Anthracycline
Doxorubicin
Adriamycin · Doxo
Anthracycline · approved 1974 · 9 references
The classic anthracycline whose podocyte-injury model defines experimental FSGS, though clinical proteinuria is rare.
- Signature injury
- Glomerular Injury / Proteinuria
- Severity
- Mild
- Reversibility
- Variable
- Onset
- Subacute in models (over weeks); clinical events rare and variable.
Signature kidney injury & incidence
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. Separately, doxorubicin — especially the pegylated liposomal formulation — is an increasingly recognized but underreported cause of kidney-limited thrombotic microangiopathy (a vascular/endothelial lesion), described in biopsy-proven case reports and drug-induced-TMA series.
Source: Lee & Harris, Nephrology (Carlton) 2011 (model review)
Reported injury signatures: Glomerular Injury / Proteinuria, Thrombotic Microangiopathy, Hemorrhagic Cystitis.
Renal toxicity profile
- Glomerular Injury / ProteinuriaPrimary
- Thrombotic MicroangiopathySecondary
- Hemorrhagic CystitisRareIntravesical instillation only - chemical cystitis in randomized instillation trials, not a systemic-route toxicity.
Onset timing & rechallenge
Subacute (~1–6 weeks) — Glomerular injury develops subacutely over weeks in models, with clinical events rare and variable.
Mechanism of kidney injury
Clinical presentation
Management
Risk factors
- High cumulative exposure (experimental)
- Pre-existing glomerular disease or podocyte susceptibility
Prevention
- Adhere to cumulative dose limits (primarily for cardiotoxicity)
Renal dose adjustment
Dialyzability & ESKD dosing
Differential diagnosis
Monitoring
- Cumulative anthracycline dose and cardiac function (LVEF) — the principal dose-limiting toxicity
- Urinalysis/UPCR in patients who develop edema or proteinuria
- Urine protein in susceptible patients
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.
- Chemical cystitis is an intravesical-route doxorubicin toxicity documented in randomized instillation trials (irritative symptoms, occasionally contracted bladder); systemic doxorubicin is almost always cyclophosphamide-paired, so systemic hemorrhagic-cystitis reports mostly belong to the partner drug.
Anticancer mechanism
Note
Guidelines & consensus
Each recommendation below is this atlas's faithful summary of the source, not a quotation from it — follow the PubMed link for the wording the society published. Summaries may be superseded; consult the current full text and individualize to the patient.
- ADQI (2026) — The nephrotoxic effects of anti-cancer therapies: consensus report of the 34th Acute Disease Quality Initiative workgroupProvides expert-based statements (modified Delphi) on preventing and managing cisplatin/platinum-associated AKI, including isotonic IV hydration, attention to volume status and concomitant nephrotoxins, and incorporates evidence that IV magnesium supplementation may reduce cisplatin-associated AKI; emphasizes risk stratification and standardized AKI definitions.Nat Rev Nephrol · PMID 41361704
- SIRM (2022) — SIRM-SIN-AIOM: appropriateness criteria for evaluation and prevention of renal damage in the patient undergoing contrast medium examinations-consensus statements from Italian College of Radiology (SIRM), Italian College of Nephrology (SIN) and Italian Association of Medical Oncology (AIOM)Recommends eGFR-based renal risk assessment and pre/post-contrast isotonic saline or sodium bicarbonate hydration; advises maintaining a 5-7 day interval between iodinated contrast administration and cisplatin in cancer patients to reduce additive nephrotoxicity.Radiol Med · PMID 35303246
- KDIGO (2020) — KDIGO Controversies Conference on onco-nephrology: understanding kidney impairment and solid-organ malignancies, and managing kidney cancerIdentifies platinum compounds (especially cisplatin) as leading cytotoxic causes of acute tubular injury, AKI, and electrolyte/magnesium wasting; calls for interdisciplinary onco-nephrology care, accurate GFR estimation, and individualized drug dosing in patients with reduced kidney function.Kidney Int · PMID 33126977
- KDIGO (2020) — KDIGO Controversies Conference on onco-nephrology: kidney disease in hematological malignancies and the burden of cancer after kidney transplantationAddresses chemotherapy-associated AKI/CKD in hematologic cancer, GFR estimation and chemotherapy dosing in patients with reduced kidney function, and management priorities and research gaps for onco-nephrology care.Kidney Int · PMID 33276867
- ADDIKD (2025) — Integrating International Consensus Guidelines for Anticancer Drug Dosing in Kidney Dysfunction (ADDIKD) into everyday practiceProvides GRADE-based, drug-specific dose-adjustment recommendations for anticancer agents in kidney dysfunction (illustrated for methotrexate, cisplatin, carboplatin and nivolumab); the recommendations build on Part 1's standardised CKD-EPI eGFR assessment rather than Cockcroft-Gault creatinine clearance.EClinicalMedicine · PMID 40290844
- ADDIKD (2025) — Aligning kidney function assessment in patients with cancer to global practices in internal medicineThree consensus recommendations: assess kidney function by GFR (measured GFR or CKD-EPI eGFR), classify it using KDIGO categories, and use this uniform approach to dose anticancer drugs — moving cancer medicine away from Cockcroft-Gault estimated creatinine clearance.EClinicalMedicine · PMID 40290845
