Renal thrombotic microangiopathy and podocytopathy associated with the use of carfilzomib in a patient with multiple myeloma

BMC Nephrology

Juan Carlos Q Velez³  Sally E Self¹  Liliane Hobeika² 

[1] Department of Pathology, Medical University of South Carolina, Charleston, SC, USA;Division of Nephrology and Hypertension, Department of Medicine, University of Louisville, 615 South Preston Street, Louisville, KY 40202, USA;Division of Nephrology, Department of Medicine, Medical University of South Carolina, Charleston, SC, USA

关键词: Proteinuria;    Proteasome inhibitor;    Malignant hypertension;    Thrombotic microangiopathy;   

Others  :  1082606
DOI  :  10.1186/1471-2369-15-156

 received in 2014-04-08, accepted in 2014-09-22,  发布年份 2014

【 摘 要 】

Background

Proteasome inhibitors are a relatively new class of chemotherapeutic agents. Bortezomib is the first agent of this class and is currently being used for the treatment of multiple myeloma. However, recent reports have linked exposure to bortezomib with the development of thrombotic microangiopathy. A new agent in this class, carfilzomib, has been recently introduced as alternative therapy for relapsing and refractory multiple myeloma. We report a case of renal thrombotic microangiopathy associated with the use of carfilzomib in a patient with refractory multiple myeloma.

Case presentation

A 62 year-old Caucasian man with hypertension and a 4-year history of multiple myeloma, had been previously treated with lenalidomide, bortezomib and two autologous hematopoietic stem cell transplants. After the second hematopoietic stem cell transplant, he developed acute kidney injury secondary to septic shock and required dialysis for 4 weeks. Subsequently, his serum creatinine stabilized at 2.1 mg/dL (185.64 μmol/L). Seventeen months after the second hematopoietic stem cell transplant, he was initiated on carfilzomib for relapse of multiple myeloma. Six weeks later, he developed abrupt worsening of lower extremity edema and hypertension, and new onset proteinuria. His kidney function remained stable. Kidney biopsy findings were consistent with thrombotic microangiopathy. Eight weeks after discontinuation of carfilzomib, proteinuria and hypertension improved. Due to progression of multiple myeloma, he died a few months later.

Conclusion

In view of the previously reported association of bortezomib with thrombotic microangiopathy, the temporal association of the clinical picture with the initiation of carfilzomib, and the partial resolution of symptoms after discontinuation of the drug, we conclude that carfilzomib may have precipitated a case of clinically evident renal thrombotic microangiopathy in our patient.

【 授权许可】

   
2014 Hobeika et al.; licensee BioMed Central Ltd.

【 图 表 】

Figure 1.

Figure 2.

