Is kidney injury from Momelotinib reversible?

Reversible. Typical onset: Any tumor-lysis risk is early; otherwise no defined renal onset..

How should kidney function be monitored during Momelotinib therapy?

CBC with platelets (dose-limiting thrombocytopenia); Creatinine, electrolytes and uric acid at initiation in high-burden disease; Peripheral neuropathy assessment and infection/HBV reactivation surveillance; Serum creatinine and electrolytes periodically on therapy, not only at initiation.

How can kidney injury from Momelotinib be prevented?

TLS awareness/hydration at initiation in high-burden disease Renal-appropriate dosing per label

Who is at higher risk of kidney injury from Momelotinib?

High-burden myelofibrosis (TLS risk at initiation); Pre-existing CKD; Infection/cytopenia-related volume depletion.

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Printable monograph

JAK/ACVR1 inhibitor

Momelotinib

Ojjaara · MOME

JAK/ACVR1 inhibitor · approved 2023 · 7 citations · FAERS AKI reporting ROR 2.18 (95% CI 1.42–3.35, 21 AKI reports)

Up to date· through 2026

Deeply sourced8/9 · 7 signals

Met: 7 citations
Not met: 12+ references
Met: Accrued over 10+ years (span: 11y)
Met: Beyond single case reports
Met: High-impact journal
Met: Landmark reference
Met: Current through 2026
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 JAK1/2 plus ACVR1 inhibitor for anemic myelofibrosis whose characteristic renal signal is a frequent, low-grade creatinine rise without true GFR loss.

MildJAK1/2 + ACVR1 inhibitor

Myelofibrosis with anemia

§01

Signature kidney injury

Signature lesion

Pseudo-AKI

Representative incidence29%

17–29% range across studies

Treatment-emergent 'nephropathy' — a predominantly low-grade, isolated serum-creatinine rise — is now a recognized and frequent momelotinib signal, reported in ~17-29% across real-world cohorts (~29% in first-line real-world use; ~17% CTCAE grade 1-2 creatinine increase in a retrospective real-world cohort). Momelotinib pharmacokinetics are unchanged across renal impairment, arguing the creatinine rise reflects altered tubular handling rather than a true GFR fall (a pseudo-AKI). Tumor-lysis at initiation in high-burden disease remains a separate, indirect risk.Source: Tefferi et al., Am J Hematol 2026

Onset & rechallenge

Time to injuryVariable / unpredictable

Any tumor-lysis risk is early, but otherwise there is no defined renal onset.

Distilled from: “Any tumor-lysis risk is early; otherwise no defined renal onset.”

§02

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.

Pseudo-AKI#1 · Signaturequalitative — no citable incidence
The great mimic — a rise in creatinine from blocked tubular secretion (OCT2/MATE), NOT true injury. The GFR is intact; confirm with cystatin C before stopping effective therapy.
Prerenal / Hemodynamic AKISecondaryqualitative — no citable incidence
Renal hypoperfusion from capillary leak and cytokine storm — IL-2 and CAR-T cytokine release syndrome.

Toxicity fingerprint

Tap a signature to trace where it strikes the nephron.

29%incidence

SeverityMild

ReversibilityReversible

Evidence7 citations

Nephron map

Vasculature / Endothelium

Proximal TubuleBulk reabsorption + drug uptake (OCT2, OATs)

Pseudo-AKI

The great mimic — a rise in creatinine from blocked tubular secretion (OCT2/MATE), NOT true injury. The GFR is intact; confirm with cystatin C before stopping effective therapy.

§03

Kidney injury

Mechanism of kidney injury

The defining renal event is a frequent, mostly low-grade isolated creatinine elevation without evidence of true GFR loss — momelotinib exposure is unchanged in moderate-to-severe renal impairment — consistent with interference in tubular creatinine handling (a pseudo-AKI) rather than structural nephron injury. The ACVR1/hepcidin mechanism targets systemic iron metabolism, not the kidney. A separate, indirect prerenal/tumor-lysis risk applies at initiation in high-burden disease.

Clinical presentation

Typically an isolated, low-grade serum-creatinine rise emerging on treatment with an otherwise bland urinalysis and stable clinical picture; checking a cystatin C-based eGFR helps confirm preserved true GFR before attributing it to structural injury. Early metabolic derangements if tumor lysis occurs at initiation.

