What kind of kidney injury does Glasdegib 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 Glasdegib therapy?

ECG/QTc at baseline, ~1 week, then periodically; Serum potassium and magnesium frequently (correct before/during therapy); Serum creatinine and TLS labs (uric acid, phosphate, potassium) early in treatment; CBC each cycle; volume status.

How can kidney injury from Glasdegib be prevented?

Correct potassium and magnesium and obtain baseline/serial ECGs Maintain hydration; manage nausea/mucositis proactively TLS prophylaxis (hydration +/- allopurinol/rasburicase) when tumor burden warrants Avoid additive QT-prolonging and nephrotoxic agents; caution in severe renal impairment

Who is at higher risk of kidney injury from Glasdegib?

Older, comorbid AML population with baseline CKD; Concurrent QT-prolonging drugs and electrolyte depletion; Dehydration from nausea/mucositis or sepsis; High tumor burden at initiation (tumor-lysis risk).

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Printable monograph

Hedgehog (SMO) inhibitor

Glasdegib

Daurismo · GLA

Hedgehog (SMO) inhibitor · approved 2018 · 6 citations

Recent· through 2023

Deeply sourced7/9 · 6 signals

Met: 6 citations
Not met: 12+ references
Met: Accrued over 10+ years (span: 13y)
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.

Hedgehog/SMO inhibitor for AML whose QT prolongation and muscle spasms are the safety signals; renal risk is indirect via dehydration and leukemia-related tumor lysis.

MildHedgehog pathway inhibitor era (AML)

Newly diagnosed acute myeloid leukemia in adults >=75 years or with comorbidities precluding intensive induction (with low-dose cytarabine)

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Signature kidney injury

Signature lesion

Prerenal / Hemodynamic AKI

Muscle spasms, QT prolongation, cytopenias, edema, nausea and mucositis are the labeled toxicities; the FDA notes a use limitation in severe renal impairment (a renal-impairment trial was a post-marketing requirement). Direct nephrotoxicity is not a defined signal, and AKI is largely secondary (dehydration, sepsis, tumor lysis).Source: Norsworthy et al., Clin Cancer Res 2019 (FDA approval summary, BRIGHT AML 1003)

Onset & rechallenge

Time to injuryVariable / unpredictable

Muscle spasms and QT changes appear in early cycles, while prerenal/electrolyte issues track intercurrent illness and intake.

Distilled from: “Muscle spasms and QT changes within early cycles; prerenal/electrolyte issues track intercurrent illness and intake.”

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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).

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Kidney injury

Mechanism of kidney injury

Glasdegib itself has no characteristic direct renal lesion. Its renal relevance is twofold and indirect: (1) gastrointestinal toxicity (nausea, mucositis) and the underlying AML reduce intake and cause volume depletion and prerenal azotemia; (2) QT prolongation is exacerbated by electrolyte derangements (hypokalemia, hypomagnesemia) that demand renal-relevant correction. In the leukemic context, treatment-related tumor lysis can cause uric-acid/phosphate crystal nephropathy and ATN, though glasdegib's cytoreduction is modest. There is a labeling caution in severe renal impairment pending dedicated data.

Clinical presentation

Muscle cramps, fatigue, edema, nausea/mucositis and cytopenias; ECG QTc prolongation. Renally, a prerenal creatinine rise during poor intake/dehydration, and electrolyte disturbances (hypokalemia, hypomagnesemia) that aggravate QT. Tumor-lysis labs (hyperuricemia, hyperphosphatemia, hyperkalemia) if cytoreduction is brisk.

