Pivekimab sunirine

Prerenal / Hemodynamic AKI.

There is no published pivekimab-specific incidence of acute kidney injury as a discrete endpoint, and the drug's own renal signal is thin; the risk is best understood as indirect and inherited from its target and disease setting. In the first-in-human phase 1/2 study in relapsed/refractory acute myeloid leukemia (Daver, Lancet Oncol 2024; n=91), the dose-limiting toxicities were reversible hepatic veno-occlusive disease and neutropenia, and the most common grade ≥3 events at the recommended phase 2 dose were febrile neutropenia, infusion-related reactions, and anemia — not a discrete renal lesion. The renal-risk framing therefore rests on two things: (1) tumor lysis syndrome, an on-target hazard whenever a large CD123-positive leukemic or BPDCN mass is lysed rapidly, and (2) capillary-leak syndrome, the class concern of CD123-directed therapy documented most clearly with the other approved BPDCN agent, tagraxofusp (capillary-leak syndrome in ~19–21%, with hypoalbuminemia and edema and occasional deaths; Pemmaraju, NEJM 2019 and JCO 2022). Pivekimab-specific capillary-leak/AKI rates are not established and should not be overstated.

Source: No drug-specific AKI incidence; risk indirect — TLS in CD123+ disease plus the CD123-class capillary-leak concern (tagraxofusp, Pemmaraju NEJM 2019 / JCO 2022). Pivekimab DLT was reversible VOD (Daver, Lancet Oncol 2024)

Reported injury signatures: Prerenal / Hemodynamic AKI, Crystal / Obstructive Nephropathy, Electrolyte Disturbance, Acute Tubular Necrosis.

1. Prerenal / Hemodynamic AKIPrimary
2. Crystal / Obstructive NephropathySecondary
3. Electrolyte DisturbanceSecondary
4. Acute Tubular NecrosisSecondary

Acute (~1–7 days) — Tumor lysis clusters in the first days after effective cytoreduction (first cycle, highest burden); capillary-leak physiology tends to appear during the early treatment cycles and around infusions.

• High tumor burden / high circulating blast mass (greater tumor-lysis and cytokine/endothelial load)
• High baseline LDH, uric acid, or phosphate (tumor-lysis-prone biochemistry)
• The first treatment cycle and early infusions (peak lysis and capillary-leak window)
• Baseline hypoalbuminemia or a tendency to third-spacing/edema
• Pre-existing chronic kidney disease or volume depletion
• Concurrent nephrotoxins, sepsis, or infection in a heavily pretreated host
• Combination regimens that increase depth/speed of cytoreduction (e.g., with azacitidine/venetoclax)

• Risk-stratify for tumor lysis before dosing (tumor bulk, LDH, uric acid, phosphate, renal function) and give prophylaxis accordingly
• IV hydration around the early, high-risk doses to protect renal perfusion and dilute tubular urate/phosphate
• Allopurinol for standard tumor-lysis risk; rasburicase for high risk or established hyperuricemia (avoid in G6PD deficiency)
• Monitor weight, albumin, and volume status for capillary-leak physiology, and premedicate/observe around infusions per protocol
• Correct volume depletion and minimize concurrent nephrotoxins before and during the early cycles
• Frequent tumor-lysis labs and vital-sign monitoring through the first cycle

• Tumor-lysis panel (uric acid, phosphate, potassium, calcium, LDH, creatinine) at baseline and frequently through the first cycle
• Daily weight, serum albumin, and volume/edema assessment for capillary-leak physiology
• Serial creatinine/eGFR to detect and grade AKI
• Vital signs around infusions for infusion-related reactions and hypotension
• Liver function and signs of veno-occlusive disease (the documented dose-limiting toxicity)
• Infection surveillance given the heavily pretreated, cytopenic population

• Pivekimab sunirine phase 1/2 in relapsed/refractory AML (Daver, Lancet Oncol 2024) — first-in-human dose-escalation/expansion (n=91) that defined the 0.045 mg/kg recommended phase 2 dose; dose-limiting toxicities were reversible hepatic veno-occlusive disease and neutropenia, and the leading grade ≥3 events were febrile neutropenia, infusion-related reactions, and anemia — establishing that the drug's own toxicity is hematologic/endothelial rather than a discrete renal lesion.
• Tagraxofusp in BPDCN (Pemmaraju, NEJM 2019) — the pivotal trial of the other approved CD123-directed BPDCN agent, documenting capillary-leak syndrome in ~19% (with deaths), hypoalbuminemia in 55%, and peripheral edema in 51% — the class capillary-leak → hemodynamic-renal-risk model applied to CD123 targeting.
• Long-term tagraxofusp in BPDCN (Pemmaraju, JCO 2022) — extended follow-up confirming capillary-leak syndrome in 21% (grade ≥3 in 7%), reinforcing capillary leak as the durable class-level renal-relevant hazard to watch for with CD123 agents.

• The kidney is a bystander here twice over: pivekimab's renal risk rides on tumor lysis in a lysis-prone disease and on the capillary-leak concern shared by CD123-targeting agents — not on tubular poisoning.
• Its own documented dose-limiting toxicity was reversible hepatic veno-occlusive disease, an endothelial/sinusoidal injury — a reminder to watch endothelial complications, including capillary leak, even though VOD itself is hepatic.
• Borrow the tagraxofusp playbook for capillary leak — track weight, albumin, and volume, and support perfusion without flooding a leaky vasculature.
• Tumor lysis is front-loaded in the first cycle when blast burden is highest; hydration and rasburicase/allopurinol belong at initiation.
• The conjugate is a large biologic cleared by catabolism, so renal function does not drive its exposure and dialysis does not remove it — but renal replacement therapy is still the right tool for refractory tumor-lysis metabolites or oliguric AKI.
• No pivekimab-specific AKI rate is published — state the risk as indirect and class-inferred, and let mature BPDCN trial data refine it.

• 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