What kind of kidney injury does Sonidegib cause?

Acute Tubular Necrosis — Direct death of tubular epithelial cells — the dose-limiting lesion of the platinums and zoledronate.

How should kidney function be monitored during Sonidegib therapy?

Creatine kinase at baseline and periodically (and with any muscle symptoms); Serum creatinine, potassium and phosphate during/after a CK rise; Urinalysis (heme-positive dip without RBCs suggests myoglobinuria); Volume status and urine output during suspected rhabdomyolysis.

How can kidney injury from Sonidegib be prevented?

Counsel on muscle pain/dark urine; maintain hydration Avoid/limit concurrent myotoxins where possible Hold drug for marked CK rise or muscle symptoms per label; rule out rhabdomyolysis

Who is at higher risk of kidney injury from Sonidegib?

Concurrent statins or other myotoxic drugs; Strenuous exertion, dehydration or volume depletion; Pre-existing CKD; Older age and reduced muscle mass masking CK interpretation.

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Printable monograph

Hedgehog (SMO) inhibitor

Sonidegib

Odomzo · SON

Hedgehog (SMO) inhibitor · approved 2015 · 6 citations

Recent· through 2023

Fairly sourced4/9 · 4 signals

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

Hedgehog/SMO inhibitor distinguished by frequent creatine-kinase elevation and rare rhabdomyolysis — the path to pigment (myoglobin) nephropathy and ATN.

MildHedgehog pathway inhibitor era

Locally advanced basal cell carcinoma recurrent after surgery/radiation or not amenable to those modalities

§01

Signature kidney injury

Signature lesion

Acute Tubular Necrosis

Asymptomatic creatine-kinase elevation is more common with sonidegib than vismodegib (a class-distinguishing signal), and rhabdomyolysis is a labeled but rare event. Clinically significant pigment nephropathy/ATN is uncommon but is the feared renal consequence.Source: Dummer et al., Br J Dermatol 2019 (BOLT 42-month); Lear et al., J Eur Acad Dermatol Venereol 2017 (BOLT 30-month)

Onset & rechallenge

Time to injurySubacute (~1–6 weeks)

CK elevations over the first weeks to months; rhabdomyolysis-driven AKI follows a significant muscle-injury event.

Distilled from: “CK elevations during the first weeks-to-months of therapy; rhabdomyolysis-driven AKI would follow a significant muscle-injury event.”

§02

Renal toxicities, ranked

This agent's defining kidney lesion — its #1 signature. Cited incidence is shown where a citable figure exists; otherwise the tier stands qualitatively.

Acute Tubular Necrosis#1 · Signaturequalitative — no citable incidence
Direct death of tubular epithelial cells — the dose-limiting lesion of the platinums and zoledronate.

§03

Kidney injury

Mechanism of kidney injury

Hedgehog inhibition in skeletal muscle causes myalgia and, more than with vismodegib, biochemical muscle injury with rising creatine kinase. In the uncommon event of frank rhabdomyolysis, released myoglobin is freely filtered and precipitates with Tamm-Horsfall protein in the distal/proximal tubule, causing direct heme-pigment tubular toxicity, intratubular cast obstruction and renal vasoconstriction — i.e. pigment (myoglobinuric) ATN. Volume depletion amplifies cast formation and ischemic injury.

Clinical presentation

Muscle aches and weakness with elevated CK; in severe cases dark (tea-colored) urine, dipstick blood without red cells on microscopy (myoglobinuria), rising creatinine and a muddy-brown-cast ATN picture, often with hyperkalemia and hyperphosphatemia. Most CK rises are asymptomatic and isolated.

Management

For rhabdomyolysis: stop sonidegib, give aggressive isotonic IV fluids to maintain brisk urine output, correct electrolytes (hyperkalemia, hyperphosphatemia), and support kidney function — dialysis if refractory hyperkalemia, acidosis or volume overload. Isolated asymptomatic CK elevation is monitored with dose interruption per thresholds. Renal recovery is common with prompt volume resuscitation.Lesion-level management framework

Risk factors

Concurrent statins or other myotoxic drugs
Strenuous exertion, dehydration or volume depletion
Pre-existing CKD
Older age and reduced muscle mass masking CK interpretation

Prevention

Counsel on muscle pain/dark urine; maintain hydration
Avoid/limit concurrent myotoxins where possible
Hold drug for marked CK rise or muscle symptoms per label; rule out rhabdomyolysis

Anticancer mechanism· how it treats cancer

Oral selective inhibitor of Smoothened (SMO) in the Hedgehog pathway, used for locally advanced basal cell carcinoma. Like vismodegib it shuts down constitutive Hedgehog signaling driven by PTCH1 loss or SMO mutation.

Note · The renal link is indirect: sonidegib's distinguishing toxicity is biochemical muscle injury (CK elevation) and rare rhabdomyolysis, which only then causes pigment-induced ATN. Clinically significant nephropathy is uncommon and not precisely quantified.

§04

Clinical depth

Renal dose adjustment

No specific renal dose adjustment in labeling for mild-moderate impairment; not studied in severe impairment/ESKD. Dosing is fixed (200 mg daily); modifications are driven by musculoskeletal toxicity/CK.

Dialyzability & ESKD dosing

Highly protein-bound; not meaningfully dialyzable. Hemodialysis is used for the metabolic complications of pigment-induced ATN, not to remove the drug.

