Ramucirumab
Cyramza · Anti-VEGFR2 antibody
Hypertension and proteinuria, class effect.
HTNGLOMTMA
ModerateOpen →
RET inhibitor
Pralsetinib
Gavreto · Pral
A selective RET inhibitor — hypertension is its main vascular signal, with AKI rare.
MildRET inhibitor · approved 2020
RET fusion-positive NSCLCRET-altered thyroid cancer
Signature kidney injury
Hypertension
Representative incidence11%
Hypertension is among the more common grade >=3 treatment-related adverse events (about 11% grade >=3 in the ARROW NSCLC cohort); clinically significant intrinsic AKI is rare.
Source: Gainor et al., Lancet Oncol 2021
Toxicity fingerprint
Tap a signature to trace where it strikes the nephron.
0%incidence
SeverityMild
ReversibilityReversible
Evidence0 refs
Nephron map
GlomerulusFiltration barrier (podocytes + endothelium)
Vasculature / EndotheliumGlomerular & peritubular capillaries
Proximal Tubule
Hypertension
On-target loss of endothelial nitric oxide from VEGF-pathway blockade — so consistent it marks drug activity.
Mechanism of kidney injury
Hypertension reflects an on/near-target vascular effect of RET-pathway inhibition. Intrinsic nephrotoxicity is not characteristic; any creatinine rise may partly reflect hemodynamic effects (from hypertension) or tubular-secretion inhibition rather than true filtration loss.
Clinical presentation
New or worsened hypertension; AKI is uncommon. Cytopenias (neutropenia, anemia, lymphopenia) and transaminitis are prominent non-renal toxicities; pneumonitis is a notable class concern.
Onset
Hypertension within the first weeks to months.
Reversibility
Reversible
Anticancer mechanism
Highly potent, selective RET inhibitor targeting RET fusions and mutations; approved for RET fusion-positive NSCLC and thyroid cancers.
Management
Standard antihypertensives; dose-interrupt then reduce for medically uncontrolled BP. Supportive care and standard workup if AKI develops; confirm whether a creatinine rise is true injury or a transporter artifact.
Risk factors
- Pre-existing hypertension
- Cardiovascular disease
- Concurrent nephrotoxins
Prevention
- Blood-pressure monitoring at baseline and during therapy
- Optimize antihypertensives
- Periodic creatinine checks; cystatin C if GFR change is ambiguous
Note · Renal signal is dominated by hypertension; significant AKI is rare. Newer agent — conservative renal interpretation.
Clinical depth
Renal dose adjustment
No dose adjustment for mild-moderate renal impairment; severe impairment is not well characterized and dialysis is not studied (use with caution). Modifications are driven by hypertension, pneumonitis, cytopenias, and hepatotoxicity.
Dialyzability & ESKD dosing
Highly protein-bound oral small molecule; not expected to be appreciably dialyzed. No validated ESKD dosing.
Differential diagnosis
Drug-induced hypertension vs other causes; uncommon true AKI vs transporter-mediated creatinine rise (stable cystatin C). If creatinine and cystatin C diverge, suspect the transporter effect rather than parenchymal injury.
Monitoring
- Blood pressure at baseline and regularly during therapy
- CBC for neutropenia/anemia; liver enzymes per label
- Serum creatinine periodically; cystatin C if a true GFR change is suspected
Key trials & series
- ARROW (RET fusion-positive NSCLC and RET-altered thyroid)
- Hamidi 2024 hereditary-MTC RET-inhibitor safety series
Clinical pearls
- Hypertension dominates the renal-relevant profile; significant intrinsic AKI is rare.
- Newer agent — interpret the renal signal conservatively and lean on cystatin C for ambiguous creatinine changes.
- Do not overlook pneumonitis and cytopenias, which more often drive dose modification than any renal event.
Where it strikes
Nephron segments
Vasculature / Endothelium
Glomerular & peritubular capillaries
Proximal Tubule
Bulk reabsorption + drug uptake (OCT2, OATs)
Injury signatures
HypertensionPrerenal / Hemodynamic AKI
Evidence
6 peer-reviewed references. Citation metadata via PubMed / NLM.
LandmarkPralsetinib for RET fusion-positive non-small-cell lung cancer (ARROW): a multi-cohort, open-label, phase 1/2 study.Gainor JF et al. · Lancet Oncol 2021 · PMID 34118197Pivotal ARROW trial reporting hypertension among the most common grade >=3 treatment-related events (~11%).PMIDEfficacy and Safety of Selective RET Inhibitors in Patients with Advanced Hereditary Medullary Thyroid Carcinoma.Hamidi S et al. · Thyroid 2024 · PMID 39630530Real-world hMTC series including pralsetinib, quantifying hypertension and other adverse events.PMIDTargeted Cancer Therapies Causing Elevations in Serum Creatinine Through Tubular Secretion Inhibition: A Case Report and Review of the Literature.Mach T et al. · Can J Kidney Health Dis 2022 · PMID 35756332Frames TKI creatinine elevation as frequently transporter-mediated, confirmable with cystatin C.PMIDNavigating the Complexities of Cancer Treatment-Induced Hypertension.Arriola-Montenegro J et al. · J Cardiovasc Dev Dis 2025 · PMID 40558670Reviews kinase-inhibitor hypertension pathophysiology and antihypertensive selection.PMIDReal-World Creatinine-Based Estimates of Acute and Chronic Kidney Dysfunction in Patients with Advanced ALK-Rearranged Non-Small-Cell Lung Cancer Receiving Tyrosine Kinase Inhibitors.Pinard L et al. · Clin Lung Cancer 2025 · PMID 40382267Onconephrology cohort showing creatinine-based eGFR changes on lung-cancer TKIs often overstate true injury vs cystatin C.PMIDCurrent Trends in Anti-Cancer Molecular Targeted Therapies: Renal Complications and Their Histological Features.Tonooka A et al. · J Nippon Med Sch 2021 · PMID 34840210Onconephrology review of TKI-associated vascular and renal effects.
Related agents
Other agents sharing the same signature kidney injury.