Bosutinib
Bosulif · BCR-ABL TKI
Reversible eGFR decline.
PSEUDOPRE
MildOpen →
CDK4/6 inhibitor
Ribociclib
Kisqali · Ribo
CDK4/6 inhibitor whose creatinine bump is mostly transporter inhibition, with QT prolongation to watch.
MildCDK4/6 inhibitor · approved 2017
HR-positive HER2-negative breast cancer
Signature kidney injury
Pseudo-AKI
Like other CDK4/6 inhibitors, ribociclib produces a frequent, reversible creatinine rise via inhibition of tubular creatinine secretion (pseudo-AKI ~14% in a class-effect analysis); clinically meaningful structural AKI is uncommon. A retrospective cohort of palbociclib/ribociclib patients found a >=20% creatinine-clearance decline in about 23%.
Source: Avci et al., Ther Adv Med Oncol 2026 (~23% ≥20% CrCl decline in a mixed palbociclib/ribociclib cohort; most ribociclib creatinine rise is transporter-mediated pseudo-AKI, not structural injury)
Toxicity fingerprint
Tap a signature to trace where it strikes the nephron.
Incidence not quantified
SeverityMild
ReversibilityReversible
Evidence0 refs
Nephron map
Vasculature / Endothelium
Proximal TubuleBulk reabsorption + drug uptake (OCT2, OATs)
Distal Tubule / Collecting Duct
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
Inhibits proximal-tubular OCT2 and MATE transporters that secrete creatinine, elevating serum creatinine independent of GFR. Ribociclib additionally carries dose-dependent QTc prolongation, so co-existing hypokalemia, hypomagnesemia, and hypocalcemia must be corrected to limit torsades risk; these electrolyte disturbances are a distinct safety axis rather than a sign of tubular injury.
Clinical presentation
Early asymptomatic creatinine rise with preserved cystatin-C-based/measured GFR and bland urinalysis. Separately, monitor ECG/QTc and serum electrolytes per labeling, especially in the first cycles.
Onset
First cycles (median onset roughly 6 weeks for the creatinine signal); reversible on hold or discontinuation. QTc effects are dose- and concentration-dependent and seen early.
Reversibility
Reversible
Anticancer mechanism
Selective CDK4/6 inhibitor that halts the cell cycle at the G1/S checkpoint by preventing Rb phosphorylation; combined with endocrine therapy in HR-positive, HER2-negative advanced/metastatic breast cancer, with a demonstrated overall-survival benefit (e.g. MONALEESA-7: median OS 58.7 vs 48.0 months).
Management
Treat as pseudo-AKI when cystatin C/measured GFR is stable and sediment is bland; continue therapy. Manage QTc and electrolytes per protocol (hold/reduce if QTcF >480-500 ms). Reserve dose modification for genuine renal decline.
Risk factors
- Older age
- Elevated baseline renal indices
- Concurrent QT-prolonging drugs or baseline electrolyte abnormalities
- Strong CYP3A4 inhibitors increasing exposure
Prevention
- Confirm true GFR (cystatin C / measured GFR) before attributing a creatinine rise to nephrotoxicity
- Correct and monitor potassium, magnesium, and calcium before and during therapy
- Baseline and on-treatment ECG; avoid unnecessary QT-prolonging or nephrotoxic co-medications
Note · Creatinine rise plus QTc prolongation; the renal signal is largely artefactual OCT2/MATE inhibition, while the electrolyte/QT axis is the clinically actionable safety concern.
Clinical depth
Renal dose adjustment
No adjustment for mild-moderate renal impairment; the label provides a reduced starting dose (e.g. 200 mg) for severe impairment. Avoid strong CYP3A4 inhibitors or reduce dose accordingly.
Dialyzability & ESKD dosing
Extensively hepatically metabolized (CYP3A4), highly protein-bound; not expected to be removed by hemodialysis. No HD-timed dosing established.
Differential diagnosis
Transporter-mediated pseudo-AKI (stable cystatin C) vs prerenal azotemia vs rare true ATN/AIN. QTc prolongation with electrolyte derangement is a separate toxicity, not evidence of kidney injury.
Monitoring
- Serum creatinine each cycle (with cystatin-C eGFR if it rises)
- Serum potassium, magnesium, and total/ionized calcium
- ECG/QTc at baseline, ~day 14, and start of cycle 2
- LFTs and CBC per label
Key trials & series
- MONALEESA-2 / MONALEESA-3 / MONALEESA-7 (OS benefit)
- NATALEE (adjuvant)
- Avci Ther Adv Med Oncol 2026 nephrotoxicity cohort
Clinical pearls
- Ribociclib is the CDK4/6 inhibitor most associated with QT prolongation - check Mg/K/Ca, not just creatinine.
- A rising creatinine with a normal cystatin C means keep dosing.
- Strong CYP3A4 inhibitors raise both renal-transporter and QT effects by increasing exposure.
Where it strikes
Nephron segments
Proximal Tubule
Bulk reabsorption + drug uptake (OCT2, OATs)
Vasculature / Endothelium
Glomerular & peritubular capillaries
Injury signatures
Pseudo-AKIPrerenal / Hemodynamic AKIElectrolyte Wasting
Evidence
6 peer-reviewed references. Citation metadata via PubMed / NLM.
LandmarkPseudo acute kidney injury in patients receiving CDK4/6 inhibitors.Buijs SM et al. · Br J Cancer 2025 · PMID 39930149Explains transporter-mediated creatinine elevation underlying CDK4/6-inhibitor pseudo-AKI, confirmed by cystatin C.PMIDNephrotoxicity secondary to CDK 4/6 inhibitors in advanced breast cancer patients and its impact on survival.Avci T et al. · Ther Adv Med Oncol 2026 · PMID 41523909Cohort quantifying creatinine-clearance decline (~23%) with palbociclib/ribociclib and its risk factors.PMIDRenal adverse events associated with cyclin-dependent kinase 4/6 inhibitors.Izzedine H et al. · Cancer Treat Rev 2025 · PMID 41385991Reviews CDK4/6-inhibitor renal effects including pseudo-AKI, hypertension, and electrolyte imbalance (hypokalemia, hyponatremia).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-centre analysis placing ribociclib pseudo-creatinine elevation at ~14%, comparable to palbociclib and abemaciclib.PMIDUpdated Overall Survival of Ribociclib plus Endocrine Therapy versus Endocrine Therapy Alone in Pre- and Perimenopausal Patients with HR+/HER2- Advanced Breast Cancer in MONALEESA-7.Lu YS et al. · Clin Cancer Res 2022 · PMID 34965945Landmark OS data (58.7 vs 48.0 months) establishing ribociclib efficacy context for risk-benefit of continuing therapy through pseudo-AKI.PMIDOnconephrology: Update in Anticancer Drug-Related Nephrotoxicity.García-Carro C et al. · Nephron 2022 · PMID 35717937Practical onconephrology review of targeted-therapy renal effects and management.