What kind of kidney injury does Vismodegib cause?

SIADH / Hyponatremia — Inappropriate water retention at the collecting duct — high-dose cyclophosphamide. Other reported patterns: Electrolyte Disturbance.

How should kidney function be monitored during Vismodegib therapy?

Serum sodium and electrolytes at baseline and periodically; Creatine kinase if severe or persistent muscle symptoms; Volume status and weight; Pregnancy testing per REMS in patients of childbearing potential.

How can kidney injury from Vismodegib be prevented?

Maintain hydration; review concomitant hyponatremia-inducing drugs Counsel on muscle-cramp symptoms and supportive measures Avoid pregnancy (potent teratogen) per REMS

Who is at higher risk of kidney injury from Vismodegib?

Concurrent thiazides or other hyponatremia-inducing drugs; Volume depletion from nausea/vomiting or poor intake; Older age and baseline electrolyte disturbance; Polypharmacy in elderly BCC patients.

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Printable monograph

Hedgehog (SMO) inhibitor

Vismodegib

Erivedge · VIS

Hedgehog (SMO) inhibitor · approved 2012 · 6 citations

Recent· through 2023

Fairly sourced6/9 · 5 signals

Met: 6 citations
Not met: 12+ references
Met: Accrued over 10+ years (span: 10y)
Met: Beyond single case reports
Not met: Peer-reviewed sources
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.

First-in-class Hedgehog/SMO inhibitor whose muscle spasms and reported hyponatremia are the renal-relevant signals — a SIADH-type electrolyte story, not a structural lesion.

MildHedgehog pathway inhibitor era

Metastatic basal cell carcinomaLocally advanced basal cell carcinoma recurrent after surgery or not amenable to surgery/radiationBasal cell nevus (Gorlin) syndrome

§01

Signature kidney injury

Signature lesion

SIADH / Hyponatremia

Muscle spasms are near-universal (~64-71%), with dysgeusia and alopecia close behind; hyponatremia is reported but uncommon and not precisely quantified for an SIADH mechanism. Direct kidney injury is rare.Source: Sekulic et al., J Am Acad Dermatol 2015 (ERIVANCE); Chang et al., J Am Acad Dermatol 2014

Onset & rechallenge

Time to injuryVariable / unpredictable

Muscle spasms arise within the first weeks-to-months, but the hyponatremia is sporadic and variable in timing.

Distilled from: “Muscle spasms within the first weeks-to-months; hyponatremia is sporadic and variable in timing.”

§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.

SIADH / Hyponatremia#1 · Signature10.3%PMID 21300762 (opens PubMed in a new tab)
Grade 3 hyponatremia in 10.3% (most common grade 3 AE) plus grade 4 hyponatremia, phase I, n=68
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

The dominant toxicity is muscle spasm (myalgia) from Hedgehog inhibition in muscle, occasionally with creatine kinase elevation. The renal-relevant signal is an electrolyte one: hyponatremia, in some reports of an SIADH pattern (euvolemic, inappropriately concentrated urine, low serum osmolality), reflecting disordered free-water handling at the collecting duct rather than tubular toxicity. Volume loss from vomiting/diarrhea or poor intake can additionally contribute to hyponatremia and prerenal physiology.

Clinical presentation

Painful muscle cramps, dysgeusia/ageusia, alopecia and weight loss are the hallmark adverse events. When hyponatremia occurs it is usually mild and asymptomatic but can present with nausea, lethargy or confusion; labs show low serum sodium and osmolality with inappropriately concentrated urine when SIADH-type.

Management

Manage muscle spasms supportively (hydration, dose interruptions; some use calcium-channel blockers or L-carnitine empirically). For hyponatremia, determine volume status: fluid-restrict and treat the underlying SIADH-type physiology if euvolemic, or rehydrate if hypovolemic; correct sodium at a safe rate. Dose-interrupt for intolerable spasms. Most electrolyte effects reverse with management.Lesion-level management framework

Risk factors

Concurrent thiazides or other hyponatremia-inducing drugs
Volume depletion from nausea/vomiting or poor intake
Older age and baseline electrolyte disturbance
Polypharmacy in elderly BCC patients

Prevention

Maintain hydration; review concomitant hyponatremia-inducing drugs
Counsel on muscle-cramp symptoms and supportive measures
Avoid pregnancy (potent teratogen) per REMS

Anticancer mechanism· how it treats cancer

Oral small-molecule inhibitor of Smoothened (SMO), a transmembrane component of the Hedgehog signaling pathway. In basal cell carcinoma, constitutive Hedgehog activation (PTCH1 loss or SMO mutation) drives tumor growth; vismodegib blocks SMO to shut down the pathway.

Note · The renal link is indirect and electrolyte-based: muscle spasms dominate the safety profile, and the kidney-relevant signal is reported hyponatremia (sometimes SIADH-type), not a structural nephropathy. Precise hyponatremia/SIADH rates are not well quantified.

§04

Clinical depth

Renal dose adjustment

No dose adjustment recommended for mild-moderate renal impairment; not formally studied in severe impairment/ESKD. Hepatic metabolism predominates and dosing is fixed (150 mg daily).

Dialyzability & ESKD dosing

Very highly protein-bound (>99%); not expected to be dialyzable and no ESKD dosing established.

Differential diagnosis

For hyponatremia, separate SIADH-type (euvolemic, concentrated urine) from hypovolemic hyponatremia (volume depletion, low urine sodium) and drug interactions (thiazides). Muscle symptoms with high CK should prompt evaluation for rhabdomyolysis (more a sonidegib concern).