Management

Supportive; tumor-lysis management if it occurs, treat infection, correct prerenal factors. No drug-specific renal therapy; intrinsic nephrotoxicity has not been established.Lesion-level management framework

Risk factors

High-burden myelofibrosis (TLS risk at initiation)
Pre-existing CKD
Infection/cytopenia-related volume depletion

Prevention

TLS awareness/hydration at initiation in high-burden disease
Renal-appropriate dosing per label

Anticancer mechanism· how it treats cancer

Oral inhibitor of JAK1/JAK2 and ACVR1 (ALK2). ACVR1 inhibition lowers hepcidin via the BMP6/ACVR1/SMAD axis, increasing iron availability and improving anemia — distinguishing it from other JAK inhibitors. Approved for intermediate/high-risk myelofibrosis with anemia.

Note · 2023 approval. Treatment-emergent nephropathy — an isolated low-grade creatinine rise — is now documented in real-world cohorts (Tefferi 2026; Jilg 2024), and unchanged pharmacokinetics across renal impairment support a tubular pseudo-AKI rather than true GFR loss. The prerenal/TLS framing remains indirect class reasoning.

§04

Clinical depth

Renal dose adjustment

No dose adjustment is needed for mild-to-severe renal impairment per the registrational program; momelotinib is hepatically metabolized (with an active metabolite). Data in dialysis are limited. Dose modification is driven primarily by cytopenias rather than renal function.

Dialyzability & ESKD dosing

Not characterized; highly protein-bound, hepatically cleared. Not expected to be meaningfully dialyzed. No ESKD-specific dosing guidance.

Differential diagnosis

Distinguish the frequent isolated low-grade creatinine rise (pseudo-AKI: bland urinalysis, preserved cystatin C-based eGFR) from early tumor-lysis AKI, infection/cytopenia-related prerenal AKI, and unrelated intrinsic renal disease; structural nephrotoxicity is not established.

Monitoring

CBC with platelets (dose-limiting thrombocytopenia)
Creatinine, electrolytes and uric acid at initiation in high-burden disease
Peripheral neuropathy assessment and infection/HBV reactivation surveillance
Serum creatinine and electrolytes periodically on therapy, not only at initiation

Key trials & series

MOMENTUM and SIMPLIFY-1 — registrational myelofibrosis-with-anemia trials (clinical context)

Clinical pearls

Momelotinib's distinguishing trick is lowering hepcidin (ACVR1) to improve anemia — a non-renal mechanism.
Watch for peripheral neuropathy, a class-distinct momelotinib toxicity.
The common renal event is an isolated low-grade creatinine rise without true GFR loss — a pseudo-AKI, not a reason to dose-reduce.

§05

References

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

Evidence accrual

7 references · 2015–2026 · 2 since 2024

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 1,339 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.
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· 15.5% of reports w/ death · 22.6% w/ hospitalization

15.5%

Reported with a death outcome

208 of 1,339 reports

22.6%

Reported with hospitalization

303 of 1,339 reports

Reports per year

Yearly FAERS report volume · most recent year is partial.

FAERS adverse-event signal — all organ systems· 8 systems · 1,339 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 2.1895% CI 1.42–3.35· 21 AKI reports ·AKI is reported disproportionately more often than for other drugs (CI entirely above 1) — a hypothesis-generating signal, not proof of causation.

Renal & urinary

Renal Impairment35Urinary Tract Infection34

Blood & lymphatic

Thrombocytopenia109Anaemia84Platelet Count Decreased55Haemoglobin Decreased53Neutropenia34

General / constitutional

Fatigue62Asthenia45Pyrexia40Fall29Malaise28

Nervous system

Dizziness56Neuropathy Peripheral54Headache30

Gastrointestinal

Diarrhoea71Nausea52

Immune / infection

Pneumonia67

Respiratory

Dyspnoea26

Vascular

Hypotension26

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 Momelotinib 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

Vimseltinib

Romvimza · CSF1R tyrosine kinase inhibitor

Profile

A clean-kidney targeted TKI — watch the CPK, not the nephron.

PSEUDOPRE

Mild#1 · 100% phenotype match

Alectinib

Alecensa · ALK TKI

Profile

Creatinine rise via reduced tubular secretion.

PSEUDOPRE

Mild#2 · 86% phenotype match

Bosutinib

Bosulif · BCR-ABL TKI

Profile

Reversible eGFR decline.

PSEUDOPRE

Mild#3 · 86% phenotype match

Ceritinib

Zykadia · ALK TKI

Profile

GI-driven prerenal AKI.

PREPSEUDO

Mild#4 · 86% phenotype match

Pralsetinib

Gavreto · RET inhibitor

Profile

Hypertension; rare AKI.

HTNPREPSEUDO

Mild#5 · 81% phenotype match

Vorasidenib

Voranigo · Mutant IDH1/2 inhibitor

Profile

A brain-penetrant IDH inhibitor whose kidney footprint is a benign creatinine bump, not true AKI.

PSEUDOPRE

Mild#6 · 77% phenotype match

Compare Momelotinib 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.