Management

Keep potassium and magnesium replete and monitor QTc; hold/adjust for significant QT prolongation. Treat prerenal AKI with volume repletion and source control of nausea/sepsis. Manage tumor lysis with hydration, urate-lowering therapy and electrolyte correction, escalating to renal replacement if needed. Use caution and monitor closely in severe renal impairment given limited data.Lesion-level management framework

Risk factors

Older, comorbid AML population with baseline CKD
Concurrent QT-prolonging drugs and electrolyte depletion
Dehydration from nausea/mucositis or sepsis
High tumor burden at initiation (tumor-lysis risk)

Prevention

Correct potassium and magnesium and obtain baseline/serial ECGs
Maintain hydration; manage nausea/mucositis proactively
TLS prophylaxis (hydration +/- allopurinol/rasburicase) when tumor burden warrants
Avoid additive QT-prolonging and nephrotoxic agents; caution in severe renal impairment

Anticancer mechanism· how it treats cancer

Oral Smoothened (SMO) inhibitor that blocks Hedgehog signaling implicated in leukemic stem-cell maintenance. Combined with low-dose cytarabine (LDAC) it improves survival in newly diagnosed AML patients unfit for intensive chemotherapy.

Note · The renal link is indirect — QT-relevant electrolyte derangements, dehydration, and leukemia/treatment-related tumor lysis rather than a direct renal lesion. The FDA labeled a limitation of use in severe renal impairment pending further study.

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Clinical depth

Renal dose adjustment

No dose adjustment recommended for mild-moderate renal impairment; safety/PK in severe renal impairment were not established at approval (labeled limitation; post-marketing study required). Hepatic CYP3A4 metabolism predominates.

Dialyzability & ESKD dosing

Highly protein-bound small molecule; not expected to be appreciably dialyzable, and ESKD dosing is not established.

Differential diagnosis

Distinguish prerenal AKI (volume-responsive) from tumor-lysis crystalline nephropathy (hyperuricemia/hyperphosphatemia, often early), sepsis-associated ATN, and electrolyte-driven QT effects. The leukemic context makes multifactorial AKI the rule.

Monitoring

ECG/QTc at baseline, ~1 week, then periodically
Serum potassium and magnesium frequently (correct before/during therapy)
Serum creatinine and TLS labs (uric acid, phosphate, potassium) early in treatment
CBC each cycle; volume status

Key trials & series

BRIGHT AML 1003 (Cortes, J Hematol Oncol 2020; Norsworthy FDA summary, Clin Cancer Res 2019) — registrational glasdegib + LDAC dataset

Clinical pearls

Glasdegib's renal story is indirect — QT/electrolytes and dehydration in a frail AML population, not a primary nephropathy.
Magnesium and potassium repletion does double duty: it protects the kidney's milieu and the QT interval.
Heed the labeled caution in severe renal impairment — dedicated data were lacking at approval.
Assess tumor-lysis risk at initiation even though glasdegib's cytoreduction is modest.

Where it strikes· nephron segments & injury signatures

Nephron segments

Vasculature / Endothelium

Glomerular & peritubular capillaries

Distal Tubule / Collecting Duct

Fine-tuning of Na, K, Mg, acid & water

Injury signatures

Prerenal / Hemodynamic AKI Electrolyte Disturbance

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References

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

Evidence accrual

6 references · 2010–2023 · 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 (Dec 2025) — not paraphrased or interpreted. Full label on DailyMed .

Boxed warning

WARNING: EMBRYO-FETAL TOXICITY DAURISMO can cause embryo-fetal death or severe birth defects when administered to a pregnant woman. DAURISMO is embryotoxic, fetotoxic, and teratogenic in animals [see Warnings and Precautions (5.1) , Use in Specific Populations (8.1) ] . Conduct pregnancy testing in females of reproductive potential prior to initiation of DAURISMO treatment. Advise females of reproductive potential to use effective contraception during treatment with DAURISMO and for at least 30 days after the last dose [see Warnings and Precautions (5.1) , Use in Specific Populations (8.1 , 8.3) ] . Advise males of the potential risk of DAURISMO exposure through semen and to use condoms with a pregnant partner or a female partner of reproductive potential during treatment with DAURISMO and for at least 30 days after the last dose to avoid potential drug exposure [see Warnings and Precautions (5.1) , Use in Specific Populations (8.3) ] . WARNING: EMBRYO-FETAL TOXICITY See full prescribing information for complete boxed warning. • DAURISMO can cause embryo-fetal death or severe birth defects when administered to a pregnant woman. DAURISMO is embryotoxic, fetotoxic, and teratogenic in animals. ( 5.1 , 8.1 ) • Conduct pregnancy testing in females of reproductive potential prior to initiation of DAURISMO treatment. Advise females of reproductive potential to use effective…

