Is kidney injury from Lorlatinib reversible?

Reversible. Typical onset: Metabolic effects and edema appear within weeks of starting therapy..

How should kidney function be monitored during Lorlatinib therapy?

Fasting lipid panel at baseline, then periodically (triglycerides, cholesterol); Weight and edema assessment; Mood/cognition (CNS effects); Serum creatinine, interpreting benign, secretion-mediated rises.

How can kidney injury from Lorlatinib be prevented?

Baseline and on-treatment lipid monitoring; start statin/fibrate per thresholds

Who is at higher risk of kidney injury from Lorlatinib?

Pre-existing dyslipidemia or metabolic syndrome; Chronic kidney disease; Concurrent nephrotoxins.

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Printable monograph

ALK TKI

Lorlatinib

Lorbrena · LORL

ALK TKI · approved 2018 · 8 citations

Up to date· through 2025

Deeply sourced7/9 · 6 signals

Met: 8 citations
Not met: 12+ references
Met: Accrued over 10+ years (span: 10y)
Met: Beyond single case reports
Met: High-impact journal
Met: Landmark reference
Met: Current through 2025
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 third-generation ALK/ROS1 inhibitor whose renal relevance is tied to edema and prominent metabolic effects.

MildALK/ROS1 tyrosine kinase inhibitor

ALK-positive non-small-cell lung cancer

§01

Signature kidney injury

Signature lesion

Pseudo-AKI

Lorlatinib is characterized by prominent metabolic effects - hypercholesterolemia and hypertriglyceridemia occur in the majority of patients (the leading grade 3/4 toxicity in the CROWN trial) - plus peripheral edema. Direct renal toxicity is limited and, like other ALK inhibitors, creatinine elevations are generally mild and reversible. Renal effects are not well quantified specifically for lorlatinib.Source: Shaw et al., N Engl J Med 2020 (CROWN); Bonilla et al., Clin Kidney J 2022

Onset & rechallenge

Time to injurySubacute (~1–6 weeks)

Metabolic effects and edema appear within weeks of starting therapy.

Distilled from: “Metabolic effects and edema appear within weeks of starting therapy.”

§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.

Pseudo-AKI#1 · Signature10%PMID 40382267 (opens PubMed in a new tab)
Class-level: ~10% AKI by creatinine (KDIGO) within 90d across ALK-TKIs (incl. lorlatinib); largely reversible tubular-secretion effect on serum creatinine
Prerenal / Hemodynamic AKISecondaryqualitative — no citable incidence
Renal hypoperfusion from capillary leak and cytokine storm — IL-2 and CAR-T cytokine release syndrome.
Glomerular Injury / ProteinuriaRarequalitative — no citable incidence
Case-level dose-dependent proteinuria and biopsy-proven minimal change disease - distinct from the MATE-1 creatinine artifact.

Toxicity fingerprint

Tap a signature to trace where it strikes the nephron.

Incidence not quantified

SeverityMild

ReversibilityReversible

Evidence8 citations

Nephron map

Glomerulus

Vasculature / Endothelium

Proximal TubuleBulk reabsorption + drug uptake (OCT2, OATs)

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

Deep divePseudo-AKI: the creatinine rises and the kidney is fineCreatinine does not only filter — a fifth of it is pushed into the urine by tubular transporters, and a drug that blocks those transporters raises the number without touching the glomerulus, producing a rise that looks like acute kidney injury on every axis except the one that matters.

Mechanism of kidney injury

Kidney involvement is largely indirect: prominent edema and severe dyslipidemia reflect off-target metabolic effects, and any creatinine change is consistent with the ALK-inhibitor pattern of reduced tubular creatinine secretion rather than structural injury. Edema can reflect fluid shifts relevant to perfusion; marked hypertriglyceridemia rarely contributes to pancreatitis.

Clinical presentation

Peripheral edema, hypercholesterolemia/hypertriglyceridemia, weight change, and CNS/cognitive effects; mild creatinine elevations; overt AKI is uncommon.

