Bosutinib
Bosulif · BCR-ABL TKI
Reversible eGFR decline.
PSEUDOPRE
MildOpen →
ALK TKI
Ceritinib
Zykadia · CERI
An ALK inhibitor whose substantial GI toxicity can drive prerenal acute kidney injury through volume depletion.
MildALK tyrosine kinase inhibitor · approved 2014
ALK-positive non-small-cell lung cancer
Signature kidney injury
Pseudo-AKI
Ceritinib causes frequent gastrointestinal toxicity (nausea, vomiting, diarrhea in the majority of patients), which can lead to volume depletion and prerenal AKI; as an ALK inhibitor it can also produce generally mild, reversible creatinine elevations. The prerenal AKI risk is largely a downstream effect of GI losses and is not precisely quantified.
Source: Bonilla et al., Clin Kidney J 2022; Pinard et al., Clin Lung Cancer 2025
Mechanism of kidney injury
The dominant renal mechanism is prerenal: GI fluid losses cause hypovolemia and reduced renal perfusion. Like other ALK inhibitors, ceritinib may also raise serum creatinine through reduced tubular secretion (a pseudo-AKI artifact). Structural intrinsic injury is uncommon.
Clinical presentation
Volume depletion with rising creatinine, low urine output, and a prerenal urine profile (high urine osmolality, low FeNa) in the setting of significant nausea, vomiting, or diarrhea; mild creatinine elevations otherwise. Hepatotoxicity and hyperglycemia are additional class effects.
Onset
Prerenal AKI can occur whenever GI toxicity causes significant fluid loss, often early in therapy.
Reversibility
Reversible
Anticancer mechanism
Potent ALK tyrosine kinase inhibitor (also targeting IGF-1R and ROS1) used in ALK-positive non-small-cell lung cancer, including after crizotinib.
Management
Treat GI toxicity and restore volume with fluids; prerenal AKI typically reverses with rehydration. Dose-reduce or interrupt for severe or persistent toxicity, and correct electrolyte disturbances. Distinguish true volume-depletion AKI from a secretion-mediated creatinine artifact.
Risk factors
- Severe GI toxicity (vomiting/diarrhea)
- Inadequate oral intake / dehydration
- Diuretic use and pre-existing CKD
- Older age
Prevention
- Aggressive antiemetic and antidiarrheal management
- Maintain hydration and monitor volume status
- Take with food per current labeling to mitigate GI effects; monitor creatinine
Note · Renal injury is mainly GI-driven and prerenal; correcting volume status is the key intervention.
Clinical depth
Renal dose adjustment
No starting-dose change for mild-to-moderate renal impairment (negligible renal excretion); severe-impairment/ESKD data are limited, so use clinical monitoring. The practical 'renal' adjustment is interruption/reduction when GI toxicity threatens volume status. Hepatic impairment requires dose reduction.
Dialyzability & ESKD dosing
Highly protein-bound (~97%) and hepatically metabolized; not expected to be dialyzed and no supplemental dosing established.
Differential diagnosis
Distinguish GI-driven prerenal AKI (volume responsive, prerenal indices) from the ALK-class secretion artifact (cystatin C-based eGFR preserved) and from intrinsic injury (uncommon).
Monitoring
- Serum creatinine and volume status, especially during GI toxicity
- Electrolytes
- Liver enzymes and fasting glucose (class effects)
Key trials & series
- Bonilla et al. ALK-inhibitor renal review (class context)
- Pinard et al. real-world ALK-inhibitor AKI/CKD cohort (includes ceritinib)
Clinical pearls
- Ceritinib’s renal risk is mostly its GI toxicity - manage nausea/diarrhea and hydration to prevent prerenal AKI.
- Taking ceritinib with food (current guidance) reduces GI toxicity and the associated volume losses.
- Confirm whether a creatinine rise is true volume depletion or a tubular-secretion artifact before changing dose.
Where it strikes
Nephron segments
Vasculature / Endothelium
Glomerular & peritubular capillaries
Proximal Tubule
Bulk reabsorption + drug uptake (OCT2, OATs)
Injury signatures
Pseudo-AKIPrerenal / Hemodynamic AKI
Beyond the kidney
Class-level context for the major non-renal toxicities of alk tkis.
Ophthalmic
Keratopathy, uveitis, retinopathy
- Visual disturbance (crizotinib)
Hepatic / Liver
Transaminitis, hepatitis, VOD/SOS
- Transaminitis
Neurologic
Neuropathy, encephalopathy, ICANS, PRES
- CNS effects (lorlatinib)
Evidence
6 peer-reviewed references. Citation metadata via PubMed / NLM.
LandmarkAnaplastic lymphoma kinase inhibitors and their effect on the kidney.Bonilla M et al. · Clin Kidney J 2022 · PMID 35892021ALK-inhibitor renal review providing class context including ceritinib.PMIDThe renal effects of ALK inhibitors.Izzedine H et al. · Invest New Drugs 2016 · PMID 27468827Class review of ALK-inhibitor (crizotinib, ceritinib, alectinib) renal effects.PMIDReal-World Creatinine-Based Estimates of Acute and Chronic Kidney Dysfunction in Patients with Advanced ALK-Rearranged Non-Small-Cell Lung Cancer Receiving Tyrosine Kinase Inhibitors.Pinard L et al. · Clin Lung Cancer 2025 · PMID 40382267Real-world cohort including ceritinib: mostly mild, reversible creatinine-based renal changes.PMIDNew drug toxicities in the onco-nephrology world.Perazella MA et al. · Kidney Int 2015 · PMID 25671763Onco-nephrology class context for targeted-agent renal effects.PMIDPharmacological nephrotoxicity profile in a comprehensive cancer center: What changed in two decades and predictors for the need for haemodialysis and mortality.Ferreira A et al. · Nefrologia (Engl Ed) 2025 · PMID 40783302Cancer-center AKI series reflecting the growing role of TKIs in drug-induced AKI.PMIDOnconephrology: mitigation of renal injury in chemotherapy administration.Selamet U et al. · Curr Opin Nephrol Hypertens 2024 · PMID 38095483Onconephrology review framing monitoring and mitigation of ceritinib/GI-driven renal change.