Dordaviprone
Modeyso · Imipridone (ONC201; DRD2/ClpP)
2025 imipridone for H3 K27M glioma; renally well tolerated — QT prolongation, not nephrotoxicity, is the safety focus.
PRE
Mild#1 · 89% phenotype match
Type II pan-RAF (BRAF) inhibitor
Tovorafenib
Ojemda · TOVO
Type II pan-RAF (BRAF) inhibitor · approved 2024 · 4 citations
Recent· through 2024
Thinly sourced3/9 · 3 signals
- Not met: 4 citations
- Not met: 12+ references
- Not met: Accrued over 10+ years (span: 1y)
- Met: Beyond single case reports
- Not met: Peer-reviewed sources
- Met: Landmark reference
- Met: Current through 2024
- 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 pediatric type II RAF inhibitor for BRAF-altered glioma — kidney signal limited to modest creatinine shifts.
MildType II RAF inhibitor
Pediatric relapsed/refractory low-grade glioma with BRAF alterations
§01
Signature kidney injury
Signature lesion
No established intrinsic nephrotoxicity. In FIREFLY-1 the prominent toxicities were hair-color change, rash, anemia and fatigue; renal events were not a defining signal, and any creatinine elevation is described qualitatively rather than as a quantified AKI rate.Source: Kilburn et al., Nat Med 2023
Onset & rechallenge
Time to injuryVariable / unpredictable
Not well defined; any change emerges during ongoing therapy rather than at a fixed onset.
Distilled from: “Not well defined; any change emerges during ongoing therapy rather than at a fixed onset.”
§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.
Renal hypoperfusion from capillary leak and cytokine storm — IL-2 and CAR-T cytokine release syndrome.
§03
Kidney injury
Mechanism of kidney injury
No characterized direct tubular or glomerular injury. A mild creatinine rise, if seen, is most consistent with hemodynamic/prerenal effects, MAPK-pathway-associated fluid shifts/edema, or non-renal creatinine fluctuation (muscle mass, growth) rather than structural nephron damage. In children, intercurrent vomiting/poor intake commonly drives transient prerenal azotemia.
Clinical presentation
When present, a small reversible creatinine increase without active urinary sediment; possible peripheral/periorbital edema; electrolytes generally stable.
Management
Supportive; ensure euvolemia and review concomitant nephrotoxins before attributing AKI to the drug. Dose interruption/reduction per protocol for significant toxicity. Intrinsic renal injury has not been characterized.Lesion-level management framework
Risk factors
- Intercurrent volume depletion (vomiting, poor intake) in children
- Concurrent nephrotoxins
- Pre-existing renal impairment
Prevention
- Maintain hydration during intercurrent illness
- Interpret pediatric creatinine against growth-adjusted norms (consider cystatin C / eGFR equations)
Anticancer mechanism· how it treats cancer
Oral type II pan-RAF inhibitor that blocks both monomeric and dimeric RAF signaling in the MAPK/ERK pathway, overcoming paradoxical activation seen with type I RAF inhibitors. Approved for relapsed/refractory pediatric low-grade glioma harboring BRAF fusions/rearrangements or BRAF V600 mutation.
Note · 2024 pediatric approval with minimal renal data. The prerenal/vascular framing is conservative and class/hemodynamic-based; no quantified renal incidence exists. Flag as low-certainty.
§04
Clinical depth
Renal dose adjustment
No established renal dose adjustment; tovorafenib is hepatically metabolized with low renal elimination, so meaningful exposure change with reduced GFR is not expected. Pediatric dosing is body-surface-area based and unchanged for renal function in label-described populations.
Dialyzability & ESKD dosing
Not characterized; as a highly protein-bound small molecule with non-renal clearance it is unlikely to be appreciably dialyzed. No dialysis dosing data in this pediatric population.
Differential diagnosis
In a child on therapy, distinguish benign creatinine fluctuation / prerenal azotemia (intercurrent illness, dehydration) from true AKI using urinalysis, volume assessment and trend — structural drug nephrotoxicity has not been described.
Monitoring
- Hemoglobin (anemia is a common class effect)
- Weight/edema and growth parameters
- Hepatic function and CK per label
Key trials & series
- FIREFLY-1 (Kilburn, Nat Med 2023) — pivotal phase 2
- LOGGIC/FIREFLY-2 (van Tilburg, BMC Cancer 2024) — confirmatory phase 3
Clinical pearls
- Interpret pediatric creatinine carefully — muscle mass and growth move the number independent of true GFR.
- Hydrate through intercurrent vomiting/diarrhea; that, not the drug, is the usual cause of a creatinine bump.
Where it strikes· nephron segments & injury signatures
Nephron segments
Vasculature / Endothelium
Glomerular & peritubular capillaries
Injury signatures
Beyond the kidney — non-renal toxicities· 4 organ systems
Class-level context for the major non-renal toxicities of the Type II pan-RAF (BRAF) inhibitor class.
Dermatologic
Rash, HFS, SJS/TEN, vitiligo
- Rash, photosensitivity, squamous-cell carcinomas (BRAF)
Cardiac
Cardiomyopathy, QT, ischemia, myocarditis
- Reduced LVEF (MEK)
Ophthalmic
Keratopathy, uveitis, retinopathy
- Retinopathy / retinal vein occlusion (MEK)
Vascular
Hypertension, VTE/ATE, bleeding, aneurysm
- Pyrexia syndrome, hypertension
§05
References
4 primary references — trials, cohorts, mechanism, and reviews. Citation metadata via PubMed / NLM.