Management

Manage dyslipidemia with lipid-lowering therapy (statins, and fibrates/omega-3 for severe hypertriglyceridemia) and edema with supportive measures and dose adjustment as needed. Renal function is generally preserved; reserve renal-directed dose changes for true AKI.Lesion-level management framework

Risk factors

Pre-existing dyslipidemia or metabolic syndrome
Chronic kidney disease
Concurrent nephrotoxins

Prevention

Baseline and on-treatment lipid monitoring; start statin/fibrate per thresholds

Anticancer mechanism· how it treats cancer

Third-generation, highly CNS-penetrant macrocyclic ALK/ROS1 inhibitor active against most resistance mutations including the compound G1202R/L1196M. Used in ALK-positive non-small-cell lung cancer, first-line and after prior ALK inhibitors.

Note · Edema and metabolic effects dominate; lorlatinib-specific renal data are limited and extrapolated from the ALK-inhibitor class.

§04

Clinical depth

Renal dose adjustment

No starting-dose change for mild-to-moderate renal impairment. For severe renal impairment (eGFR <30 mL/min not on dialysis), reduce the dose (e.g., from 100 mg to 75 mg once daily) per labeling. Avoid strong CYP3A inducers/inhibitors.

Dialyzability & ESKD dosing

Hepatically metabolized and protein-bound; not expected to be meaningfully dialyzed, and ESKD data are limited - monitor clinically.

Differential diagnosis

Separate benign secretion-mediated creatinine rise (cystatin C-based eGFR preserved) from true AKI; attribute edema and metabolic derangement to drug effect rather than renal failure.

Monitoring

Fasting lipid panel at baseline, then periodically (triglycerides, cholesterol)
Weight and edema assessment
Mood/cognition (CNS effects)
Serum creatinine, interpreting benign, secretion-mediated rises

Key trials & series

CROWN (phase 3 lorlatinib vs crizotinib, first-line; dyslipidemia the leading grade 3/4 AE)
Pinard et al. real-world ALK-inhibitor AKI/CKD cohort (includes lorlatinib)

Clinical pearls

Lorlatinib’s signature toxicities are metabolic (severe dyslipidemia) and edema - lipid management is central, the kidney usually spared.
Reduce the dose when eGFR <30; otherwise no renal adjustment.
An isolated creatinine bump is likely a transporter artifact, as with the ALK class.
Beyond the MATE-1 creatinine artifact, lorlatinib has genuine glomerular reports: dose-dependent proteinuria and biopsy-proven minimal change disease, proposed as a driver of its dyslipidemia.

Beyond the kidney — non-renal toxicities· 3 organ systems

Class-level context for the major non-renal toxicities of the ALK TKI class.

Ophthalmic

Keratopathy, uveitis, retinopathy

Visual disturbance (crizotinib)

Hepatic / Liver

Transaminitis, hepatitis, VOD/SOS

Transaminitis

Neurologic

Neuropathy, encephalopathy, ICANS, PRES

CNS effects (lorlatinib)

§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 · 2015–2025 · 2 since 2023

Primary (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.

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.

CaseB · ModerateA possible mechanism of hyperlipidemia in a patient with metastatic non-small cell lung cancer on lorlatinib therapy.McGee K et al. · J Oncol Pharm Pract 2021 · PMID 33789526Describes nephrotic-range proteinuria with biopsy-proven minimal change disease in a patient on lorlatinib, proposed as the cause of drug-induced hyperlipidemia.CaseC · LimitedLorlatinib induced proteinuria: A case report.Lee CS et al. · J Oncol Pharm Pract 2021 · PMID 32996364Reports dose-dependent proteinuria attributed to lorlatinib in a ROS1-rearranged NSCLC patient, improving with dose reduction.

FDA label — boxed warning & renal dosing· renal impairment

Quoted verbatim from this agent's current FDA label (Jun 2026) — not paraphrased or interpreted. Full label on DailyMed .

Renal impairment — from the label

In patients with CL cr 15 to <30 mL/min (estimated by Cockcroft‑Gault), the recommended dosage of LORBRENA is 75 mg orally once daily [see Dosage and Administration (2.6) and Clinical Pharmacology (12.3) ] . No dose adjustment is recommended for patients with CLcr 30 to 89 mL/min (estimated by Cockcroft‑Gault) [see Clinical Pharmacology (12.3) ] .

