Is kidney injury from Fruquintinib reversible?

Reversible. Typical onset: Within weeks of starting therapy (hypertension often earliest)..

How should kidney function be monitored during Fruquintinib therapy?

Blood pressure (including home monitoring) weekly early, then each cycle; Urine protein (dipstick/UPCR) at baseline and periodically; CBC and creatinine; add LDH/haptoglobin/smear if TMA suspected.

How can kidney injury from Fruquintinib be prevented?

Early, proactive antihypertensive therapy Dose modification per proteinuria/hypertension grade

Who is at higher risk of kidney injury from Fruquintinib?

Pre-existing hypertension; Baseline proteinuria or CKD; Prior anti-angiogenic therapy (bevacizumab, other VEGFR-TKIs).

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Printable monograph

VEGFR TKI

Fruquintinib

Fruzaqla · Fruq

VEGFR TKI · approved 2023 · 10 citations

Up to date· through 2025

Fairly sourced5/9 · 5 signals

Met: 10 citations
Not met: 12+ references
Not met: Accrued over 10+ years (span: 6y)
Met: Beyond single case reports
Met: High-impact journal
Met: Landmark reference
Met: Current through 2025
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 VEGFR1-3 TKI for refractory colorectal cancer — hypertension and proteinuria, by class.

ModerateVEGFR tyrosine-kinase inhibitor

Refractory metastatic colorectal cancer

§01

Signature kidney injury

Signature lesion

Hypertension

Representative incidence28.9%

Hypertension and proteinuria are characteristic VEGFR-TKI class effects; in the FRESCO-2 safety analysis hypertension was the most frequent treatment-related adverse event of special interest, occurring in 28.9% of fruquintinib-treated patients all-grade and 10.7% at grade ≥3, with proteinuria also reported (1.3% of patients required a dose reduction for it). Renal-specific TMA is rare but described across the VEGF-inhibitor class.Source: Eng et al., Oncologist 2025 (FRESCO-2 safety; hypertension 28.9% all-grade, 10.7% grade ≥3)

Onset & rechallenge

Time to injurySubacute (~1–6 weeks)

Within weeks of starting; hypertension often earliest.

Distilled from: “Within weeks of starting therapy (hypertension often earliest).”

§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 · Signature55.4%PMID 32901330 (opens PubMed in a new tab)
55.4% all-grade, 21.2% grade >=3 (FRESCO phase 3)
Glomerular Injury / ProteinuriaSecondary42.1%PMID 32901330 (opens PubMed in a new tab)
proteinuria 42.1% all-grade, 3.2% grade >=3 (FRESCO phase 3)
Thrombotic MicroangiopathyRarequalitative — no citable incidence
Endothelial injury with microvascular thrombi, hemolysis and thrombocytopenia — gemcitabine, mitomycin C, anti-VEGF.

Toxicity fingerprint

Tap a signature to trace where it strikes the nephron.

28.9%incidence

SeverityModerate

ReversibilityReversible

Evidence10 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

VEGF-A signaling through VEGFR-2 maintains glomerular endothelial fenestrae and the podocyte–endothelial crosstalk of the filtration barrier and supports endothelial nitric-oxide production. Pharmacologic VEGF blockade reduces NO-mediated vasodilation (raising systemic blood pressure) and damages the glomerular endothelium and podocyte, opening the filtration barrier to cause proteinuria; histologically this manifests as a renal-limited thrombotic microangiopathy and, with downstream kinase effects, podocytopathies (minimal change/FSGS-like lesions). Sustained or high-grade blockade can precipitate overt glomerular TMA with hemolysis.

Clinical presentation

New or worsened hypertension and proteinuria (often sub-nephrotic, occasionally nephrotic) with usually preserved or mildly reduced GFR. Rarely TMA: microangiopathic hemolytic anemia, schistocytes, thrombocytopenia and worsening renal function.

Management

Control blood pressure to target (ACE inhibitors/ARBs are rational given concurrent proteinuria); monitor and manage proteinuria with dose interruption/reduction for nephrotic-range or rising protein; discontinue for confirmed TMA and manage supportively. Most hypertension/proteinuria reverses on dose modification or cessation.Lesion-level management framework

§ Receptor target map

Which kinases Fruquintinib 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
Prior anti-angiogenic therapy (bevacizumab, other VEGFR-TKIs)

Prevention

Early, proactive antihypertensive therapy
Dose modification per proteinuria/hypertension grade

Anticancer mechanism· how it treats cancer

Potent, highly selective oral inhibitor of VEGFR-1, -2 and -3 tyrosine kinases, blocking VEGF-driven tumor angiogenesis with relatively little off-target kinase activity. Approved for previously treated metastatic colorectal cancer.

