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Pediatric Nephrology

Erschienen in:

01.08.2015 | Brief Report

Accelerated rejection, thrombosis, and graft failure with angiotensin II type 1 receptor antibodies

verfasst von: Meghan H. Pearl, Richard K. Leuchter, Elaine F. Reed, Qiuheng Zhang, Robert B. Ettenger, Eileen W. Tsai

Erschienen in: Pediatric Nephrology | Ausgabe 8/2015

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Abstract

Background

Angiotensin II type 1 receptor antibodies (AT₁R-Abs) have been implicated in renal transplant rejection and failure; however, the mechanism of allograft damage, patterns of clinical presentation, and response to desensitization of AT₁R-Abs have not been clearly established.

Case diagnosis/treatment

We present the case of a 7-year-old boy with preformed AT₁R-Abs who developed accelerated vascular and cellular rejection and renal allograft thrombosis despite desensitization and treatment with angiotensin receptor blockade. Although an association between AT₁R-Abs and microvascular occlusion has been previously described, we are the first to describe an association between AT₁R-Abs and renal artery thrombosis, leading to devastating early allograft failure.

Conclusions

This case highlights the risk of allograft thrombosis associated with AT₁R-Abs and illustrates that previous treatments utilized for AT₁R-Abs may not always be effective. Further studies are needed to better characterize the mechanisms of AT₁R-Ab pathogenesis and to establish safe levels of AT₁R-Abs both pre- and post-transplantation. Given the outcome of this patient and the evidence of pro-coagulatory effects of AT₁R-Abs, we suggest that the presence of AT₁R-Ab may be a risk factor for thrombosis. The role of treatment with anti-coagulation and novel immunomodulatory agents such as tocilizumab and bortezomib require further investigation.

Morris PJ, Williams GM, Hume DM, Mickey MR, Terasaki PI (1968) Serotyping for homotransplantation. XII. Occurrence of cytotoxic antibodies following kidney transplantation in man. Transplantation 6:392–399PubMedCrossRef

Tait BD, Susal C, Gebel HM, Nickerson PW, Zachary AA, Claas FH, Reed EF, Bray RA, Campbell P, Chapman JR, Coates PT, Colvin RB, Cozzi E, Doxiadis II, Fuggle SV, Gill J, Glotz D, Lachmann N, Mohanakumar T, Suciu-Foca N, Sumitran-Holgersson S, Tanabe K, Taylor CJ, Tyan DB, Webster A, Zeevi A, Opelz G (2013) Consensus guidelines on the testing and clinical management issues associated with HLA and non-HLA antibodies in transplantation. Transplantation 95:19–47PubMedCrossRef

Mohan S, Palanisamy A, Tsapepas D, Tanriover B, Crew RJ, Dube G, Ratner LE, Cohen DJ, Radhakrishnan J (2012) Donor-specific antibodies adversely affect kidney allograft outcomes. J Am Soc Nephrol 23:2061–2071PubMedCentralPubMedCrossRef

Dragun D, Muller DN, Brasen JH, Fritsche L, Nieminen-Kelha M, Dechend R, Kintscher U, Rudolph B, Hoebeke J, Eckert D, Mazak I, Plehm R, Schonemann C, Unger T, Budde K, Neumayer HH, Luft FC, Wallukat G (2005) Angiotensin II type 1-receptor activating antibodies in renal-allograft rejection. N Engl J Med 352:558–569PubMedCrossRef

Reinsmoen NL, Lai CH, Heidecke H, Haas M, Cao K, Ong G, Naim M, Wang Q, Mirocha J, Kahwaji J, Vo AA, Jordan SC, Dragun D (2010) Anti-angiotensin type 1 receptor antibodies associated with antibody-mediated rejection in donor HLA antibody negative patients. Transplantation 90:1473–1477PubMedCrossRef

Giral M, Foucher Y, Dufay A, Van Huyen JP, Renaudin K, Moreau A, Philippe A, Hegner B, Dechend R, Heidecke H, Brouard S, Cesbron A, Castagnet S, Devys A, Soulillou JP, Dragun D (2013) Pretransplant sensitization against angiotensin II type 1 receptor is a risk factor for acute rejection and graft loss. Am J Transplant 13:2567–2576PubMedCrossRef

Taniguchi M, Rebellato LM, Cai J, Hopfield J, Briley KP, Haisch CE, Catrou PG, Bolin P, Parker K, Kendrick WT, Kendrick SA, Harland RC, Terasaki PI (2013) Higher risk of kidney graft failure in the presence of anti-angiotensin II type-1 receptor antibodies. Am J Transplant 13:2577–2589PubMedCrossRef

Zhang Q, Cecka JM, Gjertson DW, Ge P, Rose ML, Patel JK, Ardehali A, Kobashigawa JA, Fishbein MC, Reed EF (2011) HLA and MICA: targets of antibody-mediated rejection in heart transplantation. Transplantation 91:1153–1158PubMedCentralPubMedCrossRef

Kamińska M, Mogielnicki A, Stankiewicz A, Kramkowski K, Domaniewski T, Buczko W, Chabielska E (2005) Angiotensin II via AT1 receptor accelerates arterial thrombosis in renovascular hypertensive rats. J Physiol Pharmacol 56:571–585PubMed

10.

