Bendamustine
Treanda · Alkylator
Tumor lysis-mediated AKI is the principal risk; TMA is rare.
PRETMALYTE
ModerateOpen →
Nucleoside analog
Cytarabine
Cytosar · AraC
The leukemia cornerstone whose renal danger comes from the tumor burden it melts away.
ModerateNucleoside analog antimetabolite · approved 1969
Acute myeloid leukemia (induction and high-dose consolidation)Acute lymphoblastic leukemiaLymphoma / CNS prophylaxis (intrathecal)
Signature kidney injury
Prerenal / Hemodynamic AKI
Intrinsic tubular nephrotoxicity is uncommon; the major renal risk is AKI from tumor lysis syndrome during leukemia/lymphoma cytoreduction, reported at case and series level including fatal TLS. Direct cytarabine-nephrotoxicity primary literature is genuinely sparse.
Source: Seymour et al., Cancer 2002
Toxicity fingerprint
Tap a signature to trace where it strikes the nephron.
Incidence not quantified
SeverityModerate
ReversibilityReversible
Evidence0 refs
Nephron map
Vasculature / EndotheliumGlomerular & peritubular capillaries
Distal Tubule / Collecting Duct
Tubular Lumen
Prerenal / Hemodynamic AKI
Renal hypoperfusion from capillary leak and cytokine storm — IL-2 and CAR-T cytokine release syndrome.
Mechanism of kidney injury
Rapid leukemic/lymphoma cell kill releases uric acid, potassium and phosphate, producing tumor lysis syndrome with uric acid and calcium-phosphate crystal precipitation, intratubular obstruction and AKI; oliguria and electrolyte derangements dominate. High-dose cytarabine adds systemic toxicities (cerebellar, ocular, mucosal) but not characteristic tubular injury; renal clearance considerations modestly affect high-dose scheduling.
Clinical presentation
Hyperuricemia, hyperkalemia, hyperphosphatemia, hypocalcemia and rising creatinine at the start of cytoreductive therapy; oliguria in severe TLS.
Onset
Hours to days after initiating therapy in high-burden disease.
Reversibility
Reversible
Anticancer mechanism
Pyrimidine nucleoside analog phosphorylated to ara-CTP, which incorporates into DNA and inhibits DNA polymerase, halting S-phase replication. Cornerstone of acute myeloid leukemia induction/consolidation and used in lymphomas and CNS prophylaxis (intrathecal).
Management
Treat established TLS with IV fluids, rasburicase, electrolyte correction and dialysis if needed (per the 2015 British/expert TLS guidance); supportive care for high-dose toxicities. TLS-related AKI is generally reversible with prompt management.
Risk factors
- High tumor burden / high blast count
- High baseline uric acid and LDH
- Volume depletion and pre-existing renal impairment
- Bulky/aggressive lymphoma (e.g., Burkitt)
Prevention
- TLS prophylaxis: aggressive hydration plus allopurinol or rasburicase by risk
- Frequent electrolyte and renal monitoring during induction
- Avoid additive nephrotoxins
Note · The signature renal event is disease-/TLS-mediated AKI rather than direct cytarabine tubular toxicity; high-dose cytarabine toxicity is mainly neuro-ocular-mucosal, not renal.
Clinical depth
Renal dose adjustment
Standard-dose cytarabine needs little renal adjustment; for HIGH-dose cytarabine, reduced renal function (and age) increase the risk of neurotoxicity (cerebellar) so dose reduction is advised when creatinine/CrCl worsens. Renal handling is a high-dose neurotoxicity concern more than a nephrotoxicity one.
Dialyzability & ESKD dosing
Cytarabine is rapidly deaminated to inactive ara-U with a short half-life; it is not primarily managed by dialysis, though dialysis is used to treat TLS-related renal failure and electrolyte derangements.
