Bosutinib
Bosulif · BCR-ABL TKI
Reversible eGFR decline.
PSEUDOPRE
MildOpen →
ALK TKI
Alectinib
Alecensa · ALEC
A potent ALK inhibitor where creatinine rises largely reflect reduced tubular secretion rather than true kidney injury.
MildALK tyrosine kinase inhibitor · approved 2015
ALK-positive non-small-cell lung cancer
Signature kidney injury
Pseudo-AKI
Alectinib is associated with creatinine elevations that are usually benign. In a real-world ALK-inhibitor cohort, alectinib was the most-used agent (91 of 191 treatments) and creatinine-based AKI/CKD events were frequent (10% AKI within 90 days, 14% CKD at 1 year) but mostly mild and reversible, with few treatment changes attributed to AKI and none requiring dialysis.
Source: Pinard et al., Clin Lung Cancer 2025
Mechanism of kidney injury
The creatinine rise is attributed largely to inhibition of renal tubular creatinine secretion (mediated by transporters such as MATE1/OCT2), so creatinine-based eGFR falls without a corresponding true decline in measured/cystatin C-based GFR. Edema and, rarely, electrolyte disturbances can occur; structural nephrotoxicity is uncommon.
Clinical presentation
Asymptomatic creatinine elevation with reduced creatinine-based eGFR; peripheral edema; cystatin C-based eGFR is typically discordant (higher) than creatinine-based eGFR, confirming preserved true filtration.
Onset
Creatinine rise within weeks of starting therapy (mean eGFR declines over the first 90 days); reverses after discontinuation.
Reversibility
Reversible
Anticancer mechanism
Selective, CNS-penetrant ALK tyrosine kinase inhibitor with activity against several crizotinib-resistant mutations. Preferred first-line therapy for ALK-positive non-small-cell lung cancer.
Management
Most creatinine elevations require no intervention and reverse on discontinuation; continue therapy when the change reflects reduced tubular secretion (the CROWN/ALEX-era data support this). Investigate and dose-adjust only for true AKI, and manage edema supportively.
Risk factors
- Pre-existing chronic kidney disease
- Hypertension and male sex (associated with AKI in ALK-inhibitor cohorts)
- Concurrent nephrotoxins
Prevention
- Monitor creatinine and recognize secretion-mediated rises
- Consider cystatin C-based eGFR to assess true renal function
- Avoid unnecessary dose changes for isolated benign creatinine rises
Note · Apparent renal dysfunction is frequently a tubular-secretion artifact; true structural injury is uncommon.
Clinical depth
Renal dose adjustment
No starting-dose change for mild-to-moderate renal impairment; data in severe impairment/ESKD are limited (alectinib is hepatically metabolized with <1% renal excretion), so no PK-based renal adjustment is mandated. Hepatic impairment requires dose reduction.
Dialyzability & ESKD dosing
Highly protein-bound (>99%) and hepatically cleared; not dialyzable and no supplemental dosing expected in ESKD.
Differential diagnosis
The key distinction is pseudo-AKI (creatinine up, cystatin C-based eGFR stable) versus true AKI. Discordant creatinine/cystatin C confirms a transporter artifact rather than nephron injury.
Monitoring
- Serum creatinine periodically (interpret with secretion artifact)
- Cystatin C-based eGFR when true GFR matters (dosing of co-medications, trial eligibility)
- Edema and weight
- Liver enzymes, CK (myalgia), bilirubin
Key trials & series
- ALEX (phase 3 alectinib vs crizotinib, first-line ALK-positive NSCLC)
- Pinard et al. real-world ALK-inhibitor AKI/CKD cohort (alectinib-predominant)
Clinical pearls
- An isolated creatinine rise on alectinib is usually a tubular-secretion artifact - check cystatin C before changing therapy.
- True structural injury is uncommon; most patients can continue alectinib despite the eGFR dip.
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 alectinib-predominant cohort: frequent but mild, reversible creatinine-based AKI/CKD, none needing dialysis.PMIDAlectinib versus Crizotinib in Untreated ALK-Positive Non-Small-Cell Lung Cancer.Peters S et al. · N Engl J Med 2017 · PMID 28586279ALEX registrational trial establishing first-line alectinib; the safety dataset underlying its renal profile.PMIDAnaplastic lymphoma kinase inhibitors and their effect on the kidney.Bonilla M et al. · Clin Kidney J 2022 · PMID 35892021Reviews ALK-inhibitor renal effects including creatinine rise and edema.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 (including ALK-inhibitor) renal effects and pseudo-AKI.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.