Is kidney injury from Adagrasib reversible?

Reversible. Typical onset: Early — within the first weeks of therapy..

How should kidney function be monitored during Adagrasib therapy?

Serum creatinine AND cystatin C / measured GFR when true function is in question; Urinalysis for albuminuria/proteinuria (do not assume pseudo-AKI); QTc (ECG) given QT-prolongation risk; Volume status and GI symptom severity; Serum creatinine at baseline and serially on treatment; Serum electrolytes alongside QTc.

How can kidney injury from Adagrasib be prevented?

Hydration and early antiemetic/antidiarrheal support Consider cystatin C if pseudo-AKI is suspected

Who is at higher risk of kidney injury from Adagrasib?

Diarrhea/nausea/vomiting with dehydration; Concurrent nephrotoxins; Pre-existing CKD; Other tubular-secretion inhibitors (compounding pseudo-creatinine rise).

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Printable monograph

KRAS G12C inhibitor

Adagrasib

Krazati · Adagra

KRAS G12C inhibitor · approved 2022 · 6 citations · FAERS AKI reporting ROR 4.79 (95% CI 3.44–6.68, 36 AKI reports)

Up to date· through 2025

Fairly sourced6/9 · 6 signals

Met: 6 citations
Not met: 12+ references
Not met: Accrued over 10+ years (span: 3y)
Met: Beyond single case reports
Met: High-impact journal
Met: Landmark reference
Met: Current through 2025
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.

A KRAS-G12C inhibitor whose kidney signal is mostly a creatinine bump and dehydration — but watch for a real glomerular signal.

MildKRAS G12C inhibitor

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

§01

Signature kidney injury

Signature lesion

Prerenal / Hemodynamic AKI

Renal effects are usually mild: a creatinine rise (partly from inhibited tubular creatinine secretion) plus prerenal AKI from GI losses. The KRYSTAL-1 registrational program reported renal-related lab changes; a dedicated PubMed-indexed pseudo-AKI/albuminuria study for adagrasib does not yet exist, so the precise incidence is unquantified.Source: Jänne et al., NEJM 2022 (KRYSTAL-1)

Onset & rechallenge

Time to injurySubacute (~1–6 weeks)

Early — within the first weeks of therapy.

Distilled from: “Early — within the first weeks of therapy.”

§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 · Signaturequalitative — no citable incidence
Renal hypoperfusion from capillary leak and cytokine storm — IL-2 and CAR-T cytokine release syndrome.
Glomerular Injury / ProteinuriaSecondaryqualitative — no citable incidence
Damage to the filtration barrier — podocyte injury, FSGS and protein leak from VEGF and mTOR blockade.
Pseudo-AKISecondaryqualitative — no citable incidence
The great mimic — a rise in creatinine from blocked tubular secretion (OCT2/MATE), NOT true injury. The GFR is intact; confirm with cystatin C before stopping effective therapy.

Toxicity fingerprint

Tap a signature to trace where it strikes the nephron.

Incidence not quantified

SeverityMild

ReversibilityReversible

Evidence6 citations

Nephron map

Glomerulus

Vasculature / Endothelium

Proximal Tubule

Prerenal / Hemodynamic AKI

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

§03

Kidney injury

Mechanism of kidney injury

Adagrasib can raise serum creatinine partly by blocking tubular creatinine secretion ('pseudo-AKI' without true GFR loss). Clinically meaningful AKI is most often prerenal, from diarrhea/nausea/vomiting–related volume depletion, and the long half-life sustains GI toxicity. A real glomerular/albuminuria signal is increasingly described in real-world experience and should not be dismissed as pure pseudo-AKI without checking the urine.

Clinical presentation

Mild, early creatinine elevation; sometimes new albuminuria. Overt AKI usually accompanies significant GI fluid losses. QTc prolongation and GI toxicity are the other prominent adverse events.

Management

Volume repletion and GI-toxicity control. Distinguish a pure creatinine rise from true GFR decline (cystatin C-based eGFR, measured GFR); check urinalysis for proteinuria/active sediment before attributing change to benign pseudo-AKI. Dose-modify (from 600 mg twice daily) for severe GI, QTc or renal events.Lesion-level management framework

Risk factors

Diarrhea/nausea/vomiting with dehydration
Concurrent nephrotoxins
Pre-existing CKD
Other tubular-secretion inhibitors (compounding pseudo-creatinine rise)

Prevention

Hydration and early antiemetic/antidiarrheal support
Consider cystatin C if pseudo-AKI is suspected

Anticancer mechanism· how it treats cancer

Covalent KRAS G12C inhibitor with a long (~23 h) half-life and CNS penetration, irreversibly trapping mutant KRAS in its inactive GDP-bound state and blocking MAPK signaling in KRAS-G12C–mutated NSCLC and colorectal cancer.