Note · Toxicity mirrors the established VEGF/VEGFR class signature and is managed with standard anti-angiogenic monitoring. The JASN VEGF-nephrotoxicity framework explains why direct-antibody VEGF blockade favors TMA while VEGFR-TKIs add podocytopathy.

§04

Clinical depth

Renal dose adjustment

No specific renal dose adjustment for mild–moderate impairment; not adequately studied in severe renal impairment/ESKD. Modify dose for grade of hypertension/proteinuria per label rather than for GFR alone.

Dialyzability & ESKD dosing

Highly protein-bound small molecule with hepatic metabolism; not expected to be appreciably dialyzed. No established ESKD dosing — monitor blood pressure and proteinuria closely.

Differential diagnosis

VEGF-TKI hypertension/proteinuria/TMA vs pre-existing diabetic or hypertensive nephropathy vs other-cause nephrotic syndrome; schistocytes + thrombocytopenia + LDH point to drug-induced TMA rather than simple proteinuria.

Monitoring

Blood pressure (including home monitoring) weekly early, then each cycle
Urine protein (dipstick/UPCR) at baseline and periodically
CBC and creatinine; add LDH/haptoglobin/smear if TMA suspected

Key trials & series

FRESCO (China) and FRESCO-2 (global) phase III colorectal trials
Eng Oncologist 2025 FRESCO-2 dedicated safety analysis

Clinical pearls

Hypertension and proteinuria are predictable VEGFR-TKI class effects — monitor BP and urine protein from the first cycle.
Prefer an ACE inhibitor or ARB for the hypertension since it also addresses the concurrent proteinuria.
Schistocytes with falling platelets and rising LDH signal drug-induced TMA — stop the drug.
Antibody VEGF blockade classically causes TMA; VEGFR-TKIs add podocytopathy (MCD/FSGS-like) — the lesion depends on the agent.

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

7 primary references — trials, cohorts, mechanism, and reviews. Single-patient case reports are listed separately below, graded by strength. Citation metadata via PubMed / NLM.

Evidence accrual

7 references · 2019–2025 · 3 since 2023

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.

Case reports — ranked by strength· 3

Single-patient and small-series reports, graded by evidentiary strength — A Strong (biopsy-proven plus a series and/or positive rechallenge), B Moderate, and C Limited (a single clinically-diagnosed case). Strongest first. Grades are inferred automatically from each report's abstract and journal — a heuristic ranking aid, not a formal quality appraisal.

CaseB · ModerateRenal-Limited Thrombotic Microangiopathy Induced by Fruquintinib and Tislelizumab: A Case Report.Liu Q et al. · Nephrology (Carlton) 2025 · PMID 40528285Fruquintinib (with tislelizumab) triggered biopsy-confirmed renal-limited TMA with nephrotic-range proteinuria and hypertension that resolved after drug withdrawal.CaseB · ModerateFruquintinib-induced renal-limited thrombotic microangiopathy: a case report.Zhao R et al. · BMC Nephrol 2024 · PMID 38762494Single-agent fruquintinib caused biopsy-confirmed renal-limited thrombotic microangiopathy with heavy proteinuria in a patient with metastatic colon cancer.CaseB · ModerateRenal microangiopathy and immune complex glomerulonephritis induced by anti-tumour agents: A case report.Guo L et al. · Open Life Sci 2024 · PMID 39588116Tislelizumab plus fruquintinib induced biopsy-proven glomerular microangiopathy with FSGS-like lesions and immune-complex glomerulonephritis presenting as edema and foamy urine.

What gets reported — FAERS

Everything below is FAERS — adverse events someone chose to report, about 3,770 of them for this agent. Nobody counts the patients who were fine, so none of these numbers is an incidence, a risk, or a rate: they describe what gets reported, shaped by a drug's fame, its indication, and who was watching. How these numbers work.

Reporting odds ratio (ROR) — is kidney injury named in this agent's reports more often than in every other drug's? Above 1 means yes, disproportionately.
Renal phenotypes — the same question asked separately for each kind of kidney injury, so the ratios differ from the overall one and from each other.
Outcomes — a share of this agent's own reports, not of patients: how many were filed as involving a death or a hospitalization. Not a case-fatality rate.