- ADDIKD (2025) — A methodology for determining dosing recommendations for anticancer drugs in patients with reduced kidney functionEstablishes that, where RCT evidence is lacking, anticancer drug dosing recommendations in kidney dysfunction should be derived by critically appraising observational literature via GRADE combined with structured international multidisciplinary consensus voting.EClinicalMedicine · PMID 40290846
- KDIGO (2013) — Diagnosis, evaluation, and management of acute kidney injury: a KDIGO summary (Part 1)Defines/stages AKI by serum creatinine and urine output; emphasizes avoiding nephrotoxins, maintaining euvolemia/perfusion, dose-adjusting drugs to kidney function, and monitoring high-risk patients — the framework applied to nephrotoxic anti-cancer agents.Crit Care · PMID 23394211
- KDIGO (2024) — Executive summary of the KDIGO 2024 Clinical Practice Guideline for the Evaluation and Management of Chronic Kidney Disease: known knowns and known unknownsEvaluate and risk-stratify CKD, manage to delay progression and its complications, and practise explicit medication management and drug stewardship — the framework the atlas's G1–G5 eGFR banding and every renal dose-adjustment recommendation sit inside. Because the guideline excludes dialysis and transplant recipients by its own statement of scope, its recommendations do not carry to those settings, where this atlas's dialyzability and post-transplant guidance rests on other sources.Kidney Int · PMID 38519239
- KDIGO (2021) — Executive summary of the KDIGO 2021 Guideline for the Management of Glomerular DiseasesProvides the staging/treatment framework for drug-associated glomerular lesions (e.g., bisphosphonate- and interferon-related collapsing FSGS, VEGF-inhibitor podocytopathy/proteinuria), including immunosuppression and supportive RAAS-blockade strategies.Kidney Int · PMID 34556300
- KDIGO (2024) — Executive summary of the KDIGO 2024 Clinical Practice Guideline for the Management of ANCA-Associated VasculitisUpdates immunosuppressive induction (rituximab/cyclophosphamide), incorporates avacopan and lower-dose or glucocorticoid-sparing regimens — the management framework for drug- and checkpoint-inhibitor-associated ANCA/pauci-immune glomerulonephritis.Kidney Int · PMID 38388147
- KDIGO (2024) — Executive summary of the KDIGO 2024 Clinical Practice Guideline for the Management of Lupus NephritisUpdates first-line lupus nephritis therapy to combination immunosuppression with the addition of belimumab or a calcineurin inhibitor (voclosporin) — informs management of immune-complex/lupus-like glomerulonephritis encountered with immunotherapy.Kidney Int · PMID 38182299
- KDIGO (2025) — Executive summary of the KDIGO 2025 Clinical Practice Guideline for the Management of Immunoglobulin A Nephropathy (IgAN) and Immunoglobulin A Vasculitis (IgAV)Encourages liberal kidney biopsy and stricter proteinuria control (<0.5 g/d, ideally <0.3 g/d) with RAAS blockers, SGLT2 inhibitors, and targeted-release budesonide — the framework for IgA-dominant glomerular lesions, including those triggered by immune-modulating cancer therapy.Kidney Int · PMID 40975525
References
9 peer-reviewed references. Citation metadata via PubMed / NLM.
- 1.Renoprotective approaches against anthracycline nephrotoxicity.Weldemichael T, Hye Khan MA, Imig JD · Biochem Pharmacol · 2026 · PMID 41621691
- 2.Adriamycin nephropathy: a model of focal segmental glomerulosclerosis.Lee VW et al. · Nephrology (Carlton) · 2011 · PMID 21175974
- 3.Sirt6 deficiency exacerbates podocyte injury and proteinuria through targeting Notch signaling.Liu M et al. · Nat Commun · 2017 · PMID 28871079
- 4.New drug toxicities in the onco-nephrology world.Perazella MA et al. · Kidney Int · 2015 · PMID 25671763
- 5.Anticancer Drug-Induced Acute Kidney Injury.Izzedine H et al. · Kidney Int Rep · 2017 · PMID 29318217
- 6.Onconephrology: The intersections between the kidney and cancer.Rosner MH et al. · CA Cancer J Clin · 2020 · PMID 32853404
- 7.A randomized trial of intravesical doxorubicin and immunotherapy with bacille Calmette-Guérin for transitional-cell carcinoma of the bladder.Lamm DL et al. · N Engl J Med · 1991 · PMID 1922207
- 8.Intravesical epirubicin versus doxorubicin for superficial bladder tumors (stages pTa and pT1): a randomized prospective study.Ali-el-Dein B et al. · J Urol · 1997 · PMID 9186325
- 9.Epirubicin: a review of its intravesical use in superficial bladder cancer.Onrust SV et al. · Drugs Aging · 1999 · PMID 10582777
Case reports & series (3)
The weakest rung of clinical evidence — single-patient and small-series reports, strongest first. Each carries a heuristic strength grade (A Strong / B Moderate / C Limited) inferred from its abstract and journal, not a formal appraisal. Weigh well below the primary references above.
- C1.[A · Strong]Pegylated Liposomal Doxorubicin and Kidney-Limited Thrombotic Microangiopathy in a Kidney Transplant Recipient: A Case Report.Rodriguez-Ramirez S et al. · Kidney Med · 2022 · PMID 35509676
- C2.[B · Moderate]Pegylated Liposomal Doxorubicin Causes Kidney-limited Thrombotic Microangiopathy.Glezerman I et al. · Am J Kidney Dis · 2024 · PMID 37839689
- C3.[C · Limited]Pegylated-liposomal Doxorubicin-induced Glomerular Thrombotic Microangiopathy.Yokoyama S et al. · Intern Med · 2024 · PMID 38462521
Conference abstracts (1) — non-PubMed, no PMID
- A1.Drug-Induced Thrombotic Microangiopathy from Cancer Therapies: A Clinicopathologic SeriesASN Kidney Week 2024 · SA-PO198Single-center series of 53 biopsy-proven drug-induced renal TMAs — gemcitabine (49%), bevacizumab (25%), TKIs (19%), and doxorubicin (15%, flagged as underrecognized). Most showed chronic histology, suggesting smoldering endothelial injury precedes overt TMA; early drug cessation improved recovery.