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Published in: BMC Nephrology 1/2019

Open Access 01-12-2019 | Research article

Treatment with intravenous immunoglobulins and methylprednisolone may significantly decrease loss of renal function in chronic-active antibody-mediated rejection

Authors: Kasia A. Sablik, Marian C. Clahsen-van Groningen, Caspar W. N. Looman, Jeffrey Damman, Madelon van Agteren, Michiel G. H. Betjes

Published in: BMC Nephrology | Issue 1/2019

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Abstract

Background

Chronic-active antibody mediated rejection (c-aABMR) is a major contributor to long-term kidney allograft loss. We conducted a retrospective analysis to establish the efficacy of treatment with intravenous immunoglobulins (IVIG) and pulse methylprednisolone (MP) of patients with c-aABMR.

Methods

Sixty-nine patients, in the period 2005–2017, with the diagnosis (suspicious for) c-aABMR that were treated with IVIG and MP were included. Patients were administered three doses of 1 g intravenous MP combined with a single dose of IVIG (1 g/kg body weight). Primary outcome was the decline in allograft function one year post treatment. Responders to IVIG-MP therapy were defined by an eGFR one year after treatment which was at least 25% above the projected allograft function.

Results

Patients showed an average decline in eGFR of 9.8 ml/min/1.73m2 the year prior to treatment. Following treatment, a significant reduction (p < 0.001) in eGFR decline was observed (6.3 ml/min/1.73m2). Furthermore, a significant improvement in proteinuria was observed upon treatment (p < 0.001). Sixty-two percent (n = 43) of the patients were considered a responder and showed considerable slowing of graft function deterioration in the year after treatment (p < 0.001). Three and 5-year graft survival was significantly superior in responders.

