Doxorubicin
Adriamycin · Anthracycline
Experimental podocyte model; clinical proteinuria rare.
GLOM
MildOpen →
mTOR inhibitor
mTOR Inhibitors
Afinitor · Torisel · mTORi
Disrupt the podocyte's maintenance program and protein slips through.
MildmTOR inhibitor · approved 2009
Renal cellNeuroendocrineBreast
Signature kidney injury
Glomerular Injury / Proteinuria
Representative incidence12%
Everolimus all-grade proteinuria ~10–14%, high-grade ~1–2%. Temsirolimus case-level only.
Source: Vollenbröker et al., Am J Physiol Renal Physiol 2008; Letavernier et al., 2008
Toxicity fingerprint
Tap a signature to trace where it strikes the nephron.
0%incidence
SeverityMild
ReversibilityReversible
Evidence0 refs
Nephron map
GlomerulusFiltration barrier (podocytes + endothelium)
Proximal Tubule
Distal Tubule / Collecting Duct
Glomerular Injury / Proteinuria
Damage to the filtration barrier — podocyte injury, FSGS and protein leak from VEGF and mTOR blockade.
Mechanism of kidney injury
mTOR inhibition down-regulates slit-diaphragm proteins (nephrin, TRPC6) and disrupts the podocyte cytoskeleton, impairing autophagy/repair and downstream VEGF signaling — producing proteinuria and FSGS.
Clinical presentation
Proteinuria (sometimes nephrotic range), occasionally a rising creatinine.
Onset
Weeks–months.
Reversibility
Reversible
Anticancer mechanism
Everolimus and temsirolimus inhibit mTORC1 to block cell growth, proliferation and angiogenesis. Renal cell, neuroendocrine and breast cancer.
Management
ACEi/ARB, dose reduction or hold.
Risk factors
- Pre-existing CKD / proteinuria
Prevention
- Urine-protein monitoring
Note · Same drug class used in transplant (sirolimus). Temsirolimus incidence is not firmly quantified.
Where it strikes
Nephron segments
Glomerulus
Filtration barrier (podocytes + endothelium)
Proximal Tubule
Bulk reabsorption + drug uptake (OCT2, OATs)
Injury signatures
Glomerular Injury / ProteinuriaAcute Tubular Necrosis
Beyond the kidney
Class-level context for the major non-renal toxicities of mtor inhibitors.
Pulmonary
Pneumonitis, ILD, effusions, hypertension
- Non-infectious pneumonitis
Endocrine
Thyroiditis, hypophysitis, diabetes
- Hyperglycemia, hyperlipidemia
Gastrointestinal
Diarrhea, colitis, mucositis, perforation
- Stomatitis
Immune / Infusion
CRS, infusion reactions, irAEs, anaphylaxis
- Immunosuppression / infection
Evidence
5 peer-reviewed references. Citation metadata via PubMed / NLM.
LandmarkmTOR regulates expression of slit diaphragm proteins and cytoskeleton structure in podocytes.Vollenbröker B et al. · Am J Physiol Renal Physiol 2008 · PMID 19019920Molecular mechanism of mTOR-inhibitor proteinuria and FSGS.PMIDmToR inhibitors-induced proteinuria: mechanisms, significance, and management.Letavernier E et al. · Transplant Rev (Orlando) 2008 · PMID 18631865Links sirolimus/everolimus to podocyte injury and FSGS.PMIDmTOR-mediated podocyte hypertrophy regulates glomerular integrity in mice and humans.Puelles VG et al. · JCI Insight 2019 · PMID 31534053mTOR inhibition during podocyte loss causes albuminuria and glomerulosclerosis.PMIDmTOR inhibitors and renal allograft: Yin and Yang.Zaza G et al. · J Nephrol 2014 · PMID 24804854Dose- and duration-dependent renal toxicity including proteinuria.PMIDCyclosporine versus everolimus: effects on the glomerulus.Baas MC et al. · Clin Transplant 2013 · PMID 23795805Clinical/biopsy evidence on everolimus proteinuria.
Related agents
Other agents sharing the same signature kidney injury.