KIT switch-control inhibitor
Ripretinib
Qinlock · RIP
KIT switch-control inhibitor · approved 2020 · 6 references
KIT/PDGFRA switch-control inhibitor for fourth-line GIST — hypertension is the renal-relevant signal, with alopecia and PPE the dominant non-renal toxicities.
- Signature injury
- Hypertension
- Severity
- Mild
- Reversibility
- Reversible
- Onset
- Hypertension can develop within early cycles and persist.
Signature kidney injury & incidence
Hypertension — representative grade ≥3 incidence ~4%.
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)
Reported injury signatures: Hypertension.
Onset timing & rechallenge
Subacute (~1–6 weeks) — Hypertension develops within early cycles and persists.
Mechanism of kidney injury
Clinical presentation
Management
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
Renal dose adjustment
Dialyzability & ESKD dosing
Differential diagnosis
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.
Anticancer mechanism
Note
Guidelines & consensus
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.
- ADQI (2026) — The nephrotoxic effects of anti-cancer therapies: consensus report of the 34th Acute Disease Quality Initiative workgroupProvides 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.Nat Rev Nephrol · PMID 41361704
- SIRM (2022) — SIRM-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)Recommends 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.Radiol Med · PMID 35303246
- KDIGO (2020) — KDIGO Controversies Conference on onco-nephrology: understanding kidney impairment and solid-organ malignancies, and managing kidney cancerIdentifies 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.Kidney Int · PMID 33126977
- KDIGO (2020) — KDIGO Controversies Conference on onco-nephrology: kidney disease in hematological malignancies and the burden of cancer after kidney transplantationAddresses 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.Kidney Int · PMID 33276867
- ADDIKD (2025) — Integrating International Consensus Guidelines for Anticancer Drug Dosing in Kidney Dysfunction (ADDIKD) into everyday practiceProvides 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.EClinicalMedicine · PMID 40290844
- ADDIKD (2025) — Aligning kidney function assessment in patients with cancer to global practices in internal medicineThree 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.EClinicalMedicine · PMID 40290845
- ADDIKD (2025) — A methodology for determining dosing recommendations for anticancer drugs in patients with reduced kidney functionEstablishes 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.EClinicalMedicine · PMID 40290846
- KDIGO (2013) — Diagnosis, evaluation, and management of acute kidney injury: a KDIGO summary (Part 1)Defines/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.Crit Care · PMID 23394211
- KDIGO (2024) — Executive summary of the KDIGO 2024 Clinical Practice Guideline for the Evaluation and Management of Chronic Kidney Disease: known knowns and known unknownsEvaluate 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.Kidney Int · PMID 38519239
- KDIGO (2021) — Executive summary of the KDIGO 2021 Guideline for the Management of Glomerular DiseasesProvides 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.Kidney Int · PMID 34556300
- KDIGO (2024) — Executive summary of the KDIGO 2024 Clinical Practice Guideline for the Management of ANCA-Associated VasculitisUpdates 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.Kidney Int · PMID 38388147
- KDIGO (2024) — Executive summary of the KDIGO 2024 Clinical Practice Guideline for the Management of Lupus NephritisUpdates 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.Kidney Int · PMID 38182299
- KDIGO (2025) — Executive summary of the KDIGO 2025 Clinical Practice Guideline for the Management of Immunoglobulin A Nephropathy (IgAN) and Immunoglobulin A Vasculitis (IgAV)Encourages 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.Kidney Int · PMID 40975525
References
6 peer-reviewed references. Citation metadata via PubMed / NLM.
- 1.Ripretinib in patients with advanced gastrointestinal stromal tumours (INVICTUS): a double-blind, randomised, placebo-controlled, phase 3 trial.Blay JY et al. · Lancet Oncol · 2020 · PMID 32511981
- 2.Patient-reported outcomes in individuals with advanced gastrointestinal stromal tumor treated with ripretinib in the fourth-line setting: analysis from the phase 3 INVICTUS trial.Schoffski P et al. · BMC Cancer · 2022 · PMID 36514034
- 3.FDA Approval Summary: Ripretinib for Advanced Gastrointestinal Stromal Tumor.Kumar V et al. · Clin Cancer Res · 2023 · PMID 36485007
- 4.Ripretinib: A Review in Gastrointestinal Stromal Tumours as Fourth-or Later-Line of Therapy.Fung S et al. · Drugs · 2022 · PMID 36282417
- 5.Ripretinib for the treatment of advanced gastrointestinal stromal tumor.Zalcberg JR et al. · Ther Adv Gastroenterol · 2021 · PMID 33948116
- 6.Signal mining and analysis of ripretinib adverse events: a real-world pharmacovigilance analysis based on the FAERS database.Hu Y et al. · Front Pharmacol · 2025 · PMID 40078281
Case reports & series (1)
The weakest rung of clinical evidence — single-patient and small-series reports, strongest first. Each carries a heuristic strength grade (A Strong / B Moderate / C Limited) inferred from its abstract and journal, not a formal appraisal. Weigh well below the primary references above.
- C1.[C · Limited]Ripretinib-Induced Focal Segmental Glomerulosclerosis in a Patient With Gastrointestinal Stromal Tumor (GIST).Tripathi O · Cureus · 2026 · PMID 41769596