What kind of kidney injury does Dordaviprone cause?

Prerenal / Hemodynamic AKI — Renal hypoperfusion from capillary leak and cytokine storm — IL-2 and CAR-T cytokine release syndrome.

Is kidney injury from Dordaviprone reversible?

Reversible. Typical onset: No drug-specific renal onset. QT effects are the on-treatment finding to monitor; any prerenal creatinine change would follow an intercurrent volume-depleting event..

How should kidney function be monitored during Dordaviprone therapy?

ECG/QT interval per the drug's cardiac guidance (the key safety monitor); Serum potassium and magnesium (to protect the QT, and for general electrolyte health); Routine serum creatinine as part of standard care (no drug-specific renal surveillance); Volume status during intercurrent GI illness.

How can kidney injury from Dordaviprone be prevented?

Keep potassium and magnesium normal — primarily to protect the QT interval, secondarily for renal-electrolyte health Maintain hydration during intercurrent GI illness Review co-medications for additive QT prolongation

Who is at higher risk of kidney injury from Dordaviprone?

Intercurrent volume depletion (vomiting, diarrhea, poor intake) causing prerenal physiology; Electrolyte disturbances (hypokalemia, hypomagnesemia) — chiefly a QT/arrhythmia concern; Concurrent QT-prolonging drugs; Baseline CKD (lowers reserve for any intercurrent insult).

Back to explorer

Printable monograph

Imipridone (ONC201; DRD2/ClpP)

Dordaviprone

Modeyso · DOR

Imipridone (ONC201; DRD2/ClpP) · approved 2025 · 2 citations

Up to date· through 2025

Thinly sourced2/9 · 2 signals

Not met: 2 citations
Not met: 12+ references
Not met: Accrued over 10+ years (span: 1y)
Not met: Beyond single case reports
Not met: Peer-reviewed sources
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.

The first imipridone (ONC201) for H3 K27M diffuse glioma — a drug whose safety story centers on the QT interval, not the kidney, which it largely leaves alone.

MildImipridone (DRD2 antagonist / ClpP agonist)

Recurrent H3 K27M-mutant diffuse midline glioma (accelerated approval); studied in newly diagnosed disease after radiotherapyA tumor-type defined by the H3 K27M mutation, primarily affecting children and young adults

§01

Signature kidney injury

Signature lesion

Prerenal / Hemodynamic AKI

Dordaviprone carries no meaningful renal signal and no discrete published incidence of drug-related acute kidney injury. Its clinically important safety consideration is cardiac — QT-interval prolongation — rather than renal, and the intermittent oral schedule is generally well tolerated. Across its glioma program (Arrillaga-Romany, Neuro Oncol 2024, describes the phase 3 ACTION design and prior recurrent-disease efficacy), the toxicity profile is dominated by fatigue and QT effects, not nephrotoxicity. Any renal contribution would be indirect (prerenal physiology from intercurrent illness) rather than an intrinsic tubular or glomerular toxicity.Source: No meaningful renal signal; QT prolongation (not nephrotoxicity) is the safety focus (ACTION program, Arrillaga-Romany 2024)

§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.

Prerenal / Hemodynamic AKI#1 · Signaturequalitative — no citable incidence
Renal hypoperfusion from capillary leak and cytokine storm — IL-2 and CAR-T cytokine release syndrome.

§03

Kidney injury

Mechanism of kidney injury

Dordaviprone has no established direct renal toxicity. Its targets (DRD2 and mitochondrial ClpP) are not a nephron-specific injury pathway, and it is not primarily renally cleared, so the kidney is neither a target nor the elimination route. The only realistic routes to a kidney problem are indirect and non-specific: prerenal azotemia from volume depletion during an intercurrent illness, or an electrolyte disturbance that, combined with the drug's QT effect, raises arrhythmia risk (making potassium and magnesium worth keeping normal for cardiac rather than renal reasons). There is no described tubular, interstitial, or glomerular lesion attributable to the drug.

Clinical presentation

No characteristic renal presentation; renal function is expected to remain stable. The safety picture to watch is a prolonged QT (and its interaction with hypokalemia/hypomagnesemia), not a rising creatinine. A creatinine change on therapy is usually explained by an intercurrent prerenal insult rather than by the drug.

Management

No dordaviprone-specific renal management is required. Correct and maintain potassium and magnesium (for QT safety), restore volume for any prerenal creatinine rise, and address the precipitant. Investigate a progressive creatinine rise, proteinuria, or an active sediment as a separate renal process. There is no role for dialysis or drug-specific renal rescue for this agent.Lesion-level management framework

Risk factors

Intercurrent volume depletion (vomiting, diarrhea, poor intake) causing prerenal physiology
Electrolyte disturbances (hypokalemia, hypomagnesemia) — chiefly a QT/arrhythmia concern
Concurrent QT-prolonging drugs
Baseline CKD (lowers reserve for any intercurrent insult)

Prevention

Keep potassium and magnesium normal — primarily to protect the QT interval, secondarily for renal-electrolyte health
Maintain hydration during intercurrent GI illness
Review co-medications for additive QT prolongation

Anticancer mechanism· how it treats cancer

Oral small molecule, the first-in-class 'imipridone,' that acts as a selective antagonist of dopamine receptor D2/D3 (DRD2) and, more importantly for its antitumor effect, as an agonist of the mitochondrial protease ClpP; hyperactivating ClpP degrades respiratory-chain subunits, disrupting oxidative phosphorylation and triggering an integrated stress response and apoptosis, with particular activity in H3 K27M-mutant diffuse gliomas. It is given orally on an intermittent (weekly or twice-weekly) schedule.