Note · The creatinine increase may overstate true renal impairment via blocked tubular secretion, but real glomerular/albuminuria signals are emerging — so the key teaching point is to check the urine and a cystatin C before concluding it is 'just pseudo-AKI.'

§04

Clinical depth

Renal dose adjustment

No dedicated renal dose adjustment is established; standard is 600 mg orally twice daily, modified for GI/QTc/hepatic toxicity. A measured (rather than creatinine-estimated) GFR is preferred when dosing renally cleared co-medications, because adagrasib inflates serum creatinine.

Dialyzability & ESKD dosing

Not characterized; highly protein-bound, hepatically metabolized (CYP3A4) small molecule, unlikely to be appreciably dialyzed. No ESKD dosing guidance exists.

Differential diagnosis

Pseudo-AKI (blocked OCT2/MATE-mediated creatinine secretion, normal cystatin C-based eGFR, bland urine) vs true AKI: prerenal azotemia from GI losses (responds to volume) vs a glomerular lesion (new albuminuria/proteinuria). Cystatin C and urinalysis are the discriminators.

Monitoring

Serum creatinine AND cystatin C / measured GFR when true function is in question
Urinalysis for albuminuria/proteinuria (do not assume pseudo-AKI)
QTc (ECG) given QT-prolongation risk
Volume status and GI symptom severity
Serum creatinine at baseline and serially on treatment
Serum electrolytes alongside QTc

Key trials & series

Jänne et al., NEJM 2022 — KRYSTAL-1 NSCLC registrational cohort (renal/creatinine-related AEs)
Yaeger et al., NEJM 2022 — KRYSTAL-1 colorectal cohort (± cetuximab)

Clinical pearls

Adagrasib raises creatinine partly by blocking its tubular secretion — but confirm with cystatin C and a urinalysis rather than assuming pseudo-AKI.
The long half-life sustains diarrhea/nausea; most genuine AKI is prerenal volume depletion.
An inflated serum creatinine can cause inappropriate dose reductions of co-administered renally cleared drugs — use measured GFR for those decisions.

§05

References

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

Evidence accrual

6 references · 2022–2025 · 3 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 1,063 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.
Glomerular Injury / ProteinuriaNo disproportionate reporting — This phenotype IS reportable and this agent has enough reports, yet the reporting is not disproportionate — the one genuinely informative negative of the four.
Pseudo-AKINot queried in FAERS — No MedDRA term set is defined for this phenotype, so FAERS was never asked about it.

Electrolyte Disturbance

ROR 1.8795% CI 1.18–2.98· 18 reports

FAERS outcomes & reporting trend· 32.1% of reports w/ death · 37.7% w/ hospitalization

32.1%

Reported with a death outcome

341 of 1,063 reports

37.7%

Reported with hospitalization

401 of 1,063 reports

Reports per year

Yearly FAERS report volume · most recent year is partial.

FAERS adverse-event signal — all organ systems· 10 systems · 1,063 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 4.7995% CI 3.44–6.68· 36 AKI reports ·AKI is reported disproportionately more often than for other drugs (CI entirely above 1) — a hypothesis-generating signal, not proof of causation.

Renal & urinary

Acute Kidney Injury36Renal Failure33Renal Impairment18

Gastrointestinal

Diarrhoea128Nausea101Vomiting86Constipation18Abdominal Pain Upper17

General / constitutional

Asthenia70Fatigue58Weight Decreased24Peripheral Swelling19Malaise17

Metabolic & electrolyte

Decreased Appetite47Dehydration42

Respiratory

Dyspnoea36

Nervous system

Dizziness27

Vascular

Hypotension22

Psychiatric

Confusional State19

Skin

Rash19

Cardiac

Electrocardiogram Qt Prolonged17

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 Adagrasib 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

Lorlatinib

Lorbrena · ALK TKI

Profile

Edema and metabolic effects.

PSEUDOPREGLOM

Mild#1 · 81% phenotype match

Olverembatinib

Olverembatinib (HQP1351) · BCR-ABL1 tyrosine kinase inhibitor (3rd generation)

Profile

Potent T315I-active TKI with a largely renal-sparing profile

GLOMPREHTN

Mild#2 · 66% phenotype match

Vorasidenib

Voranigo · Mutant IDH1/2 inhibitor

Profile

A brain-penetrant IDH inhibitor whose kidney footprint is a benign creatinine bump, not true AKI.

PSEUDOPRE

Mild#3 · 65% phenotype match

Alectinib

Alecensa · ALK TKI

Profile

Creatinine rise via reduced tubular secretion.

PSEUDOPRE

Mild#4 · 65% phenotype match

Bosutinib

Bosulif · BCR-ABL TKI

Profile

Reversible eGFR decline.

PSEUDOPRE

Mild#5 · 65% phenotype match

Ceritinib

Zykadia · ALK TKI

Profile

GI-driven prerenal AKI.

PREPSEUDO

Mild#6 · 65% phenotype match

Compare Adagrasib 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.