What kind of kidney injury does Ziftomenib cause?

Prerenal / Hemodynamic AKI — Renal hypoperfusion from capillary leak and cytokine storm — IL-2 and CAR-T cytokine release syndrome. Other reported patterns: Electrolyte Disturbance.

How should kidney function be monitored during Ziftomenib therapy?

Daily symptom/weight/oxygenation review early on for differentiation syndrome; Creatinine, electrolytes, uric acid, phosphate (TLS screen) at initiation and through response; ECG/QTc and CBC.

How can kidney injury from Ziftomenib be prevented?

Vigilance for and prompt corticosteroid (dexamethasone) treatment of differentiation syndrome; consider hydroxyurea for leukocytosis Tumor-lysis prophylaxis (hydration, allopurinol/rasburicase)

Who is at higher risk of kidney injury from Ziftomenib?

High leukemic burden / rapid response (differentiation syndrome and TLS); KMT2A-rearranged disease (higher differentiation-syndrome severity); Baseline CKD; Concurrent nephrotoxins in the AML setting.

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Printable monograph

Menin inhibitor

Ziftomenib

Komzifti · ZIFT

Menin inhibitor · approved 2025 · 5 citations

Up to date· through 2026

Fairly sourced4/9 · 4 signals

Not met: 5 citations
Not met: 12+ references
Not met: Accrued over 10+ years (span: 5y)
Met: Beyond single case reports
Met: High-impact journal
Met: Landmark reference
Met: Current through 2026
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 menin inhibitor for NPM1-mutated AML whose chief renal hazard is differentiation syndrome and tumor lysis.

ModerateMenin inhibitor

Relapsed/refractory NPM1-mutated acute myeloid leukemiaKMT2A-rearranged acute leukemia (investigational)

§01

Signature kidney injury

Signature lesion

Prerenal / Hemodynamic AKI

Renal-specific data are not established. The class-defining serious toxicity is differentiation syndrome — reported in 12/83 (15%) of patients in the KOMET-001 phase 1 trial (with higher severity in KMT2A-rearranged patients, halting that cohort's enrollment) — which can cause capillary leak, fluid overload and AKI. Tumor-lysis risk accompanies rapid blast clearance. No drug-specific renal incidence is published.Source: Wang et al., Lancet Oncol 2024 (KOMET-001)

Onset & rechallenge

Time to injurySubacute (~1–6 weeks)

Differentiation syndrome typically arises within the first weeks of therapy as blasts differentiate; QTc prolongation is also seen.

Distilled from: “Differentiation syndrome typically within the first weeks of therapy as blasts differentiate; QTc prolongation is also seen.”

§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.

Prerenal / Hemodynamic AKI#1 · Signaturequalitative — no citable incidence
Renal hypoperfusion from capillary leak and cytokine storm — IL-2 and CAR-T cytokine release syndrome.
Electrolyte DisturbanceSecondaryqualitative — no citable incidence
Renal electrolyte derangement — magnesium/potassium/calcium wasting (cisplatin, anti-EGFR antibodies) or retention (FGFR-inhibitor hyperphosphatemia, tumor-lysis hyperkalemia/hyperphosphatemia).

§03

Kidney injury

Mechanism of kidney injury

Indirect: differentiation syndrome (analogous to that seen with IDH inhibitors and ATRA) produces a systemic inflammatory/cytokine state with capillary leak, fluid retention, weight gain, hypotension and prerenal/ischemic AKI; concurrent tumor lysis adds urate/phosphate intratubular injury. A direct tubular/glomerular lesion has not been described.

Clinical presentation

Dyspnea, pulmonary infiltrates, edema, weight gain, hypotension and rising creatinine during differentiation syndrome; metabolic derangements of tumor lysis (hyperuricemia, hyperphosphatemia, hyperkalemia) if present. Fever and leukocytosis often accompany differentiation syndrome.

Management

Treat differentiation syndrome promptly (corticosteroids, supportive care, consider drug interruption for severe cases); standard tumor-lysis management; supportive care for prerenal/ischemic AKI. Correct electrolytes (also for QT safety). No drug-specific renal antidote is defined.Lesion-level management framework

Risk factors

High leukemic burden / rapid response (differentiation syndrome and TLS)
KMT2A-rearranged disease (higher differentiation-syndrome severity)
Baseline CKD
Concurrent nephrotoxins in the AML setting

Prevention

Vigilance for and prompt corticosteroid (dexamethasone) treatment of differentiation syndrome; consider hydroxyurea for leukocytosis
Tumor-lysis prophylaxis (hydration, allopurinol/rasburicase)

Anticancer mechanism· how it treats cancer

Oral, selective inhibitor of the menin-KMT2A (MLL) protein-protein interaction. Disrupting the menin-MLL complex displaces it from target gene promoters (HOXA9/MEIS1), driving terminal differentiation of leukemic blasts. Approved (2025) as monotherapy for relapsed/refractory NPM1-mutated AML; under active development in combination and in KMT2A-rearranged leukemia.

Note · FDA-approved in 2025 for relapsed/refractory NPM1-mutated AML (first menin inhibitor). Renal-specific literature remains essentially absent; the differentiation-syndrome/TLS framing is class-based, drawn from KOMET-001 and analogy to IDH-inhibitor differentiation syndrome. Treat renal claims as low-certainty.

§04

Clinical depth

Renal dose adjustment

No dedicated renal dose adjustment is established; ziftomenib is hepatically metabolized. Dose interruption is driven by differentiation syndrome, QTc and cytopenias rather than CrCl. Data in significant renal impairment/dialysis are absent.

Dialyzability & ESKD dosing

Not characterized; a protein-bound, hepatically cleared small molecule unlikely to be appreciably dialyzed. No ESKD dosing guidance.

