Ribociclib
Kisqali · CDK4/6 inhibitor
Creatinine rise; QT prolongation.
PSEUDOPRELYTE
Mild#1 · 100% phenotype match
Palbociclib
Ibrance · Palbo
CDK4/6 inhibitor · approved 2015 · 8 citations
Up to date· through 2026
Fairly sourced4/9 · 4 signals
- Met: 8 citations
- Not met: 12+ references
- Not met: Accrued over 10+ years (span: 8y)
- Met: Beyond single case reports
- Not met: Peer-reviewed sources
- Met: Landmark reference
- Met: Current through 2026
- 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.
A CDK4/6 inhibitor that nudges creatinine up without truly injuring the kidney.
MildCDK4/6 inhibitor
HR-positive HER2-negative breast cancer
§01
Signature kidney injury
Signature lesion
Representative incidence16%
A reversible rise in serum creatinine is common, but true structural kidney injury is uncommon. CDK4/6 inhibitors block the proximal-tubule transporters that secrete creatinine, producing a 'pseudo-AKI' picture. In a single-center palbociclib cohort 16% (8 of 50) met creatinine-based AKI criteria (Ly, PMID 39648753); the 17.5% often quoted is the whole mixed CDK4/6-inhibitor cohort of 234 patients, not the palbociclib arm. Where cystatin C was available, 73% of those events proved to be pseudo-AKI rather than a true GFR decline.Source: Ly et al. (PMID 39648753) — palbociclib-specific: 16% (8/50) creatinine-based AKI. Class-wide context: Buijs et al., Br J Cancer 2025 (PMID 39930149), 17.5% of 234 CDK4/6i-treated patients; pseudo-AKI 73% (16/22).
Onset & rechallenge
Time to injurySubacute (~1–6 weeks)
Creatinine typically rises within the first 1-2 cycles (median onset roughly 30-35 days), then plateaus and reverses after dose hold or discontinuation.
Distilled from: “Often within the first 1-2 cycles (median onset roughly 30-35 days); creatinine plateaus and reverses after dose hold or discontinuation.”
§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.
Class effect: predominant renal signal is pseudo-AKI (creatinine rise from OCT2/MATE inhibition without a real GFR decline); true AKI (acute tubular injury, interstitial nephritis) is rare PMID 41385991 (opens PubMed in a new tab)
Renal hypoperfusion from capillary leak and cytokine storm — IL-2 and CAR-T cytokine release syndrome.
Hypokalemia/hyponatremia reported but uncommon relative to the near-universal creatinine change PMID 41385991 (opens PubMed in a new tab)
Toxicity fingerprint
Tap a signature to trace where it strikes the nephron.
16%incidence
SeverityMild
ReversibilityReversible
Evidence8 citations
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.
§03
Kidney injury
Mechanism of kidney injury
Inhibits proximal-tubular organic cation transporter 2 (OCT2) and the MATE1/MATE2-K efflux transporters that secrete creatinine into the tubular lumen, elevating measured serum creatinine without reducing true glomerular filtration ('pseudo-AKI'). Cystatin C, which is filtered at the glomerulus and not secreted, is unaffected, so a cystatin-C-based eGFR unmasks the artefact. Genuine prerenal or structural injury, when present, is usually driven by intercurrent illness, volume depletion, or co-medications; rare true acute tubular injury and acute interstitial nephritis have been described.
Clinical presentation
Asymptomatic, early rise in serum creatinine (typically grade 1-2) with a stable or improved cystatin-C-based eGFR; urinalysis is bland with no proteinuria or active sediment. The discordance between rising creatinine and stable cystatin C is the diagnostic hallmark.
Management
Distinguish pseudo-AKI from true AKI using a cystatin-C-based eGFR or the creatinine trend; a bland urinalysis and stable cystatin C support continuing therapy at full dose. Reserve dose reduction or interruption for genuine GFR decline. Treat real prerenal contributors (volume, drugs) conventionally; refer for biopsy only if proteinuria, active sediment, or unexplained progressive decline suggest AIN/ATN.Lesion-level management framework
Risk factors
- Older age (>=65 years)
- Higher baseline creatinine/urea
- Volume depletion or concurrent nephrotoxins
- Concomitant CYP3A4 inhibitors raising drug exposure
Prevention
- Recognize transporter-mediated pseudo-AKI before stopping effective therapy
- Maintain euvolemia; review concomitant nephrotoxins and CYP3A4 interactions
Anticancer mechanism· how it treats cancer
Selectively inhibits cyclin-dependent kinases 4 and 6, blocking retinoblastoma protein (Rb) phosphorylation and arresting the cell cycle at the G1/S checkpoint. Combined with endocrine therapy for HR-positive, HER2-negative early-stage and advanced breast cancer.
