Ramucirumab
Cyramza · Anti-VEGFR2 antibody
Hypertension and proteinuria, class effect.
HTNGLOMTMA
ModerateOpen →
VEGFR TKI
VEGFR Tyrosine Kinase Inhibitors
Sutent · Nexavar · Votrient · Inlyta · VEGFR-TKI
Hypertension so reliable it doubles as a marker that the drug is working.
ModerateAntiangiogenic TKI · approved 2006
Renal cellHepatocellularGISTThyroidSarcoma
Signature kidney injury
Hypertension
Representative incidence35%
Hypertension ~17–50%; proteinuria 8–73% across agents (all-grade ~18.7%, high-grade ~2.4%).
Source: Semeniuk-Wojtaś et al., Int J Mol Sci 2016
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 / EndotheliumGlomerular & peritubular capillaries
Hypertension
On-target loss of endothelial nitric oxide from VEGF-pathway blockade — so consistent it marks drug activity.
Mechanism of kidney injury
Intracellular disruption of the same VEGF pathway as bevacizumab: reduced nitric oxide and prostacyclin raise blood pressure, while podocyte and endothelial injury produce proteinuria and occasional TMA or collapsing/FSGS lesions.
Clinical presentation
Early hypertension (first weeks), proteinuria, sometimes microangiopathic hemolysis and a rising creatinine.
Onset
Hypertension within days–weeks; proteinuria over weeks–months.
Reversibility
Reversible
Anticancer mechanism
Sunitinib, sorafenib, pazopanib and axitinib block the VEGFR (and PDGFR, c-KIT) kinase domains to shut down angiogenesis. Renal cell, hepatocellular, GIST, thyroid and sarcoma.
Management
Antihypertensives (ACEi/ARB, dihydropyridine CCBs; avoid non-dihydropyridine CCBs that inhibit CYP3A4), dose reduction/hold, discontinue for TMA.
Risk factors
- Pre-existing hypertension / CKD
- Higher-potency agents
- Renal cell carcinoma
Prevention
- BP and urine-protein monitoring
- Proactive hypertension treatment
Note · Hypertension is considered an on-target pharmacodynamic marker.
Where it strikes
Nephron segments
Glomerulus
Filtration barrier (podocytes + endothelium)
Vasculature / Endothelium
Glomerular & peritubular capillaries
Injury signatures
HypertensionGlomerular Injury / ProteinuriaThrombotic Microangiopathy
Beyond the kidney
Class-level context for the major non-renal toxicities of vegfr tkis.
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 18337603Foundational mechanism for the whole VEGF-blockade class.PMIDThrombotic microangiopathy secondary to VEGF pathway inhibition by sunitinib.Bollée G et al. · Nephrol Dial Transplant 2009 · PMID 19054798First biopsy-proven renal TMA from a VEGFR-TKI.PMIDInfluence of Tyrosine Kinase Inhibitors on Hypertension and Nephrotoxicity in Metastatic Renal Cell Cancer Patients.Semeniuk-Wojtaś A et al. · Int J Mol Sci 2016 · PMID 27941701Systematic review quantifying hypertension and proteinuria incidence.PMIDRenal effects of anti-angiogenesis therapy: update for the internist.Gurevich F et al. · Am J Med 2009 · PMID 19332223Clinical review of anti-VEGF/VEGFR renal effects and mechanisms.PMIDRenal Toxicities of Targeted Therapies.Abbas A et al. · Target Oncol 2015 · PMID 25922090Cross-class review of targeted-therapy renal toxicity.