Differential diagnosis

Differentiate pigment (myoglobinuric) ATN — heme-positive dipstick without red cells, very high CK, muddy-brown casts — from ischemic/septic ATN, prerenal azotemia and other causes of AKI. The muscle-injury history and CK level are decisive.

Monitoring

Creatine kinase at baseline and periodically (and with any muscle symptoms)
Serum creatinine, potassium and phosphate during/after a CK rise
Urinalysis (heme-positive dip without RBCs suggests myoglobinuria)
Volume status and urine output during suspected rhabdomyolysis

Key trials & series

BOLT (Dummer, Br J Dermatol 2019; Lear, JEADV 2017) — pivotal phase 2 characterizing the CK-elevation/musculoskeletal signal
Class meta-analysis (Nguyen, Am J Clin Dermatol 2023) — sonidegib > vismodegib for increased CK

Clinical pearls

Increased creatine kinase is the lab that distinguishes sonidegib from vismodegib within the class.
A heme-positive dipstick with no red cells on microscopy = myoglobinuria until proven otherwise.
Aggressive early isotonic fluids are the cornerstone of preventing rhabdomyolysis-induced ATN.
Statin co-prescription compounds myotoxicity — review the medication list.

Where it strikes· nephron segments & injury signatures

Nephron segments

Proximal Tubule

Bulk reabsorption + drug uptake (OCT2, OATs)

Tubular Lumen

The urine flow path

Injury signatures

Acute Tubular Necrosis

§05

References

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

Evidence accrual

6 references · 2017–2023 · 3 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

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 ODOMZO can cause embryo-fetal death or severe birth defects when administered to a pregnant woman. ODOMZO is embryotoxic, fetotoxic, and teratogenic in animals [see Warnings and Precautions (5.1) and Use in Specific Populations (8.1) ] . Verify the pregnancy status of females of reproductive potential prior to initiating therapy. Advise females of reproductive potential to use effective contraception during treatment with ODOMZO and for at least 20 months after the last dose [see Warnings and Precautions (5.1) and Use in Specific Populations (8.3) ] . Advise males of the potential risk of exposure through semen and to use condoms with a pregnant partner or a female partner of reproductive potential during treatment with ODOMZO and for at least 8 months after the last dose [see Warnings and Precautions (5.1) and Use in Specific Populations (8.3) ] . WARNING: EMBRYO-FETAL TOXICITY See full prescribing information for complete boxed warning. ODOMZO can cause embryo-fetal death or severe birth defects when administered to a pregnant woman and is embryotoxic, fetotoxic, and teratogenic in animals. ( 5.1 , 8.1 ) Verify the pregnancy status of females of reproductive potential prior to initiating therapy. Advise females of reproductive potential to use effective contraception during treatment with ODOMZO and for at least 20 months after the last dose. (…

What gets reported — FAERS

Everything below is FAERS — adverse events someone chose to report, about 1,494 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· 3 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

Acute Tubular NecrosisNot measurable in reporting — Reporters cannot reliably name this lesion, so its absence from FAERS is expected and is not evidence against the documented injury.

Crystal / Obstructive Nephropathy

ROR 2.2895% CI 1.18–4.38· 9 reports

Hemorrhagic Cystitis

ROR 2.2495% CI 1.24–4.05· 11 reports

Electrolyte Disturbance

ROR 1.7095% CI 1.13–2.57· 23 reports

FAERS outcomes & reporting trend· 9.9% of reports w/ death · 18.1% w/ hospitalization

9.9%

Reported with a death outcome

148 of 1,494 reports

18.1%

Reported with hospitalization

270 of 1,494 reports

Reports per year

Yearly FAERS report volume · most recent year is partial.

FAERS adverse-event signal — all organ systems· 6 systems · 1,494 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 1.2995% CI 0.76–2.19· 14 AKI reports ·no disproportionate AKI reporting signal (CI spans 1).

General / constitutional

Fatigue99Asthenia63Weight Decreased63Fall31Pain31

Musculoskeletal

Muscle Spasms195Myalgia57Arthralgia27

Gastrointestinal

Nausea73Diarrhoea58Vomiting43

Skin

Alopecia117

Nervous system

Dysgeusia50Taste Disorder33Dizziness27

Metabolic & electrolyte

Decreased Appetite61

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 Sonidegib 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

Samarium-153 lexidronam

Quadramet · Bone-seeking radiopharmaceutical (153Sm-EDTMP)

Profile

Renally excreted; dominant toxicity is reversible myelosuppression; caution in renal impairment.

ATN

Moderate#1 · 74% phenotype match

Trabectedin

Yondelis · Marine alkylating agent

Profile

Rhabdomyolysis → pigment nephropathy; hepatotoxicity.

ATNLYTE

Moderate#2 · 60% phenotype match

Sotorasib

Lumakras · KRAS G12C inhibitor

Profile

Newer agent; renal data emerging.

PREATN

Mild#3 · 58% phenotype match

Raltitrexed

Tomudex · Antifolate (TS inhibitor)

Profile

Renally cleared antifolate; exposure ~doubles in renal impairment; forerunner CB3717 withdrawn for crystal nephrotoxicity.

ATNXTAL

Moderate#4 · 58% phenotype match

Methotrexate (high-dose)

Trexall · Antifolate

Profile

Crystal nephropathy; glucarpidase rescue.

XTALATN

Moderate#5 · 57% phenotype match

Lurbinectedin

Zepzelca · Marine alkylating agent

Profile

Rhabdomyolysis risk in small-cell lung cancer.

ATNLYTEXTAL

Mild#6 · 56% phenotype match

Compare Sonidegib 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.