As a nephrologist, what renal and systemic toxicities of bevacizumab (anti‑VEGF monoclonal antibody) should I be aware of?

Bevacizumab Toxicities for Nephrologists

As a nephrologist, you must monitor for hypertension (7-36% incidence), proteinuria with potential progression to nephrotic syndrome, and thrombotic microangiopathy (TMA), as these represent the primary renal and systemic toxicities of bevacizumab that directly impact morbidity and mortality. 1, 2, 3

Primary Renal Toxicities

Hypertension

• Hypertension occurs in 7-36% of bevacizumab-treated patients, with blood pressure increases of 20-30 mmHg systolic and 9-17 mmHg diastolic 1
• Onset typically occurs within hours to the first month of treatment and reverses quickly when therapy is stopped 1
• The mechanism involves VEGF inhibition reducing nitric oxide production in arteriolar walls, causing vasoconstriction and increased peripheral resistance 1
• Severe hypertension requiring hospitalization or drug discontinuation occurs in 1.7% of patients 1

Management approach:

• Monitor blood pressure before each infusion and between cycles 1, 2
• Initiate ACE inhibitors or ARBs as first-line therapy due to beneficial effects on proteinuria and PAI-1 expression 1
• Add dihydropyridine calcium channel blockers or beta-blockers as needed 1
• Avoid non-dihydropyridine calcium channel blockers (diltiazem, verapamil) due to CYP3A4 interactions 1
• Consider dose reduction or temporary discontinuation if blood pressure exceeds 160/100 mmHg despite treatment 1

Proteinuria and Nephrotic Syndrome

• Proteinuria >3.5 g/day occurs in up to 100% of patients with bevacizumab-induced renal injury 4
• Nephrotic syndrome represents a serious complication requiring drug discontinuation 2, 3
• Monitor urine protein at baseline and before each treatment cycle using spot urine protein-to-creatinine ratio or 24-hour urine collection 2, 3

Critical thresholds:

• Suspend bevacizumab for proteinuria ≥2 g/24 hours 2
• Permanently discontinue for nephrotic syndrome 2

Thrombotic Microangiopathy (TMA)

• TMA is the most common pathological finding (50% of cases) in bevacizumab-induced renal injury 4
• Presents with progressive renal dysfunction, proteinuria, microangiopathic hemolytic anemia, and thrombocytopenia 5, 4
• TMA can progress even after bevacizumab discontinuation, particularly in patients with pre-existing chronic kidney disease 5

Monitoring strategy:

• Check complete blood count, peripheral smear, LDH, haptoglobin, and renal function if unexplained renal deterioration occurs 5, 4
• Perform renal biopsy if TMA is suspected to guide management and prognosis 5, 4
• Discontinue bevacizumab immediately upon TMA diagnosis 5, 4

Cardiovascular Toxicities Requiring Nephrologist Awareness

Arterial Thromboembolic Events

• Arterial thrombotic events occur in 3.8% of patients, including myocardial infarction, angina, stroke, and transient ischemic attacks 1
• Events are not dose-related and can occur at any time during treatment (median onset: 3 months) 1
• Mechanism involves disturbances in endothelial regeneration 1

Congestive Heart Failure

• Bevacizumab induces heart failure through multifactorial mechanisms: hypertension, reduced capillary density, cardiac fibrosis, and declined contractile function 1
• Monitor for signs of volume overload and cardiac dysfunction, especially in patients with hypertension or receiving concurrent cardiotoxic chemotherapy 1, 2

High-Risk Populations Requiring Enhanced Monitoring

Patients with pre-existing chronic kidney disease are at highest risk for progressive, non-remitting renal injury 5:

• Baseline eGFR <60 mL/min/1.73 m² increases risk of irreversible TMA 5
• More frequent monitoring (every 2 weeks initially) is warranted in this population 5, 4

Other high-risk features 3:

• History of hypertension
• Pre-existing proteinuria
• History of thromboembolism
• Cardiovascular disease

Additional Serious Toxicities

Gastrointestinal Perforation

• Risk increases in colorectal cancer patients 2, 3
• Advise patients to report severe abdominal pain, constipation, or vomiting immediately 2

Hemorrhage

• Higher risk in squamous non-small cell lung cancer 3
• Instruct patients to report hemoptysis or unusual bleeding immediately 2

Wound Healing Complications

• Discontinue bevacizumab at least 28 days before elective surgery 2
• Do not resume until surgical wound is fully healed 2

Monitoring Protocol Summary

Baseline assessment:

• Blood pressure, urinalysis with protein quantification, serum creatinine, CBC 2, 3

During treatment:

• Blood pressure at every visit 1
• Urinalysis and urine protein quantification every 2-4 weeks 2, 3
• Serum creatinine monthly 4
• CBC if clinical suspicion of TMA 5

Prognosis after discontinuation:

• 25% achieve complete recovery of renal function and proteinuria 4
• 75% have persistent mild proteinuria but stable renal function 4
• TMA may progress despite drug discontinuation, particularly with baseline CKD 5