Note · Generally renally well tolerated; the dominant 'renal' signal is an artefactual creatinine rise from OCT2/MATE inhibition rather than true nephrotoxicity.
§04
Clinical depth
Renal dose adjustment
No renal dose adjustment is specified for mild-to-moderate impairment; pharmacokinetic data in severe impairment/ESKD are limited. Do not dose-reduce for an isolated creatinine rise that is actually pseudo-AKI.
Dialyzability & ESKD dosing
Highly protein-bound, large volume of distribution, and hepatically (CYP3A4) metabolized; not meaningfully removed by hemodialysis. No HD-timed dosing established.
Differential diagnosis
Pseudo-AKI (stable cystatin C, bland urine) vs prerenal azotemia (volume signs, high BUN:Cr) vs true acute tubular injury or CDK4/6-associated AIN (proteinuria, pyuria, progressive decline). The single most useful test is a paired cystatin-C eGFR.
Monitoring
- Cystatin-C-based eGFR when creatinine rises >=0.3 mg/dL or >25% from baseline
- CBC with differential (primary dose-limiting toxicity is neutropenia)
Key trials & series
- PALOMA-2/PALOMA-3 (registrational efficacy)
- Buijs Br J Cancer 2025 pseudo-AKI cohort
- Ly J Oncol Pharm Pract 2024 class-effect pseudo-Scr analysis
Clinical pearls
- A creatinine bump in the first two cycles with a normal cystatin C is pseudo-AKI - do not stop an effective drug.
- Up to ~12% of patients have had palbociclib unjustly dose-reduced or stopped for what was only transporter inhibition.
- The effect mirrors trimethoprim and cobicistat - secretion blockade, not injury.
§05
References
6 primary references — trials, cohorts, mechanism, and reviews. Single-patient case reports are listed separately below, graded by strength. Citation metadata via PubMed / NLM.
Evidence accrual
6 references · 2020–2026 · 5 since 2024Primary (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.
- 1.LandmarkPseudo acute kidney injury in patients receiving CDK4/6 inhibitors.Buijs SM et al. · Br J Cancer · 2025 · PMID 39930149Cohort using cystatin C to show 73% of creatinine rises on CDK4/6 inhibitors are pseudo-AKI from blocked tubular secretion.
- 2.Renal adverse events associated with cyclin-dependent kinase 4/6 inhibitors.Izzedine H et al. · Cancer Treat Rev · 2025 · PMID 41385991Dedicated onconephrology review of CDK4/6-inhibitor renal effects: OCT2/MATE pseudo-AKI, rare true ATN/AIN, hypertension, and electrolyte changes.
- 3.Evaluation 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 39648753Shows pseudo-creatinine elevation is a class effect (palbociclib 16%, ribociclib 14%, abemaciclib 20%), nearly all grade 1-2.
- 4.Nephrotoxicity 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 41523909Retrospective cohort: ~23% had >=20% creatinine-clearance decline; older age and higher baseline urea/creatinine were risk factors.
- 5.Onconephrology: The intersections between the kidney and cancer.Rosner MH et al. · CA Cancer J Clin · 2020 · PMID 32853404Authoritative onconephrology review covering drug-induced renal effects and electrolyte disorders.
- 6.Onconephrology: mitigation of renal injury in chemotherapy administration.Selamet U et al. · Curr Opin Nephrol Hypertens · 2024 · PMID 38095483Reviews cell-cycle-inhibitor nephrotoxicity and strategies to mitigate chemotherapy-associated kidney injury.
Case reports — ranked by strength· 2
Single-patient and small-series reports, graded by evidentiary strength — A Strong (biopsy-proven plus a series and/or positive rechallenge), B Moderate, and C Limited (a single clinically-diagnosed case). Strongest first. Grades are inferred automatically from each report's abstract and journal — a heuristic ranking aid, not a formal quality appraisal.
CaseC · LimitedTargeted Cancer Therapies Causing Elevations in Serum Creatinine Through Tubular Secretion Inhibition: A Case Report and Review of the Literature.Mach T et al. · Can J Kidney Health Dis 2022 · PMID 35756332Palbociclib caused an asymptomatic, progressive rise in serum creatinine through inhibition of active tubular creatinine secretion (pseudo-AKI), with stable kidney function confirmed by cystatin C.CaseC · LimitedPalbociclib-Induced Thrombotic Microangiopathy in Metastatic Breast Cancer Patient Surviving for 18 Years: Case Report and Review of the Literature.Raiss H et al. · Clin Breast Cancer 2018 · PMID 29153774Reports palbociclib-induced thrombotic microangiopathy (anemia, thrombocytopenia, schistocytes) as a drug-related toxicity with potential renal microvascular involvement.
