Quizartinib
Vanflyta · FLT3 inhibitor
2023 AML FLT3 inhibitor; tumor lysis and QT.
PRELYTE
Mild#1 · 100% phenotype match
Avapritinib
Ayvakit · AVA
KIT / PDGFRA inhibitor · approved 2020 · 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: 1y)
- 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.
Potent KIT/PDGFRA inhibitor for D842V-driven GIST and mastocytosis — renal-relevant effects are edema and CNS bleeding/cognitive effects rather than direct nephrotoxicity.
MildMutation-selective KIT/PDGFRA era
Unresectable/metastatic GIST harboring a PDGFRA exon 18 (including D842V) mutationAdvanced systemic mastocytosis (aggressive SM, SM with associated hematologic neoplasm, mast cell leukemia)
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Signature kidney injury
Signature lesion
Edema (periorbital/peripheral) is very common, and intracranial hemorrhage and cognitive/CNS effects are labeled toxicities; nausea/diarrhea contribute to volume shifts. Direct nephrotoxicity is not a defined signal and AKI, when it occurs, is secondary (fluid shifts, GI losses, mastocytosis mediator release).Source: Heinrich et al., Lancet Oncol 2020 (NAVIGATOR); DeAngelo et al., Nat Med 2021 (EXPLORER)
Onset & rechallenge
Time to injuryVariable / unpredictable
Edema and cognitive effects occur across treatment, and GI-related prerenal changes track intercurrent toxicity.
Distilled from: “Edema and cognitive effects across treatment; GI-related prerenal changes track intercurrent toxicity.”
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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.
Renal hypoperfusion from capillary leak and cytokine storm — IL-2 and CAR-T cytokine release syndrome.
Renal electrolyte derangement — magnesium/potassium/calcium wasting (cisplatin, anti-EGFR antibodies) or retention (FGFR-inhibitor hyperphosphatemia, tumor-lysis hyperkalemia/hyperphosphatemia).
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Kidney injury
Mechanism of kidney injury
Avapritinib has no characteristic primary renal lesion. Its renal relevance is indirect: (1) prominent fluid retention/edema reflects vascular permeability changes and can be accompanied by intravascular volume shifts; (2) gastrointestinal toxicity (nausea, diarrhea) causes volume depletion and prerenal azotemia; (3) in mastocytosis, mast-cell mediator-release (flushing, hypotension) can transiently impair renal perfusion. The signature CNS toxicities (intracranial bleeding, cognitive effects) are not renal but dominate the safety profile.
Clinical presentation
Periorbital and peripheral edema, fatigue, nausea/diarrhea, and cognitive effects (memory/attention) or, rarely, intracranial hemorrhage. Renally, a prerenal creatinine rise with GI losses or hypotension; edema may coexist with intravascular depletion.
Management
Treat prerenal AKI with volume repletion and control of GI losses; manage edema with dose modification and supportive measures (avoid over-diuresis that worsens prerenal physiology). Hold/reduce for cognitive effects or any intracranial hemorrhage. Mast-cell mediator events are treated with antihistamines/supportive care; renal effects generally reverse with hemodynamic stabilization.Lesion-level management framework
Risk factors
- Volume depletion from nausea/diarrhea
- Pre-existing CKD and concurrent nephrotoxins
- Mast-cell mediator-release events in mastocytosis
- Older age and baseline cognitive/vascular vulnerability
Prevention
- Manage GI toxicity and maintain hydration
- Manage edema and dose-modify for significant fluid retention
- Neurologic assessment for cognitive effects/bleeding; dose-reduce per label
- Mediator-release prophylaxis in mastocytosis as indicated
Anticancer mechanism· how it treats cancer
Oral selective inhibitor of KIT and PDGFRA activation-loop mutants (notably PDGFRA exon 18/D842V and KIT exon 17), conformations resistant to imatinib. It is active in PDGFRA D842V-mutant GIST and advanced systemic mastocytosis.
Note · The renal link is indirect — fluid shifts/edema, GI-loss prerenal physiology, and mastocytosis mediator release rather than a direct renal lesion. The defining toxicities (intracranial bleeding, cognitive effects) are non-renal.
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Clinical depth
Renal dose adjustment
No dose adjustment for mild-moderate renal impairment; severe impairment/ESKD not well studied (hepatic CYP3A4 metabolism). Modifications driven by edema, CNS effects and cytopenias.
Dialyzability & ESKD dosing
Highly protein-bound; not expected to be dialyzable. No established ESKD dosing.
Differential diagnosis
Separate prerenal AKI (volume-responsive) from edema with intravascular depletion (avoid aggressive diuresis), and from mediator-release hypotension in mastocytosis. CNS symptoms require distinguishing cognitive toxicity from intracranial hemorrhage by imaging.
