ALK TKI
Alectinib
Alecensa · ALEC
ALK TKI · approved 2015 · 6 references
A potent ALK inhibitor where creatinine rises largely reflect reduced tubular secretion rather than true kidney injury.
- Signature injury
- Pseudo-AKI
- Severity
- Mild
- Reversibility
- Reversible
- Onset
- Creatinine rise within weeks of starting therapy (mean eGFR declines over the first 90 days); reverses after discontinuation.
Signature kidney injury & incidence
Pseudo-AKI.
Alectinib is associated with creatinine elevations that are usually benign. In a real-world five-agent ALK-inhibitor cohort (114 patients, 191 treatments; alectinib the most-used at 91), creatinine-based AKI/CKD events were frequent — 10% AKI within 90 days and 14% CKD at 1 year across the cohort, with no alectinib-specific rate reported — but mostly mild and reversible, with few treatment changes attributed to AKI and none requiring dialysis.
Source: Pinard et al., Clin Lung Cancer 2025
Reported injury signatures: Pseudo-AKI, Prerenal / Hemodynamic AKI.
Renal toxicity profile
- Pseudo-AKIPrimary~10%AKI by creatinine (KDIGO) within 90d in ~10% of ALK-TKI-treated NSCLC; mean eGFR dips then recovers off-drug — largely reduced tubular creatinine secretion, not true injury
- Prerenal / Hemodynamic AKIRareTrue intrinsic AKI (biopsy-proven ATN/AIN, anuric AKI needing dialysis) reported in <1% — case-level
Onset timing & rechallenge
Subacute (~1–6 weeks) — Creatinine rises within weeks of starting, with mean eGFR declining over the first 90 days and reversing after discontinuation.
Mechanism of kidney injury
Clinical presentation
Management
Risk factors
- Pre-existing chronic kidney disease
- Hypertension and male sex (associated with AKI in ALK-inhibitor cohorts)
- Concurrent nephrotoxins
Prevention
- Avoid unnecessary dose changes for isolated benign creatinine rises
Renal dose adjustment
Dialyzability & ESKD dosing
Differential diagnosis
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.
Anticancer mechanism
Note
Guidelines & consensus
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.
- ADQI (2026) — The nephrotoxic effects of anti-cancer therapies: consensus report of the 34th Acute Disease Quality Initiative workgroupProvides 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.Nat Rev Nephrol · PMID 41361704
- SIRM (2022) — SIRM-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)Recommends 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.Radiol Med · PMID 35303246
- KDIGO (2020) — KDIGO Controversies Conference on onco-nephrology: understanding kidney impairment and solid-organ malignancies, and managing kidney cancerIdentifies 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.Kidney Int · PMID 33126977
- KDIGO (2020) — KDIGO Controversies Conference on onco-nephrology: kidney disease in hematological malignancies and the burden of cancer after kidney transplantationAddresses 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.Kidney Int · PMID 33276867
- ADDIKD (2025) — Integrating International Consensus Guidelines for Anticancer Drug Dosing in Kidney Dysfunction (ADDIKD) into everyday practiceProvides 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.EClinicalMedicine · PMID 40290844
- ADDIKD (2025) — Aligning kidney function assessment in patients with cancer to global practices in internal medicineThree 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.EClinicalMedicine · PMID 40290845
- ADDIKD (2025) — A methodology for determining dosing recommendations for anticancer drugs in patients with reduced kidney functionEstablishes 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.EClinicalMedicine · PMID 40290846
- KDIGO (2013) — Diagnosis, evaluation, and management of acute kidney injury: a KDIGO summary (Part 1)Defines/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.Crit Care · PMID 23394211
- KDIGO (2024) — Executive summary of the KDIGO 2024 Clinical Practice Guideline for the Evaluation and Management of Chronic Kidney Disease: known knowns and known unknownsEvaluate 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.Kidney Int · PMID 38519239
- KDIGO (2021) — Executive summary of the KDIGO 2021 Guideline for the Management of Glomerular DiseasesProvides 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.Kidney Int · PMID 34556300
- KDIGO (2024) — Executive summary of the KDIGO 2024 Clinical Practice Guideline for the Management of ANCA-Associated VasculitisUpdates 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.Kidney Int · PMID 38388147
- KDIGO (2024) — Executive summary of the KDIGO 2024 Clinical Practice Guideline for the Management of Lupus NephritisUpdates 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.Kidney Int · PMID 38182299
- KDIGO (2025) — Executive summary of the KDIGO 2025 Clinical Practice Guideline for the Management of Immunoglobulin A Nephropathy (IgAN) and Immunoglobulin A Vasculitis (IgAV)Encourages 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.Kidney Int · PMID 40975525
References
6 peer-reviewed references. Citation metadata via PubMed / NLM.
- 1.Real-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 40382267
- 2.Alectinib versus Crizotinib in Untreated ALK-Positive Non-Small-Cell Lung Cancer.Peters S et al. · N Engl J Med · 2017 · PMID 28586279
- 3.Anaplastic lymphoma kinase inhibitors and their effect on the kidney.Bonilla M et al. · Clin Kidney J · 2022 · PMID 35892021
- 4.The renal effects of ALK inhibitors.Izzedine H et al. · Invest New Drugs · 2016 · PMID 27468827
- 5.New drug toxicities in the onco-nephrology world.Perazella MA et al. · Kidney Int · 2015 · PMID 25671763
- 6.Pharmacological 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 40783302
Case reports & series (3)
The weakest rung of clinical evidence — single-patient and small-series reports, strongest first. Each carries a heuristic strength grade (A Strong / B Moderate / C Limited) inferred from its abstract and journal, not a formal appraisal. Weigh well below the primary references above.
- C1.[B · Moderate]Alectinib - induced acute renal failure.Prado-Mel E et al. · J Oncol Pharm Pract · 2026 · PMID 37021408
- C2.[B · Moderate]Acute kidney injury and long-term renal effects of alectinib in anaplastic lymphoma kinase-positive non-small cell lung carcinoma: a case report.van Londen M et al. · J Med Case Rep · 2022 · PMID 36176005
- C3.[C · Limited]Unraveling the unforeseen: anuric acute kidney injury induced by alectinib.Tran VN et al. · Hosp Pract (1995) · 2025 · PMID 39977274