Anti Phospholipase A2 Receptor 1 Antibodies and Membranous Nephropathy Recurrence After Kidney Transplantation

Introduction: Membranous nephropathy can lead to end-stage kidney disease, for which kidney transplantation is the preferred therapy. However, the disease often relapses, which can impact allograft survival.

Methods: We conducted a prospective multicenter study in France involving 72 patients with membranous nephropathy who were awaiting and then underwent kidney transplantation. In addition, we established a retrospective validation cohort of 65 patients. The primary objective was to evaluate the prognostic significance of pretransplant anti phospholipase A2 receptor 1 (PLA2R1) antibodies on the recurrence of membranous nephropathy. The study also assessed the incidence rate, time to onset, and risk factors for recurrence, as well as allograft outcome.

Results: The prospective cohort showed a 26% cumulative incidence of membranous nephropathy recurrence after a median follow-up of 23.5 months. This was confirmed by a 28% cumulative incidence after a median follow-up of 67 months in the retrospective cohort. A strong association was found between the presence of anti-PLA2R1 antibodies prior to transplantation and the risk of disease recurrence (risk ratio = 5.9; 95% confidence interval [CI]: 2.3-15.7; < 0.0001). These results were confirmed in the retrospective cohort. Monitoring of anti-PLA2R1 antibodies in the immediate posttransplant period is of limited value, because recurrence occurred early in the first 6 months (median delay of 5 [3-14] months) after transplantation despite decreasing antibody levels.

Conclusion: The presence of anti-PLA2R1 antibodies prior to transplantation was a strong predictor of recurrence of allograft membranous nephropathy. An individualized immunomonitoring and management strategy for kidney transplant candidates with anti-PLA2R1-associated membranous nephropathy should be considered.

References

Sprangers B, Lefkowitz G, Cohen S, Stokes M, Valeri A, Appel G . Beneficial effect of rituximab in the treatment of recurrent idiopathic membranous nephropathy after kidney transplantation. Clin J Am Soc Nephrol. 2010; 5(5):790-7. PMC: 2863969. DOI: 10.2215/CJN.04120609. View

Grupper A, Cornell L, Fervenza F, Beck Jr L, Lorenz E, Cosio F . Recurrent Membranous Nephropathy After Kidney Transplantation: Treatment and Long-Term Implications. Transplantation. 2016; 100(12):2710-2716. DOI: 10.1097/TP.0000000000001056. View

Rodriguez E, Cosio F, Nasr S, Sethi S, Fidler M, Stegall M . The pathology and clinical features of early recurrent membranous glomerulonephritis. Am J Transplant. 2012; 12(4):1029-38. DOI: 10.1111/j.1600-6143.2011.03903.x. View

Buxeda A, Caravaca-Fontan F, Vigara L, Perez-Canga J, Calatayud E, Coloma A . High exposure to tacrolimus is associated with spontaneous remission of recurrent membranous nephropathy after kidney transplantation. Clin Kidney J. 2023; 16(10):1644-1655. PMC: 10539211. DOI: 10.1093/ckj/sfad077. View

Schieppati A, Mosconi L, Perna A, MECCA G, Bertani T, Garattini S . Prognosis of untreated patients with idiopathic membranous nephropathy. N Engl J Med. 1993; 329(2):85-9. DOI: 10.1056/NEJM199307083290203. View

Quintana L, Blasco M, Seras M, Perez N, Lopez-Hoyos M, Villarroel P . Antiphospholipase A2 Receptor Antibody Levels Predict the Risk of Posttransplantation Recurrence of Membranous Nephropathy. Transplantation. 2015; 99(8):1709-14. DOI: 10.1097/TP.0000000000000630. View

Pippias M, Stel V, Areste-Fosalba N, Couchoud C, Fernandez-Fresnedo G, Finne P . Long-term Kidney Transplant Outcomes in Primary Glomerulonephritis: Analysis From the ERA-EDTA Registry. Transplantation. 2015; 100(9):1955-62. DOI: 10.1097/TP.0000000000000962. View

Sethi S, Beck Jr L, Glassock R, Haas M, De Vriese A, Caza T . Mayo Clinic consensus report on membranous nephropathy: proposal for a novel classification. Kidney Int. 2023; 104(6):1092-1102. DOI: 10.1016/j.kint.2023.06.032. View

Hullekes F, Uffing A, Verhoeff R, Seeger H, Moos S, Mansur J . Recurrence of membranous nephropathy after kidney transplantation: A multicenter retrospective cohort study. Am J Transplant. 2024; 24(6):1016-1026. DOI: 10.1016/j.ajt.2024.01.036. View

10.