Monitoring
- Volume status, weight and edema assessment
- Cognitive/neurologic status; prompt imaging for new neurologic symptoms (bleed)
- Serum creatinine and electrolytes with GI toxicity
- CBC per schedule
Key trials & series
- NAVIGATOR (Heinrich, Lancet Oncol 2020) — registrational GIST trial (PDGFRA D842V)
- EXPLORER/PATHFINDER (DeAngelo, Nat Med 2021; Gotlib, Nat Med 2021) — advanced systemic mastocytosis safety/efficacy
Clinical pearls
- Edema with concurrent GI losses can mask intravascular volume depletion — assess true volume status before diuresing.
- Intracranial hemorrhage and cognitive effects are the signature (non-renal) toxicities — they drive dose decisions.
- In mastocytosis, mediator-release events can transiently impair renal perfusion.
- There is no characteristic direct avapritinib nephropathy; AKI is secondary.
Where it strikes· nephron segments & injury signatures
Nephron segments
Vasculature / Endothelium
Glomerular & peritubular capillaries
Injury signatures
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References
5 primary references — trials, cohorts, mechanism, and reviews. Citation metadata via PubMed / NLM.
Evidence accrual
5 references · 2020–2021 · 5 since 2019Primary (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.
- 1.LandmarkAvapritinib in advanced PDGFRA D842V-mutant gastrointestinal stromal tumour (NAVIGATOR): a multicentre, open-label, phase 1 trial.Heinrich MC et al. · Lancet Oncol · 2020 · PMID 32615108Registrational GIST trial defining efficacy and the edema/CNS safety profile.
- 2.Avapritinib Versus Regorafenib in Locally Advanced Unresectable or Metastatic GI Stromal Tumor: A Randomized, Open-Label Phase III Study.Kang YK et al. · J Clin Oncol · 2021 · PMID 34343033Phase 3 comparative safety dataset.
- 3.Efficacy and safety of avapritinib in advanced systemic mastocytosis: interim analysis of the phase 2 PATHFINDER trial.Gotlib J et al. · Nat Med · 2021 · PMID 34873345Phase 2 PATHFINDER trial in advanced systemic mastocytosis; principal grade >=3 toxicities were cytopenias (neutropenia, thrombocytopenia, anemia).
- 4.Safety and efficacy of avapritinib in advanced systemic mastocytosis: the phase 1 EXPLORER trial.DeAngelo DJ et al. · Nat Med · 2021 · PMID 34873347Pivotal mastocytosis efficacy/safety confirming the toxicity pattern.
- 5.Optimal Avapritinib Treatment Strategies for Patients with Metastatic or Unresectable Gastrointestinal Stromal Tumors.Joseph CP et al. · Oncologist · 2021 · PMID 33301227Practical management of edema, cognitive effects and bleeding.
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 Avapritinib 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.
Phenotype-similar agents· the numbered markers on the map above
Profile
Imetelstat
Rytelo · Telomerase inhibitor
2024 MDS agent; tumor lysis risk.
PRELYTE
Mild#2 · 89% phenotype match
Zanidatamab
Ziihera · HER2 bispecific antibody
2024 biliary-tract HER2 bispecific; renal data emerging.
PRELYTE
Mild#3 · 89% phenotype match
Zenocutuzumab
Bizengri · HER2×HER3 bispecific antibody
2024 NRG1-fusion bispecific; mostly grade 1-2 AEs — at most diarrhea-related prerenal risk, no CRS/TLS mechanism.
PRELYTE
Mild#4 · 89% phenotype match
Mirdametinib
Gomekli · MEK inhibitor
2025 NF1 MEK inhibitor; creatinine rise and edema.
PRELYTE
Mild#5 · 89% phenotype match
Midostaurin
Rydapt · FLT3 / multikinase inhibitor
Tumor lysis, edema and QT in AML/mastocytosis.
PRELYTE
Mild#6 · 88% phenotype match
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.
- 1PexidartinibPRE — Prerenal / Hemodynamic AKIMild
- 2RipretinibHTN — HypertensionMild
- 3Avapritinib· this agentPRE — Prerenal / Hemodynamic AKIMild
- 4FedratinibLYTE — Electrolyte DisturbanceMild
- 5MidostaurinPRE — Prerenal / Hemodynamic AKIMild
- 6QuizartinibPRE — Prerenal / Hemodynamic AKIMild
- 7VimseltinibPSEUDO — Pseudo-AKIMild
- 8PralsetinibHTN — HypertensionMild
- 9RuxolitinibPRE — Prerenal / Hemodynamic AKIMild
- 10MomelotinibPSEUDO — Pseudo-AKIFAERS AKIMild
- 11GilteritinibPRE — Prerenal / Hemodynamic AKIModerate
- 12PacritinibPRE — Prerenal / Hemodynamic AKIModerate
- 13SelpercatinibHTN — HypertensionModerate
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.