What kind of kidney injury does Pexidartinib cause?

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

How should kidney function be monitored during Pexidartinib therapy?

Liver tests (AST, ALT, bilirubin) frequently per REMS schedule; Volume status and serum creatinine during hepatic/systemic illness; Electrolytes with GI toxicity; Signs of jaundice/cholestasis.

How can kidney injury from Pexidartinib be prevented?

Avoid concurrent hepatotoxins; maintain hydration Prompt drug interruption for transaminase/bilirubin elevations per thresholds

Who is at higher risk of kidney injury from Pexidartinib?

Baseline hepatic dysfunction; Concurrent hepatotoxic or nephrotoxic drugs; Volume depletion from GI toxicity; Pre-existing CKD.

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Printable monograph

CSF1R inhibitor

Pexidartinib

Turalio · PEX

CSF1R inhibitor · approved 2019 · 5 citations

Recent· through 2023

Fairly sourced4/9 · 4 signals

Not met: 5 citations
Not met: 12+ references
Not met: Accrued over 10+ years (span: 4y)
Met: Beyond single case reports
Met: High-impact journal
Met: Landmark reference
Met: Current through 2023
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.

CSF1R inhibitor for tenosynovial giant cell tumor with boxed hepatotoxicity — renal effects are secondary (cholestatic illness, dehydration), not a direct nephropathy.

MildCSF1R-targeted era

Symptomatic tenosynovial giant cell tumor not amenable to surgery

§01

Signature kidney injury

Signature lesion

Prerenal / Hemodynamic AKI

The defining toxicity is serious, sometimes cholestatic, hepatotoxicity (boxed warning, REMS program); hair-color change, fatigue and GI effects are common. Direct nephrotoxicity is not a recognized signal, and renal effects are secondary (dehydration during illness, hepatorenal physiology in severe liver injury).Source: Tap et al., Lancet 2019 (ENLIVEN); Lewis et al., Oncologist 2020

Onset & rechallenge

Time to injuryVariable / unpredictable

Hepatotoxicity may occur early or later, and secondary renal effects track the severity of the systemic/hepatic illness rather than a fixed onset.

Distilled from: “Hepatotoxicity can occur early (often within the first 1-2 months) or later; secondary renal effects track the severity of the systemic/hepatic illness.”

§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

Pexidartinib has no characteristic direct renal lesion. Its renal relevance is indirect: severe hepatotoxicity (mixed/cholestatic, occasionally with ductopenia) can cause systemic illness, reduced intake and, in the most severe cases, hepatorenal-type physiology with prerenal azotemia and functional AKI. Routine GI toxicity and anorexia contribute to volume depletion. CSF1R inhibition also affects tissue macrophages broadly, but a specific renal injury is not established.

Clinical presentation

Rising transaminases and bilirubin (cholestatic pattern), fatigue, hair-color change, nausea; renally, a prerenal creatinine rise during severe hepatobiliary illness or dehydration rather than an acute structural lesion.

Management

Manage hepatotoxicity per REMS: interrupt/discontinue for protocol-defined liver-test elevations and treat supportively. For secondary prerenal AKI, restore volume and treat the underlying illness; in severe cholestatic liver injury, manage hepatorenal physiology with volume expansion and specialist input. Renal effects generally reverse as the hepatic/systemic illness resolves.Lesion-level management framework

Risk factors

Baseline hepatic dysfunction
Concurrent hepatotoxic or nephrotoxic drugs
Volume depletion from GI toxicity
Pre-existing CKD

Prevention

Avoid concurrent hepatotoxins; maintain hydration
Prompt drug interruption for transaminase/bilirubin elevations per thresholds

Anticancer mechanism· how it treats cancer

Oral inhibitor of colony-stimulating-factor-1 receptor (CSF1R), with activity against KIT and FLT3-ITD. In tenosynovial giant cell tumor (TGCT), CSF1 overexpression recruits CSF1R-bearing macrophage-lineage cells that form the tumor; CSF1R blockade depletes this population.

Note · The renal link is indirect: there is no direct pexidartinib nephrotoxicity. AKI, when it occurs, is secondary to severe (cholestatic) hepatotoxicity and dehydration. No pexidartinib-specific renal paper exists; class/onconephrology context is cited.

§04

Clinical depth

Renal dose adjustment

The label recommends a reduced starting dose for mild-to-severe renal impairment (CrCl 15-89 mL/min); the other critical dose modifications are for hepatotoxicity, which predominates in hepatic metabolism.

Dialyzability & ESKD dosing

Highly protein-bound; not expected to be dialyzable. No established ESKD dosing.

Differential diagnosis

Distinguish secondary prerenal/hepatorenal AKI (volume-responsive, in the setting of severe liver injury) from intrinsic renal causes and from other drug nephrotoxicity. The dominant clinical event is hepatic, not renal.