FAERS reported renal phenotypes· 2 signals

Only significant signals appear (95% CI lower bound above 1) — a phenotype missing here was tested and did not reach significance, except Prerenal / Hemodynamic AKI, Pseudo-AKI, Renal Cysts, Chronic Interstitial Nephropathy — outside the clinician-reviewed MedDRA term map, never queried — and ATN and AIN, queried but biopsy-bound: real cases are filed as generic “acute kidney injury”, so their absence is not a negative. As of 2026-10-01.

What reporting says about this profile's documented lesions

Glomerular Injury / Proteinuriacorroborated · ROR 26.43 — on the terms that name the lesion (ROR 18.07)
Hypertensioncorroborated · ROR 7.52 — on the terms that name the lesion (ROR 5.18)
Thrombotic MicroangiopathyNo disproportionate reporting — This phenotype IS reportable and this agent has enough reports, yet the reporting is not disproportionate — the one genuinely informative negative of the four.

Glomerular Injury / Proteinuria

ROR 26.4395% CI 22.23–31.44· 133 reports

Hypertension

ROR 7.5295% CI 6.83–8.29· 465 reports

FAERS outcomes & reporting trend· 33% of reports w/ death · 30.3% w/ hospitalization

33%

Reported with a death outcome

1,245 of 3,770 reports

30.3%

Reported with hospitalization

1,141 of 3,770 reports

Reports per year

Yearly FAERS report volume · most recent year is partial.

FAERS adverse-event signal — all organ systems· 10 systems · 3,770 reports

Bars rank systems by summed reaction-term mentions (a report counts once per term it names) — an ordinal “more vs less reported” cue, not a tally of distinct reports. Renal & urinary first. As of 2026-10-01.

Disproportionality (acute kidney injury):ROR 0.6695% CI 0.41–1.04· 18 AKI reports ·no disproportionate AKI reporting signal (CI spans 1).

Renal & urinary

Proteinuria101

General / constitutional

Fatigue470Asthenia233Pain152Malaise112Weight Decreased82

Gastrointestinal

Diarrhoea275Nausea179Vomiting116Stomatitis102Constipation87

Vascular

Blood Pressure Increased269Hypertension193

Metabolic & electrolyte

Decreased Appetite239

Nervous system

Headache125Neuropathy Peripheral98

Blood & lymphatic

Myelosuppression217

Respiratory

Dysphonia209

Skin

Palmar-Plantar Erythrodysaesthesia Syndrome124

Musculoskeletal

Pain In Extremity90

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 Fruquintinib 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

Axitinib

Inlyta · VEGFR TKI

Profile

Potent VEGFR-TKI; hypertension and proteinuria dominate.

HTNGLOMTMA

Moderate#1 · 88% phenotype match

Pazopanib

Votrient · VEGFR TKI

Profile

VEGFR-TKI; hypertension, proteinuria, TMA.

GLOMHTNTMA

Moderate#2 · 87% phenotype match

Ziv-aflibercept

Zaltrap · VEGF trap

Profile

Hypertension and proteinuria like bevacizumab.

HTNGLOMTMA

Moderate#3 · 85% phenotype match

Bevacizumab

Avastin · Anti-VEGF antibody

Profile

Proteinuria, hypertension, glomerular TMA.

GLOMHTNTMA

Moderate#4 · 85% phenotype match

Ramucirumab

Cyramza · Anti-VEGFR2 antibody

Profile

Hypertension and proteinuria, class effect.

HTNGLOMTMA

Moderate#5 · 85% phenotype match

VEGFR TKIs (sunitinib · sorafenib · pazopanib · axitinib)

VEGFR TKI

Profile

Hypertension as an on-target marker; proteinuria.

HTNGLOMTMA

Moderate#6 · 85% phenotype match

Compare Fruquintinib 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.

Who studies this

The leading contributors to Fruquintinib’s clinical kidney literature on PubMed, ranked by a blend of publication volume and citation impact — filtered toward clinical work via the PubMed Humans heading and clinical publication types (trials, cohorts, case reports, guidelines, reviews). Names link to that author’s work on Fruquintinib; the PMIDs beside each name are up to three of their most recent papers on it, not the full count.

Ranked by a 50/50 blend of publication volume and a position-weighted, capped Relative Citation Ratio (NIH iCite) on this agent’s renal literature; the citation count shown is the raw total, not the ranking score — counted over the 10 clinical records among all 19 PubMed matches, so counts are within-sample — bibliometric context, not an endorsement or a measure of clinical authority.