What kind of kidney injury does Sotorasib cause?

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

How should kidney function be monitored during Sotorasib therapy?

AST/ALT and bilirubin before and during therapy (primary safety concern); Hydration/volume status; Immunosuppressant trough levels in transplant recipients.

How can kidney injury from Sotorasib be prevented?

Manage GI toxicity early Dose-adjust immunosuppressants to their measured levels in transplant recipients (CYP3A/P-gp interactions shift exposure)

Who is at higher risk of kidney injury from Sotorasib?

Volume depletion from diarrhea/vomiting; Concurrent nephrotoxins; Pre-existing CKD; Solid-organ transplant on calcineurin/mTOR inhibitors (drug-interaction risk).

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Printable monograph

KRAS G12C inhibitor

Sotorasib

Lumakras · Sotor

KRAS G12C inhibitor · approved 2021 · 6 citations

Up to date· through 2025

Fairly sourced5/9 · 5 signals

Met: 6 citations
Not met: 12+ references
Not met: Accrued over 10+ years (span: 4y)
Met: Beyond single case reports
Met: High-impact journal
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.

The first KRAS-G12C inhibitor — renal injury is largely a rat-specific metabolite story, with sparse human signal.

MildKRAS G12C inhibitor

KRAS-G12C-mutated NSCLCKRAS-G12C-mutated colorectal cancer

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Signature kidney injury

Signature lesion

Prerenal / Hemodynamic AKI

Clinically significant nephrotoxicity is uncommon and case-level in humans (the dominant on-target/off-tumor toxicity is hepatotoxicity). Proximal tubular toxicity is prominent in rats via a reactive mercapturate-pathway metabolite. Human renal incidence is not well quantified.Source: Werner et al., Toxicol Appl Pharmacol 2021 (rat mechanism)

Onset & rechallenge

Time to injurySubacute (~1–6 weeks)

Acute AKI during the first weeks to months of therapy, typically tracking GI toxicity.

Distilled from: “When AKI occurs, it is acute during the first weeks–months of therapy, typically tracking GI toxicity.”

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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.
Acute Tubular NecrosisSecondaryno population incidence denominator
Proximal-tubular necrosis localized to the outer stripe of the outer medulla, dose- and time-dependent and tracking urinary tubular-injury biomarkers, driven by a reactive mercapturate/beta-lyase pathway metabolite (mechanistic, Sprague-Dawley rat; species-dependent, informs the human proximal-tubular signal). PMID 34004237 (opens PubMed in a new tab)

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Kidney injury

Mechanism of kidney injury

In Sprague-Dawley rats, sotorasib is bioactivated through the cysteine-conjugate β-lyase (mercapturate) pathway to a nephrotoxic thiol metabolite that concentrates in and damages the proximal tubule (outer-stripe degeneration/necrosis). Human relevance appears limited. Clinically observed AKI is largely hemodynamic/prerenal — from diarrhea/vomiting-related volume depletion — rather than the defining metabolite lesion.

Clinical presentation

Usually no clinically meaningful renal change; transient creatinine rises occur mainly with GI losses and dehydration. The clinically dominant adverse events are transaminase elevation/hepatotoxicity and diarrhea.

Management

Supportive care, volume repletion, and hold/dose-modify for GI toxicity; monitor renal and liver function. Sotorasib carries a major hepatotoxicity signal, so liver monitoring is integral.Lesion-level management framework

Risk factors

Volume depletion from diarrhea/vomiting
Concurrent nephrotoxins
Pre-existing CKD
Solid-organ transplant on calcineurin/mTOR inhibitors (drug-interaction risk)

Prevention

Manage GI toxicity early
Dose-adjust immunosuppressants to their measured levels in transplant recipients (CYP3A/P-gp interactions shift exposure)

Anticancer mechanism· how it treats cancer

First-in-class covalent inhibitor that binds the mutant cysteine-12 of KRAS G12C and locks the oncoprotein in its inactive GDP-bound state, blocking downstream RAF-MEK-ERK (MAPK) signaling in KRAS-G12C–mutated non-small cell lung cancer (NSCLC) and colorectal cancer.

Note · The defining renal toxicology is a rat-specific metabolite finding; human renal data remain sparse. A reported transplant drug interaction (markedly reduced tacrolimus/everolimus levels) is an onconephrology-relevant hazard to graft function.

