Is kidney injury from Tivozanib reversible?

Reversible. Typical onset: Within the first weeks of therapy..

How should kidney function be monitored during Tivozanib therapy?

Blood pressure regularly, especially in the first 1-2 months; Urine protein (dipstick/UPCR) before each cycle.

How can kidney injury from Tivozanib be prevented?

Blood pressure optimization before and during therapy

Who is at higher risk of kidney injury from Tivozanib?

Pre-existing hypertension; Baseline proteinuria or CKD.

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Printable monograph

VEGFR TKI

Tivozanib

Fotivda · Tivo

VEGFR TKI · approved 2021 · 5 citations

Aging evidence· through 2021

Thinly sourced3/9 · 3 signals

Not met: 5 citations
Not met: 12+ references
Not met: Accrued over 10+ years (span: 8y)
Met: Beyond single case reports
Met: High-impact journal
Met: Landmark reference
Not met: Current through 2021
Not met: Real-world FAERS signal

Describes how this page is sourced, not how dangerous the drug is. Thinly sourced means fewer of the sourcing signals are met — not that the agent is kidney-safe. A rule-based summary, not a formal certainty appraisal.

A highly selective VEGFR inhibitor for refractory RCC, with hypertension as its hallmark on-target toxicity.

ModerateSelective VEGFR inhibitor

Relapsed or refractory advanced renal cell carcinoma

§01

Signature kidney injury

Signature lesion

Hypertension

Representative grade ≥3 incidence20%

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.Source: Rini et al., Lancet Oncol 2020 (TIVO-3, grade 3-4 hypertension)

Onset & rechallenge

Time to injurySubacute (~1–6 weeks)

Within the first weeks of therapy.

Distilled from: “Within the first weeks of therapy.”

§02

Renal toxicities, ranked

This agent's kidney lesions ordered by prominence — the #1 signature lesion first, then secondary and rare patterns. Cited incidence is shown where a citable figure exists; otherwise the tier stands qualitatively.

Hypertension#1 · Signature20%PMID 31810797 (opens PubMed in a new tab)
Grade 3/4 hypertension in 20% (35/173) — the most common grade 3/4 treatment-related adverse event in the phase III TIVO-3 trial (third/fourth-line metastatic RCC).
Glomerular Injury / ProteinuriaSecondaryqualitative — no citable incidence
Damage to the filtration barrier — podocyte injury, FSGS and protein leak from VEGF and mTOR blockade.

Toxicity fingerprint

Tap a signature to trace where it strikes the nephron.

20%grade ≥3 incidence

SeverityModerate

ReversibilityReversible

Evidence5 citations

Nephron map

GlomerulusFiltration barrier (podocytes + endothelium)

Vasculature / EndotheliumGlomerular & peritubular capillaries

Hypertension

Raised blood pressure — archetypally on-target loss of endothelial nitric oxide from VEGF-pathway blockade, studied as a pharmacodynamic marker of drug exposure. Other agents raise it too: vascular effects of BCR-ABL, BTK and RET inhibitors and of copanlisib; abiraterone's mineralocorticoid excess; androgen suppression or blockade.

§03

Kidney injury

Mechanism of kidney injury

Highly selective VEGFR tyrosine kinase inhibition reduces glomerular VEGF and nitric-oxide signaling, raising vascular tone (the dominant on-target hypertension) and potentially injuring the glomerular filtration barrier (proteinuria); the TKI class can produce an FSGS/MCD-pattern podocytopathy. Because off-target kinase inhibition is minimal, hypertension predominates over other toxicities.

Clinical presentation

New or worsening hypertension, sometimes with proteinuria; creatinine may rise in more severe or volume-depleted cases.

Management

Antihypertensive therapy (ACE inhibitor/ARB favored); interrupt or dose-reduce per label for grade 3 hypertension or significant proteinuria; discontinue for nephrotic syndrome or hypertensive crisis. Effects generally improve with dose modification or withdrawal.Lesion-level management framework

§ Receptor target map

Which kinases Tivozanib blocks — and where the blockade reaches the kidney

3targeted

VEGFR2 is the target with documented renal consequences across every VEGFR TKI; multi-kinase breadth beyond it (PDGFR-β, FGFR, and off-target receptor kinases) adds further renal and hypertensive liability. Select a lit receptor for its renal consequence.