Evidence accrual
4 references · 2023–2024 · 4 since 2022Primary (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.LandmarkThe type II RAF inhibitor tovorafenib in relapsed/refractory pediatric low-grade glioma: the phase 2 FIREFLY-1 trial.Kilburn LB et al. · Nat Med · 2023 · PMID 37978284Pivotal efficacy/safety trial; toxicity profile is non-renal-dominant, supporting the low/qualitative renal assessment.
- 2.LOGGIC/FIREFLY-2: a phase 3, randomized trial of tovorafenib vs. chemotherapy in pediatric and young adult patients with newly diagnosed low-grade glioma harboring an activating RAF alteration.van Tilburg CM et al. · BMC Cancer · 2024 · PMID 38291372Confirmatory phase 3 design/rationale documenting the safety-monitoring framework for the agent.
- 3.Acute and chronic kidney injury during therapy for pediatric acute leukemia: A report from the Leukemia Electronic Abstraction of Records Network (LEARN).Hsiao W et al. · Pediatr Blood Cancer · 2023 · PMID 37776085Pediatric oncology AKI cohort illustrating how definition (CTCAE vs KDIGO) and growth-related creatinine variability shape apparent renal-injury rates in children.
- 4.Onconephrology: mitigation of renal injury in chemotherapy administration.Selamet U et al. · Curr Opin Nephrol Hypertens · 2024 · PMID 38095483Onconephrology review of kinase-inhibitor renal effects framing low direct-tubular risk for MAPK-pathway agents.
FDA label — boxed warning & renal dosing· renal impairment
Quoted verbatim from this agent's current FDA label (Sep 2025) — not paraphrased or interpreted. Full label on DailyMed .
Renal impairment — from the label
No dose adjustment is recommended for patients with mild-to-moderate renal impairment (eGFR ≥ 30 mL/min/1.73 m 2 calculated by Schwartz equation or MDRD equation). OJEMDA has not been studied in patients with severe renal impairment (eGFR <30 mL/min/1.73 m 2 ) [see Clinical Pharmacology (12.3) ] .
What gets reported — FAERS
Everything below is FAERS — adverse events someone chose to report, about 292 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.
- 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
- Prerenal / Hemodynamic AKINot queried in FAERS — No MedDRA term set is defined for this phenotype, so FAERS was never asked about it.
Electrolyte Disturbance
ROR 2.2895% CI 1.02–5.12· 6 reports
FAERS outcomes & reporting trend· 4.1% of reports w/ death · 11.6% w/ hospitalization
4.1%
Reported with a death outcome
12 of 292 reports
11.6%
Reported with hospitalization
34 of 292 reports
Reports per year
- 2015: 0 reports
- 2016: 0 reports
- 2017: 0 reports
- 2018: 0 reports
- 2019: 0 reports
- 2020: 0 reports
- 2021: 0 reports
- 2022: 0 reports
- 2023: 0 reports
- 2024: 69 reports
- 2025: 179 reports
- 2026: 44 reports
Yearly FAERS report volume · most recent year is partial.
FAERS adverse-event signal — all organ systems· 8 systems · 292 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.
Skin
Rash26Dermatitis Acneiform9Photosensitivity Reaction7Erythema5
General / constitutional
Fatigue21Weight Decreased7Asthenia5
Gastrointestinal
Nausea9Constipation5Vomiting5
Nervous system
Headache15
Vascular
Intracranial Tumour Haemorrhage10
Blood & lymphatic
Anaemia7
Psychiatric
Insomnia5
Musculoskeletal
Arthralgia4
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 Tovorafenib 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
Elacestrant
Orserdu · Oral selective estrogen-receptor degrader (SERD)
2023 oral SERD; nausea-dominant, minimal intrinsic nephrotoxicity.
PRE
Mild#2 · 89% phenotype match
Iberdomide
Zenbexus · Cereblon E3 ligase modulator (CELMoD)
2026 first-in-class CELMoD; no attributable lesion (renal impairment 11% vs 8% on the comparator arm) but exposure rises 1.8x below eGFR 30 off dialysis.
PRE
Mild#3 · 89% phenotype match
Vepdegestrant
Veppanu · PROTAC estrogen-receptor degrader
2026 first PROTAC ER degrader; no meaningful intrinsic renal signal.
PRE
Mild#4 · 89% phenotype match
Zidesamtinib
Jideytro · ROS1-selective TKI
2026 TRK-sparing ROS1 TKI; no creatinine abnormality reached the label's >=20% lab-table cutoff — unlike the class's benign pseudo-AKI rise. Renally quiet so far.
PRE
Mild#5 · 89% phenotype match
Casdatifan
HIF-2α inhibitor (investigational)
Trial-stage RCC HIF-2α inhibitor; renal profile being defined.
PRE
Mild#6 · 89% 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 BRAF / MEK 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.
- 1Tovorafenib· this agentPRE — Prerenal / Hemodynamic AKIMild
- 2MirdametinibPRE — Prerenal / Hemodynamic AKIMild
- 3SelumetinibPRE — Prerenal / Hemodynamic AKIMild
- 4BRAF / MEK inhibitors (vemurafenib · dabrafenib · trametinib)ATN — Acute Tubular NecrosisMild
- 5BinimetinibATN — Acute Tubular NecrosisFAERS AKIMild
- 6CobimetinibATN — Acute Tubular NecrosisFAERS AKIMild
- 7EncorafenibATN — Acute Tubular NecrosisFAERS AKIMild
- 8DabrafenibAIN — Acute Interstitial NephritisFAERS AKIMild
- 9AvutometinibLYTE — Electrolyte DisturbanceModerate
- 10TrametinibPRE — Prerenal / Hemodynamic AKIFAERS AKIModerate
- 11VemurafenibATN — Acute Tubular NecrosisFAERS AKIModerate
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.