Monitoring

Liver tests (AST, ALT, bilirubin) frequently per REMS schedule
Volume status and serum creatinine during hepatic/systemic illness
Electrolytes with GI toxicity
Signs of jaundice/cholestasis

Key trials & series

ENLIVEN (Tap, Lancet 2019) — registrational RCT defining efficacy and the boxed hepatotoxicity
Lewis et al. (Oncologist 2020) — characterization of pexidartinib hepatic toxicity

Clinical pearls

The story here is the liver — a boxed hepatotoxicity warning with a REMS program; the kidney is collateral.
Severe cholestatic injury can produce hepatorenal-type prerenal AKI; treat with volume and source control.
No characteristic direct pexidartinib nephropathy exists.
Hair-color change (depigmentation) is a benign but characteristic on-target effect.

Where it strikes· nephron segments & injury signatures

Nephron segments

Vasculature / Endothelium

Glomerular & peritubular capillaries

Injury signatures

Prerenal / Hemodynamic AKI

§05

References

5 primary references — trials, cohorts, mechanism, and reviews. Citation metadata via PubMed / NLM.

Evidence accrual

5 references · 2019–2023 · 1 since 2021

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.

FDA label — boxed warning & renal dosing· boxed warning · renal impairment

Quoted verbatim from this agent's current FDA label (Jan 2025) — not paraphrased or interpreted. Full label on DailyMed .

Boxed warning

WARNING: HEPATOTOXICITY TURALIO can cause serious and potentially fatal liver injury, including vanishing bile duct syndrome [see Warnings and Precautions (5.1) ] . Monitor liver tests prior to initiation of TURALIO and at specified intervals during treatment. Withhold and dose reduce or permanently discontinue TURALIO based on severity of hepatotoxicity. Monitoring and prompt cessation of TURALIO may not eliminate the risk of serious and potentially fatal liver injury [see Dosage and Administration (2.2) , Warnings and Precautions (5.1) ] . TURALIO is available only through a restricted program called the TURALIO Risk Evaluation and Mitigation Strategy (REMS) Program [see Warnings and Precautions (5.2) ] . WARNING: HEPATOTOXICITY See full prescribing information for complete boxed warning. TURALIO can cause serious and potentially fatal liver injury, including vanishing bile duct syndrome. ( 5.1 ) Monitor liver tests prior to initiation of TURALIO and at specified intervals during treatment. Withhold and dose reduce or permanently discontinue TURALIO based on severity of hepatotoxicity. Monitoring and prompt cessation of TURALIO may not eliminate the risk of serious and potentially fatal liver injury. ( 2.2 , 5.1 ) TURALIO is available only through a restricted program called the TURALIO Risk Evaluation and Mitigation Strategy (REMS) Program. ( 5.2 )

Renal impairment — from the label

Reduce the dosage for patients with mild to severe renal impairment. ( 2.5 , 8.6 )

What gets reported — FAERS

Everything below is FAERS — adverse events someone chose to report, about 713 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· 2 signals

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.

Hypertension

ROR 4.0395% CI 3.02–5.37· 50 reports

Crystal / Obstructive Nephropathy

ROR 3.7295% CI 1.77–7.84· 7 reports

FAERS outcomes & reporting trend· 1.5% of reports w/ death · 7.4% w/ hospitalization

1.5%

Reported with a death outcome

11 of 713 reports

7.4%

Reported with hospitalization

53 of 713 reports

Reports per year

Yearly FAERS report volume · most recent year is partial.

FAERS adverse-event signal — all organ systems· 8 systems · 713 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 0.1995% CI 0.03–1.36· 1 AKI reports ·no disproportionate AKI reporting signal (CI spans 1).

General / constitutional

Fatigue252Pain75Asthenia45

Gastrointestinal

Nausea139Diarrhoea65Constipation48Vomiting48Abdominal Discomfort39

Skin

Pruritus113Rash86Skin Discolouration43Alopecia39

Nervous system

Headache73Dizziness48

Musculoskeletal

Arthralgia61

Metabolic & electrolyte

Decreased Appetite51

Immune / infection

Covid-1944

Eye

Eye Swelling41

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 Pexidartinib 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

Tisotumab vedotin

Tivdak · Antibody-drug conjugate (tissue factor/MMAE)

Profile

Ocular/bleeding toxicity dominates; renal involvement essentially unreported.

PRE

Mild#1 · 89% phenotype match

Elacestrant

Orserdu · Oral selective estrogen-receptor degrader (SERD)

Profile

2023 oral SERD; nausea-dominant, minimal intrinsic nephrotoxicity.

PRE

Mild#2 · 89% phenotype match

Elotuzumab

Empliciti · Anti-SLAMF7 mAb

Profile

Kidney-neutral antibody; unchanged PK in severe impairment and dialysis; no renal dose adjustment.

PRE

Mild#3 · 89% phenotype match

Tovorafenib

Ojemda · Type II pan-RAF (BRAF) inhibitor

Profile

2024 pediatric glioma RAF inhibitor; creatinine rise.

PRE

Mild#4 · 89% phenotype match

Radium-223 dichloride

Xofigo · Radiopharmaceutical (alpha-emitter)

Profile

Bone-seeking alpha emitter; minimal direct renal toxicity.

PRE

Mild#5 · 89% phenotype match

Dordaviprone

Modeyso · Imipridone (ONC201; DRD2/ClpP)

Profile

2025 imipridone for H3 K27M glioma; renally well tolerated — QT prolongation, not nephrotoxicity, is the safety focus.

PRE

Mild#6 · 89% phenotype match

Compare Pexidartinib 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.