Differential diagnosis
TLS-AKI (hyperuricemia, hyperphosphatemia, hyperkalemia, oliguria after cytoreduction) vs prerenal azotemia (volume-responsive) vs leukemic renal infiltration. With high-dose cytarabine, distinguish renal-function-driven cerebellar neurotoxicity from CNS disease - the kidney shapes neurotoxicity risk more than it manifests injury.
Monitoring
- TLS panel (uric acid, K, phosphate, calcium, creatinine) frequently during induction
- Neurologic/cerebellar exam with high-dose cytarabine, especially if renal function declines
- Urine output and volume status
Key trials & series
- Seymour Cancer 2002 (cisplatin-fludarabine-cytarabine salvage) - cytarabine-containing regimen with fatal TLS
- KDIGO onco-nephrology controversies conference (Malyszko Kidney Int 2020) - AKI/TLS in hematologic malignancy
- British/expert TLS management guidance (rasburicase, hydration)
Clinical pearls
- The renal threat is the tumor, not the drug: anticipate and prophylax TLS at induction in high-burden AML/lymphoma.
- With HIGH-dose cytarabine, a falling CrCl is a cerebellar-toxicity red flag - reduce dose and examine for nystagmus/ataxia.
- Rasburicase plus hydration is the workhorse for cytarabine-era TLS-AKI, which is usually reversible.
Where it strikes
Nephron segments
Vasculature / Endothelium
Glomerular & peritubular capillaries
Injury signatures
Prerenal / Hemodynamic AKICrystal / Obstructive NephropathyElectrolyte Wasting
Beyond the kidney
Class-level context for the major non-renal toxicities of nucleoside analogs.
Gastrointestinal
Diarrhea, colitis, mucositis, perforation
- Mucositis and diarrhea
Hepatic / Liver
Transaminitis, hepatitis, VOD/SOS
- Transaminitis (methotrexate)
Hematologic
Cytopenias, thrombosis, TMA
- Myelosuppression
Pulmonary
Pneumonitis, ILD, effusions, hypertension
- Methotrexate / gemcitabine pneumonitis
Evidence
6 peer-reviewed references. Citation metadata via PubMed / NLM.
LandmarkKDIGO Controversies Conference on onco-nephrology: kidney disease in hematological malignancies and the burden of cancer after kidney transplantation.Malyszko J et al. · Kidney Int 2020 · PMID 33276867Authoritative onco-nephrology review of AKI/TLS in leukemia/lymphoma (cytarabine-treated diseases).PMIDCisplatin, fludarabine, and cytarabine: a novel, pharmacologically designed salvage therapy for patients with refractory, histologically aggressive or mantle cell non-Hodgkin's lymphoma.Seymour JF et al. · Cancer 2002 · PMID 11857288Cytarabine-containing salvage therapy with a fatal tumor lysis syndrome event.PMIDVenetoclax plus low-dose cytarabine in patients with newly diagnosed acute myeloid leukemia ineligible for intensive chemotherapy: an expanded access study in Japan.Asada N et al. · Jpn J Clin Oncol 2023 · PMID 37017320Low-dose cytarabine-venetoclax cohort with TLS prophylaxis/hydration and treatment-related AKI.PMID[Analysis of the 2015 British guidelines on the prevention and management of tumor lysis syndrome].Dupre A et al. · Rev Med Interne 2016 · PMID 27659746TLS prevention/management (rasburicase, hydration) relevant to AraC-treated leukemia AKI.PMIDAdvanced Burkitt Lymphoma in Sub-Saharan Africa Pediatric Units: Results of the Third Prospective Multicenter Study of the Groupe Franco-Africain d'Oncologie Pediatrique.Bouda GC et al. · J Glob Oncol 2019 · PMID 31794283Cytarabine/methotrexate-containing high-burden lymphoma therapy with tumor lysis syndrome risk.PMIDAnticancer drug-induced kidney disorders.Kintzel PE · Drug Saf 2001 · PMID 11219485Onconephrology review of antimetabolite and tumor-lysis-related renal injury.
Related agents
Other agents sharing the same signature kidney injury.