Bosutinib
Bosulif · BCR-ABL TKI
Reversible eGFR decline.
PSEUDOPRE
MildOpen →
CDK4/6 inhibitor
Abemaciclib
Verzenio · Abema
A CDK4/6 inhibitor that raises creatinine by blocking its tubular secretion — a 'pseudo-AKI' with intact true GFR.
MildCDK4/6 inhibitor · approved 2017
HR-positive, HER2-negative breast cancer (early and advanced)
Signature kidney injury
Pseudo-AKI
Representative incidence20%
A benign serum-creatinine rise occurs in roughly one-fifth of patients (~20% in a single-center series; a class effect across CDK4/6 inhibitors), almost always grade 1–2 and without true GFR loss. In a dedicated CDK4/6-inhibitor cohort, ~73% of creatinine rises were confirmed pseudo-AKI by cystatin C–based eGFR.
Source: Ly et al., J Oncol Pharm Pract 2024 (~20% abemaciclib)
Toxicity fingerprint
Tap a signature to trace where it strikes the nephron.
0%incidence
SeverityMild
ReversibilityReversible
Evidence0 refs
Nephron map
Vasculature / Endothelium
Proximal TubuleBulk reabsorption + drug uptake (OCT2, OATs)
Pseudo-AKI
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.
Mechanism of kidney injury
Abemaciclib (and its active metabolites) inhibit the renal proximal-tubule transporters OCT2, MATE1 and MATE2-K that secrete creatinine into the tubular lumen, raising serum creatinine WITHOUT reducing actual glomerular filtration — a 'pseudo-AKI.' Measured GFR and other kidney biomarkers stay intact; cystatin C–based estimates (cystatin C is not secreted by these transporters) clarify true function. Genuine AKI (volume depletion from diarrhea, rare interstitial nephritis) remains possible and must not be missed.
Clinical presentation
Asymptomatic, early, mild creatinine elevation (cystatin C may also rise modestly but measured/true GFR is preserved); no proteinuria, electrolyte derangement or active sediment. Diarrhea is the dominant clinical toxicity and can cause superimposed prerenal azotemia.
Onset
Early — within the first weeks (median onset ~3 weeks), stable thereafter, reversible on discontinuation.
Reversibility
Reversible
Anticancer mechanism
Cyclin-dependent kinase 4/6 inhibitor that prevents RB phosphorylation and arrests the G1–S cell-cycle transition, used with endocrine therapy in HR-positive, HER2-negative breast cancer (early and advanced); among CDK4/6 inhibitors it has the most continuous dosing and the strongest GI (diarrhea) signal.
Management
No intervention is needed for an isolated creatinine rise; do not reflexively reduce dose or stop the drug. Confirm with cystatin C or measured GFR. Remain alert that genuine AKI (prerenal from diarrhea, rare AIN) can still occur and warrants standard workup (urinalysis, volume assessment).
Risk factors
- Baseline reduced renal reserve (interpretation issue)
- Concomitant tubular-secretion inhibitors (e.g., trimethoprim, cimetidine)
- Diarrhea-related volume depletion (for true superimposed AKI)
Prevention
- Recognize the pattern to avoid unnecessary dose changes or imaging
- Use cystatin C / measured GFR when true function is in question
- Maintain hydration and manage diarrhea to prevent genuine prerenal AKI
Note · The creatinine rise reflects blocked tubular secretion (pseudo-AKI), not parenchymal injury; do not mistake it for true nephrotoxicity. Pharmacovigilance data nonetheless capture occasional true ATN/interstitial nephritis, so 'pseudo-AKI' is the rule, not an absolute.
Clinical depth
Renal dose adjustment
No dose adjustment for mild-to-moderate renal impairment; severe renal impairment and ESKD are not well characterized (hepatic, not renal, impairment drives reduction). Critically, the drug-induced serum-creatinine rise should NOT trigger dose reduction by itself — verify true GFR first.
