Skip Navigation LinksHome > September 2009 - Volume 4 - Issue 9 > Acute Renal Failure in a Patient Receiving Anti-VEGF Therapy...
Journal of Thoracic Oncology:
doi: 10.1097/JTO.0b013e3181b2362f
Letter to the Editor

Acute Renal Failure in a Patient Receiving Anti-VEGF Therapy for Advanced Non-small Cell Lung Cancer

Zhao, Jing MD; Li, Hang MD; Wang, Mengzhao MD

Free Access
Article Outline
Collapse Box

Author Information

Department of Respiratory Medicine; Peking Union Medical College Hospital; Peking, People’s Republic of China (Zhao)

Department of Nephrology; Peking Union Medical College Hospital; Peking, People’s Republic of China (Li)

Department of Respiratory Medicine; Peking Union Medical College Hospital; Peking, People’s Republic of China; (Wang)

Disclosure: The authors declare no conflicts of interest.

Back to Top | Article Outline

To the Editor:

Bevacizumab, a monoclonal hybrid antibody that binds to and neutralizes vascular endothelial growth factor, has shown promising efficacy in the adjunctive treatment of patients with several cancers. However, significant side effects are associated with bevacizumab, especially hypertention and proteinuria, but rarely acute renal failure. Here, we report a 67-year-old man, habitted smoker, who developed new-onset acute renal failure after receiving bevacizumab for stage IV non-small cell lung cancer. On January 16, 2008, treatment with paclitaxel 300 mg (175 mg/m2), carboplatin 580 mg (AUC = 6) plus bevacizumab 900 mg (15 mg/kg) intravenously every 3 weeks was initiated. During the first two cycles, the patient’s serum creatinine was stable at approximately 76 μmol/liter and urinalysis was unremarkable. On March 2, 2008, his serum creatinine level was 461 μmol/liter. Then he had a progressive increase in creatinine levels and became oliguric requiring intermittent hemodialysis. Dysmorphic red blood cells and a few coarse granular casts were presented in the urine sediment. Twenty-four hour urine total protein was 9.47 g. So, the scheduled third cycle was withheld. Other laboratory tests including liver function, coagulation status, autoimmune antibodies, etc. showed normal. Kidney ultrasound showed enhanced echo signal in cortex area and normal sized kidneys with no hydronephrosis. Renal vessels were normal. Fortunately, the patient’s renal function continued to improve and dialysis was no longer required. And the treatment for non-small cell lung cancer was changed to Gefitinib 250 mg once per day because of PD proven by computed tomography. An ultrasound-guided renal biopsy was delayed until the patient became more clinically stable. In kidney biopsy, glomeruli were characterized by intense glomerular hypercellularity. Much of this hypercellularity was mesangial and segmental endothelial proliferation, giving the glomerular tuft a ‘lobular’ appearance (Figure 1A). The glomerular basement membrane thickening with the appearance of double contours was caused by mesangial cell and mesangial matrix interposition into the subendothelial zone of the capillary loops, which caused capillary loops narrow and occluded (Figure 1B). Immuno-fluorescence microscopy showed bright diffuse granular glomerular capillary wall and mesangial staining for C3 (Figure 1C), but others were negative. In electron microscopy examination, there was mesangial hypercellularity and increased mesangial matrix, which were obviously inserted into subendothelium. The electron dense deposited in mesangial and subendothelial area and the glomerular basement membrane was thickened diffusely. Few dense deposits were presented in subepithelial region. Segmental foot process effacement was observed (Figure 1D). The final kidney biopsy findings were interpreted as type III membranoproliferative glomerulonephritis. To our surprise, at discharge on April 3, 2008, his serum creatinine stabilized at 107 μmol/liter and urinalysis showed normal. In an 8-month follow-up, the patient’s renal function was still normal.

