How should kidney function be monitored during Enasidenib therapy?

Daily symptom/weight/oxygenation assessment for differentiation syndrome during the first 1–2 months; CBC with differential (track blast maturation and rising WBC); Tumor-lysis labs (uric acid, potassium, phosphate, calcium, creatinine) during early response; Total/indirect bilirubin (UGT1A1 inhibition mimics hyperbilirubinemia).

How can kidney injury from Enasidenib be prevented?

Vigilance for early differentiation-syndrome symptoms Prompt corticosteroids at first suspicion Cytoreduction (e.g., hydroxyurea) for hyperleukocytosis TLS prophylaxis with hydration and urate-lowering therapy

Who is at higher risk of kidney injury from Enasidenib?

High bone-marrow or peripheral blast burden; Hyperleukocytosis; Elevated LDH; Rapid leukemic response; Volume depletion.

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Printable monograph

IDH2 inhibitor

Enasidenib

Idhifa · Enasi

IDH2 inhibitor · approved 2017 · 8 citations

Up to date· through 2025

Fairly sourced4/9 · 4 signals

Met: 8 citations
Not met: 12+ references
Not met: Accrued over 10+ years (span: 8y)
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.

An IDH2 inhibitor that cures by forcing leukemic blasts to mature — and that maturation itself can flood the kidneys.

ModerateIDH2 inhibitor

IDH2-mutated relapsed/refractory AML

§01

Signature kidney injury

Signature lesion

Prerenal / Hemodynamic AKI

Representative incidence10%

IDH-inhibitor differentiation syndrome (the main route to AKI) occurs in roughly 10% of enasidenib-treated AML patients (10.4% any-grade in a pooled trial analysis; ~7% grade ≥3 in the first-in-human study). Tumor lysis is a secondary risk. Direct tubular nephrotoxicity is not well quantified.Source: Montesinos et al., Blood Adv 2024 (10.4% any-grade)

Onset & rechallenge

Time to injurySubacute (~1–6 weeks)

Differentiation syndrome typically appears days to weeks after starting, with a median onset around 30 days and a reported range from days to roughly 4-5 months.

Distilled from: “Differentiation syndrome typically days to weeks after starting (median onset ~30 days; reported range days to ~4–5 months).”

§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 · Signatureno population incidence denominator
IDH2-inhibitor differentiation syndrome (fluid retention, capillary leak -> prerenal/hemodynamic AKI) occurred as a grade 3-4 enasidenib-related event in 7% of relapsed/refractory AML patients. PMID 28588020 (opens PubMed in a new tab)
Acute Tubular NecrosisSecondaryqualitative — no citable incidence
Direct death of tubular epithelial cells — the dose-limiting lesion of the platinums and zoledronate.
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).

Toxicity fingerprint

Tap a signature to trace where it strikes the nephron.

10%incidence

SeverityModerate

ReversibilityReversible

Evidence8 citations

Nephron map

Vasculature / Endothelium

Proximal Tubule

Distal Tubule / Collecting Duct

Prerenal / Hemodynamic AKI

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

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Kidney injury

Mechanism of kidney injury

Drug-induced differentiation of IDH2-mutant blasts triggers a cytokine-driven systemic inflammatory (differentiation) syndrome with capillary leak, fluid shifts, hypotension and weight gain, producing hemodynamic (prerenal) AKI that can progress to ischemic ATN. Concurrent rapid cytoreduction can release urate/phosphate and add tumor-lysis intratubular injury; hyperleukocytosis amplifies the inflammatory cascade.

Clinical presentation

Differentiation syndrome with dyspnea/hypoxia, pulmonary infiltrates, fever, peripheral edema, weight gain, pleural/pericardial effusions and a rising creatinine; sometimes hyperuricemia/hyperphosphatemia/hyperkalemia from tumor lysis. Indirect hyperbilirubinemia (UGT1A1 inhibition) is a characteristic accompanying lab finding but is not renal.

Management

Start dexamethasone (e.g., 10 mg IV q12h) at first suspicion of differentiation syndrome; supportive hemodynamics, diuresis for fluid overload and oxygen. Hold enasidenib for severe/refractory syndrome and resume once resolved. Manage tumor lysis with IV hydration and rasburicase or allopurinol; correct electrolytes.Lesion-level management framework

Risk factors

High bone-marrow or peripheral blast burden
Hyperleukocytosis
Elevated LDH
Rapid leukemic response
Volume depletion

Prevention

Vigilance for early differentiation-syndrome symptoms
Prompt corticosteroids at first suspicion
Cytoreduction (e.g., hydroxyurea) for hyperleukocytosis
TLS prophylaxis with hydration and urate-lowering therapy

Anticancer mechanism· how it treats cancer

Oral, first-in-class allosteric inhibitor of mutant isocitrate dehydrogenase-2 (IDH2). Mutant IDH2 neomorphically converts α-ketoglutarate to the oncometabolite 2-hydroxyglutarate (2-HG), which causes DNA/histone hypermethylation and blocks myeloid differentiation; enasidenib lowers 2-HG and releases this block, driving leukemic blasts to terminally mature in IDH2-mutated acute myeloid leukemia (AML).

Note · Renal injury is a downstream consequence of differentiation syndrome and tumor lysis rather than direct tubular toxicity. Inducing differentiation (not cytotoxicity) is the therapeutic mechanism, so the same biology that drives response drives the renal risk.

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Clinical depth

Renal dose adjustment

No dedicated renal dose adjustment is established; enasidenib was not studied in severe renal impairment/ESKD. Standard dose is 100 mg orally once daily, modified for toxicity (including differentiation syndrome and indirect hyperbilirubinemia), not for CrCl.