Conference abstracts & journal reports· 1 non-PubMed
Non-PubMed sources — conference abstracts (e.g. ASN Kidney Week, badged Abstract) and case reports from non-indexed field journals (e.g. Journal of Onco-Nephrology, badged Journal). Included for completeness; weigh below peer-reviewed PubMed citations.
FDA label — boxed warning & renal dosing· renal impairment
Quoted verbatim from this agent's current FDA label (Jul 2026) — not paraphrased or interpreted. Full label on DailyMed .
Renal impairment — from the label
No dose adjustment is required in patients with mild, moderate, or severe renal impairment (CrCl >15 mL/min). Based on a pharmacokinetic trial in subjects with varying degrees of renal function, the total palbociclib exposure (AUC INF ) increased by 39%, 42%, and 31% with mild (60 mL/min ≤ CrCl <90 mL/min), moderate (30 mL/min ≤ CrCl <60 mL/min), and severe (CrCl <30 mL/min) renal impairment, respectively, relative to subjects with normal renal function. Peak palbociclib exposure (C max ) increased by 17%, 12%, and 15% for mild, moderate, and severe renal impairment, respectively, relative to subjects with normal renal function. The pharmacokinetics of palbociclib have not been studied in patients requiring hemodialysis [see Clinical Pharmacology (12.3) ] .
What gets reported — FAERS
Everything below is FAERS — adverse events someone chose to report, about 94,825 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.
- 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 outcomes & reporting trend· 11.2% of reports w/ death · 15.1% w/ hospitalization
11.2%
Reported with a death outcome
10,577 of 94,825 reports
15.1%
Reported with hospitalization
14,349 of 94,825 reports
Reports per year
- 2015: 2,602 reports
- 2016: 5,940 reports
- 2017: 8,621 reports
- 2018: 9,067 reports
- 2019: 11,018 reports
- 2020: 12,868 reports
- 2021: 10,117 reports
- 2022: 12,585 reports
- 2023: 10,007 reports
- 2024: 6,069 reports
- 2025: 4,727 reports
- 2026: 1,183 reports
Yearly FAERS report volume · most recent year is partial.
FAERS adverse-event signal — all organ systems· 8 systems · 94,825 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 0.5195% CI 0.46–0.57· 355 AKI reports ·AKI is reported less often than for other drugs (CI entirely below 1) — no disproportionate signal.
General / constitutional
Fatigue15,729Asthenia3,797Pain3,483Malaise3,353
Blood & lymphatic
White Blood Cell Count Decreased11,437Neutropenia6,728Platelet Count Decreased2,308Neutrophil Count Decreased2,284Anaemia2,277
Gastrointestinal
Nausea8,548Diarrhoea5,984Vomiting3,161Stomatitis2,817Constipation2,790
Skin
Alopecia6,369Rash2,325
Respiratory
Dyspnoea3,293Cough2,331
Nervous system
Headache2,771Dizziness2,533
Metabolic & electrolyte
Decreased Appetite3,488
Musculoskeletal
Arthralgia3,100
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 Palbociclib 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.
Phenotype-similar agents· the numbered markers on the map above
Profile
Alectinib
Alecensa · ALK TKI
Creatinine rise via reduced tubular secretion.
PSEUDOPRE
Mild#2 · 73% phenotype match
Bosutinib
Bosulif · BCR-ABL TKI
Reversible eGFR decline.
PSEUDOPRE
Mild#3 · 73% phenotype match
Ceritinib
Zykadia · ALK TKI
GI-driven prerenal AKI.
PREPSEUDO
Mild#4 · 73% phenotype match
Selumetinib
Koselugo · MEK inhibitor
Creatinine rise in neurofibromatosis.
PRELYTE
Mild#5 · 73% phenotype match
Abemaciclib
Verzenio · CDK4/6 inhibitor
Benign creatinine rise via tubular secretion block.
PSEUDOPRE
Mild#6 · 73% phenotype match
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 CDK4/6 inhibitors
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.
- 1Palbociclib· this agentPSEUDO — Pseudo-AKIMild
- 2AbemaciclibPSEUDO — Pseudo-AKIFAERS AKIMild
- 3RibociclibPSEUDO — Pseudo-AKIFAERS AKIMild
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.