The Injury Atlas See it on the nephron
HTN
Hypertension
On-target loss of endothelial nitric oxide from VEGF-pathway blockade — so consistent it marks drug activity.
27agents
Where it strikes
Vasculature / Endothelium
Glomerular & peritubular capillaries
Glomerulus
Filtration barrier (podocytes + endothelium)
Severity mix
Severe· 2Moderate· 16Mild· 9
Reversibility
Partially reversible· 1Variable· 6Reversible· 20
Signature offenders
21Agents for which hypertension is the defining renal lesion.
VEGFR Tyrosine Kinase InhibitorsHypertension within days–weeks; proteinuria over weeks–months.Hypertension ~17–50%; proteinuria 8–73% across agents (all-grade ~18.7%, high-grade ~2.4%).ModerateRamucirumabWithin the first one to two cycles (weeks).Hypertension and proteinuria are common class effects; nephrotic syndrome is a less frequent but reported event, sometimes after only 1-2 doses and typically accompanied by hypertension.ModerateZiv-afliberceptWithin weeks to a few months of therapy.Hypertension and proteinuria are common class effects; in the registrational VELOUR trial, grade 3-4 hypertension and proteinuria were notably more frequent with aflibercept plus FOLFIRI than with FOLFIRI alone. Nephrotic-range proteinuria and renal thrombotic microangiopathy are documented, including with the ophthalmic formulation, indicating a direct VEGF-trap mechanism.ModerateLenvatinibWithin the first weeks of therapy (hypertension early; proteinuria over weeks).Hypertension is among the most common adverse events; in the SELECT thyroid-cancer trial hypertension occurred in about 68% (grade >=3 ~42%) and proteinuria in roughly 31%. In KEYNOTE-B61 (lenvatinib plus pembrolizumab) grade 3-4 hypertension occurred in ~23%. Proteinuria is a frequent renal AE with lenvatinib.ModerateCabozantinibWithin weeks of starting therapy.Hypertension and proteinuria are common; in pivotal RCC trials (e.g., METEOR, CABOSUN) hypertension was among the most frequent adverse events with grade >=3 rates around 15-28%. Cabozantinib is one of the TKIs most often associated with proteinuria, with case reports of nephrotic syndrome.ModerateRegorafenibWithin the first weeks of therapy.Hypertension is a common, frequently grade 3 adverse event (in the CORRECT trial hypertension occurred in about 28%, grade 3 ~7%); proteinuria also occurs as a VEGF-pathway class effect. Drug-specific quantitative renal data are otherwise limited.ModerateVandetanibWithin the first weeks of therapy.In the pivotal phase III ZETA trial, any-grade hypertension occurred in about 32% of vandetanib-treated patients versus 5% with placebo; proteinuria occurs as an antiangiogenic class effect.ModerateTivozanibWithin the first weeks of therapy.In the phase III TIVO-3 trial, hypertension was the most common grade 3-4 treatment-related adverse event, occurring in about 20% of tivozanib-treated patients; proteinuria occurs as a VEGFR class effect but is comparatively less prominent.ModeratePonatinibHypertension can emerge early; arterial occlusive events accrue over months, with dose reduction mitigating risk.Ponatinib carries a black-box warning for arterial occlusive and thrombotic events and has the highest cardiovascular event rate among CML TKIs (about 41% in one comparative cohort; cumulative arterial occlusive events ~31% over 5 years in the PACE trial). Treatment-emergent hypertension is common; renal injury is largely a downstream consequence of hypertension and vascular disease.ModerateSelpercatinibHypertension within the first weeks to months; creatinine changes early.Hypertension is among the most common adverse events in LIBRETTO-001 (a frequent grade >=3 event), and a reversible serum-creatinine increase is also recognized. A single-center hereditary-MTC series found hypertension in ~26% on selective RET inhibitors.ModerateIbrutinibHypertension develops over weeks–months (can be early); tumor lysis is early (first cycle); glomerular/interstitial lesions are case-level over weeks to months.New or worsened hypertension is common (~26% in a real-world CLL cohort comparing it with acalabrutinib; higher with longer follow-up). AKI at CLL presentation and with tumor lysis is well described. Drug-attributable AKI from interstitial nephritis or glomerular endotheliosis is case-level.ModerateFruquintinibWithin weeks of starting therapy (hypertension often earliest).Hypertension and proteinuria are characteristic VEGFR-TKI class effects; in the FRESCO-2 safety analysis hypertension was among the most frequent grade ≥3 adverse events, with proteinuria also reported. Renal-specific TMA is rare but described across the VEGF-inhibitor class.ModerateCopanlisibAcute and infusion-bound — within hours of each dose, resolving within ~24 h.On-infusion-day hyperglycemia occurs in ~50-56% (grade 3+ ~40%) and transient hypertension in ~30-40% (grade 3 ~25-30%), both peaking within hours of the infusion and largely resolving by the next day. Sustained renal injury is uncommon.ModerateNintedanibOver months of therapy in reported cases.Renal effects are uncommon; proteinuria and rare biopsy-proven renal thrombotic microangiopathy have been reported, consistent with VEGF-pathway inhibition. Renal incidence is not well quantified (case-level), and much of the published renal experience comes from pulmonary-fibrosis rather than oncology cohorts.MildNiraparibHypertension typically emerges within the first weeks to months of therapy.Hypertension is a characteristic, class-distinctive adverse event: a FAERS pharmacovigilance plus RCT meta-analysis estimated ~16.9% any-grade hypertension, disproportionately higher with niraparib than other PARP inhibitors. A small reversible serum-creatinine rise is also seen across the class (pooled OR for creatinine elevation ~5 vs placebo), but grade >=3 nephrotoxicity is <1%.MildPralsetinibHypertension within the first weeks to months.