Tasonermin

Prerenal / Hemodynamic AKI.

No robust drug-specific renal AKI incidence exists. In the large multicenter TNF-alpha + melphalan limb-perfusion series, systemic toxicity was 'minimal to moderate,' readily managed, with no toxic deaths, and clinically significant renal injury was uncommon when systemic leakage was controlled (Eggermont, Ann Surg 1996). Renal insufficiency clusters in the minority with high systemic TNF-alpha leakage: transient renal insufficiency was seen in leak-affected patients during early TNF-alone perfusions (Posner 1995), whereas a series that tolerated even 12-65% leakage found hypotension the dominant toxicity and observed no renal toxicity (Stam 2000). Reported risk is therefore leakage-dependent rather than a fixed rate, so incidencePct is left null.

Source: Eggermont et al., Ann Surg 1996 (PMID 8968230); Stam et al., Ann Surg Oncol 2000 (PMID 10819366)

Reported injury signatures: Prerenal / Hemodynamic AKI, Acute Tubular Necrosis.

1. Prerenal / Hemodynamic AKIPrimary
2. Acute Tubular NecrosisSecondary

Acute (~1–7 days) — Procedure-linked: with systemic leakage, hypotension/SIRS appear within hours of the perfusion (peak TNF-alpha at 3-12 h) and azotemia over the first 24-48 h.

• High systemic leakage of TNF-alpha from the perfusion circuit (the dominant driver of renal risk)
• High perfusion flow rate or inadequate limb isolation (tourniquet/Esmarch)
• Baseline volume depletion or borderline pre-existing renal function
• Severe regional reaction with rhabdomyolysis, myoglobinuria, and/or compartment syndrome
• Concomitant nephrotoxins or hypotension-prone cardiac status
• Older age / limited physiologic reserve

• Continuous intraoperative leak monitoring (radiolabeled-albumin or technetium-99m precordial counting) to detect and limit systemic TNF-alpha escape
• Meticulous limb isolation and controlled/lower perfusion flow to minimize leakage (lower flow demonstrably reduces leak and systemic toxicity)
• Maintain euvolemia with generous peri-procedure IV fluids; support renal perfusion
• Post-procedure ICU/high-dependency monitoring for SIRS/hypotension during the first 24 h
• Monitor CK/myoglobin and compartment pressures; alkaline diuresis and timely fasciotomy for rhabdomyolysis/compartment syndrome
• Avoid additional nephrotoxins in the peri-procedure window

• Continuous systemic leak measurement during perfusion (radiolabeled albumin / technetium-99m)
• Blood pressure, heart rate, cardiac index / hemodynamics, and urine output during peri-procedure ICU observation
• Serum creatinine and electrolytes over the first 24-72 h
• CK and serum/urine myoglobin, plus limb compartment pressures, for rhabdomyolysis/compartment syndrome
• SIRS markers (temperature, IL-6 trend where available) and lactate

• Eggermont et al., Ann Surg 1996 (PMID 8968230) — 186-patient cumulative multicenter European TNF-alpha + melphalan ILP series (registrational safety/efficacy basis for tasonermin): 82% limb salvage, systemic toxicity minimal-to-moderate, no toxic deaths
• Eggermont et al., J Clin Oncol 1996 (PMID 8874324) — multicenter TNF-alpha + interferon-gamma + melphalan ILP for nonresectable extremity soft-tissue sarcoma
• Stam et al., Ann Surg Oncol 2000 (PMID 10819366) — systemic cytokine/toxicity kinetics after high-leakage ILP; hypotension the principal, fluid-responsive toxicity with no renal toxicity observed

• The kidney is a bystander: renal risk tracks systemic TNF-alpha leakage, not the drug dose — obsessive intraoperative leak monitoring is the real nephroprotection.
• Systemic MTD of TNF-alpha is ~10x below the effective antitumor dose; the isolated circuit is what makes the dose survivable — a leak turns a therapeutic dose into a septic-shock dose.
• Fix the circulation and the kidney follows — the AKI is hemodynamic (prerenal/distributive), typically fluid- and pressor-responsive, and reverses as leaked cytokine clears.
• Watch the limb, not just the blood pressure: rhabdomyolysis and compartment syndrome are a separate, ILP-specific route to pigment ATN — check CK/myoglobin and compartment pressures and don't delay fasciotomy.
• In large modern series, systemic toxicity was minimal-to-moderate with no toxic deaths and little renal injury when leakage was controlled — significant AKI is uncommon, not routine.

• 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 (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