What kind of kidney injury does Ripretinib cause?

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.

Is kidney injury from Ripretinib reversible?

Reversible. Typical onset: Hypertension can develop within early cycles and persist..

How should kidney function be monitored during Ripretinib therapy?

Blood pressure at baseline and regularly through treatment; Skin/hand-foot assessment; Cardiac function (ejection fraction) per label.

How can kidney injury from Ripretinib be prevented?

Proactive antihypertensive treatment, started before pressure climbs Cardiovascular risk-factor optimization Dose interruption/reduction for grade 3+ hypertension per label

Who is at higher risk of kidney injury from Ripretinib?

Pre-existing hypertension or cardiovascular disease; Prior VEGF/TKI vascular toxicity; Baseline CKD; Concurrent agents raising blood pressure.

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Printable monograph

KIT switch-control inhibitor

Ripretinib

Qinlock · RIP

KIT switch-control inhibitor · approved 2020 · 7 citations

Up to date· through 2026

Fairly sourced5/9 · 5 signals

Met: 7 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 2026
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.

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

Advanced gastrointestinal stromal tumor after >=3 prior kinase inhibitors (fourth-line)

§01

Signature kidney injury

Signature lesion

Hypertension

Representative grade ≥3 incidence4%

Hypertension is the recognized renal-relevant toxicity: in the INVICTUS phase 3 trial (n=85), grade 3-4 hypertension occurred in 3 patients (4%) — the second most common grade 3-4 treatment-related event after lipase increase — 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, PMID 32511981, grade 3-4 hypertension 3/85)

Onset & rechallenge

Time to injurySubacute (~1–6 weeks)

Hypertension develops within early cycles and persists.

Distilled from: “Hypertension can develop within early cycles and persist.”

§02

Renal toxicities, ranked

This agent's defining kidney lesion — its #1 signature. Cited incidence is shown where a citable figure exists; otherwise the tier stands qualitatively.

Hypertension#1 · Signaturequalitative — no citable incidence
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

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.

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.Lesion-level management framework

Risk factors

Pre-existing hypertension or cardiovascular disease
Prior VEGF/TKI vascular toxicity
Baseline CKD
Concurrent agents raising blood pressure

Prevention

Proactive antihypertensive treatment, started before pressure climbs
Cardiovascular risk-factor optimization
Dose interruption/reduction for grade 3+ hypertension per label

Anticancer mechanism· how it treats cancer

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.

Note · The renal link is indirect and hypertension-mediated; there is no characteristic direct ripretinib nephrotoxicity. Quantified grade 3 hypertension rates are modest.

§04

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; a tubular/glomerular lesion is atypical, though biopsy-proven focal segmental glomerulosclerosis with nephrotic-range proteinuria has been reported.

Monitoring

Blood pressure at baseline and regularly through treatment
Skin/hand-foot assessment
Cardiac function (ejection fraction) per label

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 & injury signatures

Nephron segments

Vasculature / Endothelium

Glomerular & peritubular capillaries

Injury signatures

Hypertension

§05

References

6 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

6 references · 2020–2025 · 2 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· 1

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.

CaseC · LimitedRipretinib-Induced Focal Segmental Glomerulosclerosis in a Patient With Gastrointestinal Stromal Tumor (GIST).Tripathi O · Cureus 2026 · PMID 41769596Case report of a GIST patient who developed focal segmental glomerulosclerosis with acute kidney injury and nephrotic-range proteinuria attributed to ripretinib-induced podocyte injury, resolving after drug cessation and steroids.

What gets reported — FAERS

Everything below is FAERS — adverse events someone chose to report, about 5,217 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· 1 signal

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

Hypertensioncorroborated · ROR 3.62 — on the terms that name the lesion (ROR 3.9)

Hypertension

ROR 3.6295% CI 3.24–4.05· 331 reports

FAERS outcomes & reporting trend· 9.5% of reports w/ death · 20.1% w/ hospitalization

9.5%

Reported with a death outcome

494 of 5,217 reports

20.1%

Reported with hospitalization

1,048 of 5,217 reports

Reports per year

Yearly FAERS report volume · most recent year is partial.

FAERS adverse-event signal — all organ systems· 6 systems · 5,217 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 0.2495% CI 0.12–0.45· 9 AKI reports ·AKI is reported less often than for other drugs (CI entirely below 1) — no disproportionate signal.

General / constitutional

Fatigue687Pain295Asthenia246

Skin

Alopecia592Dry Skin220Palmar-Plantar Erythrodysaesthesia Syndrome186Pruritus182

Gastrointestinal

Nausea338Constipation292Diarrhoea276Vomiting176

Musculoskeletal

Muscle Spasms259Pain In Extremity218Myalgia200

Metabolic & electrolyte

Decreased Appetite224

Vascular

Hypertension207

Guidelines & consensus· 13

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.

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 Ripretinib 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

Leuprolide

Lupron · GnRH agonist

Profile

Metabolic syndrome; indirect renal risk.

HTN

Mild#1 · 86% phenotype match

Copanlisib

Aliqopa · Pan-PI3K inhibitor

Profile

Transient infusion-related hypertension and hyperglycemia.

HTN

Moderate#2 · 83% phenotype match

Asciminib

Scemblix · BCR-ABL STAMP inhibitor

Profile

Hypertension and pancreatitis; allosteric BCR-ABL inhibitor.

HTNPRE

Mild#3 · 65% phenotype match

Enzalutamide

Xtandi · Androgen-receptor inhibitor

Profile

Hypertension; rare electrolyte effects.

HTNLYTE

Mild#4 · 62% phenotype match

Acalabrutinib

Calquence · BTK inhibitor

Profile

Tumor lysis; lower hypertension than ibrutinib.

HTNPREXTAL

Mild#5 · 54% phenotype match

Pralsetinib

Gavreto · RET inhibitor

Profile

Hypertension; rare AKI.

HTNPREPSEUDO

Mild#6 · 54% phenotype match

Compare Ripretinib 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 Other kinase inhibitors

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.