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.MildAcalabrutinibTumor lysis early (first cycle); hypertension over weeks–months.Hypertension occurs but is less frequent than with ibrutinib (~15% vs ~26% in a matched real-world cohort; ELEVATE-RR confirmed lower hypertension and atrial fibrillation head-to-head). One single-center cardio-oncology cohort still found ~49% new/worsened hypertension by sensitive criteria, so it is not negligible. Tumor lysis is the principal route to AKI; direct nephrotoxicity is case-level.MildEnzalutamideHypertension emerges over weeks to months of therapy.Hypertension is the dominant renovascular signal. A 2024 JAMA Oncology meta-analysis of androgen-receptor signaling inhibitors found a markedly increased risk of grade ≥3 hypertension (relative risk ~2.25); an earlier meta-analysis showed the same for enzalutamide specifically. Direct intrinsic kidney injury is uncommon; rare hyponatremia appears mainly in combination regimens.MildLeuprolideMonths to years (metabolic/cardiovascular and skeletal).No characteristic direct nephrotoxicity. Androgen-deprivation therapy is associated with metabolic syndrome, insulin resistance, dyslipidemia and increased cardiovascular disease, which raise long-term renovascular risk; a large matched cohort (n≈19,079) found CKD to be an independent risk factor for ADT-associated fracture, and preclinical models show GnRH-agonist-induced metabolic syndrome and atherosclerosis.MildAsciminibHypertension can emerge across treatment; pancreatitis often early.Hypertension and pancreatitis (with amylase/lipase elevations) are recognized toxicities; thrombocytopenia/neutropenia are common. Asciminib has a notably cleaner profile than prior TKIs, and direct nephrotoxicity is not a defined signal — renal effects are largely hypertension-mediated.MildRipretinibHypertension can develop within early cycles and persist.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.Mild
Also associated
6Agents that cause hypertension as a secondary pattern alongside a different signature lesion.
GemcitabineDelayed — months of cumulative exposure.~0.015–2.2%; best single estimate ~0.31% cumulative. Historically high mortality.SevereCarfilzomibVariable — frequently early (first cycles), but TMA can also appear later, sometimes after a treatment break and re-escalation.Renal complications are common and a recognized class concern: in a 114-patient real-world cohort, ~17% had carfilzomib-attributable renal events (TMA ~5%, albuminuria >1 g/day ~6%, otherwise-unexplained grade >=3 AKI ~5%), occurring mostly early and unpredictably. On the prospective CARDAMON trial, TMA occurred at ~1.6-4.2 events per 1,000 patient-cycles, with most patients hypertensive and almost all developing AKI. Pharmacovigilance (FAERS) shows carfilzomib carries by far the strongest TMA signal among proteasome inhibitors.SevereBevacizumabWeeks to months; dose-dependent.All-grade proteinuria ~20–40%; high-grade ~2.2%. Hypertension RR 3–7.5. Nephrotic syndrome RR 7.78.ModerateAbirateroneWithin the first weeks of therapy; recurs if glucocorticoid coverage is inadequate or interrupted.Mineralocorticoid-excess effects are common: in COU-AA-301 fluid retention, hypertension and hypokalemia were all more frequent than with placebo-prednisone. Severe (grade 3–4) hypokalemia, occasionally to 1.7–2.1 mEq/L, is reported even with concomitant prednisone. Meta-analysis confirms an increased relative risk of hypertension.ModerateDinutuximabInfusion-associated and acute — pain, capillary leak and blood-pressure swings occur during/around each infusion.Severe neuropathic pain is near-universal, and capillary-leak syndrome and hypertension are common, sometimes severe, infusion-associated toxicities (driven partly by concurrent IL-2). The resulting fluid shifts and prerenal AKI are managed proactively but not separately quantified.ModerateNilotinibVascular events accrue over months to years of therapy.Nilotinib carries a recognized risk of arterial occlusive events and metabolic effects (dysglycemia, hyperlipidemia), but direct renal toxicity is limited; in comparative CML cohorts nilotinib generally did not cause significant eGFR decline relative to imatinib. Any kidney impact is largely mediated through vascular disease and perfusion rather than intrinsic nephrotoxicity.Mild