VEGFR family

PDGFR

PDGFR-αPDGFR-β

Other receptor kinases

FGFRKITRETMETEGFRFLT3AXLCSF1RTIE2RAF-1/BRAF

VEGFR2 · renal target

Glomerular endothelial VEGFR2: loss of podocyte-derived paracrine VEGF signaling → fenestrae loss, nephrin downregulation, nitric-oxide depletion → hypertension, proteinuria, and thrombotic microangiopathy.

renal consequence (1)targetednot a target

Risk factors

Pre-existing hypertension
Baseline proteinuria or CKD

Prevention

Blood pressure optimization before and during therapy

Anticancer mechanism· how it treats cancer

Potent, highly selective inhibitor of VEGFR1-3 with a long half-life, suppressing tumor angiogenesis with relatively few off-target kinase effects (which contributes to a comparatively clean non-renal toxicity profile). Approved for relapsed or refractory advanced renal cell carcinoma after two or more prior systemic therapies.

Note · High VEGFR selectivity makes hypertension the dominant on-target renal-vascular toxicity; proteinuria data are more limited than for less-selective TKIs such as lenvatinib and cabozantinib.

§04

Clinical depth

Renal dose adjustment

No dose adjustment for mild-to-moderate renal impairment; tivozanib has not been studied in severe renal impairment, and it is primarily hepatically metabolized, so renal dosing rules are minimal. Monitor closely if used in advanced CKD.

Dialyzability & ESKD dosing

Highly protein-bound with a long half-life and hepatic clearance; not appreciably dialyzable and not adjusted for HD. Data in dialysis patients are sparse.

Differential diagnosis

On-target VEGFR-TKI hypertension (and less commonly proteinuria/podocytopathy) versus baseline hypertensive/diabetic nephropathy and prerenal AKI. In RCC, also account for reduced renal mass from prior nephrectomy when interpreting creatinine.

Monitoring

Blood pressure regularly, especially in the first 1-2 months
Urine protein (dipstick/UPCR) before each cycle

Key trials & series

TIVO-3 phase III trial (tivozanib vs sorafenib in heavily pretreated metastatic RCC) — hypertension the leading grade 3-4 AE
TIVO-1 (first-line RCC) — earlier hypertension safety signal

Clinical pearls

Tivozanib's selectivity makes hypertension its signature toxicity, with fewer competing off-target effects.
Anticipate hypertension early and pretreat/optimize BP, as it is the most common grade 3-4 event.
Proteinuria is less prominent than with lenvatinib/cabozantinib but should still be tracked.

Beyond the kidney — non-renal toxicities· 4 organ systems

Class-level context for the major non-renal toxicities of the VEGFR TKI class.

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

§05

References

5 primary references — trials, cohorts, mechanism, and reviews. Citation metadata via PubMed / NLM.

Evidence accrual

5 references · 2013–2021 · 3 since 2019

Primary (non–case-report) references per year — a proxy for how actively the agent's renal literature is accruing. Recent years are highlighted. Reflects curation depth, not a systematic bibliometric count.

Guidelines & consensus· 17

Each recommendation below is this atlas's faithful summary of the source, not a quotation from it — follow the PubMed link for the wording the society published. Summaries may be superseded; consult the current full text and individualize to the patient.

KDIGOManagement of Blood Pressure in Patients With Chronic Kidney Disease Not Receiving Dialysis: Synopsis of the 2021 KDIGO Clinical Practice GuidelineAnn Intern Med 2021 · PMID 34152826Recommends standardized office BP measurement and a target systolic BP <120 mm Hg for most CKD patients, with RAAS inhibitors first-line when albuminuria is present — the BP-management basis for anti-VEGF/TKI-induced hypertension and proteinuria.ESC2022 ESC Guidelines on cardio-oncology developed in collaboration with the European Hematology Association (EHA), the European Society for Therapeutic Radiology and Oncology (ESTRO) and the International Cardio-Oncology Society (IC-OS)Eur Heart J 2022 · PMID 36017568For VEGF/VEGFR inhibitors, perform baseline cardiovascular risk assessment, monitor blood pressure (weekly during the first cycle, then regularly) and treat to a target <140/90 mmHg with ACE inhibitors/ARBs and dihydropyridine calcium-channel blockers; manage VEGFi-associated hypertension and proteinuria with interruption/dose modification when severe.ESCEuropean Society of Cardiology quality indicators for the prevention and management of cancer therapy-related cardiovascular toxicity in cancer treatmentEur Heart J Qual Care Clin Outcomes 2022 · PMID 36316010Adherence quality indicators require documented baseline cardiovascular risk assessment and structured monitoring of cardiovascular complications (including hypertension) during cancer therapy such as VEGF-pathway inhibitors.UK Consensus PanelUsing bevacizumab to treat metastatic cancer: UK consensus guidelinesBr J Hosp Med (Lond) 2010 · PMID 21135762Assess and monitor blood pressure and proteinuria during bevacizumab therapy; treat emergent hypertension to standard targets and interrupt/discontinue the drug for uncontrolled hypertension, nephrotic-range proteinuria or other severe vascular toxicity.