Dialyzability & ESKD dosing
Not characterized; abemaciclib is highly protein-bound and hepatically (CYP3A4) metabolized, so it is unlikely to be appreciably dialyzed. No ESKD dosing guidance exists.
Differential diagnosis
Pseudo-AKI (creatinine rise, normal cystatin C–based/measured GFR, bland urine, early/stable) vs true AKI: prerenal azotemia from diarrhea (responds to volume) or, rarely, acute interstitial nephritis/ATN (active sediment, progressive). Cystatin C and urinalysis are the discriminators.
Monitoring
- Serum creatinine at baseline and early; if elevated, obtain cystatin C / measured GFR before acting
- Urinalysis if proteinuria/active sediment is suspected (to exclude true injury)
- Volume status and diarrhea severity (to catch superimposed prerenal AKI)
Key trials & series
- Ly et al., J Oncol Pharm Pract 2024 — single-center series quantifying pseudo-creatinine elevation as a CDK4/6-inhibitor class effect (~20% abemaciclib)
- Buijs et al., Br J Cancer 2025 — cohort confirming ~73% of CDK4/6-inhibitor creatinine rises are pseudo-AKI by cystatin C
- monarchE / MONARCH registrational programs — established the abemaciclib creatinine-elevation signal
Clinical pearls
- Abemaciclib raises creatinine by blocking OCT2/MATE-mediated tubular secretion — it is pseudo-AKI; confirm with cystatin C and do NOT reflexively cut the dose.
- Other renally cleared co-medications dosed off this inflated creatinine may be under-dosed — use measured GFR for those.
- Pseudo-AKI is the rule but not absolute: diarrhea can cause real prerenal AKI and rare true intrinsic injury occurs — keep checking the urine and volume status.
Where it strikes
Nephron segments
Proximal Tubule
Bulk reabsorption + drug uptake (OCT2, OATs)
Injury signatures
Pseudo-AKIPrerenal / Hemodynamic AKI
Evidence
7 peer-reviewed references. Citation metadata via PubMed / NLM.
LandmarkRenal adverse events associated with cyclin-dependent kinase 4/6 inhibitors.Izzedine H et al. · Cancer Treat Rev 2025 · PMID 41385991Definitive onconephrology review of CDK4/6-inhibitor renal effects: OCT2/MATE pseudo-AKI vs true AKI, cystatin C, abemaciclib highest creatinine signal.PMIDEvaluation of cyclin-dependent kinase 4/6 inhibitor-induced serum creatinine elevations in patients with hormone receptor positive breast cancer.Ly E et al. · J Oncol Pharm Pract 2026 · PMID 39648753Single-center series quantifying pseudo-creatinine elevation as a CDK4/6-inhibitor class effect (~20% abemaciclib, all grade 1–2).PMIDPseudo acute kidney injury in patients receiving CDK4/6 inhibitors.Buijs SM et al. · Br J Cancer 2025 · PMID 39930149Cohort: ~73% of creatinine rises were pseudo-AKI confirmed by cystatin C–based eGFR.PMIDChallenges of Renal Function Assessment in Breast Cancer Patients Treated With Abemaciclib: A Case Report.Ferreira A et al. · Cureus 2024 · PMID 39318897Case showing creatinine/cystatin-C rise without true GFR decline on scintigraphy.PMIDAbemaciclib-Induced Pseudo-AKI: an underrecognised finding.Markley P et al. · BMJ Case Rep 2025 · PMID 40449940Abemaciclib-specific pseudo-AKI case with cystatin C workup.PMIDThe adverse events of CDK4/6 inhibitors for HR+/HER2- breast cancer: an umbrella review of meta-analyses of randomized controlled trials.Pu D et al. · Front Pharmacol 2024 · PMID 38288438Umbrella review linking abemaciclib specifically with elevated blood creatinine.PMIDCyclin-dependent kinase inhibitors and kidney injury: Analysis of the French pharmacovigilance database.Lagarce L et al. · Therapie 2026 · PMID 42097936Pharmacovigilance distinguishing pseudo-renal failure from true ATN/interstitial nephritis across CDK4/6 inhibitors.