§04

Clinical depth

Renal dose adjustment

No renal-impairment dose adjustment is established; dordaviprone is an orally administered small molecule given on an intermittent schedule and is not primarily renally cleared. Dose interruption/modification is driven by tolerability and by QT/cardiac considerations rather than by GFR.

Dialyzability & ESKD dosing

Not characterized as dialyzable and not clinically relevant: dordaviprone is not primarily renally eliminated, and there is no renal-clearance or drug-removal scenario in which dialysis is relevant. Renal replacement therapy would only ever address an unrelated AKI.

Differential diagnosis

Any renal abnormality in a patient on dordaviprone should be attributed to a cause other than the drug: prerenal volume depletion, a concurrent nephrotoxin, contrast, obstruction, or disease. The drug's own safety signal to track is the QT interval, amplified by hypokalemia/hypomagnesemia — an electrolyte-and-cardiac concern, not a tubular-injury one. A true renal lesion warrants an independent workup.

Monitoring

ECG/QT interval per the drug's cardiac guidance (the key safety monitor)
Serum potassium and magnesium (to protect the QT, and for general electrolyte health)
Routine serum creatinine as part of standard care (no drug-specific renal surveillance)
Volume status during intercurrent GI illness

Key trials & series

ACTION (Arrillaga-Romany, Neuro Oncol 2024) — randomized phase 3 design of dordaviprone (ONC201) in newly diagnosed H3 K27M-mutant diffuse glioma after radiotherapy, following demonstrated efficacy in recurrent disease; the pivotal program whose toxicity profile centers on tolerability and QT rather than renal injury.
Emerging targeted therapies in pediatric brain tumors (Terashima, No Shinkei Geka 2025) — review situating dordaviprone's accelerated approval for H3 K27M diffuse midline glioma within the precision-oncology landscape.

Clinical pearls

Watch the heart, not the kidney: dordaviprone's safety signal is QT prolongation, and the nephron is largely a bystander.
Keep potassium and magnesium normal mainly to protect the QT interval — a cardiac motive for an electrolyte habit.
A creatinine rise on dordaviprone is almost always intercurrent volume depletion or another cause — investigate accordingly.
Its dose is modified for tolerability and QT, not for GFR.
The 'imipridone' class (ClpP agonism) does not carry a known nephron-specific toxicity.

Where it strikes· nephron segments & injury signatures

Nephron segments

Vasculature / Endothelium

Glomerular & peritubular capillaries

Injury signatures

Prerenal / Hemodynamic AKI

§05

References

2 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

2 references · 2024–2025 · 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.

What gets reported — FAERS

Everything below is FAERS — adverse events someone chose to report, about 77 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.

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 outcomes & reporting trend· 62.3% of reports w/ death · 23.4% w/ hospitalization

62.3%

Reported with a death outcome

48 of 77 reports

23.4%

Reported with hospitalization

18 of 77 reports

Reports per year

Yearly FAERS report volume · most recent year is partial.

FAERS adverse-event signal — all organ systems· 7 systems · 77 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 2026-08-08.

General / constitutional

Fatigue8Asthenia4Fall2Malaise2

Gastrointestinal

Nausea6Constipation4Vomiting3Dysphagia2

Nervous system

Seizure4Dizziness3Headache3

Musculoskeletal

Muscular Weakness4Musculoskeletal Stiffness2

Metabolic & electrolyte

Decreased Appetite2

Respiratory

Dyspnoea2

Immune / infection

Pneumonia2

Guidelines & consensus· 12

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 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 Dordaviprone 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

Casdatifan

HIF-2α inhibitor (investigational)

Profile

Trial-stage RCC HIF-2α inhibitor; renal profile being defined.

PRE

Mild#1 · 100% phenotype match

Belzutifan

Welireg · HIF-2α inhibitor

Profile

Anemia/hypoxia; emerging renal profile in VHL/RCC.

PRE

Mild#2 · 97% phenotype match

Denileukin diftitox

Lymphir · Immunotoxin (IL-2–diphtheria)

Profile

Capillary-leak syndrome → prerenal AKI.

PRE

Moderate#3 · 94% phenotype match

Tovorafenib

Ojemda · Type II pan-RAF (BRAF) inhibitor

Profile

2024 pediatric glioma RAF inhibitor; creatinine rise.

PRE

Mild#4 · 89% phenotype match

Vepdegestrant

Veppanu · PROTAC estrogen-receptor degrader

Profile

2026 first PROTAC ER degrader; no meaningful intrinsic renal signal.

PRE

Mild#5 · 89% phenotype match

Zidesamtinib

Jideytro · ROS1-selective TKI

Profile

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#6 · 89% phenotype match

Compare Dordaviprone 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 targeted agents

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.