Monitoring

Serum sodium and electrolytes at baseline and periodically
Creatine kinase if severe or persistent muscle symptoms
Volume status and weight
Pregnancy testing per REMS in patients of childbearing potential

Key trials & series

ERIVANCE BCC (Sekulic, J Am Acad Dermatol 2015) — pivotal phase 2 defining the muscle-spasm-dominant safety profile
Expanded-access study (Chang, J Am Acad Dermatol 2014) — large safety confirmation

Clinical pearls

Muscle spasms are the signature, treatment-limiting toxicity — counsel every patient.
Hyponatremia is the renal-relevant signal; check volume status before treating to avoid overcorrection.
Vismodegib is a potent teratogen — strict pregnancy prevention (REMS) is mandatory.
Dysgeusia and weight loss compound dehydration risk in elderly patients.

Where it strikes· nephron segments & injury signatures

Nephron segments

Distal Tubule / Collecting Duct

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

Injury signatures

SIADH / Hyponatremia Electrolyte Disturbance

§05

References

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

Evidence accrual

6 references · 2013–2023 · 2 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 2024) — not paraphrased or interpreted. Full label on DailyMed .

Boxed warning

WARNING: EMBRYO-FETAL TOXICITY ERIVEDGE can cause embryo-fetal death or severe birth defects when administered to a pregnant woman. ERIVEDGE is embryotoxic, fetotoxic, and teratogenic in animals. Teratogenic effects included severe midline defects, missing digits, and other irreversible malformations [see Warnings and Precautions (5.1) , Use in Specific Populations (8.1) ] . Verify the pregnancy status of females of reproductive potential within 7 days prior to initiating ERIVEDGE. Advise pregnant women of the potential risks to a fetus. Advise females of reproductive potential to use effective contraception during and after ERIVEDGE [ see Dosage and Administration (2.1) , Warnings and Precautions (5.1) , Use in Specific Populations (8.1 , 8.3) ] . Advise males of the potential risk of ERIVEDGE exposure through semen and to use condoms with a pregnant partner or a female partner of reproductive potential [see Warnings and Precautions (5.1) , Use in Specific Populations (8.3) ] . WARNING: EMBRYO-FETAL TOXICITY See full prescribing information for complete boxed warning. ERIVEDGE can cause embryo-fetal death or severe birth defects when administered to a pregnant woman. ERIVEDGE is embryotoxic, fetotoxic, and teratogenic in animals. Teratogenic effects included severe midline defects, missing digits, and other irreversible malformations. ( 5.1 , 8.1 ) Verify the pregnancy status…

Renal impairment — from the label

No dose adjustment is required in patients with renal impairment [see Clinical Pharmacology (12.3) ] .

What gets reported — FAERS

Everything below is FAERS — adverse events someone chose to report, about 8,850 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

SIADH / Hyponatremiacorroborated · ROR 2.31 — but the naming terms alone are not disproportionate, so this rests on terms merely consistent with the lesion
Electrolyte Disturbancecorroborated · ROR 1.72 — but the naming terms alone are not disproportionate, so this rests on terms merely consistent with the lesion

SIADH / Hyponatremia

ROR 2.3195% CI 1.85–2.88· 78 reports

Electrolyte Disturbance

ROR 1.7295% CI 1.46–2.04· 138 reports

FAERS outcomes & reporting trend· 11.2% of reports w/ death · 13% w/ hospitalization

11.2%

Reported with a death outcome

987 of 8,850 reports

13%

Reported with hospitalization

1,147 of 8,850 reports

Reports per year

Yearly FAERS report volume · most recent year is partial.

FAERS adverse-event signal — all organ systems· 6 systems · 8,850 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 0.3195% CI 0.20–0.48· 20 AKI reports ·AKI is reported less often than for other drugs (CI entirely below 1) — no disproportionate signal.

Musculoskeletal

Muscle Spasms2,065Arthralgia283Myalgia218

General / constitutional

Fatigue970Weight Decreased738Asthenia294Pain248Malaise161

Gastrointestinal

Nausea714Diarrhoea472Constipation379Vomiting259Abdominal Pain Upper120

Skin

Alopecia1,401Rash140

Nervous system

Dysgeusia747Taste Disorder240Headache187Dizziness130

Metabolic & electrolyte

Decreased Appetite706Dehydration130

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 Vismodegib 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

Lazertinib

Lazcluze · EGFR TKI (3rd-gen)

Profile

2024 EGFR TKI; hyponatremia like osimertinib.

SIADHLYTE

Mild#1 · 88% phenotype match

Melphalan

Alkeran · Alkylator

Profile

SIADH in high-dose myeloma conditioning; renally cleared.

SIADHLYTE

Mild#2 · 87% phenotype match

Temozolomide

Temodar · Alkylator

Profile

Occasional SIADH; generally renally well tolerated.

SIADHLYTE

Mild#3 · 87% phenotype match

Vinblastine

Velban · Vinca alkaloid

Profile

SIADH and rare Raynaud/vascular events.

SIADHLYTE

Mild#4 · 87% phenotype match

Vincristine

Oncovin · Vinca alkaloid

Profile

SIADH → hyponatremia.

SIADHLYTE

Mild#5 · 87% phenotype match

Vinorelbine

Navelbine · Vinca alkaloid

Profile

SIADH reports.

SIADHLYTE

Mild#6 · 87% phenotype match

Compare Vismodegib 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.