Bendamustine
Treanda · Alkylator
Tumor lysis-mediated AKI is the principal risk; TMA is rare.
PRETMALYTE
ModerateOpen →
Purine analog
Cladribine
Leustatin · CLAD
A purine analog that is renally quiet at standard hairy-cell doses — its kidney risk is tumor lysis, not the drug.
MildPurine nucleoside analog · approved 1993
Hairy-cell leukemiaOff-label: chronic lymphocytic leukemia, low-grade non-Hodgkin lymphoma, Langerhans-cell histiocytosis, AML regimens (CLAG)
Signature kidney injury
Prerenal / Hemodynamic AKI
At standard hairy-cell-leukemia doses cladribine is renally quiet; clinically significant nephrotoxicity is uncommon and dose-related, worst at historical high investigational doses. The dominant renal hazard is tumor lysis syndrome in bulky/leukocytotic disease, reported at the case level rather than as a population incidence.
Source: Saven et al., Blood 1998
Toxicity fingerprint
Tap a signature to trace where it strikes the nephron.
Incidence not quantified
SeverityMild
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
Renal injury is largely indirect: rapid lysis of bulky disease causes tumor lysis syndrome with hyperuricemia (urate crystal nephropathy and intratubular obstruction), hyperphosphatemia (calcium-phosphate deposition) and hyperkalemia, producing crystal/obstructive and hemodynamic AKI. Cladribine is not a direct tubular toxin at standard doses; a dose-related intrinsic nephrotoxicity emerges only with the high doses used historically.
Clinical presentation
When tumor lysis occurs: a rising uric acid, phosphate and potassium with a falling calcium and rising creatinine within 24-72 h of starting therapy in high-burden disease. Profound and prolonged CD4 lymphopenia follows treatment (opportunistic-infection risk).
Onset
Tumor-lysis AKI is acute (24-72 h); high-dose sensorimotor neuropathy is delayed (weeks).
Reversibility
Reversible
Anticancer mechanism
Purine nucleoside analog of deoxyadenosine; the 2-chloro substitution resists adenosine deaminase. Phosphorylated by deoxycytidine kinase to 2-chloro-dATP, which accumulates selectively in lymphocytes and monocytes (high deoxycytidine kinase, low 5'-nucleotidase), causing DNA strand breaks, NAD/ATP depletion and apoptosis of both dividing and resting cells.
Management
Standard tumor-lysis management: aggressive hydration, rasburicase for hyperuricemia (avoid urinary alkalinization with rasburicase), correct electrolytes, and dialysis for refractory derangements. Supportive care for myelosuppression and infection surveillance.
Risk factors
- High tumor burden/leukocytosis and bulky disease
- Pre-existing renal impairment and volume depletion
- High cumulative or high-dose regimens
- High baseline uric acid
Prevention
- Tumor-lysis prophylaxis by risk: IV hydration plus allopurinol (intermediate) or rasburicase (high)
- Electrolyte and uric-acid monitoring in high-burden disease
- PJP and herpesvirus prophylaxis for prolonged CD4 lymphopenia
- Reduce/space the dose in significant CKD rather than withholding
Note · Established (1993) agent; renal events are tumor-lysis-driven and case-level, not population-quantified. Direct nephrotoxicity is a high-dose phenomenon.
Clinical depth
Renal dose adjustment
Substantially renally eliminated; the label advises caution and consideration of dose reduction with close monitoring in renal impairment. No firmly validated CrCl bands exist; published practice uses reduced/spaced (e.g. every-other-week) dosing in severe CKD, where complete remission is still achievable.
Dialyzability & ESKD dosing
Not reliably characterized and not considered readily dialyzable for drug removal; dialysis is used to manage tumor-lysis metabolic derangements.
Differential diagnosis
Tumor lysis (most likely with bulky disease) versus prerenal volume depletion, neutropenic-sepsis ATN, concurrent nephrotoxins and disease infiltration/CKD. The metabolic panel and tumor burden anchor the diagnosis.
Monitoring
- CBC with differential (profound, prolonged myelosuppression and CD4 lymphopenia)
- Creatinine/eGFR and tumor-lysis panel in high-burden disease
- Infection surveillance (opportunistic infections)
- Neurologic exam at higher doses
Key trials & series
- Scripps long-term HCL cohort (Saven, Blood 1998) — 91% CR, standard of care
- Dann NEJM 1993 — classic case linking cladribine to tumor lysis syndrome
Clinical pearls
- At standard hairy-cell doses cladribine is renally quiet — the dominant risk is tumor lysis, which scales with tumor burden, not drug exposure.
- Reduce/space the dose and monitor in CKD rather than withholding — complete remission is achievable even in severe renal failure.
- The feared high-dose toxicity is delayed, potentially irreversible sensorimotor neuropathy.
- Profound durable CD4 lymphopenia is the rule — plan opportunistic-infection prophylaxis.
Where it strikes
Nephron segments
Vasculature / Endothelium
Glomerular & peritubular capillaries
Tubular Lumen
The urine flow path
Injury signatures
Prerenal / Hemodynamic AKICrystal / Obstructive NephropathyElectrolyte Wasting
Beyond the kidney
Class-level context for the major non-renal toxicities of purine 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
8 peer-reviewed references. Citation metadata via PubMed / NLM.
LandmarkLong-term follow-up of patients with hairy cell leukemia after cladribine treatment.Saven A et al. · Blood 1998 · PMID 9731048Pivotal Scripps cohort establishing cladribine as standard of care in hairy-cell leukemia.PMIDMechanism of deoxyadenosine and 2-chlorodeoxyadenosine toxicity to nondividing human lymphocytes.Seto S et al. · J Clin Invest 1985 · PMID 2579098Foundational mechanism: kills resting lymphocytes via DNA strand breaks and NAD/ATP depletion.PMID2-Chlorodeoxyadenosine: a newer purine analog active in the treatment of indolent lymphoid malignancies.Saven A et al. · Ann Intern Med 1994 · PMID 7908507Authoritative early review of mechanism, pharmacology and trials.PMIDBrief report: tumor lysis syndrome following treatment with 2-chlorodeoxyadenosine for refractory chronic lymphocytic leukemia.Dann EJ et al. · N Engl J Med 1993 · PMID 8105383Classic case linking cladribine to tumor lysis syndrome — the key renal/metabolic signal.PMIDTherapeutic and neurotoxic effects of 2-chlorodeoxyadenosine in adults with acute myeloid leukemia.Vahdat L et al. · Blood 1994 · PMID 7949097Dose-escalation defining high-dose dose-limiting toxicities (delayed neuropathy and tumor lysis).PMIDCladribine Efficacy in a Patient with Hairy Cell Leukemia and Severe Renal Insufficiency.Gozzetti A et al. · Rev Recent Clin Trials 2023 · PMID 37779396Dosing in renal impairment — a spaced schedule achieving complete remission in severe CKD.PMIDRecommendations for the evaluation of risk and prophylaxis of tumour lysis syndrome (TLS) in adults and children with malignant diseases: an expert TLS panel consensus.Cairo MS et al. · Br J Haematol 2010 · PMID 20331465Expert consensus on tumor-lysis risk stratification and prophylaxis.PMIDOnconephrology: The intersections between the kidney and cancer.Rosner MH et al. · CA Cancer J Clin 2020 · PMID 32853404Comprehensive onconephrology reference covering AKI, tumor lysis and CKD in cancer.
Related agents
Other agents sharing the same signature kidney injury.