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Trifunctional bispecific (EpCAM×CD3)

Catumaxomab

Removab · Catux

Trifunctional bispecific (EpCAM×CD3) · approved 2009 · 3 references

An intraperitoneal trifunctional antibody whose cytokine-release storm threatens the kidney prerenally.

Signature injury
Prerenal / Hemodynamic AKI
Severity
Moderate
Reversibility
Reversible
Onset
Cytokine-release symptoms within hours of each intraperitoneal infusion; any prerenal AKI follows the inflammatory/volume insult.

Signature kidney injury & incidence

Prerenal / Hemodynamic AKI.

No characteristic intrinsic nephrotoxicity. The dominant treatment-related toxicity is cytokine-release-related (pyrexia, nausea, vomiting, chills, fatigue) plus intraperitoneal-administration effects (abdominal pain); transient transaminase rises and lymphopenia are common but usually clinically minor. Cytokine release with fever, GI losses, and large-volume ascites/paracentesis creates a setting for prerenal/hemodynamic AKI rather than a direct renal lesion. Drug-specific renal incidence is not quantified.

Source: Berek et al., Int J Gynecol Cancer 2014 (phase II); Frampton, Drugs 2012 (pivotal II/III review)

Reported injury signatures: Prerenal / Hemodynamic AKI, Electrolyte Disturbance.

Renal toxicity profile

  1. Prerenal / Hemodynamic AKIPrimary
  2. Electrolyte DisturbanceSecondary

Onset timing & rechallenge

Acute (~1–7 days) — Cytokine-release symptoms within hours of each intraperitoneal infusion; prerenal AKI follows the inflammatory/volume insult.

Mechanism of kidney injury

Catumaxomab's renal risk is hemodynamic and indirect. By cross-linking tumor cells, T cells, and Fc-receptor-bearing accessory cells, it triggers a brisk cytokine release (TNF-alpha, IL-6, IFN-gamma), producing fever, vomiting, and a systemic inflammatory/vasodilatory state; combined with the fluid shifts of malignant ascites and therapeutic paracentesis, this can cause volume depletion and renal hypoperfusion — a prerenal acute kidney injury pattern — and contribute to electrolyte disturbance. There is no described direct tubular, glomerular, or crystal toxicity from the antibody itself. Management is supportive and hemodynamic.

Clinical presentation

Cytokine-release symptoms (fever, chills, nausea, vomiting) and abdominal pain after intraperitoneal dosing; if AKI develops it is typically prerenal — oliguria with a bland sediment, responsive to volume — in the context of fever, GI losses, and ascites management. Transient transaminitis and lymphopenia are expected and usually benign.

Management

Supportive: treat fever and GI losses, restore volume for prerenal AKI, and correct electrolytes. The antibody requires no renal dose adjustment; manage the hemodynamic/inflammatory insult and the underlying ascites.

Risk factors

  • Large-volume malignant ascites and frequent paracentesis
  • Pre-existing volume depletion or CKD
  • Severe cytokine-release reaction (high fever, vomiting)
  • Concurrent nephrotoxins or diuretics

Prevention

  • Premedicate and manage cytokine-release symptoms (antipyretics, antiemetics)
  • Maintain euvolemia around paracentesis and infusions

Renal dose adjustment

No renal dose adjustment defined; the agent is given intraperitoneally as an antibody and is not renally cleared. The actionable interventions are hemodynamic/supportive rather than renal dosing.

Dialyzability & ESKD dosing

A large trifunctional antibody — not dialyzable and cleared by proteolysis; no ESKD dosing guidance. Renal management is volume- and electrolyte-focused.

Differential diagnosis

Distinguish cytokine-release-/ascites-driven prerenal AKI (bland sediment, volume-responsive, fever and GI losses) from intrinsic renal disease or obstruction; a fixed, non-volume-responsive creatinine rise should prompt search for an alternative cause.

Monitoring

  • Electrolytes and volume status (especially around paracentesis)
  • Temperature and cytokine-release symptoms
  • Liver function tests (transient rises expected)

Key trials & series

  • Pivotal phase II/III malignant-ascites trial (Frampton Drugs 2012 review)
  • Berek Int J Gynecol Cancer 2014 phase II in chemotherapy-refractory ovarian cancer

Clinical pearls

  • Expect transient transaminitis and lymphopenia — usually benign and not a renal warning.

Anticancer mechanism

Trifunctional rat/mouse hybrid bispecific antibody binding EpCAM on tumor cells and CD3 on T cells, while its intact Fc region engages Fc-gamma-receptor-positive accessory immune cells (macrophages, NK cells, dendritic cells). This tri-cell complex drives potent T-cell- and accessory-cell-mediated tumor killing. Administered intraperitoneally for malignant ascites due to EpCAM-positive tumors.

