Case Presentation: A 66-year-old woman with a history of metastatic colon cancer, CKD stage 4 (baseline creatinine 2.3–2.4 mg/dL), insulin-dependent type 2 diabetes, and hypothyroidism presented to the emergency department in September 2025 with hypoxia, bradycardia, and hypothermia. She had been receiving FOLFOX4 and bevacizumab since February 2024. On admission, she was found to have severe hypothyroidism (TSH 155 mIU/L, free T4 0.4 ng/dL) and was admitted for suspected myxedema coma. Her hospital course was complicated by acute worsening of kidney function (creatinine increased to 3.6 mg/dL), severe acidosis (pH 7.1, CO₂ 56 mmHg, low-to-normal bicarbonate), and persistent hypoxemia. She required BIPAP and was transferred to the ICU for management of mixed respiratory and non-anion gap metabolic acidosis. Nephrology was consulted for emergent dialysis. The patient had been followed by nephrology for CKD 3a since 2019, with progressive decline in renal function following a right hemicolectomy for small bowel obstruction in January 2024. Notably, her creatinine had steadily increased, and she developed heavy proteinuria after initiation of bevacizumab and 5-FU in February 2024. During this admission, a renal biopsy was performed, which confirmed anti-VEGF-related glomerulopathy. Her kidney function improved and did not require ongoing dialysis at discharge. Her oncology team was made aware, and Bevacizumab was discontinued with consideration of alternate therapy.
Discussion: This case underscores the risk of rapid CKD progression and severe glomerular injury in patients with pre-existing renal disease receiving VEGF inhibitor therapy. Avastin (bevacizumab) can cause kidney injury, with a median onset of proteinuria at 5.6 months (range 15 days to 37 months) after starting therapy. Severe proteinuria or nephrotic syndrome can occur as early as 2–8 weeks in susceptible patients, especially with pre-existing CKD or hypertension. The underlying mechanism is not fully understood but may involve disruption of glomerular endothelial integrity due to VEGF inhibition, leading to various patterns of glomerular injury, including immune-complex-mediated disease and thrombotic microangiopathy. This patient demonstrated classic features of VEGF-inhibitor nephrotoxicity, including hypertension, heavy proteinuria and biopsy-confirmed TMA. Early detection and regular monitoring of urine protein and renal function are essential. Most cases show partial or complete resolution of proteinuria and renal dysfunction upon drug withdrawal.
Conclusions: This case highlights the importance of vigilance for renal complications in patients receiving bevacizumab. Early recognition and cessation of the offending agent can result in reversibility of nephropathy. Clinicians should monitor renal function and proteinuria for patients on bevacizumab, and consider discussing with oncology to find alternative therapy for patients with preexisting chronic kidney disease.