Angiotensin II Type 1 Receptor Antibodies and Native Kidney Function in Pediatric Liver and Intestinal Transplant Recipients

Overview

Journal Pediatr Nephrol

Specialties Nephrology
Pediatrics

Date 2023 Jul 11

PMID 37432534

Authors

Rachel Stern

Lucia Chen

Alvin P Chan

Laura J Wozniak

Meghan Pearl

Affiliations

Soon will be listed here.

Abstract

Background: Angiotensin II type-1 receptor antibody (AT1R-Ab) has been associated with vascular injury and kidney dysfunction in pediatric kidney transplant recipients. The role of AT1R-Ab in the development of chronic kidney disease in pediatric liver and intestinal transplant recipients has not been explored.

Methods: Twenty-five pediatric intestinal transplant recipients and 79 pediatric liver transplant recipients had AT1R-Ab levels measured at varying time points in the post-transplant period. Estimated glomerular filtration rate (eGFR) was determined using creatinine based CKiD U25 equation and measured at time of AT1R-Ab measurement, at 1 year post-AT1R-Ab measurement, at 5 years post-AT1R-Ab measurement, and at the most recent routine clinic visit. The prevalence of hypertension and antihypertensive medication use were also evaluated.

Results: Younger age at time of AT1R-Ab measurement was associated with AT1R-Ab positivity in liver transplant recipients. There was no association between AT1R-Ab status and change in eGFR, prevalence of hypertension, or use of antihypertensive medications at the described time points.

Conclusions: AT1R-Ab positivity was not associated with a decline in eGFR or hypertension in pediatric liver and intestinal transplant recipients. Further studies are needed using other markers of kidney function, such as cystatin C, to validate this finding. A higher resolution version of the Graphical abstract is available as Supplementary information.

References

Dragun D, Muller D, Brasen J, Fritsche L, Nieminen-Kelha M, Dechend R . Angiotensin II type 1-receptor activating antibodies in renal-allograft rejection. N Engl J Med. 2005; 352(6):558-69. DOI: 10.1056/NEJMoa035717. View

Sun Q, Liu Z, Yin G, Chen H, Chen J, Li L . Detectable circulating antiendothelial cell antibodies in renal allograft recipients with C4d-positive acute rejection: a report of three cases. Transplantation. 2005; 79(12):1759-62. DOI: 10.1097/01.tp.0000163290.19788.e7. View

Dandona P, Dhindsa S, Ghanim H, Chaudhuri A . Angiotensin II and inflammation: the effect of angiotensin-converting enzyme inhibition and angiotensin II receptor blockade. J Hum Hypertens. 2006; 21(1):20-7. DOI: 10.1038/sj.jhh.1002101. View

Ruiz-Ortega M, Lorenzo O, Ruperez M, Konig S, Wittig B, Egido J . Angiotensin II activates nuclear transcription factor kappaB through AT(1) and AT(2) in vascular smooth muscle cells: molecular mechanisms. Circ Res. 2000; 86(12):1266-72. DOI: 10.1161/01.res.86.12.1266. View

Lefaucheur C, Viglietti D, Bouatou Y, Philippe A, Pievani D, Aubert O . Non-HLA agonistic anti-angiotensin II type 1 receptor antibodies induce a distinctive phenotype of antibody-mediated rejection in kidney transplant recipients. Kidney Int. 2019; 96(1):189-201. DOI: 10.1016/j.kint.2019.01.030. View

Bjerre A, Tangeraas T, Heidecke H, Dragun D, Dechend R, Staff A . Angiotensin II type 1 receptor antibodies in childhood kidney transplantation. Pediatr Transplant. 2016; 20(5):627-32. DOI: 10.1111/petr.12728. View

Kang Z, Liu C, Liu W, Li D . Effect of anti-angiotensin II type 1 receptor antibodies on the outcomes of kidney transplantation: a systematic review and meta-analysis. Nephrol Dial Transplant. 2021; 37(6):1171-1180. DOI: 10.1093/ndt/gfab344. View

Giral M, Foucher Y, Dufay A, Duong van Huyen J, Renaudin K, Moreau A . Pretransplant sensitization against angiotensin II type 1 receptor is a risk factor for acute rejection and graft loss. Am J Transplant. 2013; 13(10):2567-76. DOI: 10.1111/ajt.12397. View

Banasik M, Boratynska M, Koscielska-Kasprzak K, Kaminska D, Zmonarski S, Mazanowska O . Non-HLA antibodies: angiotensin II type 1 receptor (anti-AT1R) and endothelin-1 type A receptor (anti-ETAR) are associated with renal allograft injury and graft loss. Transplant Proc. 2014; 46(8):2618-21. DOI: 10.1016/j.transproceed.2014.09.029. View

10.