【 参考文献 】

• [1]Sanders PW, Booker BB: Pathobiology of cast nephropathy from human Bence Jones proteins. J Clin Invest 1992, 89(2):630. doi:10.1172/JCI115629
• [2]Smolens P, Barnes JL, Kreisberg R: Hypercalcemia can potentiate the nephrotoxicity of Bence Jones proteins. J Lab Clin Med 1987, 110:460-465.
• [3]Markowitz GS, Fine PL, Stack JI, Kunis CL, Radhakrishnan J, Palecki W, Park J, Nasr SH, Hoh S, Siegel DS, D’Agati VD: Toxic acute tubular necrosis following treatment with zoledronate. Kidney Int 2003, 64(1):281-289.
• [4]Batts ED, Sanchorawala V, Hegerfeldt Y, Lazarus HM: Azotemia associated with use of lenalidomide in plasma cell dyscrasias. Leuk Lymphoma 2008, 49(6):1108-1115. doi:10.1080/10428190802023707
• [5]Parikh CR, Coca SG: Acute renal failure in hematopoietic cell transplantation. Kidney Int 2006, 69(3):430-435.
• [6]Changsirikulchai S, Myerson D, Guthrie KA, McDonald GB, Alpers CE, Hingorani SR: Renal thrombotic microangiopathy after hematopoietic cell transplant: role of GVHD in pathogenesis. Clin J Am Soc Nephrol 2009, 4(2):345-353. doi:10.2215/CJN.02070508
• [7]Choi MK, Hong JY, Jang JH, Lim HY: TTP-HUS associated with sunitinib. Cancer Res Treat 2008, 40(4):211-213. doi:10.4143/crt.2008.40.4.211
• [8]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(11):1129-1136. doi:10.1056/NEJMoa0707330
• [9]Naranjo CA, Busto U, Sellers EM, Sandor P, Ruiz I, Roberts EA, Janecek E, Domecq C, Greenblatt DJ: A method for estimating the probability of adverse drug reactions. Clin Pharmacol Ther 1981, 30(2):239-245.
• [10]Iacopino P, Pucci G, Arcese W, Bosi A, Falda M, Locatelli F, Marenco P, Miniero R, Morabito F, Rossetti F, Sica S, Uderzo C, Bacigalupo A: Severe thrombotic microangiopathy: an infrequent complication of bone marrow transplantation. Bone Marrow Transplant 1999, 24(1):47-51.
• [11]Griffiths MH, Crowe AV, Papadaki L, Banner NR, Yacoub MH, Thompson FD, Neild GH: Cyclosporin nephrotoxicity in heart and lung transplant patients. Q J Med 1996, 89(10):751-763.
• [12]Roy V, Rizvi MA, Vesely SK, George JN: Thrombotic thrombocytopenic purpura-like syndromes following bone marrow transplantation: an analysis of associated conditions and clinical outcomes. Bone Marrow Transplant 2001, 27(6):641-646.
• [13]Lugassy G, Ducach A, Blumenthal R: Fatal chronic relapsing thrombotic thrombocytopenic purpura following autologous bone marrow transplantation for chronic myeloid leukemia. Bone Marrow Transplant 1998, 21(8):859-860.
• [14]Ohno E, Ohtsuka E, Iwashita T, Uno N, Ogata M, Kikuchi H, Nasu M: Hemolytic uremic syndrome following autologous peripheral blood stem cell transplantation in a patient with malignant lymphoma. Bone Marrow Transplant 1997, 19(10):1045-1047.
• [15]Morita R, Hashino S, Shirai S, Fujita N, Onozawa M, Kahata K, Kondo T, Imamura M, Asaka M: Thrombotic microangiopathy after treatment with bortezomib and dexamethasone in a patient with multiple myeloma. Int J Hematol 2008, 88(2):248-250. doi:10.1007/s12185-008-0140-1
• [16]Moore H, Romeril K: Multiple myeloma presenting with a fever of unknown origin and development of thrombotic thrombocytopenic purpura post-bortezomib. Intern Med J 2011, 41(4):348-350. doi:10.1111/j.1445-5994.2011.02458.x
• [17]Salmenniemi U, Remes K: Thrombotic microangiopathy associated with bortezomib treatment in a patient with relapsed multiple myeloma. Hematol Rep 2012, 4(2):e13. doi:10.4081/hr.2012.e13
• [18]Mehta N, Saxena A, Niesvizky R: Bortezomib-induced thrombotic thrombocytopaenic purpura. BMJ Case Rep 2012, bcr2012006461. doi:10.1136/bcr-2012-006461
• [19]Karin M, Cao Y, Greten FR, Li ZW: NF-kappaB in cancer: from innocent bystander to major culprit. Nat Rev Cancer 2002, 2(4):301-310.
• [20]Usui J, Glezerman IG, Salvatore SP, Chandran CB, Flombaum CD, Seshan SV: Clinicopathological spectrum of kidney diseases in cancer patients treated with vascular endothelial growth factor inhibitors: a report of 5 cases and review of literature. Hum Pathol 2014, 45(9):1918-1927. doi:10.1016/j.humpath.2014.05.015. Epub 2014 Jun 12
• [21]Vigneau C, Lorcy N, Dolley-Hitze T, Jouan F, Arlot-Bonnemains Y, Laguerre B, Verhoest G, Goujon JM, Belaud-Rotureau MA, Rioux-Leclercq N: All anti-vascular endothelial growth factor drugs can induce ‘pre-eclampsia-like syndrome’: a RARe study. Nephrol Dial Transplant 2014, 29(2):325-332. doi:10.1093/ndt/gft465. Epub 2013 Dec 2
• [22]Mateos MV, San Miguel JF: Bortezomib in multiple myeloma. Best Pract Res Clin Haematol 2007, 20(4):701-715.
• [23]Horowitz JR, Rivard A, van der Zee R, Hariawala M, Sheriff DD, Esakof DD, Chaudhry GM, Symes JF, Isner JM: Vascular endothelial growth factor/vascular permeability factor produces nitric oxide-dependent hypotension: evidence for a maintenance role in quiescent adult endothelium. Arterioscler Thromb Vasc Biol 1997, 17(11):2793-2800.
• [24]Robinson ES, Khankin EV, Karumanchi SA, Humphreys BD: Hypertension induced by vascular endothelial growth factor signaling pathway inhibition: mechanisms and potential use as a biomarker. Semin Nephrol 2010, 30(6):591-601. doi:10.1016/j.semnephrol.2010.09.007
• [25]Yang KS, Jeon H, Park Y, Jo IH, Kim JI, Moon IS, Choi BS, Park CW, Yang CW, Kim YS, Chung BH: Use of bortezomib as anti-humoral therapy in kidney transplantation. J Korean Med Sci 2014, 29(5):648-651. doi:10.3346/jkms.2014.29.5.648. Epub 2014 Apr 25
• [26]Zinn MD, L’Ecuyer TJ, Fagoaga OR, Aggarwal S: Bortezomib use in a pediatric cardiac transplant center. Pediatr Transplant 2014, 18(5):469-476. doi:10.1111/petr.12300. Epub 2014 Jun 14. PMID: 24931171[PubMed - in process]
• [27]Eskandary F, Bond G, Schwaiger E, Kikic Z, Winzer C, Wahrmann M, Marinova L, Haslacher H, Regele H, Oberbauer R, Böhmig GA: Bortezomib in late antibody-mediated kidney transplant rejection (BORTEJECT Study): study protocol for a randomized controlled trial. Trials 2014, 15:107. doi:10.1186/1745-6215-15-107 BioMed Central Full Text
• [28]Demo SD, Kirk CJ, Aujay MA, Buchholz TJ, Dajee M, Ho MN, Jiang J, Laidig GJ, Lewis ER, Parlati F, Shenk KD, Smyth MS, Sun CM, Vallone MK, Woo TM, Molineaux CJ, Bennett MK: Antitumor activity of PR-171, a novel irreversible inhibitor of the proteasome. Cancer Res 2007, 67(13):6383-6391.