Dobado-Berrios PM, Lopez-Pedrera C, Velasco F, Cuadrado MJ (2001) The role of tissue factor in the antiphospholipid syndrome. Arthritis Rheum 44:2467–2476PubMedCrossRef

11.

Holschermann H, Bohle RM, Schmidt H, Zeller H, Fink L, Stahl U, Grimm H, Tillmanns H, Haberbosch W (2000) Hirudin reduces tissue factor expression and attenuates graft arteriosclerosis in rat cardiac allografts. Circulation 102:357–363PubMedCrossRef

12.

Lukitsch I, Kehr J, Chaykovska L, Wallukat G, Nieminen-Kelha M, Batuman V, Dragun D, Gollasch M (2012) Renal ischemia and transplantation predispose to vascular constriction mediated by angiotensin II type 1 receptor-activating antibodies. Transplantation 94:8–13PubMedCrossRef

13.

Samama MM (2011) The mechanism of action of rivaroxaban–an oral, direct Factor Xa inhibitor–compared with other anticoagulants. Thromb Res 127:497–504PubMedCrossRef

14.

Berry CN, Girardot C, Lecoffre C, Lunven C (1994) Effects of the synthetic thrombin inhibitor argatroban on fibrin- or clot-incorporated thrombin: comparison with heparin and recombinant Hirudin. Thromb Haemost 72:381–386PubMed

15.

Giugliano RP, Wiviott SD, Stone PH, Simon DI, Schweiger MJ, Bouchard A, Leesar MA, Goulder MA, Deitcher SR, McCabe CH, Braunwald E, Investigators A-T- (2007) Recombinant nematode anticoagulant protein c2 in patients with non-ST-segment elevation acute coronary syndrome: the ANTHEM-TIMI-32 trial. J Am Coll Cardiol 49:2398–2407PubMedCrossRef

16.

Lee A, Agnelli G, Buller H, Ginsberg J, Heit J, Rote W, Vlasuk G, Costantini L, Julian J, Comp P, van Der Meer J, Piovella F, Raskob G, Gent M (2001) Dose–response study of recombinant factor VIIa/tissue factor inhibitor recombinant nematode anticoagulant protein c2 in prevention of postoperative venous thromboembolism in patients undergoing total knee replacement. Circulation 104:74–78PubMedCrossRef

17.

Amaral LM, Kiprono L, Cornelius DC, Shoemaker C, Wallace K, Moseley J, Wallukat G, Martin JN Jr, Dechend R, LaMarca B (2014) Progesterone supplementation attenuates hypertension and the autoantibody to the angiotensin II type I receptor in response to elevated interleukin-6 during pregnancy. Am J Obstet Gynecol 211(158):e151–e156

18.

Kim I, Wu G, Chai NN, Klein AS, Jordan S (2014) Anti-interleukin 6 receptor antibodies attenuate antibody recall responses in a mouse model of allosensitization. Transplantation. doi:10.1097/TP.0000000000000437

19.

Perry DK, Burns JM, Pollinger HS, Amiot BP, Gloor JM, Gores GJ, Stegall MD (2009) Proteasome inhibition causes apoptosis of normal human plasma cells preventing alloantibody production. Am J Transplant 9:201–209PubMedCrossRef

Titel: Accelerated rejection, thrombosis, and graft failure with angiotensin II type 1 receptor antibodies
verfasst von: Meghan H. Pearl
Richard K. Leuchter
Elaine F. Reed
Qiuheng Zhang
Robert B. Ettenger
Eileen W. Tsai
Publikationsdatum: 01.08.2015
Verlag: Springer Berlin Heidelberg
Erschienen in: Pediatric Nephrology / Ausgabe 8/2015
Print ISSN: 0931-041X
Elektronische ISSN: 1432-198X
DOI: https://doi.org/10.1007/s00467-015-3123-5

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Accelerated rejection, thrombosis, and graft failure with angiotensin II type 1 receptor antibodies