Ramucirumab
Cyramza · Anti-VEGFR2 antibody
Hypertension and proteinuria, class effect.
HTNGLOMTMA
ModerateOpen →
KIT switch-control inhibitor
Ripretinib
Qinlock · RIP
KIT/PDGFRA switch-control inhibitor for fourth-line GIST — hypertension is the renal-relevant signal, with alopecia and PPE the dominant non-renal toxicities.
MildSwitch-control TKI era · approved 2020
Advanced gastrointestinal stromal tumor after >=3 prior kinase inhibitors (fourth-line)
Signature kidney injury
Hypertension
Hypertension is a recognized toxicity (any-grade roughly one-quarter of patients, grade 3 a minority in INVICTUS), alongside alopecia, palmar-plantar erythrodysesthesia, fatigue and myalgia. Direct nephrotoxicity is not a defined signal; renal effects are hypertension-mediated.
Source: Blay et al., Lancet Oncol 2020 (INVICTUS)
Mechanism of kidney injury
Ripretinib's renal relevance is vascular: class-typical treatment-emergent hypertension (impaired endothelial/nitric-oxide and VEGF-related signaling) raises systemic and intraglomerular pressure and, if sustained and uncontrolled, can drive hypertensive kidney injury. There is no characteristic direct tubular or glomerular lesion; the prominent toxicities (alopecia, hand-foot skin reaction) are dermatologic.
Clinical presentation
New or worsening hypertension on routine checks; alopecia, palmar-plantar erythrodysesthesia, myalgia and fatigue. Renally, a hypertension-associated creatinine trend rather than an acute structural picture.
Onset
Hypertension can develop within early cycles and persist.
Reversibility
Reversible
Anticancer mechanism
Oral switch-control tyrosine kinase inhibitor that locks KIT and PDGFRA in an inactive conformation by binding both the switch pocket and activation loop, providing broad activity across primary and secondary resistance mutations in advanced GIST.
Management
Control blood pressure with standard antihypertensives to protect the kidney from pressure-mediated injury; interrupt/reduce ripretinib for severe or refractory hypertension. Manage dermatologic toxicities supportively. Renal effects are reversible with blood-pressure control.
Risk factors
- Pre-existing hypertension or cardiovascular disease
- Prior VEGF/TKI vascular toxicity
- Baseline CKD
- Concurrent agents raising blood pressure
Prevention
- Baseline and regular blood-pressure monitoring with proactive antihypertensive treatment
- Cardiovascular risk-factor optimization
- Dose interruption/reduction for grade 3+ hypertension per label
- Avoid additive nephrotoxins
Note · The renal link is indirect and hypertension-mediated; there is no characteristic direct ripretinib nephrotoxicity. Quantified grade 3 hypertension rates are modest.
Clinical depth
Renal dose adjustment
No dose adjustment for mild-moderate renal impairment in labeling; severe impairment/ESKD not characterized (hepatic CYP3A4 metabolism). Modifications driven by hypertension, PPE and cardiac effects.
Dialyzability & ESKD dosing
Highly protein-bound; not expected to be dialyzable. No established ESKD dosing.
Differential diagnosis
Distinguish hypertension-mediated renal effects from other TKI vascular toxicity and essential hypertension; the absence of a tubular/glomerular lesion is characteristic.
Monitoring
- Blood pressure at baseline and regularly through treatment
- Skin/hand-foot assessment
- Cardiac function (ejection fraction) per label
- Serum creatinine periodically in hypertensive/CKD patients
Key trials & series
- INVICTUS (Blay, Lancet Oncol 2020) — registrational placebo-controlled phase 3 quantifying hypertension and other toxicities
Clinical pearls
- Hypertension is the renal-relevant signal — monitor BP every cycle and treat early.
- Alopecia and palmar-plantar erythrodysesthesia dominate the (non-renal) toxicity picture.
- Switch-control mechanism gives broad anti-KIT/PDGFRA coverage in heavily pretreated GIST.
- No characteristic direct ripretinib nephropathy — protect the kidney by controlling pressure.
Where it strikes
Nephron segments
Vasculature / Endothelium
Glomerular & peritubular capillaries
Injury signatures
Hypertension
Evidence
6 peer-reviewed references. Citation metadata via PubMed / NLM.
LandmarkRipretinib in patients with advanced gastrointestinal stromal tumours (INVICTUS): a double-blind, randomised, placebo-controlled, phase 3 trial.Blay JY et al. · Lancet Oncol 2020 · PMID 32511981Registrational RCT establishing efficacy and the hypertension/dermatologic safety profile.PMIDPatient-reported outcomes with ripretinib in advanced gastrointestinal stromal tumor (INVICTUS).Schoffski P et al. · BMC Cancer 2022 · PMID 36514034Tolerability/quality-of-life context for the toxicity burden.PMIDFDA Approval Summary: Ripretinib for Advanced Gastrointestinal Stromal Tumors.Kumar V et al. · Clin Cancer Res 2023 · PMID 36485007Regulatory summary codifying the hypertension and cardiac warnings.PMIDRipretinib: A Review in Advanced Gastrointestinal Stromal Tumour.Dhillon S et al. · Drugs 2022 · PMID 36282417Comprehensive drug review of efficacy and adverse-event management.PMIDRipretinib: mechanism of action as a switch-control inhibitor of KIT and PDGFRA.Zalcberg JR et al. · Future Oncol 2021 · PMID 33948116Mechanistic basis of the switch-control inhibition.PMIDReal-world adverse event profile of ripretinib: a pharmacovigilance analysis.Hu Y et al. · Front Pharmacol 2025 · PMID 40078281FAERS disproportionality characterizing real-world toxicity signals including hypertension.
Related agents
Other agents sharing the same signature kidney injury.