Dialyzability & ESKD dosing

Not characterized; enasidenib is highly protein-bound and hepatically metabolized, so it is not expected to be appreciably removed by hemodialysis. No HD-specific dosing guidance exists.

Differential diagnosis

Distinguish differentiation syndrome from sepsis/pneumonia (overlapping fever, infiltrates, hypotension), cardiogenic pulmonary edema, and transfusion reactions; the constellation of weight gain, effusions and rising WBC during blast maturation favors differentiation syndrome. Separate prerenal/differentiation AKI from tumor-lysis crystal nephropathy by the electrolyte/uric-acid profile.

Monitoring

Daily symptom/weight/oxygenation assessment for differentiation syndrome during the first 1–2 months
CBC with differential (track blast maturation and rising WBC)
Tumor-lysis labs (uric acid, potassium, phosphate, calcium, creatinine) during early response
Total/indirect bilirubin (UGT1A1 inhibition mimics hyperbilirubinemia)

Key trials & series

Stein et al., Blood 2017 — first-in-human AG221-C-001 phase 1/2 (registrational R/R AML data, 40.3% ORR, 7% grade ≥3 differentiation syndrome)
Montesinos et al., Blood Adv 2024 — pooled 4-trial analysis defining 10.4% differentiation-syndrome incidence

Clinical pearls

Differentiation syndrome — not direct nephrotoxicity — is the reason enasidenib threatens the kidney; treat early with steroids and do not necessarily stop the drug.
Indirect hyperbilirubinemia from UGT1A1 inhibition is expected and benign; do not confuse it with hepatorenal or hemolytic processes.
A rising WBC during therapy reflects intended blast maturation, not relapse — but it heralds differentiation-syndrome and tumor-lysis risk.

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

Class-level context for the major non-renal toxicities of the IDH2 inhibitor class.

Pulmonary

Pneumonitis, ILD, effusions, hypertension

Differentiation syndrome

Cardiac

Cardiomyopathy, QT, ischemia, myocarditis

QT prolongation

§05

References

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

Evidence accrual

8 references · 2017–2025 · 5 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.

FDA label — boxed warning & renal dosing· boxed warning

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

Boxed warning

WARNING: DIFFERENTIATION SYNDROME Patients treated with IDHIFA have experienced symptoms of differentiation syndrome, which can be fatal if not treated. Symptoms may include fever, dyspnea, acute respiratory distress, pulmonary infiltrates, pleural or pericardial effusions, rapid weight gain or peripheral edema, lymphadenopathy, bone pain, and hepatic, renal, or multi-organ dysfunction. If differentiation syndrome is suspected, initiate corticosteroid therapy and hemodynamic monitoring until symptom resolution [see Warnings and Precautions (5.1) and Adverse Reactions (6.1) ] . WARNING: DIFFERENTIATION SYNDROME See full prescribing information for complete boxed warning. Patients treated with IDHIFA have experienced symptoms of differentiation syndrome, which can be fatal if not treated. If differentiation syndrome is suspected, initiate corticosteroid therapy and hemodynamic monitoring until symptom resolution ( 5.1 , 6.1 ).

What gets reported — FAERS

Everything below is FAERS — adverse events someone chose to report, about 3,296 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· 24.9% of reports w/ death · 25.6% w/ hospitalization

24.9%

Reported with a death outcome

822 of 3,296 reports

25.6%

Reported with hospitalization

843 of 3,296 reports

Reports per year

Yearly FAERS report volume · most recent year is partial.

FAERS adverse-event signal — all organ systems· 8 systems · 3,296 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 0.2995% CI 0.14–0.61· 7 AKI reports ·AKI is reported less often than for other drugs (CI entirely below 1) — no disproportionate signal.

General / constitutional

Fatigue219Asthenia91Pyrexia74Fall42Malaise42

Gastrointestinal

Nausea195Diarrhoea141Constipation62Vomiting61

Blood & lymphatic

Platelet Count Decreased125White Blood Cell Count Decreased73Haemoglobin Decreased54

Metabolic & electrolyte

Decreased Appetite118

Immune / infection

Pneumonia67Infection39

Nervous system

Dizziness51Headache44

Respiratory

Dyspnoea63

Skin

Rash41

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 Enasidenib 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

Arsenic trioxide

Trisenox · Differentiating agent

Profile

Differentiation syndrome; QT prolongation.

PREATNLYTE

Moderate#1 · 100% phenotype match

Ivosidenib

Tibsovo · IDH1 inhibitor

Profile

Differentiation syndrome → AKI; tumor lysis.

PRELYTEATN

Moderate#2 · 100% phenotype match

Gallium nitrate

Ganite · Antineoplastic metal salt

Profile

Dose-limiting acute tubular necrosis; potentiated by dehydration and concurrent nephrotoxins.

ATNPRELYTE

Moderate#3 · 88% phenotype match

Lifileucel

Amtagvi · Tumor-infiltrating lymphocyte (TIL) therapy

Profile

2024 cellular therapy; high-dose IL-2 conditioning → capillary leak AKI.

PREATNLYTE

Moderate#4 · 85% phenotype match

Tretinoin (ATRA)

Vesanoid · Retinoid (differentiating agent)

Profile

Differentiation syndrome → capillary leak and AKI.

PREATN

Moderate#5 · 84% phenotype match

Tagraxofusp

Elzonris · IL-3 immunotoxin

Profile

Capillary-leak syndrome → AKI.

PREATN

Moderate#6 · 84% phenotype match

Compare Enasidenib 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.