Liu C, Kang Z, Yin Z, Xiao Y, Liu W, Zhao Y . Levels of angiotensin II type-1 receptor antibodies and endothelin-1 type-A receptor antibodies correlate with antibody-mediated rejection and poor graft function in kidney-transplantation patients. Transpl Immunol. 2022; 74:101674. DOI: 10.1016/j.trim.2022.101674. View

11.

Senev A, Ray B, Lerut E, Hariharan J, Heylen C, Kuypers D . The Pre-Transplant Non-HLA Antibody Burden Associates With the Development of Histology of Antibody-Mediated Rejection After Kidney Transplantation. Front Immunol. 2022; 13:809059. PMC: 8888449. DOI: 10.3389/fimmu.2022.809059. View

12.

Taniguchi M, Rebellato L, Cai J, Hopfield J, Briley K, Haisch C . Higher risk of kidney graft failure in the presence of anti-angiotensin II type-1 receptor antibodies. Am J Transplant. 2013; 13(10):2577-89. DOI: 10.1111/ajt.12395. View

13.

Pearl M, Zhang Q, Palma Diaz M, Grotts J, Rossetti M, Elashoff D . Angiotensin II Type 1 receptor antibodies are associated with inflammatory cytokines and poor clinical outcomes in pediatric kidney transplantation. Kidney Int. 2017; 93(1):260-269. PMC: 5750071. DOI: 10.1016/j.kint.2017.06.034. View

14.

Hesemann L, Subramanian V, Mohanakumar T, Dharnidharka V . De novo development of antibodies to kidney-associated self-antigens angiotensin II receptor type I, collagen IV, and fibronectin occurs at early time points after kidney transplantation in children. Pediatr Transplant. 2015; 19(5):499-503. PMC: 4485575. DOI: 10.1111/petr.12531. View

15.

Fichtner A, Susal C, Schroder C, Hocker B, Rieger S, Waldherr R . Association of angiotensin II type 1 receptor antibodies with graft histology, function and survival in paediatric renal transplant recipients. Nephrol Dial Transplant. 2018; 33(6):1065-1072. DOI: 10.1093/ndt/gfy008. View

16.

Pearl M, Grotts J, Rossetti M, Zhang Q, Gjertson D, Weng P . Cytokine Profiles Associated With Angiotensin II Type 1 Receptor Antibodies. Kidney Int Rep. 2019; 4(4):541-550. PMC: 6451195. DOI: 10.1016/j.ekir.2018.12.011. View

17.

Chan A, Guerra M, Rossetti M, Hickey M, Venick R, Marcus E . Non-HLA AT1R antibodies are highly prevalent after pediatric intestinal transplantation. Pediatr Transplant. 2021; 25(3):e13987. PMC: 8058288. DOI: 10.1111/petr.13987. View

18.

Wozniak L, Hickey M, Chan A, Venick R, Farmer D, Busuttil R . Angiotensin II Type-1 Receptor Antibodies Are Associated With Active Allograft Dysfunction Following Pediatric Liver Transplantation. Transplantation. 2020; 104(12):2547-2556. DOI: 10.1097/TP.0000000000003206. View

19.

Ohe H, Uchida Y, Yoshizawa A, Hirao H, Taniguchi M, Maruya E . Association of anti-human leukocyte antigen and anti-angiotensin II type 1 receptor antibodies with liver allograft fibrosis after immunosuppression withdrawal. Transplantation. 2014; 98(10):1105-11. DOI: 10.1097/TP.0000000000000185. View

20.

Williams C, Borges K, Banh T, Vasilevska-Ristovska J, Chanchlani R, Ng V . Patterns of kidney injury in pediatric nonkidney solid organ transplant recipients. Am J Transplant. 2017; 18(6):1481-1488. DOI: 10.1111/ajt.14638. View