Ziv-aflibercept

Hypertension — representative incidence ~42.4%.

Hypertension and proteinuria are common class effects; in the registrational VELOUR trial, grade 3-4 hypertension and proteinuria were more frequent with aflibercept plus FOLFIRI than with FOLFIRI alone. Nephrotic-range proteinuria and renal thrombotic microangiopathy are documented, including with the ophthalmic formulation, indicating a direct VEGF-trap mechanism. A meta-analysis of 15 trials (4,451 patients) put the summary all-grade hypertension incidence at 42.4%.

Source: Qi et al., Clin Drug Investig 2014 (meta-analysis, all-grade hypertension 42.4%); Van Cutsem et al., VELOUR (J Clin Oncol 2012 / Target Oncol 2016)

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

1. HypertensionPrimary~44.2%All-grade hypertension 44.2% (95% CI 39.7-48.7), grade III/IV 22.6%, in a meta-analysis of aflibercept plus chemotherapy for metastatic colorectal cancer (2,889 pts, 10 studies); RR 6.30 vs control.
2. Glomerular Injury / ProteinuriaSecondary~31.3%All-grade proteinuria 31.3% (95% CI 19.3-43.3), grade III/IV 7.4% (VEGF-trap podocyte injury), from the same aflibercept mCRC meta-analysis.
3. Thrombotic MicroangiopathyRare

Subacute (~1–6 weeks) — Within weeks to a few months of therapy.

• Pre-existing hypertension
• Diabetes or baseline proteinuria/CKD

• Aggressive blood pressure control before and during therapy

• Blood pressure every 2 weeks or with each cycle
• Urine dipstick and/or UPCR during therapy (in practice, before each dose); 24-h collection if dipstick >=2+ or UPCR >1
• Serum creatinine; CBC/LDH/haptoglobin and smear if TMA suspected

• VELOUR phase III trial of aflibercept + FOLFIRI in second-line metastatic colorectal cancer (carrying the hypertension/proteinuria signal)
• Kikuchi et al. biopsy-proven aflibercept-associated renal TMA case (BMC Nephrol 2022)

• As a VEGF ligand trap, aflibercept causes a TMA-type glomerular lesion, mirroring bevacizumab and the Eremina knockout model.
• Even intravitreal aflibercept has caused renal TMA, underscoring how little systemic VEGF blockade the glomerulus tolerates.

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 Summaries may be superseded; consult the current full text and individualize to the patient.

• KDIGO (2021) — Management of Blood Pressure in Patients With Chronic Kidney Disease Not Receiving Dialysis: Synopsis of the 2021 KDIGO Clinical Practice GuidelineRecommends standardized office BP measurement and a target systolic BP <120 mm Hg for most CKD patients, with RAAS inhibitors first-line when albuminuria is present — the BP-management basis for anti-VEGF/TKI-induced hypertension and proteinuria.Ann Intern Med · PMID 34152826
• ESC (2022) — 2022 ESC Guidelines on cardio-oncology developed in collaboration with the European Hematology Association (EHA), the European Society for Therapeutic Radiology and Oncology (ESTRO) and the International Cardio-Oncology Society (IC-OS)For VEGF/VEGFR inhibitors, perform baseline cardiovascular risk assessment, monitor blood pressure (weekly during the first cycle, then regularly) and treat to a target <140/90 mmHg with ACE inhibitors/ARBs and dihydropyridine calcium-channel blockers; manage VEGFi-associated hypertension and proteinuria with interruption/dose modification when severe.Eur Heart J · PMID 36017568
• ESC (2022) — European Society of Cardiology quality indicators for the prevention and management of cancer therapy-related cardiovascular toxicity in cancer treatmentAdherence quality indicators require documented baseline cardiovascular risk assessment and structured monitoring of cardiovascular complications (including hypertension) during cancer therapy such as VEGF-pathway inhibitors.Eur Heart J Qual Care Clin Outcomes · PMID 36316010
• UK Consensus Panel (2010) — Using bevacizumab to treat metastatic cancer: UK consensus guidelinesAssess and monitor blood pressure and proteinuria during bevacizumab therapy; treat emergent hypertension to standard targets and interrupt/discontinue the drug for uncontrolled hypertension, nephrotic-range proteinuria or other severe vascular toxicity.Br J Hosp Med (Lond) · PMID 21135762
• 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