, thrombosis-, and hemodynamics-mediated; not a direct nephrotoxin and not renally cleared.
Clinical depth
Renal dose adjustment
Large protein cleared by reticuloendothelial proteolysis, not renal filtration - no renal dose adjustment. Management is toxicity-driven (hold/switch for pancreatitis, severe hypersensitivity, or thrombosis).
Dialyzability & ESKD dosing
Large enzyme; not dialyzable. Dialysis/CRRT is used to support AKI or refractory hyperammonemia, not to clear the drug.
Differential diagnosis
Pancreatitis- or sepsis-driven prerenal/ischemic AKI vs thrombotic vascular events vs tumor lysis at induction. The accompanying pancreatitis, coagulopathy, or thrombosis points away from a primary renal lesion.
Monitoring
- Amylase/lipase and abdominal symptoms (pancreatitis)
- Fibrinogen and antithrombin III; signs of thrombosis
- Ammonia if encephalopathy; glucose, triglycerides, LFTs
- Creatinine/volume status with any complication
Key trials & series
- Pediatric ALL backbone regimens (e.g. COG/Berlin-Frankfurt-Munster protocols) defining the asparaginase toxicity profile
Clinical pearls
- Asparaginase rarely touches the kidney directly - look for pancreatitis, thrombosis, or shock as the cause of AKI.
- It depletes antithrombin III and fibrinogen, so its renal/vascular risk is thrombotic as much as hemodynamic.
- Because clearance is proteolytic, no renal dose adjustment is needed.
Where it strikes
Nephron segments
Vasculature / Endothelium
Glomerular & peritubular capillaries
Injury signatures
Prerenal / Hemodynamic AKI
Evidence
5 peer-reviewed references. Citation metadata via PubMed / NLM.
LandmarkAsparaginase-associated toxicity in children with acute lymphoblastic leukemia.Hijiya N et al. · Leuk Lymphoma 2016 · PMID 26457414Comprehensive review of asparaginase toxicities (hypersensitivity, pancreatitis, thrombosis, hepatotoxicity) underlying secondary AKI.PMIDAdverse reactions of L-asparaginase.Cairo MS · Am J Pediatr Hematol Oncol 1982 · PMID 6959544Classic catalog of asparaginase toxicities including pancreatitis, coagulopathy, and reported nephrotoxicity.PMIDAsparaginase-associated hyperammonemia.Raja RA et al. · Haematologica 2025 · PMID 40270200Reviews hyperammonemia and the broader metabolic toxicity spectrum that can accompany hemodynamic/renal compromise.PMIDAsparaginase toxicity in Hispanic adult and pediatric patients with acute lymphoblastic leukemia: current understanding.Alqahtani A et al. · Expert Opin Drug Metab Toxicol 2023 · PMID 37410014Summarizes incidence of pancreatitis, thrombosis, and other toxicities driving secondary organ injury.PMIDOnconephrology.Kala J et al. · Crit Care Clin 2021 · PMID 33752861Context for prerenal/ischemic AKI mechanisms accompanying chemotherapy complications.
Related agents
Other agents sharing the same signature kidney injury.