Note

Renal injury is indirect (cytokine-release- and ascites/paracentesis-driven prerenal AKI), not a direct antibody nephrotoxin. Catumaxomab was withdrawn from the EU market in 2017 for commercial reasons; profile retained for onconephrology completeness. Drug-specific renal data are sparse and conservative.

Guidelines & consensus

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.

  • ASCO (2021) — Management of Immune-Related Adverse Events in Patients Treated With Chimeric Antigen Receptor T-Cell Therapy: ASCO GuidelineGrade toxicities by ASTCT criteria; manage CRS with supportive care escalating to tocilizumab with or without corticosteroids, and manage moderate-to-severe ICANS with corticosteroids and supportive care given potential for rapid decline.J Clin Oncol · PMID 34724386
  • TLS Expert Panel (2008) — Guidelines for the management of pediatric and adult tumor lysis syndrome: an evidence-based reviewPrevention is the best management: hydration plus prophylactic rasburicase for high-risk patients, hydration plus allopurinol or rasburicase for intermediate-risk, and monitoring for low-risk; for established TLS add aggressive hydration and diuresis plus allopurinol or rasburicase for hyperuricemia. Urinary alkalinization is NOT recommended.J Clin Oncol · PMID 18509186
  • TLS Consensus Panel (2010) — Recommendations for the evaluation of risk and prophylaxis of tumour lysis syndrome (TLS) in adults and children with malignant diseases: an expert TLS panel consensusStratify each patient as low/intermediate/high TLS risk using tumor type, bulk/stage, proliferation rate, baseline laboratory TLS, and renal impairment/involvement, then match prophylaxis intensity (monitoring vs allopurinol vs rasburicase) to the assigned risk level.Br J Haematol · PMID 20331465
  • BCSH (2015) — Guidelines for the management of tumour lysis syndrome in adults and children with haematological malignancies on behalf of the British Committee for Standards in HaematologyRisk-adapted prophylaxis and management of TLS in haematological malignancy: hydration with allopurinol for lower-risk and rasburicase for high-risk patients, with monitoring of electrolytes and renal function to prevent and treat AKI.Br J Haematol · PMID 25876990
  • Cairo-Bishop (2004) — Tumour lysis syndrome: new therapeutic strategies and classificationDefines the Cairo-Bishop criteria distinguishing laboratory TLS (>=2 metabolic abnormalities: hyperuricemia, hyperkalemia, hyperphosphatemia, hypocalcemia within 3 days before to 7 days after therapy) from clinical TLS (laboratory TLS plus AKI, cardiac arrhythmia, or seizure), with a severity grading scheme adopted by subsequent guidelines.Br J Haematol · PMID 15384972
  • ASTCT (2019) — ASTCT Consensus Grading for Cytokine Release Syndrome and Neurologic Toxicity Associated with Immune Effector CellsGrade CRS by fever, hypotension and hypoxia (grades 1-4) and grade ICANS using the ICE/encephalopathy score plus level of consciousness, seizures, motor findings and raised intracranial pressure/edema; this is the standard severity framework that triggers tocilizumab and corticosteroid escalation in CAR-T and bispecific antibody toxicity (the Lee 2019 consensus).Biol Blood Marrow Transplant · PMID 30592986
  • 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

References

3 peer-reviewed references. Citation metadata via PubMed / NLM.

  1. 1.Catumaxomab for the treatment of malignant ascites in patients with chemotherapy-refractory ovarian cancer: a phase II study.Berek JS et al. · Int J Gynecol Cancer · 2014 · PMID 25254563
  2. 2.Catumaxomab: in malignant ascites.Frampton JE et al. · Drugs · 2012 · PMID 22676343
  3. 3.Acute Kidney Injury in Patients with Cancer.Rosner MH et al. · N Engl J Med · 2017 · PMID 28467867

Case reports & series (1)

The weakest rung of clinical evidence — single-patient and small-series reports, strongest first. Each carries a heuristic strength grade (A Strong / B Moderate / C Limited) inferred from its abstract and journal, not a formal appraisal. Weigh well below the primary references above.

  1. C1.[C · Limited]Treatment of malignant ascites with a second cycle of catumaxomab in gastric signet cell carcinoma--a report of 2 cases.Thomaidis T et al. · Oncol Res Treat · 2014 · PMID 25427585
Educational monograph from NephTox (nephtox.com). Not medical advice — verify against current guidelines before any clinical decision.