Conclusions

More than 60% of patients with c-aABMR with a progressive decline in eGFR respond favorably to treatment with IVIG-MP resulting in a significant improvement of graft survival (Sablik, Am J Transplant 18, 2018).
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Literature
1.
go back to reference Pirsch JD, Miller J, Deierhoi MH, Vincenti F. Filo RS. A comparison of tacrolimus (FK506) and cyclosporine for immunosuppression after cadaveric renal transplantation. FK506 kidney transplant study group. Transplantation. 1997;63(7):977–83.CrossRef Pirsch JD, Miller J, Deierhoi MH, Vincenti F. Filo RS. A comparison of tacrolimus (FK506) and cyclosporine for immunosuppression after cadaveric renal transplantation. FK506 kidney transplant study group. Transplantation. 1997;63(7):977–83.CrossRef
2.
go back to reference Merion RM, White DJ, Thiru S, Evans DB, Calne RY. Cyclosporine: five years' experience in cadaveric renal transplantation. N Engl J Med. 1984;310(3):148–54.CrossRef Merion RM, White DJ, Thiru S, Evans DB, Calne RY. Cyclosporine: five years' experience in cadaveric renal transplantation. N Engl J Med. 1984;310(3):148–54.CrossRef
3.
go back to reference Ciancio G, Burke GW, Miller J. Induction therapy in renal transplantation : an overview of current developments. Drugs. 2007;67(18):2667–80.CrossRef Ciancio G, Burke GW, Miller J. Induction therapy in renal transplantation : an overview of current developments. Drugs. 2007;67(18):2667–80.CrossRef
4.
go back to reference Lamb KE, Lodhi S, Meier-Kriesche HU. Long-term renal allograft survival in the United States: a critical reappraisal. Am J Transplant. 2011;11(3):450–62.CrossRef Lamb KE, Lodhi S, Meier-Kriesche HU. Long-term renal allograft survival in the United States: a critical reappraisal. Am J Transplant. 2011;11(3):450–62.CrossRef
5.
go back to reference Fehr T, Gaspert A. Antibody-mediated kidney allograft rejection: therapeutic options and their experimental rationale. Transpl Int. 2012;25(6):623–32.CrossRef Fehr T, Gaspert A. Antibody-mediated kidney allograft rejection: therapeutic options and their experimental rationale. Transpl Int. 2012;25(6):623–32.CrossRef
6.
go back to reference Bartel G, Schwaiger E, Bohmig GA. Prevention and treatment of alloantibody-mediated kidney transplant rejection. Transpl Int. 2011;24(12):1142–55.CrossRef Bartel G, Schwaiger E, Bohmig GA. Prevention and treatment of alloantibody-mediated kidney transplant rejection. Transpl Int. 2011;24(12):1142–55.CrossRef
7.
go back to reference Cosio FG, Gloor JM, Sethi S, Stegall MD. Transplant glomerulopathy. Am J Transplant. 2008;8(3):492–6.CrossRef Cosio FG, Gloor JM, Sethi S, Stegall MD. Transplant glomerulopathy. Am J Transplant. 2008;8(3):492–6.CrossRef
8.
go back to reference Gaston RS, Cecka JM, Kasiske BL, Fieberg AM, Leduc R, Cosio FC, et al. Evidence for antibody-mediated injury as a major determinant of late kidney allograft failure. Transplantation. 2010;90(1):68–74.CrossRef Gaston RS, Cecka JM, Kasiske BL, Fieberg AM, Leduc R, Cosio FC, et al. Evidence for antibody-mediated injury as a major determinant of late kidney allograft failure. Transplantation. 2010;90(1):68–74.CrossRef
9.
go back to reference Redfield RR, Ellis TM, Zhong W, Scalea JR, Zens TJ, Mandelbrot D, et al. Current outcomes of chronic active antibody mediated rejection - a large single center retrospective review using the updated BANFF 2013 criteria. Hum Immunol. 2016;77(4):346–52.CrossRef Redfield RR, Ellis TM, Zhong W, Scalea JR, Zens TJ, Mandelbrot D, et al. Current outcomes of chronic active antibody mediated rejection - a large single center retrospective review using the updated BANFF 2013 criteria. Hum Immunol. 2016;77(4):346–52.CrossRef
10.
go back to reference Gloor JM, Sethi S, Stegall MD, Park WD, Moore SB, DeGoey S, et al. Transplant glomerulopathy: subclinical incidence and association with alloantibody. Am J Transplant. 2007;7(9):2124–32.CrossRef Gloor JM, Sethi S, Stegall MD, Park WD, Moore SB, DeGoey S, et al. Transplant glomerulopathy: subclinical incidence and association with alloantibody. Am J Transplant. 2007;7(9):2124–32.CrossRef
11.
go back to reference Sis B, Campbell PM, Mueller T, Hunter C, Cockfield SM, Cruz J, et al. Transplant glomerulopathy, late antibody-mediated rejection and the ABCD tetrad in kidney allograft biopsies for cause. Am J Transplant. 2007;7(7):1743–52.CrossRef Sis B, Campbell PM, Mueller T, Hunter C, Cockfield SM, Cruz J, et al. Transplant glomerulopathy, late antibody-mediated rejection and the ABCD tetrad in kidney allograft biopsies for cause. Am J Transplant. 2007;7(7):1743–52.CrossRef
12.
go back to reference Patri P, Seshan SV, Matignon M, Desvaux D, Lee JR, Lee J, et al. Development and validation of a prognostic index for allograft outcome in kidney recipients with transplant glomerulopathy. Kidney Int. 2015. Patri P, Seshan SV, Matignon M, Desvaux D, Lee JR, Lee J, et al. Development and validation of a prognostic index for allograft outcome in kidney recipients with transplant glomerulopathy. Kidney Int. 2015.
