Cyclophosphamide
Cytoxan · Oxazaphosphorine alkylator
Vasopressin-independent hyponatremia; hemorrhagic cystitis.
SIADHCYST
MildOpen →
Vinca alkaloid
Vinblastine
Velban · VBL
A vinca alkaloid linked to SIADH-type hyponatremia and rare vascular events.
MildVinca alkaloid · approved 1965
Hodgkin lymphomaTesticular/germ-cell cancerBladder cancer
Signature kidney injury
SIADH / Hyponatremia
As a vinca alkaloid, vinblastine can cause SIADH with hyponatremia; this is a recognized class effect reported at case level rather than as a quantified rate. Rare Raynaud phenomenon and other vascular events (especially in germ-cell regimens) are also described.
Source: Zhong et al., Expert Opin Drug Saf 2024
Mechanism of kidney injury
Promotes inappropriate antidiuresis (SIADH) with enhanced collecting-duct water reabsorption, producing dilutional, euvolemic hyponatremia. There is no characteristic direct tubular or glomerular toxin effect; vascular events reflect endothelial/vasospastic phenomena rather than intrinsic nephrotoxicity.
Clinical presentation
Euvolemic hyponatremia with low plasma osmolality and inappropriately concentrated urine (urine osm >100, urine Na >30); symptoms scale with severity and the rate of sodium fall. Watch for digital ischemia/Raynaud as a separate vascular signal.
Onset
Days after administration, generally within the first cycles.
Reversibility
Reversible
Anticancer mechanism
Microtubule-destabilizing vinca alkaloid that binds beta-tubulin, blocks mitotic spindle formation, and arrests dividing cells at metaphase. Used in Hodgkin lymphoma (ABVD), germ-cell tumors, and bladder cancer.
Management
Fluid restriction for mild cases; 3% hypertonic saline for severe/symptomatic hyponatremia with a controlled correction rate (<=8 mmol/L/24 h). Withhold the drug and manage any vascular complications supportively.
Risk factors
- Concurrent SIADH-promoting medications or conditions
- Excess hypotonic fluid intake
- Combination vinca-containing or platinum-containing regimens (vascular events)
Prevention
- Monitor serum sodium during therapy
- Avoid excess free water in at-risk patients
- Plan controlled sodium correction if hyponatremia develops
Note · SIADH and rare Raynaud/vascular events define the profile; the kidneys are not directly injured.
Clinical depth
Renal dose adjustment
Hepatically metabolized (CYP3A) and biliary excreted - no renal dose adjustment; reduce for hepatic impairment/hyperbilirubinemia. Never give intrathecally.
Dialyzability & ESKD dosing
Large volume of distribution and extensive tissue binding; not dialyzable. Manage hyponatremia with fluid/sodium strategies.
Differential diagnosis
Vinca-induced SIADH (euvolemic, concentrated urine) vs hypovolemic or hypervolemic hyponatremia vs paraneoplastic ectopic ADH. Volume status and urine indices distinguish them; Raynaud is a distinct vascular adverse effect.
Monitoring
- Serum sodium and osmolality during early cycles
- Urine osmolality/sodium if hyponatremia develops
- Assessment for Raynaud/digital ischemia
Key trials & series
- Zhong Expert Opin Drug Saf 2024 FAERS vinca-alkaloid disproportionality analysis
Clinical pearls
- Treat vinblastine hyponatremia as SIADH - water restriction first.
- Keep correction <=8 mmol/L/24 h to avoid osmotic demyelination.
- Digital ischemia/Raynaud is a recognized vinca vascular effect, separate from the renal electrolyte signal.
Where it strikes
Nephron segments
Distal Tubule / Collecting Duct
Fine-tuning of Na, K, Mg, acid & water
Injury signatures
SIADH / HyponatremiaElectrolyte Wasting
Beyond the kidney
Class-level context for the major non-renal toxicities of vinca alkaloids.
Ophthalmic
Keratopathy, uveitis, retinopathy
- Visual disturbance (crizotinib)
Hepatic / Liver
Transaminitis, hepatitis, VOD/SOS
- Transaminitis
Neurologic
Neuropathy, encephalopathy, ICANS, PRES
- CNS effects (lorlatinib)
Evidence
5 peer-reviewed references. Citation metadata via PubMed / NLM.
LandmarkA real-world pharmacovigilance study using disproportionality analysis of FDA Adverse Event Reporting System events for vinca alkaloids: comparing vinorelbine and vincristine.Zhong C et al. · Expert Opin Drug Saf 2024 · PMID 39340205FAERS disproportionality analysis identifying inappropriate ADH secretion among vinca-alkaloid adverse events.PMIDPathophysiology of Drug-Induced Hyponatremia.Kim GH et al. · J Clin Med 2022 · PMID 36233678Mechanistic review of drug-induced SIADH/hyponatremia relevant to vinca alkaloids.PMIDDiagnosis and Management of Hyponatremia: A Review.Adrogué HJ et al. · JAMA 2022 · PMID 35852524Authoritative SIADH management guidance including safe correction limits.PMIDAnti-Microtubule Drugs.Florian S et al. · Methods Mol Biol 2016 · PMID 27193863Reviews the tubulin-binding mechanism shared by vinblastine and other vinca alkaloids.PMIDOnconephrology: The intersections between the kidney and cancer.Rosner MH et al. · CA Cancer J Clin 2020 · PMID 32853404Onconephrology review covering chemotherapy-associated electrolyte disorders.