Doxorubicin
Adriamycin · Anthracycline
Experimental podocyte model; clinical proteinuria rare.
GLOM
MildOpen →
Cytokine
Interferon-α
Intron A · Roferon-A · IFN
A podocyte poison — the classic trigger of collapsing FSGS in APOL1 carriers.
SevereCytokine immunotherapy · approved 1986
MelanomaRenal cellCMLKaposi sarcoma
Signature kidney injury
Glomerular Injury / Proteinuria
Rare; best characterized by an 11-case biopsy series, disproportionately in Black patients (APOL1).
Source: Markowitz et al., CJASN 2010
Mechanism of kidney injury
Direct interferon-induced podocyte injury (a podocytopathy), with endothelial tubuloreticular inclusions on electron microscopy — strongly associated with APOL1 high-risk genotype.
Clinical presentation
Nephrotic-range proteinuria (mean ~9.7 g/day), AKI (mean creatinine ~3.5 mg/dL) and edema.
Onset
Subacute — weeks to months of therapy.
Reversibility
Variable
Anticancer mechanism
Immunomodulatory, antiproliferative cytokine. Historically melanoma, renal cell, CML and Kaposi sarcoma.
Management
Discontinue interferon (the primary treatment); supportive nephrotic care. Immunosuppression is generally ineffective.
Risk factors
- Black race / APOL1 high-risk genotype
Prevention
- Monitor proteinuria and renal function
Note · Largely historical, but a key teaching case for collapsing FSGS and APOL1.
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 cytokines.
Immune / Infusion
CRS, infusion reactions, irAEs, anaphylaxis
- Flu-like syndrome, capillary leak (IL-2)
Neurologic
Neuropathy, encephalopathy, ICANS, PRES
- Depression, fatigue (interferon)
Evidence
3 peer-reviewed references. Citation metadata via PubMed / NLM.
LandmarkTreatment with IFN-α, -β, or -γ is associated with collapsing focal segmental glomerulosclerosis.Markowitz GS et al. · Clin J Am Soc Nephrol 2010 · PMID 20203164Landmark series establishing interferon as a cause of collapsing FSGS.PMIDRenal diseases secondary to interferon-β treatment: a multicentre clinico-pathological study and systematic literature review.Dauvergne M et al. · Clin Kidney J 2021 · PMID 34950468Largest IFN-β nephropathy series defining the TMA/FSGS spectrum.PMIDCollapsing glomerulopathy in a young woman with APOL1 risk alleles following acute parvovirus B19 infection: a case report investigation.Besse W et al. · BMC Nephrol 2016 · PMID 27600725Links APOL1, interferon-mediated immunity and collapsing glomerulopathy.
Related agents
Other agents sharing the same signature kidney injury.