Can bevacizumab (bevacizumab) cause hematuria in a patient with metastatic rectal adenocarcinoma?

Can Bevacizumab Cause Hematuria?

Yes, bevacizumab can cause hematuria, though it is not among the most commonly reported hemorrhagic complications of this anti-VEGF therapy. The primary hemorrhagic risks are gastrointestinal bleeding and mucosal bleeding, but hematuria can occur as part of bevacizumab's broader renal toxicity profile.

Mechanism and Renal Toxicity Profile

Bevacizumab causes significant renal injury through multiple mechanisms that can lead to hematuria:

• Proteinuria is the most common renal manifestation, occurring in 20% of patients (all grades), with Grade 3-4 proteinuria ranging from 0.7% to 7% in clinical studies 1
• Thrombotic microangiopathy (TMA) develops in some patients, characterized by glomerular capillary damage, endothelial injury, and subendothelial protein accumulation that can cause microscopic or gross hematuria 2, 3
• Glomerular microangiopathy creates a distinctive pseudothrombotic pattern with hyaline pseudothrombi occluding dilated glomerular capillaries, leading to nephrotic syndrome in most affected patients 3

Clinical Evidence for Hematuria

While the NCCN guidelines and ESMO guidelines focus primarily on gastrointestinal hemorrhage, mucosal bleeding, hypertension, and proteinuria as the main bevacizumab-related adverse events 4, case reports document hematuria:

• Gross hematuria has been reported even with intravitreal bevacizumab administration in a patient with undiagnosed urothelial carcinoma, demonstrating systemic absorption and hemorrhagic effects 5
• Hematuria can occur as part of bevacizumab-induced TMA, where glomerular injury leads to blood in the urine alongside proteinuria and renal dysfunction 2

Hemorrhagic Risk Profile

The documented hemorrhagic complications of bevacizumab include:

• Gastrointestinal hemorrhage is significantly increased, though overall risk remains low 4
• Mucosal bleeding is a recognized class-related side effect 4
• Hemorrhage accounts for 23.5% of treatment-related mortality in patients receiving bevacizumab with chemotherapy 4
• Pulmonary hemorrhage occurred in 31% of patients with squamous NSCLC receiving bevacizumab 1

Monitoring Recommendations

For patients with metastatic rectal adenocarcinoma receiving bevacizumab:

• Monitor for proteinuria by dipstick urinalysis with serial testing during therapy 1
• Patients with 2+ or greater urine dipstick should undergo 24-hour urine collection for quantification 1
• Withhold bevacizumab for proteinuria ≥2 grams per 24 hours and resume when <2 grams per 24 hours 1
• Discontinue permanently in patients who develop nephrotic syndrome 1
• Monitor blood pressure every 2-3 weeks, as hypertension (Grades 3-4 in 5-18% of patients) can exacerbate renal injury 1

Important Clinical Caveats

• Median onset of proteinuria is 5.6 months (range: 15 days to 37 months) after initiating bevacizumab, so hematuria may develop at any point during treatment 1
• Proteinuria did not resolve in 40% of patients after median follow-up of 11.2 months, indicating potentially irreversible renal damage 1
• Serum creatinine elevation (1.5 to 1.9 times baseline) occurs more frequently with bevacizumab, and approximately one-third of patients do not return to baseline 1
• Kidney biopsy findings in bevacizumab-treated patients show thrombotic microangiopathy with distinctive features different from classic TMA 2, 3

Clinical Context for Metastatic Rectal Cancer

In your patient with metastatic rectal adenocarcinoma:

• Bevacizumab remains a standard component of first-line and second-line therapy when combined with chemotherapy 4, 6
• If hematuria develops, evaluate for proteinuria, perform urinalysis, and consider 24-hour urine collection 1
• Rule out other causes including urinary tract infection, nephrolithiasis, or genitourinary malignancy before attributing to bevacizumab
• Consider holding bevacizumab if significant hematuria occurs with proteinuria ≥2 grams per 24 hours or evidence of renal dysfunction 1