General onco-nephrology references

ADQIThe nephrotoxic effects of anti-cancer therapies: consensus report of the 34th Acute Disease Quality Initiative workgroupNat Rev Nephrol 2026 · PMID 41361704Provides expert-based statements (modified Delphi) on preventing and managing cisplatin/platinum-associated AKI, including isotonic IV hydration, attention to volume status and concomitant nephrotoxins, and incorporates evidence that IV magnesium supplementation may reduce cisplatin-associated AKI; emphasizes risk stratification and standardized AKI definitions.SIRMSIRM-SIN-AIOM: appropriateness criteria for evaluation and prevention of renal damage in the patient undergoing contrast medium examinations-consensus statements from Italian College of Radiology (SIRM), Italian College of Nephrology (SIN) and Italian Association of Medical Oncology (AIOM)Radiol Med 2022 · PMID 35303246Recommends eGFR-based renal risk assessment and pre/post-contrast isotonic saline or sodium bicarbonate hydration; advises maintaining a 5-7 day interval between iodinated contrast administration and cisplatin in cancer patients to reduce additive nephrotoxicity.KDIGOKDIGO Controversies Conference on onco-nephrology: understanding kidney impairment and solid-organ malignancies, and managing kidney cancerKidney Int 2020 · PMID 33126977Identifies platinum compounds (especially cisplatin) as leading cytotoxic causes of acute tubular injury, AKI, and electrolyte/magnesium wasting; calls for interdisciplinary onco-nephrology care, accurate GFR estimation, and individualized drug dosing in patients with reduced kidney function.KDIGOKDIGO Controversies Conference on onco-nephrology: kidney disease in hematological malignancies and the burden of cancer after kidney transplantationKidney Int 2020 · PMID 33276867Addresses chemotherapy-associated AKI/CKD in hematologic cancer, GFR estimation and chemotherapy dosing in patients with reduced kidney function, and management priorities and research gaps for onco-nephrology care.ADDIKDIntegrating International Consensus Guidelines for Anticancer Drug Dosing in Kidney Dysfunction (ADDIKD) into everyday practiceEClinicalMedicine 2025 · PMID 40290844Provides GRADE-based, drug-specific dose-adjustment recommendations for anticancer agents in kidney dysfunction (illustrated for methotrexate, cisplatin, carboplatin and nivolumab); the recommendations build on Part 1's standardised CKD-EPI eGFR assessment rather than Cockcroft-Gault creatinine clearance.ADDIKDAligning kidney function assessment in patients with cancer to global practices in internal medicineEClinicalMedicine 2025 · PMID 40290845Three consensus recommendations: assess kidney function by GFR (measured GFR or CKD-EPI eGFR), classify it using KDIGO categories, and use this uniform approach to dose anticancer drugs — moving cancer medicine away from Cockcroft-Gault estimated creatinine clearance.ADDIKDA methodology for determining dosing recommendations for anticancer drugs in patients with reduced kidney functionEClinicalMedicine 2025 · PMID 40290846Establishes that, where RCT evidence is lacking, anticancer drug dosing recommendations in kidney dysfunction should be derived by critically appraising observational literature via GRADE combined with structured international multidisciplinary consensus voting.KDIGODiagnosis, evaluation, and management of acute kidney injury: a KDIGO summary (Part 1)Crit Care 2013 · PMID 23394211Defines/stages AKI by serum creatinine and urine output; emphasizes avoiding nephrotoxins, maintaining euvolemia/perfusion, dose-adjusting drugs to kidney function, and monitoring high-risk patients — the framework applied to nephrotoxic anti-cancer agents.KDIGOExecutive summary of the KDIGO 2024 Clinical Practice Guideline for the Evaluation and Management of Chronic Kidney Disease: known knowns and known unknownsKidney Int 2024 · PMID 38519239Evaluate and risk-stratify CKD, manage to delay progression and its complications, and practise explicit medication management and drug stewardship — the framework the atlas's G1–G5 eGFR banding and every renal dose-adjustment recommendation sit inside. Because the guideline excludes dialysis and transplant recipients by its own statement of scope, its recommendations do not carry to those settings, where this atlas's dialyzability and post-transplant guidance rests on other sources.KDIGOExecutive summary of the KDIGO 2021 Guideline for the Management of Glomerular DiseasesKidney Int 2021 · PMID 34556300Provides the staging/treatment framework for drug-associated glomerular lesions (e.g., bisphosphonate- and interferon-related collapsing FSGS, VEGF-inhibitor podocytopathy/proteinuria), including immunosuppression and supportive RAAS-blockade strategies.KDIGOExecutive summary of the KDIGO 2024 Clinical Practice Guideline for the Management of ANCA-Associated VasculitisKidney Int 2024 · PMID 38388147Updates immunosuppressive induction (rituximab/cyclophosphamide), incorporates avacopan and lower-dose or glucocorticoid-sparing regimens — the management framework for drug- and checkpoint-inhibitor-associated ANCA/pauci-immune glomerulonephritis.KDIGOExecutive summary of the KDIGO 2024 Clinical Practice Guideline for the Management of Lupus NephritisKidney Int 2024 · PMID 38182299Updates first-line lupus nephritis therapy to combination immunosuppression with the addition of belimumab or a calcineurin inhibitor (voclosporin) — informs management of immune-complex/lupus-like glomerulonephritis encountered with immunotherapy.KDIGOExecutive summary of the KDIGO 2025 Clinical Practice Guideline for the Management of Immunoglobulin A Nephropathy (IgAN) and Immunoglobulin A Vasculitis (IgAV)Kidney Int 2025 · PMID 40975525Encourages liberal kidney biopsy and stricter proteinuria control (<0.5 g/d, ideally <0.3 g/d) with RAAS blockers, SGLT2 inhibitors, and targeted-release budesonide — the framework for IgA-dominant glomerular lesions, including those triggered by immune-modulating cancer therapy.

