Bosutinib
Bosulif · BCR-ABL TKI
Reversible eGFR decline.
PSEUDOPRE
MildOpen →
ALK TKI
Brigatinib
Alunbrig · BRIG
A next-generation ALK inhibitor with usually benign creatinine elevations as its main renal footprint.
MildALK tyrosine kinase inhibitor · approved 2017
ALK-positive non-small-cell lung cancer
Signature kidney injury
Pseudo-AKI
As an ALK inhibitor, brigatinib is associated with creatinine elevations that are generally benign. In a real-world ALK-inhibitor cohort, creatinine-based AKI/CKD events occurred but were mostly mild and reversible across agents including brigatinib; class reviews note elevated creatinine, occasional edema, and rare electrolyte disturbances. A distinct, early-onset pulmonary event (within the first week) is a separate non-renal class concern.
Source: Pinard et al., Clin Lung Cancer 2025
Mechanism of kidney injury
Creatinine elevation is thought to reflect, at least in part, reduced tubular creatinine secretion (transporter inhibition) rather than true GFR loss, consistent with the ALK-inhibitor class. Peripheral edema and rare electrolyte disorders may occur; structural nephrotoxicity is uncommon.
Clinical presentation
Asymptomatic creatinine rise with reduced creatinine-based eGFR; occasional edema or mild electrolyte abnormalities; overt AKI is uncommon. Watch for early pulmonary symptoms (non-renal) in the first days of therapy.
Onset
Creatinine changes typically emerge within weeks and tend to reverse on discontinuation.
Reversibility
Reversible
Anticancer mechanism
Potent next-generation ALK tyrosine kinase inhibitor with activity against many resistance mutations and CNS disease; also inhibits ROS1 and EGFR variants. Used in ALK-positive non-small-cell lung cancer.
Management
Most creatinine elevations are benign and need no specific therapy; reserve dose adjustment for true AKI. Manage edema and electrolytes supportively.
Risk factors
- Pre-existing chronic kidney disease
- Hypertension
- Concurrent nephrotoxins
Prevention
- Monitor creatinine and electrolytes
- Recognize secretion-mediated creatinine rises and consider cystatin C if true GFR is in question
- Use the recommended step-up dosing to mitigate early pulmonary events
Note · Creatinine elevation is usually benign; renal data are partly extrapolated from ALK-inhibitor class experience.
Clinical depth
Renal dose adjustment
Reduce the dose for severe renal impairment (eGFR <30 mL/min/1.73 m2) - e.g., decrease the maintenance dose by ~50% per labeling. No adjustment is needed for mild-to-moderate impairment. Hepatic impairment also warrants reduction.
Dialyzability & ESKD dosing
Highly protein-bound (~91%) and hepatically metabolized; not expected to be meaningfully dialyzed. ESKD data are limited - monitor clinically.
Differential diagnosis
As with other ALK inhibitors, distinguish pseudo-AKI (creatinine up, cystatin C-based eGFR preserved) from true AKI; reserve workup and dose change for genuine GFR loss.
Monitoring
- Serum creatinine periodically (interpret with secretion artifact)
- Electrolytes and CK/lipase per labeling
- Pulmonary symptoms early in therapy
Key trials & series
- Pinard et al. real-world ALK-inhibitor AKI/CKD cohort (includes brigatinib)
Clinical pearls
- Brigatinib creatinine rises are usually benign secretion artifacts - confirm with cystatin C before acting.
- Reduce the dose when eGFR <30; mild-to-moderate impairment needs no change.
- The early pulmonary event in the first week is the more clinically urgent class concern, not the kidney.
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.
LandmarkReal-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 brigatinib: mostly mild, reversible creatinine-based renal changes.PMIDAnaplastic lymphoma kinase inhibitors and their effect on the kidney.Bonilla M et al. · Clin Kidney J 2022 · PMID 35892021ALK-inhibitor renal review covering creatinine rise, edema, and electrolyte effects.PMIDThe renal effects of ALK inhibitors.Izzedine H et al. · Invest New Drugs 2016 · PMID 27468827Class review of ALK-inhibitor renal adverse effects.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 TKI-associated renal change.