Figure 1
Figure 1
Image Tools

The nephrotoxicity encountered here was more likely secondary to bevacizumab and not to concomitant paclitaxel treatment in the absence of evidence of a prior association with this agent. Carboplatin administration could lead to renal impairment but was frequently associated with tubular dysfunction.1 Other potential causes of acute renal failure were excluded. The pathogenesis of bevacizumab-associated renal toxicities was still unclear. Some proposed mechanisms of bevacizumab included the following. (1) Secondary to hypertension. (2) Human and animal data suggested that appropriate vascular endothelial growth factor expression in the kidney was important to maintain the structure and function of the glomerulus. So, bevacizumab may cause an alteration in vascular endothelial growth factor expression through its on-target effects and lead to endothelial cell dysfunction and promote glomerular disease.2 (3) Bevacizumab stimulated antibody production, which leaded to circulating immune complexes or injury to glomerular structures. The membranoproliferative glomerulonephritis picture on biopsy in our patient suggested that stimulated antibody production that, in turn, leaded to antigen-antibody complex-mediated glomerulonephritis. (4) Bevacizumab was a kind of protein so it could lead to allergic reaction and induced interstitial nephritis.3

As we know, only 12 renal biopsy findings were published.2–7 Thrombotic microangiopathy was the main pathologic type, which presented in seven cases and other pathologic types could also be found including two cases of immune-complex-mediated glomerulonephritis, one case of cryoglobulinemic glomerulonephritis, one case of focal segmental glomerular sclerosis, one case of interstitial nephritis, and our case of membranoproliferative glomerulonephritis.

Jing Zhao, MD

Department of Respiratory Medicine

Peking Union Medical College Hospital

Peking, People’s Republic of China

Hang Li, MD

Department of Nephrology

Peking Union Medical College Hospital

Peking, People’s Republic of China

Mengzhao Wang, MD

Department of Respiratory Medicine

Peking Union Medical College Hospital

Peking, People’s Republic of China

Back to Top | Article Outline


1. Suzuki H, Inoue T, Matsushita T, et al. In vitro gene expression analysis of nephrotoxic drugs in rat primary renal cortical tubular cells. J Appl Toxicol 2008;28:237–248.

2. George BA, Zhou XJ, Toto R. Nephrotic syndrome after bevacizumab: case report and literature review. Am J Kidney Dis 2007;49:E23–E29.

3. Barakat RK, Singh N, Lal R, Verani RR, Finkel KW, Foringer JR. Interstitial nephritis secondary to bevacizumab treatment in metastatic leiomyosarcoma. Ann Phamacother 2007;41:707–710.

4. Johnson DH, Fehrenbacher L, Novotny WF, et al. Randomized phase II trial comparing bevacizumab plus carboplatin and paclitaxel with carboplatin and paclitaxel alone in previously untreated locally advanced or metastatic non-small-cell lung cancer. J Clin Oncol 2004;22:2184–2191.

5. Frangie C, Lefaucheur C, Medioni J, Jacquot C, Hill GS, Nochy D. Renal thrombotic microangiopathy caused by anti-VEGF-antibody treatment for metastatic renal-cell carcinoma. Lancet Oncol 2007;8:177–178.

6. Roncone D, Satoskar A, Nadasdy T, Monk JP, Rovin BH. Proteinuria in a patient receiving anti-VEGF therapy for metastatic renal cell carcinoma. Nat Clin Pract Nephrol 2007;3:287–293.

7. Eremina V, Jefferson JA, Kowalewska J, et al. VEGF inhibition and renal thrombotic microangiopathy. N Engl J Med 2008;358:1129–1136.

Cited By:

This article has been cited 1 time(s).

Journal of Ocular Pharmacology and Therapeutics
Ursodeoxycholic Acid and Tauroursodeoxycholic Acid Suppress Choroidal Neovascularization in a Laser-Treated Rat Model
Woo, SJ; Kim, JH; Yu, HG
Journal of Ocular Pharmacology and Therapeutics, 26(3): 223-229.
Back to Top | Article Outline

© 2009International Association for the Study of Lung Cancer


Article Tools



Other Ways to Connect



Visit on your smartphone. Scan this code (QR reader app required) with your phone and be taken directly to the site.

 For additional oncology content, visit LWW Oncology Journals on Facebook.