Vimseltinib

Pseudo-AKI.

No clinically significant direct nephrotoxicity was identified in the pivotal MOTION phase 3 trial. There is no recognized signature renal lesion (no ATN, AIN, TMA, or glomerular injury attributable to the drug). The kidney-relevant practical issue is interpretive: the dominant laboratory abnormality is treatment-emergent creatine phosphokinase (CPK) elevation — grade 3/4 in 8/83 (10%) of vimseltinib patients in MOTION — together with peripheral/periorbital edema, either of which can perturb serum creatinine or muscle-derived markers without true GFR loss. Renal-specific events were not reported as a notable safety signal.

Source: MOTION phase 3 (Gelderblom et al., Lancet 2024; PMID 38843860): the only grade 3/4 TEAE occurring in >5% of vimseltinib patients was increased blood CPK (10%); no clinically significant direct nephrotoxicity reported.

Reported injury signatures: Pseudo-AKI, Prerenal / Hemodynamic AKI.

1. Pseudo-AKIPrimaryIn the phase 3 MOTION trial (n=83) the predominant grade 3/4 laboratory abnormality was increased blood creatine phosphokinase (10%); CSF1R inhibition characteristically produces asymptomatic creatinine/muscle-enzyme elevations (pseudo-AKI) rather than true GFR loss or structural injury.
2. Prerenal / Hemodynamic AKIRare

Subacute (~1–6 weeks) — CPK elevations, edema, and any linked creatinine change emerge early, typically within the first 1-2 twenty-eight-day cycles (through ~day 56).

• Baseline volume depletion or concurrent diuretics/RAAS blockade (amplifies any prerenal creatinine rise)
• Pre-existing CKD limiting renal reserve
• High baseline muscle mass or strenuous activity (confounds CPK interpretation)
• Concomitant nephrotoxins or contrast that could unmask hemodynamic susceptibility
• Significant peripheral edema with intravascular volume contraction

• Establish baseline serum creatinine, electrolytes, and CPK before starting
• Do not reflexively discontinue for isolated asymptomatic CPK elevation — follow per-label monitoring and dose-modification guidance

• CPK at baseline and during treatment (dominant lab signal; per-label monitoring)
• Volume/edema assessment at each visit
• Urinalysis if creatinine rises, to confirm bland sediment / exclude proteinuria or active sediment
• LFTs per label (hepatic, not renal, is the principal organ of concern for the CSF1R class)

• MOTION (NCT05059262) — phase 3, double-blind, placebo-controlled; ORR 40% vs 0%; grade 3/4 CPK elevation in 10%, no significant direct nephrotoxicity (PMID 38843860)
• MOTION protocol/design paper (PMID 37593881)
• Pexidartinib long-term pooled analysis — class read-across showing hepatic, not renal, organ risk (PMID 33197285)

• Vimseltinib is essentially a kidney-sparing targeted agent — there is no signature renal lesion; the practical onconephrology task is interpreting creatinine in the setting of CPK elevation and edema, not managing drug-induced AKI.
• The headline lab abnormality is CPK elevation (grade 3/4 ~10% in MOTION), which is a CSF1R-class effect and usually asymptomatic — do not mistake it for rhabdomyolysis-driven AKI without supporting urine myoglobin/creatinine evidence.
• For the CSF1R inhibitor class (vimseltinib, pexidartinib), the organ to watch is the liver, not the kidney — pexidartinib carries a hepatotoxicity boxed warning, while vimseltinib in MOTION showed no cholestatic hepatotoxicity or drug-induced liver injury.

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