Oxaliplatin

Thrombotic Microangiopathy.

Lowest nephrotoxic potential of the platinums; AKI is rare and case-level, in some cases immune-mediated.

Source: Gupta et al., Adv Chronic Kidney Dis 2021

Reported injury signatures: Thrombotic Microangiopathy, Acute Tubular Necrosis.

1. Thrombotic MicroangiopathyPrimaryRare, characteristic complication (drug-induced TMA/HUS with microangiopathic hemolytic anemia, thrombocytopenia, acute renal failure); reported in case reports, no population incidence denominator
2. Acute Tubular NecrosisSecondaryCase-level only; ATN listed among recognized oxaliplatin nephrotoxicity forms (also tubular vacuolization, RTA, interstitial nephritis); no population incidence figure

Acute (~1–7 days) — Acute when immune-mediated, characteristically on re-challenge rather than first exposure.

Rechallenge: Contraindicated — Re-exposure after a documented immune hemolytic or TMA event is avoided — reactions recur faster and more severely.

• Repeated exposure (immune reactions)
• Pre-existing CKD

• No re-challenge after a documented immune hemolytic or TMA event — reactions recur faster and more severely

• Check serum creatinine/eGFR before each cycle; oxaliplatin AKI is uncommon, so a rise should prompt a search for an alternative cause (volume depletion, obstruction, contrast, concurrent nephrotoxins).
• On re-exposure or near infusion, monitor CBC and hemoglobin for an abrupt drop plus haptoglobin, LDH, and direct antiglobulin (Coombs) test if immune hemolysis is suspected.
• If hemolysis/thrombocytopenia appears, send a peripheral smear for schistocytes to detect drug-induced TMA and stop oxaliplatin immediately.
• Document and watch for infusion-reaction symptoms (back pain, hemoglobinuria, hypotension), which can herald acute immune hemolysis with pigment-related AKI.
• Track urine output and consider urinalysis for hemoglobinuria during/after infusion in patients with prior reactions.

• MOSAIC (Andre et al., NEJM 2004) - registrational adjuvant FOLFOX trial that established oxaliplatin's standard 85 mg/m2 regimen; notable for the absence of meaningful nephrotoxicity versus cisplatin-era platinums.
• NCI Organ Dysfunction Working Group PK study (Takimoto et al., J Clin Oncol 2003) - showed unbound oxaliplatin platinum clearance falls with declining renal function yet was tolerated without added toxicity across CrCl strata, supporting limited dose adjustment in mild-moderate impairment.

• Oxaliplatin is markedly less nephrotoxic than cisplatin - it does not require forced saline diuresis and rarely causes classic dose-dependent ATN, so a significant creatinine rise should raise suspicion for an immune or hemolytic mechanism.
• The signature severe renal event is immune-mediated: drug-dependent antibodies trigger acute intravascular hemolysis and occasionally TMA, typically after multiple prior exposures rather than on first dose.
• Pigment (hemoglobin) nephropathy from acute hemolysis, not direct tubular toxicity, is a key route to AKI with oxaliplatin.
• Rechallenge after a documented immune hemolytic or TMA event is contraindicated - reactions recur faster and more severely.
• Because platinum binds plasma proteins and red cells, total platinum persists for months; this complicates interpretation of levels and limits the utility of dialysis for clearance.

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) — Conventional cytotoxic chemotherapy-associated nephrotoxicity: consensus report of the 34th Acute Disease Quality Initiative (ADQI) WorkgroupCisplatin is identified as a leading cytotoxic nephrotoxin; the workgroup details preventive measures (adequate isotonic hydration, correction of volume depletion, avoidance of concurrent nephrotoxins, attention to electrolyte/magnesium wasting) and management of cisplatin-associated AKI, with a research agenda for knowledge gaps.Kidney Int · PMID 41881107
• Expert Consensus (2022) — The Prevention of Cisplatin-Induced Nephrotoxicity: A General Consensus Statement of a Group of Oncologist-Hematologists, Adult and Pediatric Nephrologists, Radiation Oncologists, Clinical Pathologists, Clinical Pharmacologists, and Renal Physiologists on Cisplatin Therapy in Cancer PatientsConsensus on modifiable factors for cisplatin nephrotoxicity prevention, addressing hydration methods, magnesium supplementation, dextrose, avoidance of NSAIDs and renin-angiotensin system inhibitors and contrast agents around cisplatin, GFR assessment, antioxidants, and patient factors (age, sex, female hormones).Int J Prev Med · PMID 35392316
• 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