13.
go back to reference John R, Konvalinka A, Tobar A, Kim SJ, Reich HN, Herzenberg AM. Determinants of long-term graft outcome in transplant glomerulopathy. Transplantation. 2010;90(7):757–64.CrossRef John R, Konvalinka A, Tobar A, Kim SJ, Reich HN, Herzenberg AM. Determinants of long-term graft outcome in transplant glomerulopathy. Transplantation. 2010;90(7):757–64.CrossRef
14.
go back to reference Smith RN, Malik F, Goes N, Farris AB, Zorn E, Saidman S, et al. Partial therapeutic response to rituximab for the treatment of chronic alloantibody mediated rejection of kidney allografts. Transpl Immunol. 2012;27(2–3):107–13.CrossRef Smith RN, Malik F, Goes N, Farris AB, Zorn E, Saidman S, et al. Partial therapeutic response to rituximab for the treatment of chronic alloantibody mediated rejection of kidney allografts. Transpl Immunol. 2012;27(2–3):107–13.CrossRef
15.
go back to reference An GH, Yun J, Hong YA, Khvan M, Chung BH, Choi BS, et al. The effect of combination therapy with rituximab and intravenous immunoglobulin on the progression of chronic antibody mediated rejection in renal transplant recipients. J Immunol Res. 2014;2014:828732.CrossRef An GH, Yun J, Hong YA, Khvan M, Chung BH, Choi BS, et al. The effect of combination therapy with rituximab and intravenous immunoglobulin on the progression of chronic antibody mediated rejection in renal transplant recipients. J Immunol Res. 2014;2014:828732.CrossRef
16.
go back to reference Billing H, Rieger S, Susal C, Waldherr R, Opelz G, Wuhl E, et al. IVIG and rituximab for treatment of chronic antibody-mediated rejection: a prospective study in paediatric renal transplantation with a 2-year follow-up. Transpl Int. 2012;25(11):1165–73.CrossRef Billing H, Rieger S, Susal C, Waldherr R, Opelz G, Wuhl E, et al. IVIG and rituximab for treatment of chronic antibody-mediated rejection: a prospective study in paediatric renal transplantation with a 2-year follow-up. Transpl Int. 2012;25(11):1165–73.CrossRef
17.
go back to reference Kahwaji J, Najjar R, Kancherla D, Villicana R, Peng A, Jordan S, et al. Histopathologic features of transplant glomerulopathy associated with response to therapy with intravenous immune globulin and rituximab. Clin Transpl. 2014;28(5):546–53.CrossRef Kahwaji J, Najjar R, Kancherla D, Villicana R, Peng A, Jordan S, et al. Histopathologic features of transplant glomerulopathy associated with response to therapy with intravenous immune globulin and rituximab. Clin Transpl. 2014;28(5):546–53.CrossRef
18.
go back to reference Rostaing L, Guilbeau-Frugier C, Fort M, Mekhlati L, Kamar N. Treatment of symptomatic transplant glomerulopathy with rituximab. Transpl Int. 2009;22(9):906–13.CrossRef Rostaing L, Guilbeau-Frugier C, Fort M, Mekhlati L, Kamar N. Treatment of symptomatic transplant glomerulopathy with rituximab. Transpl Int. 2009;22(9):906–13.CrossRef
19.
go back to reference Bachelet T, Nodimar C, Taupin JL, Lepreux S, Moreau K, Morel D, et al. Intravenous immunoglobulins and rituximab therapy for severe transplant glomerulopathy in chronic antibody-mediated rejection: a pilot study. Clin Transpl. 2015;29(5):439–46.CrossRef Bachelet T, Nodimar C, Taupin JL, Lepreux S, Moreau K, Morel D, et al. Intravenous immunoglobulins and rituximab therapy for severe transplant glomerulopathy in chronic antibody-mediated rejection: a pilot study. Clin Transpl. 2015;29(5):439–46.CrossRef
20.
go back to reference Eskandary F, Regele H, Baumann L, Bond G, Kozakowski N, Wahrmann M, et al. A randomized trial of Bortezomib in late antibody-mediated kidney transplant rejection. J Am Soc Nephrol. 2017. Eskandary F, Regele H, Baumann L, Bond G, Kozakowski N, Wahrmann M, et al. A randomized trial of Bortezomib in late antibody-mediated kidney transplant rejection. J Am Soc Nephrol. 2017.
21.
go back to reference Solez K, Colvin RB, Racusen LC, Haas M, Sis B, Mengel M, et al. Banff 07 classification of renal allograft pathology: updates and future directions. Am J Transplant. 2008;8(4):753–60.CrossRef Solez K, Colvin RB, Racusen LC, Haas M, Sis B, Mengel M, et al. Banff 07 classification of renal allograft pathology: updates and future directions. Am J Transplant. 2008;8(4):753–60.CrossRef
22.
go back to reference Sis B, Mengel M, Haas M, Colvin RB, Halloran PF, Racusen LC, et al. Banff '09 meeting report: antibody mediated graft deterioration and implementation of Banff working groups. Am J Transplant. 2010;10(3):464–71.CrossRef Sis B, Mengel M, Haas M, Colvin RB, Halloran PF, Racusen LC, et al. Banff '09 meeting report: antibody mediated graft deterioration and implementation of Banff working groups. Am J Transplant. 2010;10(3):464–71.CrossRef
23.