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Clinical depth

Renal dose adjustment

No renal dose adjustment is recommended; sotorasib pharmacokinetics were not meaningfully affected by mild-moderate renal impairment, and severe impairment/ESKD are not well studied. Dose modifications (from 960 mg daily) are driven by hepatotoxicity and GI toxicity, not CrCl.

Dialyzability & ESKD dosing

Not characterized; as a highly protein-bound, hepatically cleared small molecule it is unlikely to be substantially dialyzed. No ESKD dosing guidance is established.

Differential diagnosis

Separate true sotorasib-related AKI from prerenal azotemia of GI fluid loss (responds to volume) and from hepatotoxicity-driven changes; the rat proximal-tubule metabolite lesion has no validated human correlate, so unexplained AKI should prompt the usual onconephrology workup rather than attribution to the drug.

Monitoring

AST/ALT and bilirubin before and during therapy (primary safety concern)
Hydration/volume status
Immunosuppressant trough levels in transplant recipients

Key trials & series

de Langen et al., Lancet 2023 — CodeBreaK 200 phase 3 (sotorasib vs docetaxel in NSCLC; safety base rate)
Pietrantonio et al., JCO 2025 — CodeBreaK 300 (sotorasib + panitumumab in KRAS-G12C colorectal cancer)

Clinical pearls

The headline sotorasib toxicity is hepatic, not renal — but watch volume status, because GI losses drive most observed creatinine bumps.
The dramatic proximal-tubule injury is a Sprague-Dawley rat metabolite phenomenon; do not over-attribute human AKI to it.
In transplant recipients, sotorasib can collapse tacrolimus/everolimus levels and threaten the graft — a true onconephrology pitfall.

Where it strikes· nephron segments & injury signatures

Nephron segments

Vasculature / Endothelium

Glomerular & peritubular capillaries

Proximal Tubule

Bulk reabsorption + drug uptake (OCT2, OATs)

Injury signatures

Prerenal / Hemodynamic AKI Acute Tubular Necrosis

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References

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

Evidence accrual

6 references · 2021–2025 · 4 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.

What gets reported — FAERS

Everything below is FAERS — adverse events someone chose to report, about 3,319 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· 1 signal

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

Prerenal / Hemodynamic AKINot queried in FAERS — No MedDRA term set is defined for this phenotype, so FAERS was never asked about it.
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.

Electrolyte Disturbance

ROR 1.8095% CI 1.37–2.35· 54 reports

FAERS outcomes & reporting trend· 23.7% of reports w/ death · 20.2% w/ hospitalization

23.7%

Reported with a death outcome

788 of 3,319 reports

20.2%

Reported with hospitalization

670 of 3,319 reports

Reports per year

Yearly FAERS report volume · most recent year is partial.

FAERS adverse-event signal — all organ systems· 7 systems · 3,319 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 0.7995% CI 0.50–1.24· 19 AKI reports ·no disproportionate AKI reporting signal (CI spans 1).

Hepatobiliary

Hepatotoxicity101Hepatic Function Abnormal95Alanine Aminotransferase Increased79Aspartate Aminotransferase Increased79Hepatic Enzyme Increased48

Gastrointestinal

Diarrhoea325Nausea113Vomiting53Constipation36

General / constitutional

Fatigue107Asthenia52Pain39

Metabolic & electrolyte

Decreased Appetite71

Immune / infection

Pneumonia59

Respiratory

Dyspnoea53

Skin

Rash44

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 Sotorasib 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

Tretinoin (ATRA)

Vesanoid · Retinoid (differentiating agent)

Profile

Differentiation syndrome → capillary leak and AKI.

PREATN

Moderate#1 · 95% phenotype match

Tagraxofusp

Elzonris · IL-3 immunotoxin

Profile

Capillary-leak syndrome → AKI.

PREATN

Moderate#2 · 95% phenotype match

Binimetinib

Mektovi · MEK inhibitor

Profile

Creatinine rise; rhabdomyolysis reports.

ATNPRE

Mild#3 · 89% phenotype match

Pegaspargase

Oncaspar · Enzyme (asparaginase)

Profile

Rare AKI; pancreatitis- and thrombosis-mediated.

PREATN

Mild#4 · 89% phenotype match

Talquetamab

Talvey · Bispecific (GPRC5D×CD3)

Profile

CRS-related AKI — emerging.

PREATN

Moderate#5 · 84% phenotype match

Teclistamab

Tecvayli · Bispecific (BCMA×CD3)

Profile

CRS-associated AKI in myeloma — emerging signal.

PREATN

Moderate#6 · 84% phenotype match

Compare Sotorasib 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.