Where Tivozanib sits in nephrotoxicity space — each dot is an anti-cancer agent, positioned so neighbors share a kidney-injury phenotype. Its 6 closest are filled and lead to a numbered marker, matching the numbered cards below.

Position is a 2-D projection (MDS) of each agent's injury signature, nephron target, severity, and class, so two dots can sit close on the page while differing on an axis the projection flattened — the numbered ranking is computed from the full metric, not from the distance you see. Open the full map.

Phenotype-similar agents· the numbered markers on the map above

Cabozantinib

Cabometyx · VEGFR/MET TKI

Profile

Hypertension and proteinuria; nephrotic case reports.

HTNGLOM

Moderate#1 · 100% phenotype match

Lenvatinib

Lenvima · VEGFR TKI

Profile

Highest-ranked TKI for hypertension; proteinuria.

HTNGLOM

Moderate#2 · 100% phenotype match

Regorafenib

Stivarga · VEGFR TKI

Profile

Hypertension and proteinuria.

HTNGLOM

Moderate#3 · 100% phenotype match

Ziv-aflibercept

Zaltrap · VEGF trap

Profile

Hypertension and proteinuria like bevacizumab.

HTNGLOMTMA

Moderate#4 · 84% phenotype match

Bevacizumab

Avastin · Anti-VEGF antibody

Profile

Proteinuria, hypertension, glomerular TMA.

GLOMHTNTMA

Moderate#5 · 84% phenotype match

Ramucirumab

Cyramza · Anti-VEGFR2 antibody

Profile

Hypertension and proteinuria, class effect.

HTNGLOMTMA

Moderate#6 · 84% phenotype match

Compare Tivozanib with its nearest agents

Nearest agents by kidney-injury phenotype (shared injuries, nephron target, severity, class) — a similarity approximation, not a claim of shared drug identity or mechanism.

Kidney risk across Anti-angiogenic (VEGF)

Same-class agents ordered by their documented kidney-injury profile — atlas severity, an acute-kidney-injury FAERS signal, and how many injury types each is documented to cause. Agents nearer the top carry the lighter documented renal profile.

A comparison of documented kidney-injury data within one drug class — not a substitution recommendation. Efficacy, indication, and non-renal toxicity differ between these agents and are out of scope here. Educational only, not medical advice.