Differential diagnosis

Distinguish differentiation-syndrome AKI (capillary leak, pulmonary infiltrates, edema, fever) from tumor-lysis AKI (urate/phosphate, early) and neutropenic-sepsis ATN; these often co-occur and the management overlaps (steroids for DS, TLS measures, supportive care).

Monitoring

Daily symptom/weight/oxygenation review early on for differentiation syndrome
Creatinine, electrolytes, uric acid, phosphate (TLS screen) at initiation and through response
ECG/QTc and CBC

Key trials & series

KOMET-001 (Wang, Lancet Oncol 2024) — phase 1/2 carrying the differentiation-syndrome safety signal
KOMET-007 (Wang, Blood 2026) — combination with venetoclax/azacitidine

Clinical pearls

Differentiation syndrome is the signature serious toxicity — fluid overload, hypoxia and AKI; treat early with dexamethasone, do not just blame volume.
Like IDH inhibitors, the menin class differentiates blasts — expect both differentiation syndrome AND tumor lysis in the first weeks.
Renal data are thin even post-approval; reason from the differentiation-syndrome/TLS analogy.

Where it strikes· nephron segments & injury signatures

Nephron segments

Vasculature / Endothelium

Glomerular & peritubular capillaries

Injury signatures

Prerenal / Hemodynamic AKI Electrolyte Disturbance

Beyond the kidney — non-renal toxicities· 2 organ systems

Class-level context for the major non-renal toxicities of the Menin inhibitor class.

Pulmonary

Pneumonitis, ILD, effusions, hypertension

Differentiation syndrome

Cardiac

Cardiomyopathy, QT, ischemia, myocarditis

QT prolongation

§05

References

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

Evidence accrual

5 references · 2021–2026 · 4 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.

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

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

Boxed warning

WARNING: DIFFERENTIATION SYNDROME Differentiation syndrome, which can be fatal, has occurred with KOMZIFTI. Signs and symptoms may include fever, joint pain, hypotension, hypoxia, dyspnea, rapid weight gain or peripheral edema, pleural or pericardial effusions, pulmonary infiltrates, acute kidney injury, and rashes. If differentiation syndrome is suspected, interrupt KOMZIFTI and initiate oral or intravenous corticosteroids with hemodynamic and laboratory monitoring until symptom resolution; resume KOMZIFTI upon symptom improvement [see Dosage and Administration ( 2.5 ), Warnings and Precautions ( 5.1 ), and Adverse Reactions ( 6.1 )] . WARNING: DIFFERENTIATION SYNDROME See full prescribing information for complete boxed warning. Differentiation syndrome, which can be fatal, has occurred with KOMZIFTI. If differentiation syndrome is suspected, interrupt KOMZIFTI and initiate oral or intravenous corticosteroids with hemodynamic and laboratory monitoring until symptom resolution; resume KOMZIFTI upon symptom improvement. ( 2.5 , 5.1 , 6.1 )

Renal impairment — from the label

No dose adjustment is required for patients with mild or moderate (CL Cr 30 to 89 mL/min) renal impairment. The effects of severe (CL Cr less than 30 mL/min) renal impairment have not been studied [see Clinical Pharmacology ( 12.3 )].

What gets reported — FAERS

Everything below is FAERS — adverse events someone chose to report, about 48 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· 14 of 48 reports w/ death · 10 w/ hospitalization

48 reports is below the 50 this atlas requires before quoting a percentage, so the counts are shown instead of shares.

14 of 48

Reported with a death outcome

too few reports to express as a share

10 of 48

Reported with hospitalization

too few reports to express as a share

Reports per year

Yearly FAERS report volume · most recent year is partial.

FAERS adverse-event signal — all organ systems· 8 systems · 48 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

Pruritus8Rash2Rash Pruritic2

General / constitutional

Asthenia4Peripheral Swelling2Back Pain1Body Temperature Fluctuation1

Cardiac

Pericarditis3Atrial Fibrillation2Pericardial Effusion2Cardiac Disorder1

Gastrointestinal

Nausea4Dry Mouth1

Blood & lymphatic

Platelet Count Decreased4

Immune / infection

Bacterial Infection2Drug Hypersensitivity1

Psychiatric

Anxiety1

Metabolic & electrolyte

Decreased Appetite1

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 Ziftomenib 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

Afamitresgene autoleucel (Afami-cel)

Tecelra · MAGE-A4 TCR-T cell therapy

Profile

First TCR-T cell therapy for a solid tumor; CRS-associated hemodynamic AKI.

PRELYTE

Moderate#1 · 100% phenotype match

Imetelstat

Rytelo · Telomerase inhibitor

Profile

2024 MDS agent; tumor lysis risk.

PRELYTE

Mild#2 · 94% phenotype match

Capivasertib

Truqap · AKT inhibitor

Profile

2023 breast-cancer AKT inhibitor; AKI with diarrhea/hyperglycemia.

PRELYTE

Moderate#3 · 89% phenotype match

Loncastuximab tesirine

Zynlonta · Antibody-drug conjugate (CD19/PBD)

Profile

Capillary-leak-type edema, effusions and AKI.

PRELYTE

Moderate#4 · 89% phenotype match

Olutasidenib

Rezlidhi · IDH1 inhibitor

Profile

Differentiation syndrome and tumor lysis in AML.

PRELYTE

Moderate#5 · 88% phenotype match

Catumaxomab

Removab · Trifunctional bispecific (EpCAM×CD3)

Profile

Intraperitoneal; cytokine-release- and ascites/paracentesis-driven prerenal AKI; withdrawn (EU) 2017.

PRELYTE

Moderate#6 · 88% phenotype match

Compare Ziftomenib 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.