Predictors of graft outcome in renal transplant recipients with antibody-mediated rejection

DOI: https://doi.org/10.31450/ukrjnd.3(71).2021.04
Keywords: renal transplantation, antibody-mediated rejection, graft survival.

Abstract

Abstract. Active and chronic antibody-mediated rejection (ABMR) is a common cause of graft failure. Prognostic markers of this complication are not well defined. We aimed to find out the demographic, histopathological and clinical characteristics of transplant recipients who developed ABMR and evaluate the impact of these features,  and anti-rejection treatment modalities on graft survival.  

Methods. Thirty-two patients who developed ABMR (22 male; mean age 40.59±12.52 years) were included in this study. Data were evaluated retrospectively and graft survival was analyzed. All transplant biopsies were evaluated according to Banff's 2013 classification.

Results. Among the 32 cases, 26  were transplanted from living donors. Mean serum creatinine at the time of biopsy was 1.99 ±0.09 mg/dL. Proteinuria was  1566.06±353.92 mg/day at the time of biopsy.  The need for hemodialysis was significantly related with initial creatinine (p = 0.003); creatinine after three months (p < 0.001) and final creatinine (p < 0.001) as well as initial proteinuria (p = 0.005); proteinuria after three months (p < 0.001) and final proteinuria (p < 0.001). 6 cases showed diffuse C4d positivity, 26  cases showed focal c4d positivity. Five of 6 patients with diffuse C4d staining in renal biopsy were hemodialyzed at first and third months despite anti-rejection therapy (p=0.029 and 0.041,  respectively).

Mean survival time was 1654.67±220.40 (95% CI 1222.68-2086.66) days for focal staining C4d cases and 366.16±36.44 (95% CI 294.73-437.60) days for diffuse staining C4d cases. The difference was statistically significant (p=0.012). Two of the patients died, 15 experienced graft loss and 17 survived with functioning grafts. Mean survival time between anti-rejection treatment modalities showed no statistical significance (p=0.15)

Conclusions. Serum creatinine, proteinuria at the time of biopsy, diffuse peritubular C4d staining were significantly associated with graft survival. Early diagnosis is important to improve success in the treatment of ABMR and graft survival

Downloads

Download data is not yet available.

References

Womer K, Rabb H. Immunologic Principles in Kidney Transplantation. In Comprehensive Clinical Nephrology. Elsevier Inc. 2010. p. 1119-1133 doi:10.1016/B978-0-323-05876-6.00096-4.

Nast CC, Cohen AH. Pathology of kidney transplantation. In Handbook of Kidney Transplantation. 5th ed. Philadelphia, PA: Lippincott Williams and Wilkins. 2017. p. 311–329.

Haas M, Loupy A, Lefaucheur C, et al. The Banff 2017 Kidney Meeting Report: Revised diagnostic criteria for chronic active T cell-mediated rejection, antibody-mediated rejection, and prospects for integrative endpoints for next-generation clinical trials. Am J Transplant. 2018;18(2):293-307. doi:10.1111/ajt.14625.

Farkash EA, Colvin RB. Diagnostic challenges in chronic antibody-mediated rejection. Nat Rev Nephrol. 2012;8(5):255-7. doi: 10.1038/nrneph.2012.61.

Drachenberg CB, Papadimitriou JC. Endothelial injury in renal antibody-mediated allograft rejection: a schematic view based on pathogenesis. Transplantation. 2013;95(9):1073-83. doi: 10.1097/TP.0b013e31827e6b45.

Singh N, Pirsch J, Samaniego M. Antibody-mediated rejection: treatment alternatives and outcomes. Transplant Rev (Orlando). 2009;23(1):34-46. doi:10.1016/j.trre.2008.08.004.

Perry DK, Burns JM, Pollinger HS, Amiot BP, Gloor JM, Gores GJ, Stegall MD. Proteasome inhibition causes apoptosis of normal human plasma cells preventing alloantibody production. Am J Transplant. 2009;9(1):201-9. doi: 10.1111/j.1600-6143.2008.02461.x.

Faguer S, Kamar N, Guilbeaud-Frugier C, Fort M, Modesto A, Mari A, et al. Rituximab therapy for acute humoral rejection after kidney transplantation. Transplantation. 2007;83(9):1277-80. doi:10.1097/01.tp.0000261113.30757.d1.

Montgomery RA, Zachary AA, Racusen LC, Leffell MS, King KE, Burdick J, et al. Plasmapheresis and intravenous immune globulin provides effective rescue therapy for refractory humoral rejection and allows kidneys to be successfully transplanted into cross-match-positive recipients. Transplantation. 2000;70(6):887-95. doi:10.1097/00007890-200009270-00006.

Akagun T, Yazici H, Caliskan Y, Ozluk Y, Sahin S, Turkmen A, et al. The effect of histopathologic and clinical features on allograft survival in renal transplant patients with antibody-mediated rejection. Ren Fail. 2017;39(1):19-25. doi:10.1080/0886022X.2016.1244073.

Yilmaz VT, Suleymanlar G, Koksoy S, Ulger BV, Ozdem S, Akbas H, et al. Therapy Modalities for Antibody Mediated Rejection in Renal Transplant Patients. J Invest Surg. 2016;29(5):282-8. doi:10.3109/08941939.2016.1154626.

Carpio VN, Rech C, Eickhoff EI, Pegas KL, Edelweiss MI, Gonçalves LF, Manfro RC, Veronese FV. Clinical and pathological correlations of C4d immunostaining and its influence on the outcome of kidney transplant recipients. J Bras Nefrol. 2011;33(3):329-37. doi:10.1590/s0101-28002011000300009.

Colvin RB. Antibody-mediated renal allograft rejection: diagnosis and pathogenesis. J Am Soc Nephrol. 2007;18(4):1046-56. doi:10.1681/ASN.2007010073.

Lederer SR, Kluth-Pepper B, Schneeberger H, Albert E, Land W, Feucht HE. Impact of humoral alloreactivity early after transplantation on the long-term survival of renal allografts. Kidney Int. 2001;59(1):334-41. doi:10.1046/j.1523-1755.2001.00495.x.

Rocha PN, Butterly DW, Greenberg A, Reddan DN, Tuttle-Newhall J, Collins BH, et al. Beneficial effect of plasmapheresis and intravenous immunoglobulin on renal allograft survival of patients with acute humoral rejection. Transplantation. 2003;75(9):1490-5. doi:10.1097/01.TP.0000060252.57111.AC.

Yalcintas A, Sayin B, Turgut D, Atay G, Colak T, Haberal M. Risk Factors of Antibody-Mediated Rejection and Predictors of Outcome in Kidney Transplant Recipients. Exp Clin Transplant. 2020;18(Suppl 1):29-31. doi: 10.6002/ect.TOND-TDTD2019.O1.

Venetz JP, Pascual M. New treatments for acute humoral rejection of kidney allografts. Expert Opin Investig Drugs. 2007;16(5):625-33. doi: 10.1517/13543784.16.5.625


Abstract views: 397
PDF Downloads: 16909
Published
2021-02-03
How to Cite
Parmaksız, E., Meşe, M., Yadigar, S., & Bahat, K. A. (2021). Predictors of graft outcome in renal transplant recipients with antibody-mediated rejection. Ukrainian Journal of Nephrology and Dialysis, (3(71), 28-35. https://doi.org/10.31450/ukrjnd.3(71).2021.04
Issue
No 3(71) (2021): Ukrainian Journal of Nephrology and Dialysis
Section
Original Papers