BRAF / MEK Inhibitors

Acute Tubular Necrosis — representative incidence ~21%.

Pharmacovigilance shows vemurafenib > dabrafenib. Mild creatinine elevation common, serious AKI uncommon. Reported rate: acute kidney injury in 21% — 199 patients who received dabrafenib/trametinib in a single large US healthcare system between 2010 and 2019… (Seethapathy 2022, PMID 33355659).

Source: Seethapathy et al., Nephrol Dial Transplant 2022

Reported injury signatures: Acute Tubular Necrosis, Acute Interstitial Nephritis, Electrolyte Disturbance, Pseudo-AKI, Fanconi Syndrome.

1. Acute Tubular NecrosisPrimaryTubular/tubulointerstitial injury is the documented mode of BRAF-inhibitor AKI; FAERS captured 132 vemurafenib and 13 dabrafenib acute kidney injury reports (2011-2014), with vemurafenib apparently more nephrotoxic and injury more common in men.
2. Electrolyte DisturbanceSecondaryHyponatremia (8 vemurafenib, 6 dabrafenib) and hypokalemia (6 and 2) accompanied the AKI reports in the FAERS analysis; electrolyte monitoring is advised with these agents.
3. Acute Interstitial NephritisRare
4. Pseudo-AKIRare
5. Fanconi SyndromeRare

Acute (~1–7 days) — Acute-to-subacute creatinine rise during therapy.

• Vemurafenib (vs dabrafenib)
• Volume depletion
• Concurrent nephrotoxins

• Rehydrate and treat drug-induced pyrexia early (especially on dabrafenib + trametinib) — febrile dehydration is the dominant route to AKI in this class
• Replete phosphate, potassium and magnesium for the vemurafenib Fanconi-type proximal tubular pattern

• Baseline and serial creatinine/eGFR — vemurafenib in particular causes a reversible creatinine rise (partly tubular-secretion blockade, partly true AKI), so trend it rather than react to a single value.
• Basic metabolic panel for electrolytes — watch for hypophosphatemia/hypokalemia and a Fanconi-type proximal tubular pattern reported with vemurafenib; check magnesium given concurrent GI losses.
• During any drug-induced pyrexia (especially dabrafenib/trametinib), check renal function and volume status promptly — febrile dehydration is the dominant route to prerenal AKI/ATN in this class.
• Reassess creatinine after holding/resuming or down-titrating for febrile or GI toxicity; most creatinine elevations recover, supporting the reversible class profile.
• If a MEK inhibitor causes peripheral edema/fluid retention, distinguish hemodynamic creatinine shifts from structural injury before attributing AKI to the drug.

• BRIM-3 — registrational phase 3 of single-agent vemurafenib vs dacarbazine in BRAF V600E melanoma; established the BRAF inhibitor against which the class's pyrexia/photosensitivity and creatinine-rise signal was first characterized.
• coBRIM — vemurafenib plus the MEK inhibitor cobimetinib vs vemurafenib alone; the combination context in which renal/electrolyte and edema toxicities of dual blockade were reported.
• COMBI-d / COMBI-v — phase 3 trials of dabrafenib plus trametinib (vs placebo and vs vemurafenib); defined the D+T combination whose hallmark drug-induced pyrexia is the principal driver of prerenal AKI in this class.

• Drug-induced pyrexia is the signature toxicity of dabrafenib + trametinib and is the main mechanism of AKI in this class — the kidney injury is usually febrile prerenal/ATN, reversible with antipyretics, drug hold, and rehydration.
• A Fanconi-like proximal tubulopathy (hypophosphatemia, hypokalemia, glycosuria) has been described with vemurafenib — check electrolytes, not just creatinine.
• MEK inhibitors (trametinib, cobimetinib, binimetinib) have minimal intrinsic nephrotoxicity; their renal-relevant effects are peripheral edema/fluid retention and rare CK-elevation/rhabdomyolysis, so a creatinine change usually reflects hemodynamics rather than structural damage.
• Overall the class signal is mild and reversible — most AKI is hemodynamic and recovers with supportive care and a drug hold; structural irreversible nephrotoxicity is not a defining feature.

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