What gets reported — FAERS

Everything below is FAERS — adverse events someone chose to report, about 6,977 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.
Renal phenotypes — the same question asked separately for each kind of kidney injury, so the ratios differ from the overall one and from each other.
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 reported renal phenotypes· 3 signals

Only significant signals appear (95% CI lower bound above 1) — a phenotype missing here was tested and did not reach significance, except Prerenal / Hemodynamic AKI, Pseudo-AKI, Renal Cysts, Chronic Interstitial Nephropathy — outside the clinician-reviewed MedDRA term map, never queried — and ATN and AIN, queried but biopsy-bound: real cases are filed as generic “acute kidney injury”, so their absence is not a negative. As of 2026-10-01.

What reporting says about this profile's documented lesions

Glomerular Injury / Proteinuriacorroborated · ROR 5.1 — on the terms that name the lesion (ROR 8.94)
Pseudo-AKINot queried in FAERS — No MedDRA term set is defined for this phenotype, so FAERS was never asked about it.
Prerenal / Hemodynamic AKINot queried in FAERS — No MedDRA term set is defined for this phenotype, so FAERS was never asked about it.

Glomerular Injury / Proteinuria

ROR 5.1095% CI 3.85–6.75· 49 reports

Thrombotic Microangiopathy

ROR 2.1495% CI 1.18–3.86· 11 reports

Hypertension

ROR 1.7495% CI 1.52–1.99· 220 reports

FAERS outcomes & reporting trend· 26.8% of reports w/ death · 21.9% w/ hospitalization

26.8%

Reported with a death outcome

1,867 of 6,977 reports

21.9%

Reported with hospitalization

1,530 of 6,977 reports

Reports per year

Yearly FAERS report volume · most recent year is partial.

FAERS adverse-event signal — all organ systems· 8 systems · 6,977 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 0.4995% CI 0.33–0.73· 25 AKI reports ·AKI is reported less often than for other drugs (CI entirely below 1) — no disproportionate signal.

General / constitutional

Weight Increased399Oedema269Fatigue254Oedema Peripheral253Peripheral Swelling211

Psychiatric

Hallucination404Confusional State134

Nervous system

Neuropathy Peripheral195Cognitive Disorder187Headache148

Respiratory

Dyspnoea270Pleural Effusion184

Gastrointestinal

Diarrhoea175

Metabolic & electrolyte

Hyperlipidaemia175

Immune / infection

Pneumonia149

Musculoskeletal

Arthralgia137

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 Lorlatinib 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.

Position is a 2-D projection (MDS) of each agent's injury signature, nephron target, severity, and class, so two dots can sit close on the page while differing on an axis the projection flattened — the numbered ranking is computed from the full metric, not from the distance you see. Open the full map.

Phenotype-similar agents· the numbered markers on the map above

Alectinib

Alecensa · ALK TKI

Profile

Creatinine rise via reduced tubular secretion.

PSEUDOPRE

Mild#1 · 84% phenotype match

Ceritinib

Zykadia · ALK TKI

Profile

GI-driven prerenal AKI.

PREPSEUDO

Mild#2 · 84% phenotype match

Adagrasib

Krazati · KRAS G12C inhibitor

Profile

Creatinine rise; emerging data.

PREGLOMPSEUDO

Mild#3 · 81% phenotype match

Brigatinib

Alunbrig · ALK TKI

Profile

Creatinine elevation; usually benign.

PSEUDOPREHTN

Mild#4 · 76% phenotype match

Bosutinib

Bosulif · BCR-ABL TKI

Profile

Reversible eGFR decline.

PSEUDOPRE

Mild#5 · 73% phenotype match

Capmatinib

Tabrecta · MET inhibitor

Profile

Reversible creatinine rise and edema.

PSEUDOPRE

Mild#6 · 73% phenotype match

Compare Lorlatinib with its nearest agents

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 ALK / ROS1 / MET / TRK 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.

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.