Mitomycin C

Thrombotic Microangiopathy — representative incidence ~10% (4–15% range across studies).

Dose-dependent, generally 4–15%; nearly every case in the landmark 85-patient registry had received a cumulative total dose above 60 mg. >50% historical mortality.

Source: Lesesne et al., J Clin Oncol 1989

Reported injury signatures: Thrombotic Microangiopathy, Glomerular Injury / Proteinuria, Hemorrhagic Cystitis.

1. Thrombotic MicroangiopathyPrimary~10%Mitomycin-associated (cancer-associated) HUS/TMA occurs in roughly 4-15% of treated patients; risk is cumulative-dose related, most cases after total dose >60 mg.
2. Glomerular Injury / ProteinuriaSecondary
3. Hemorrhagic CystitisRareIntravesical instillation only - direct chemical urothelial injury, not a systemic-route toxicity.

Delayed (>6 weeks / cumulative) — TMA appears after cumulative dosing, sometimes only after therapy has ended.

• Cumulative dose >60 mg total
• Concurrent 5-fluorouracil

• Cumulative-dose limits

• Track cumulative lifetime mitomycin dose — nearly every case in the landmark C-HUS registry had passed a 60 mg total cumulative dose.
• Before each cycle and during follow-up, check CBC with peripheral smear for schistocytes, platelet count, LDH, haptoglobin, and serum creatinine to detect early microangiopathic hemolysis.
• Monitor for new or worsening hypertension and proteinuria, which often accompany or herald mitomycin TMA.
• Continue surveillance after treatment ends — TMA characteristically presents weeks to months after the last dose, not only during active therapy.
• If MAHA, thrombocytopenia, and rising creatinine co-occur, stop mitomycin immediately and send ADAMTS13 to exclude TTP before attributing the picture to the drug.

• Lesesne et al. (J Clin Oncol 1989) — landmark cancer-associated HUS series that established mitomycin as a leading cause of chemotherapy-induced TMA and documented its dose dependence and high mortality.
• Cantrell et al. (Cancer 1985) — early systematic report characterizing mitomycin-induced microangiopathic hemolytic anemia with renal failure as a distinct, frequently fatal syndrome.
• Contemporary case reports/series of mitomycin-associated TMA treated with eculizumab — describe complement-pathway involvement and renal recovery in selected patients, informing modern off-label management.

• Mitomycin TMA is the prototypic cumulative-dose-dependent chemotherapy-induced microangiopathy.
• Onset is characteristically delayed, often appearing weeks to months after the last dose and even after treatment has stopped, so a normal creatinine during therapy is falsely reassuring.
• Blood transfusion can acutely precipitate or worsen the microangiopathic hemolysis and renal failure — transfuse cautiously and watch closely in affected patients.
• Plasma exchange is generally disappointing for mitomycin TMA (unlike TTP); drug discontinuation plus supportive care is the mainstay, and the renal injury is often irreversible.
• Non-cardiogenic pulmonary edema/ARDS can accompany the renal-hematologic syndrome and markedly worsens prognosis, a feature that helps separate it from idiopathic TTP-HUS.
• Chemical/hemorrhagic cystitis — occasionally with bladder contracture and calcification — is a quantified toxicity of intravesical mitomycin for bladder cancer; a route-specific lesion, not a systemic-IV toxicity.

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
• 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