go back to reference Mengel M, Sis B, Haas M, Colvin RB, Halloran PF, Racusen LC, et al. Banff 2011 meeting report: new concepts in antibody-mediated rejection. Am J Transplant. 2012;12(3):563–70.CrossRef Mengel M, Sis B, Haas M, Colvin RB, Halloran PF, Racusen LC, et al. Banff 2011 meeting report: new concepts in antibody-mediated rejection. Am J Transplant. 2012;12(3):563–70.CrossRef
24.
go back to reference Haas M, Sis B, Racusen LC, Solez K, Glotz D, Colvin RB, et al. Banff 2013 meeting report: inclusion of c4d-negative antibody-mediated rejection and antibody-associated arterial lesions. Am J Transplant. 2014;14(2):272–83.CrossRef Haas M, Sis B, Racusen LC, Solez K, Glotz D, Colvin RB, et al. Banff 2013 meeting report: inclusion of c4d-negative antibody-mediated rejection and antibody-associated arterial lesions. Am J Transplant. 2014;14(2):272–83.CrossRef
25.
go back to reference Haas M. The revised (2013) Banff classification for antibody-mediated rejection of renal allografts: update, difficulties, and future considerations. Am J Transplant. 2016;16(5):1352–7.CrossRef Haas M. The revised (2013) Banff classification for antibody-mediated rejection of renal allografts: update, difficulties, and future considerations. Am J Transplant. 2016;16(5):1352–7.CrossRef
26.
go back to reference Levey AS, Bosch JP, Lewis JB, Greene T, Rogers N, Roth D. A more accurate method to estimate glomerular filtration rate from serum creatinine: a new prediction equation. Modification of diet in renal disease study group. Ann Intern Med. 1999;130(6):461–70.CrossRef Levey AS, Bosch JP, Lewis JB, Greene T, Rogers N, Roth D. A more accurate method to estimate glomerular filtration rate from serum creatinine: a new prediction equation. Modification of diet in renal disease study group. Ann Intern Med. 1999;130(6):461–70.CrossRef
27.
go back to reference Twisk JWR. Applied multilevel analysis. A practical guide for medical researchers. 2nd revised ed. Cambridge University Press; 2013. Twisk JWR. Applied multilevel analysis. A practical guide for medical researchers. 2nd revised ed. Cambridge University Press; 2013.
28.
go back to reference Marfo K, Lu A, Ling M, Akalin E. Desensitization protocols and their outcome. Clin J Am Soc Nephrol. 2011;6(4):922–36.CrossRef Marfo K, Lu A, Ling M, Akalin E. Desensitization protocols and their outcome. Clin J Am Soc Nephrol. 2011;6(4):922–36.CrossRef
29.
go back to reference Montgomery RA, Loupy A, Segev DL. Antibody-mediated rejection: new approaches in prevention and management. Am J Transplant. 2018;(18 Suppl):3:3–17.CrossRef Montgomery RA, Loupy A, Segev DL. Antibody-mediated rejection: new approaches in prevention and management. Am J Transplant. 2018;(18 Suppl):3:3–17.CrossRef
30.
go back to reference Choi J, Aubert O, Vo A, Loupy A, Haas M, Puliyanda D, et al. Assessment of tocilizumab (anti-Interleukin-6 receptor monoclonal) as a potential treatment for chronic antibody-mediated rejection and transplant Glomerulopathy in HLA-sensitized renal allograft recipients. Am J Transplant. 2017;17(9):2381–9.CrossRef Choi J, Aubert O, Vo A, Loupy A, Haas M, Puliyanda D, et al. Assessment of tocilizumab (anti-Interleukin-6 receptor monoclonal) as a potential treatment for chronic antibody-mediated rejection and transplant Glomerulopathy in HLA-sensitized renal allograft recipients. Am J Transplant. 2017;17(9):2381–9.CrossRef
31.
go back to reference Hong YA, Kim HG, Choi SR, Sun IO, Park HS, Chung BH, et al. Effectiveness of rituximab and intravenous immunoglobulin therapy in renal transplant recipients with chronic active antibody-mediated rejection. Transplant Proc. 2012;44(1):182–4.CrossRef Hong YA, Kim HG, Choi SR, Sun IO, Park HS, Chung BH, et al. Effectiveness of rituximab and intravenous immunoglobulin therapy in renal transplant recipients with chronic active antibody-mediated rejection. Transplant Proc. 2012;44(1):182–4.CrossRef
32.
go back to reference Kim MG, Kim YJ, Kwon HY, Park HC, Koo TY, Jeong JC, et al. Outcomes of combination therapy for chronic antibody-mediated rejection in renal transplantation. Nephrology (Carlton). 2013;18(12):820–6.CrossRef Kim MG, Kim YJ, Kwon HY, Park HC, Koo TY, Jeong JC, et al. Outcomes of combination therapy for chronic antibody-mediated rejection in renal transplantation. Nephrology (Carlton). 2013;18(12):820–6.CrossRef
Metadata
Title
Treatment with intravenous immunoglobulins and methylprednisolone may significantly decrease loss of renal function in chronic-active antibody-mediated rejection
Authors
Kasia A. Sablik
Marian C. Clahsen-van Groningen
Caspar W. N. Looman
Jeffrey Damman
Madelon van Agteren
Michiel G. H. Betjes
Publication date
01-12-2019
Publisher
BioMed Central
Published in
BMC Nephrology / Issue 1/2019
Electronic ISSN: 1471-2369
DOI
https://doi.org/10.1186/s12882-019-1385-z

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