Jiang S, Kennard A, Walters G . Recurrent glomerulonephritis following renal transplantation and impact on graft survival. BMC Nephrol. 2018; 19(1):344. PMC: 6278033. DOI: 10.1186/s12882-018-1135-7. View

11.

Berchtold L, Letouze E, Alexander M, Canaud G, Logt A, Hamilton P . HLA-D and PLA2R1 risk alleles associate with recurrent primary membranous nephropathy in kidney transplant recipients. Kidney Int. 2020; 99(3):671-685. DOI: 10.1016/j.kint.2020.08.007. View

12.

El-Zoghby Z, Grande J, Fraile M, Norby S, Fervenza F, Cosio F . Recurrent idiopathic membranous nephropathy: early diagnosis by protocol biopsies and treatment with anti-CD20 monoclonal antibodies. Am J Transplant. 2009; 9(12):2800-7. DOI: 10.1111/j.1600-6143.2009.02851.x. View

13.

Moroni G, Gallelli B, Quaglini S, Leoni A, Banfi G, Passerini P . Long-term outcome of renal transplantation in patients with idiopathic membranous glomerulonephritis (MN). Nephrol Dial Transplant. 2010; 25(10):3408-15. DOI: 10.1093/ndt/gfq223. View

14.

De Vriese A, Glassock R, Nath K, Sethi S, Fervenza F . A Proposal for a Serology-Based Approach to Membranous Nephropathy. J Am Soc Nephrol. 2016; 28(2):421-430. PMC: 5280030. DOI: 10.1681/ASN.2016070776. View

15.

Tomas N, Beck Jr L, Meyer-Schwesinger C, Seitz-Polski B, Ma H, Zahner G . Thrombospondin type-1 domain-containing 7A in idiopathic membranous nephropathy. N Engl J Med. 2014; 371(24):2277-2287. PMC: 4278759. DOI: 10.1056/NEJMoa1409354. View

16.

Allen P, Chadban S, Craig J, Lim W, Allen R, Clayton P . Recurrent glomerulonephritis after kidney transplantation: risk factors and allograft outcomes. Kidney Int. 2017; 92(2):461-469. DOI: 10.1016/j.kint.2017.03.015. View

17.

Beck Jr L, Bonegio R, Lambeau G, Beck D, Powell D, Cummins T . M-type phospholipase A2 receptor as target antigen in idiopathic membranous nephropathy. N Engl J Med. 2009; 361(1):11-21. PMC: 2762083. DOI: 10.1056/NEJMoa0810457. View

18.

Seitz-Polski B, Payre C, Ambrosetti D, Albano L, Cassuto-Viguier E, Berguignat M . Prediction of membranous nephropathy recurrence after transplantation by monitoring of anti-PLA2R1 (M-type phospholipase A2 receptor) autoantibodies: a case series of 15 patients. Nephrol Dial Transplant. 2014; 29(12):2334-42. DOI: 10.1093/ndt/gfu252. View

19.

Kattah A, Ayalon R, Beck Jr L, Sethi S, Sandor D, Cosio F . Anti-phospholipase A₂ receptor antibodies in recurrent membranous nephropathy. Am J Transplant. 2015; 15(5):1349-59. PMC: 4472303. DOI: 10.1111/ajt.13133. View

20.

Dabade T, Grande J, Norby S, Fervenza F, Cosio F . Recurrent idiopathic membranous nephropathy after kidney transplantation: a surveillance biopsy study. Am J Transplant. 2008; 8(6):1318-22. DOI: 10.1111/j.1600-6143.2008.02237.x. View