Bevacizumab
Avastin · Anti-VEGF antibody
Proteinuria, hypertension, glomerular TMA.
GLOMHTNTMA
ModerateOpen →
Anthracycline
Doxorubicin
Adriamycin · Doxo
The classic anthracycline whose podocyte-injury model defines experimental FSGS, though clinical proteinuria is rare.
MildAnthracycline · approved 1974
Breast cancerHodgkin and non-Hodgkin lymphomaSarcomasAcute leukemias
Signature kidney injury
Glomerular Injury / Proteinuria
Adriamycin nephropathy is the canonical rodent model of podocyte injury and focal segmental glomerulosclerosis (FSGS); clinically significant glomerular disease from therapeutic dosing in patients is rare and largely case-level.
Source: Lee & Harris, Nephrology (Carlton) 2011 (model review)
Mechanism of kidney injury
In the experimental model, doxorubicin directly injures the podocyte: reactive oxygen species and mitochondrial dysfunction disrupt the actin cytoskeleton and slit diaphragm, causing foot-process effacement, podocyte detachment/apoptosis and a loss of glomerular permselectivity that progresses to segmental sclerosis with secondary tubulointerstitial inflammation and fibrosis. Susceptibility is strain- and gene-dependent (e.g., loci on chromosome 16 in mice), underscoring a genetic component to podocyte vulnerability. The human correlate is uncommon, which is why this is primarily a model rather than a frequent clinical toxicity.
Clinical presentation
Heavy (nephrotic-range) proteinuria, hypoalbuminemia and edema in the experimental setting; in patients, overt glomerular disease is unusual and, when seen, presents as proteinuria with or without a fall in GFR.
Onset
Subacute in models (over weeks); clinical events rare and variable.
Reversibility
Variable
Anticancer mechanism
Anthracycline antitumor antibiotic that intercalates DNA, poisons topoisomerase II (trapping the cleavable complex and producing double-strand breaks), and generates reactive oxygen species via redox cycling of its quinone moiety, driving apoptosis. Broadly used across breast cancer, lymphomas, sarcomas and acute leukemias.
Management
No specific renal therapy is established for the rare clinical glomerulopathy; supportive care with RAAS blockade (ACE inhibitor or ARB) to reduce proteinuria and management of any underlying glomerular disease. Liposomal formulations alter tissue distribution and are not associated with this glomerular signal clinically.
Risk factors
- High cumulative exposure (experimental)
- Pre-existing glomerular disease or podocyte susceptibility
Prevention
- Adhere to cumulative dose limits (primarily for cardiotoxicity)
- Monitor for proteinuria in susceptible patients
Note · Best known as an experimental podocyte-injury / FSGS model; clinical nephrotoxicity in patients is rare and largely case-level. The model's value is mechanistic insight into podocytopathy, not a warning about routine clinical use.
Clinical depth
Renal dose adjustment
No renal dose adjustment is required — doxorubicin is hepatically metabolized and biliary-excreted, so dosing is guided by hepatic function and bilirubin rather than renal function. Renal impairment does not mandate dose reduction.
Dialyzability & ESKD dosing
Not dialyzable to any clinically meaningful extent; doxorubicin is large, highly protein- and tissue-bound, with a very large volume of distribution, so hemodialysis does not remove it and no supplemental dosing is needed in ESKD.
Differential diagnosis
In a patient on doxorubicin with proteinuria, the differential is dominated by other causes of FSGS/podocytopathy (primary FSGS, viral, obesity-related, secondary maladaptive) and paraneoplastic glomerulonephritis; a kidney biopsy distinguishes drug-attributable podocyte injury from these far more common etiologies.
Monitoring
- Cumulative anthracycline dose and cardiac function (LVEF) — the principal dose-limiting toxicity
- Urinalysis/UPCR in patients who develop edema or proteinuria
Key trials & series
- No clinical trial carries a renal signal; the evidence base is the experimental adriamycin nephropathy literature
Clinical pearls
- Adriamycin nephropathy is a workhorse research model of FSGS, not a common clinical nephrotoxicity — keep the distinction clear.
- Doxorubicin is dosed by hepatic/bilirubin status, not renal function, and is not dialyzable.
- Real-world proteinuria in a doxorubicin-treated patient is more likely another glomerulopathy; biopsy before attributing it to the drug.
Where it strikes
Nephron segments
Glomerulus
Filtration barrier (podocytes + endothelium)
Injury signatures
Glomerular Injury / Proteinuria
Beyond the kidney
Class-level context for the major non-renal toxicities of anthracyclines.
Cardiac
Cardiomyopathy, QT, ischemia, myocarditis
- Dose-dependent cardiomyopathy and heart failure
Hematologic
Cytopenias, thrombosis, TMA
- Myelosuppression
Evidence
5 peer-reviewed references. Citation metadata via PubMed / NLM.
LandmarkAdriamycin nephropathy: a model of focal segmental glomerulosclerosis.Lee VW et al. · Nephrology (Carlton) 2011 · PMID 21175974Definitive review of the adriamycin nephropathy FSGS model: pharmacology, podocyte injury, genetics and pathogenesis.PMIDSirt6 deficiency exacerbates podocyte injury and proteinuria through targeting Notch signaling.Liu M et al. · Nat Commun 2017 · PMID 28871079Uses adriamycin-induced nephropathy as the experimental podocyte-injury/proteinuria model.PMIDNew drug toxicities in the onco-nephrology world.Perazella MA et al. · Kidney Int 2015 · PMID 25671763Onco-nephrology review of glomerular and other chemotherapy-associated renal injury.PMIDAnticancer Drug-Induced Acute Kidney Injury.Izzedine H et al. · Kidney Int Rep 2017 · PMID 29318217Review covering glomerular mechanisms of drug-induced kidney injury.PMIDOnconephrology: The intersections between the kidney and cancer.Rosner MH et al. · CA Cancer J Clin 2020 · PMID 32853404Reviews chemotherapy-associated glomerular disease and paraneoplastic glomerulopathy in the differential.
Related agents
Other agents sharing the same signature kidney injury.