Renal impairment — from the label

No dosage modification is recommended for patients with mild to severe renal impairment (estimated glomerular filtration rate [eGFR] 15 to 89 mL/min). Monitor patients with severe renal impairment (eGFR 15 to 29 mL/min) for increased risk of adverse reactions, including QTc interval prolongation, due to increased glasdegib concentrations [see Clinical Pharmacology (12.3) ].

What gets reported — FAERS

Everything below is FAERS — adverse events someone chose to report, about 468 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

Electrolyte Disturbancecorroborated · ROR 2.37 — but the naming terms alone are not disproportionate, so this rests on terms merely consistent with the lesion
Prerenal / Hemodynamic AKINot queried in FAERS — No MedDRA term set is defined for this phenotype, so FAERS was never asked about it.

SIADH / Hyponatremia

ROR 4.5195% CI 2.24–9.07· 8 reports

Electrolyte Disturbance

ROR 2.3795% CI 1.27–4.44· 10 reports

FAERS outcomes & reporting trend· 40.6% of reports w/ death · 47.9% w/ hospitalization

40.6%

Reported with a death outcome

190 of 468 reports

47.9%

Reported with hospitalization

224 of 468 reports

Reports per year

Yearly FAERS report volume · most recent year is partial.

FAERS adverse-event signal — all organ systems· 7 systems · 468 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 2.0895% CI 0.98–4.38· 7 AKI reports ·no disproportionate AKI reporting signal (CI spans 1).

Renal & urinary

Acute Kidney Injury7

Blood & lymphatic

Febrile Neutropenia69Neutropenia22Platelet Count Decreased9Pancytopenia8Thrombocytopenia8

Immune / infection

Pneumonia48Sepsis15Septic Shock11Infection10

Gastrointestinal

Diarrhoea9Mucosal Inflammation8Nausea8

Metabolic & electrolyte

Decreased Appetite10Hyponatraemia8

Cardiac

Electrocardiogram Qt Prolonged12

General / constitutional

Pyrexia10

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 Glasdegib 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

Darolutamide

Nubeqa · Androgen receptor inhibitor (ARSI)

Profile

Not nephrotoxic; exposure rises in severe renal impairment, so consider dose adaptation.

LYTEPRE

Mild#1 · 89% phenotype match

Sevabertinib

Hyrnuo · HER2/EGFR TKI

Profile

2025 reversible HER2/EGFR TKI; profuse diarrhea (84-91%) → prerenal AKI, plus EGFR-pathway renal magnesium wasting.

PRELYTE

Mild#2 · 88% phenotype match

Gedatolisib

Revtorpyk · Pan-PI3K inhibitor

Profile

2026 IV pan-PI3K + mTORC1/2 (breast); on-target hyperglycemia and low-grade Na/K/Mg drift — creatinine up 14% vs 8% control, grade 3-4 rare.

LYTEPRE

Mild#3 · 88% phenotype match

Lanreotide

Somatuline · Somatostatin analog

Profile

Kidney-neutral (CLARINET: diarrhea dominant); increased exposure in renal impairment.

LYTEPRE

Mild#4 · 88% phenotype match

Imetelstat

Rytelo · Telomerase inhibitor

Profile

2024 MDS agent; tumor lysis risk.

PRELYTE

Mild#5 · 88% phenotype match

Octreotide

Sandostatin · Somatostatin analog

Profile

Kidney-neutral/possibly renoprotective; renally cleared, caution in severe CKD/dialysis.

LYTEPRE

Mild#6 · 86% phenotype match

Compare Glasdegib 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.