Immunoglobulin A nephropathy with massive paramesangial deposits caused by anti-vascular endothelial growth factor therapy for metastatic rectal cancer: a case report and review of the literature

BMC Research Notes

Jun Soma⁴  Shigehisa Aoki¹  Hiroshi Sato²  Tsutomu Sakuma³  Izaya Nakaya⁴  Mayumi Yahata⁴ 

[1] Department of Pathology & Biodefense, Faculty of Medicine, Saga University, Saga 849-8501, Japan;Department of Clinical Pharmacology and Therapeutics, Tohoku University Graduate School of Pharmaceutical Sciences and Medicine, Tohoku University, Sendai 980-8578, Japan;Division of Pathology, Iwate Prefectural Central Hospital, 1-4-1 Ueda, Morioka, Iwate 020-0066, Japan;Division of Nephrology, Iwate Prefectural Central Hospital, 1-4-1 Ueda, Morioka, Iwate 020-0066, Japan

关键词: Immunoglobulin A nephropathy;    Anti-vascular endothelial growth factor therapy;    Nephrotic syndrome;    Bevacizumab;   

Others  :  1140876
DOI  :  10.1186/1756-0500-6-450

 received in 2013-08-30, accepted in 2013-11-05,  发布年份 2013

【 摘 要 】

Background

Bevacizumab, a recombinant humanized monoclonal antibody for vascular endothelial growth factor, has been widely used in various cancers offering substantial clinical benefit. It is reportedly associated with development of high-grade proteinuria and nephrotic syndrome with the histology of thrombotic microangiopathy, but there has been no report describing the development of immunoglobulin A nephropathy in bevacizumab-treated patients.

Case presentation

A 68-year-old man with metastatic rectal cancer was treated with bevacizumab. He presented with hematuria and proteinuria 15 and 17 months, respectively, after bevacizumab initiation. Bevacizumab was stopped at 17 months. Renal biopsy at 19 months revealed immunoglobulin A nephropathy, with numerous paramesangial hemispherical deposits and thrombotic microangiopathy. Electron microscopy showed numerous paramesangial electron-dense deposits of various sizes, and subendothelial injuries. Proteinuria almost completely resolved 8 months after bevacizumab cessation, although hematuria persisted. Follow-up renal biopsy 11 months after bevacizumab cessation showed a marked decrease in mesangial immunoglobulin A deposits and paramesangial electron-dense deposits, which correlated with a gradual decrease in serum immunoglobulin A.

Conclusion

This is the first case report that confirmed histologically the development and resolution of immunoglobulin A nephropathy during and after bevacizumab therapy. This case shows that there may be other mechanisms of glomerular injury by bevacizumab besides glomerular endothelial injury leading to thrombotic microangiopathy.

【 授权许可】

   
2013 Yahata et al.; licensee BioMed Central Ltd.

【 图 表 】

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【 参考文献 】

• [1]Ferrara N: Vascular endothelial growth factor: basic science and clinical progress. Endocr Rev 2004, 25:581-611.
• [2]Genentech, Inc.: Avastin® (Bevacizumab) Product Information. San Francisco, CA: Genentech, Inc.; 2009.
• [3]Wu S, Kim C, Baer L, Zhu X: Bevacizumab increases risk for severe proteinuria in cancer patients. J Am Soc Nephrol 2010, 21:1381-1389.
• [4]Eremina V, Jefferson JA, Kowalewska J, Hochster H, Haas M, Weisstuch J, Richardson C, Kopp JB, Kabir MG, Backx PH, Gerber HP, Ferrara N, Barisoni L, Alpers CE, Quaggin SE: VEGF inhibition and renal thrombotic microangiopathy. N Engl J Med 2008, 358:1129-1136.
• [5]Frangié 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]Gordon MS, Margolin K, Talpaz M, Sledge GW Jr, Holmgren E, Benjamin R, Stalter S, Shak S, Adelman D: Phase I safety and pharmacokinetic study of recombinant human anti-vascular endothelial growth factor in patients with advanced cancer. J Clin Oncol 2000, 19:843-850.
• [7]Zhu X, Wu S, Dahut WL, Parikh CR: Risks of proteinuria and hypertension with bevacizumab, an antibody against vascular endothelial growth factor: systematic review and meta-analysis. Am J Kidney Dis 2007, 49:186-193.
• [8]Schrijvers BF, Flyvbjerg A, De Vriese AS: The role of vascular endothelial growth factor (VEGF) in renal pathophysiology. Kidney Int 2004, 65:2003-2017.
• [9]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.
• [10]Johnson DH, Fehrenbacher L, Novotny WF, Herbst RS, Nemunaitis JJ, Jablons DM, Langer CJ, Devore RF 3rd, Gaudreault J, Damico LA, Holmgren E, Kabbinavar F: 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.
• [11]Miller KD, Chap LI, Holmes FA, Cobleigh MA, Marcom PK, Fehrenbacher L, Dickler M, Overmoyer BA, Reimann JD, Sing AP, Langmuir V, Rugo HS: Randomized phase III trial of capecitabine compared with bevacizumab plus capecitabine in patients with previously treated metastatic breast cancer. J Clin Oncol 2005, 23:792-799.
• [12]Stokes MB, Erazo MC, D’Agati VD: Glomerular disease related to anti-VEGF therapy. Kidney Int 2008, 74:1487-1491.
• [13]George BA, Zhou XJ, Toto R: Nephrotic syndrome after bevacizumab: case report and literature review. Am J Kidney Dis 2007, 49:E23-E29.
• [14]Yeh J, Frieze D, Martins R, Carr L: Clinical utility of bevacizumab for metastatic solid tumors. Ann Pharmacother 2010, 44:1010-1015.
• [15]Taguchi T, Von Bassewitz DB, Grundmann E, Takebayashi S: Ultrastructural changes of glomerular basement membrane in IgA nephritis: relationship to hematuria. Ultrastruct Pathol 1988, 12:17-26.
• [16]Jonkers IJ, van Buren M: Nephrotic-range proteinuria in a patient with a renal allograft treated with sorafenib for metastatic renal-cell carcinoma. Clin Exp Nephrol 2009, 13:397-401.
• [17]Melichar B, Hyspler R, Kalábová H, Dvorák J, Tichá A, Zadák Z: Gastroduodenal, intestinal and colonic permeability during anticancer therapy. Hepatogastroenterology 2011, 58:1193-1199.
• [18]Cerutti A, Chen K, Chorny A: Immunoglobulin responses at the mucosal interface. Annu Rev Immunol 2011, 29:273-293.
• [19]Pouria S, Barratt J: Secondary IgA nephropathy. Semin Nephrol 2008, 28:27-37.