Doxorubicin
Adriamycin · Anthracycline
Experimental podocyte model; clinical proteinuria rare.
GLOM
MildOpen →
Anti-VEGF antibody
Bevacizumab
Avastin · Bev
The proof that podocytes need VEGF — block it and the filter leaks.
ModerateAnti-VEGF monoclonal antibody · approved 2004
ColorectalLungRenalOvarianGlioblastoma
Signature kidney injury
Glomerular Injury / Proteinuria
Representative incidence30%
All-grade proteinuria ~20–40%; high-grade ~2.2%. Hypertension RR 3–7.5. Nephrotic syndrome RR 7.78.
Source: Wu et al., JASN 2010; Eremina et al., NEJM 2008
Toxicity fingerprint
Tap a signature to trace where it strikes the nephron.
0%incidence
SeverityModerate
ReversibilityReversible
Evidence0 refs
Nephron map
GlomerulusFiltration barrier (podocytes + endothelium)
Vasculature / Endothelium
Glomerular Injury / Proteinuria
Damage to the filtration barrier — podocyte injury, FSGS and protein leak from VEGF and mTOR blockade.
Mechanism of kidney injury
Podocytes secrete the VEGF that maintains glomerular endothelial fenestrae. Blocking it causes glomerular endotheliosis, podocyte injury, proteinuria and TMA — proven in podocyte-specific VEGF-knockout mice. Reduced endothelial nitric oxide drives the hypertension.
Clinical presentation
New or worsening hypertension, proteinuria (dipstick to nephrotic range), occasionally microangiopathic hemolysis and a rising creatinine.
Onset
Weeks to months; dose-dependent.
Reversibility
Reversible
Anticancer mechanism
Monoclonal antibody that binds and neutralizes circulating VEGF-A, starving tumor angiogenesis. Colorectal, lung, renal, ovarian and glioblastoma.
Management
Antihypertensives (ACEi/ARB preferred — they also lower proteinuria), hold for nephrotic-range proteinuria or severe hypertension, discontinue for TMA.
Risk factors
- Higher dose
- Pre-existing hypertension / CKD
- Renal cell carcinoma
Prevention
- Baseline and periodic BP and urine-protein monitoring
- Proactive hypertension treatment
Note · Eremina's NEJM 2008 paper is the landmark mechanistic proof — featured here.
Where it strikes
Nephron segments
Glomerulus
Filtration barrier (podocytes + endothelium)
Vasculature / Endothelium
Glomerular & peritubular capillaries
Injury signatures
Glomerular Injury / ProteinuriaHypertensionThrombotic Microangiopathy
Beyond the kidney
Class-level context for the major non-renal toxicities of anti-vegf antibodys.
Vascular
Hypertension, VTE/ATE, bleeding, aneurysm
- Hypertension, arterial/venous thrombosis, bleeding, impaired wound healing
Cardiac
Cardiomyopathy, QT, ischemia, myocarditis
- LV dysfunction; QT (some TKIs)
Gastrointestinal
Diarrhea, colitis, mucositis, perforation
- Diarrhea, perforation/fistula
Dermatologic
Rash, HFS, SJS/TEN, vitiligo
- Hand-foot skin reaction
Evidence
5 peer-reviewed references. Citation metadata via PubMed / NLM.
LandmarkVEGF inhibition and renal thrombotic microangiopathy.Eremina V et al. · N Engl J Med 2008 · PMID 18337603Landmark: podocyte VEGF deletion in mice reproduces the glomerular injury — establishes mechanism.LandmarkBevacizumab increases risk for severe proteinuria in cancer patients.Wu S et al. · J Am Soc Nephrol 2010 · PMID 20538785Meta-analysis (12,268 patients): high-grade proteinuria and nephrotic syndrome RR 7.78.PMIDBevacizumab-associated glomerular microangiopathy.Person F et al. · Mod Pathol 2018 · PMID 3055241617-biopsy series defining the distinctive glomerular pattern.PMIDRenal toxicity of anticancer agents targeting vascular endothelial growth factor (VEGF) and its receptors (VEGFRs).Cosmai L et al. · J Nephrol 2016 · PMID 27154025Onco-nephrology review of anti-VEGF renal safety.PMIDNephrotoxicity induced by intravitreal vascular endothelial growth factor inhibitors: emerging evidence.Hanna RM et al. · Kidney Int 2019 · PMID 31229276Extends VEGF-inhibitor renal effects to intravitreal use.
Related agents
Other agents sharing the same signature kidney injury.