Recurrence of Primary Glomerular Diseases After Kidney Transplantation: Incidence, Predictors, Characteristics and Treatment
Abstract
:1. Introduction and Background
2. Prevalence, Predictors and Risk Factors
3. Main Characteristics
3.1. IgA Nephropathy
3.2. FSGS
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- Presentation with nephrotic syndrome;
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- Rapid progression of native disease (<3 years to ESRD);
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- Whether the pathological type of FSGS has no predictive value;
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- Whether diffuse foot process effacement has no predictive value;
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- Whether the most reliable risk factor for recurrence is a prior history of recurrence in a kidney transplant, with an 80% chance of recurrence in a second transplant;
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- Whether genetic forms of FSGS are associated with a low risk of recurrence [56].
3.3. Membranous Nephropathy
3.4. Membranoproliferative Glomerulonephritis
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- Comprehensive complement genetic panel;
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- Complement functional testing;
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- Monoclonal gammopathy screen;
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- Factor H autoantibodies;
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- C3 nephritic factor.
4. Treatment for Primitive GN Recurrence
4.1. IgA Nephropathy
4.2. Focal Segmental Glomerular Sclerosis
4.3. Membranous Nephropathy
4.4. Membranoproliferative Glomerulonephritis
Summary of MPGN Recurrence
5. Conclusions
Author Contributions
Funding
Conflicts of Interest
References
- El-Zoghby, Z.M.; Stegall, M.D.; Lager, D.J.; Kremers, W.K.; Amer, H.; Gloor, J.M.; Cosio, F.G. Identifying specific causes of kidney allograft loss. Am. J. Transplant. 2009, 9, 527–535. [Google Scholar] [CrossRef] [PubMed]
- Sellarés, J.; de Freitas, D.G.; Mengel, M.; Reeve, J.; Einecke, G.; Sis, B.; Hidalgo, L.G.; Famulski, K.; Matas, A.; Halloran, P.F. Understanding the causes of kidney transplant failure: The dominant role of antibody-mediated rejection and nonadherence. Am. J. Transplant. 2012, 12, 388–399. [Google Scholar] [CrossRef]
- Allen, P.J.; Chadban, S.J.; Craig, J.C.; Lim, W.H.; Allen, R.D.M.; Clayton, P.A.; Teixeira-Pinto, A.; Wong, G. Recurrent glomerulonephritis after kidney transplantation: Risk factors and allograft outcomes. Kidney Int. 2017, 92, 461–469. [Google Scholar] [CrossRef] [PubMed]
- Alawieh, R.; Boonpheng, B.; Blosser, C.D. Recurrence of glomerulonephritis after kidney transplant. Nephrol. Dial. Transplant. 2022, 37, 2090–2092. [Google Scholar] [CrossRef] [PubMed]
- Chukwu, C.A.; Holmberg, C.; Storrar, J.; Middleton, R.; Sinha, S.; Kalra, P.A.; Shawki, H.; Rao, A. Clinical and histopathologic predictors of recurrent glomerulonephritis after kidney transplantation. Clin. Transplant. 2023, 37, e14970. [Google Scholar] [CrossRef]
- Briganti, E.M.; Russ, G.R.; McNeil, J.J.; Atkins, R.C.; Chadban, S.J. Risk of renal allograft loss from recurrent glomerulonephritis. N. Engl. J. Med. 2002, 347, 103–109. [Google Scholar] [CrossRef]
- Ponticelli, C.; Villa, M.; Cesana, B.; Montagnino, G.; Tarantino, A. Risk factors for late kidney allograft failure. Kidney Int. 2002, 62, 1848–1854. [Google Scholar] [CrossRef]
- Cosio, F.G.; Cattran, D.C. Recent advances in our understanding of recurrent primary glomerulonephritis after kidney transplantation. Kidney Int. 2017, 91, 304–314. [Google Scholar] [CrossRef]
- Golgert, W.A.; Appel, G.B.; Hariharan, S. Recurrent glomerulonephritis after renal transplantation: An unsolved problem. Clin. J. Am. Soc. Nephrol. 2008, 3, 800–807. [Google Scholar] [CrossRef]
- Chailimpamontree, W.; Dmitrienko, S.; Li, G.; Balshaw, R.; Magil, A.; Shapiro, R.J.; Landsberg, D.; Gill, J.; Keown, P.A. Genome Canada Biomarkers in Transplantation Group. Probability, predictors, and prognosis of posttransplantation glomerulonephritis. J. Am. Soc. Nephrol. 2009, 20, 843–851. [Google Scholar] [CrossRef]
- Pippias, M.; Stel, V.S.; Aresté-Fosalba, N.; Couchoud, C.; Fernandez-Fresnedo, G.; Finne, P.; Heaf, J.G.; Hoitsma, A.; De Meester, J.; Pálsson, R.; et al. Long-term Kidney Transplant Outcomes in Primary Glomerulonephritis: Analysis From the ERA-EDTA Registry. Transplantation 2016, 100, 1955–1962. [Google Scholar] [CrossRef] [PubMed]
- Hariharan, S.; Adams, M.B.; Brennan, D.C.; Davis, C.L.; First, M.R.; Johnson, C.P.; Ouseph, R.; Peddi, V.R.; Pelz, C.J.; Roza, A.M.; et al. Recurrent and de novo glomerular disease after renal transplantation: A report from Renal Allograft Disease Registry (RADR). Transplantation 1999, 68, 635–641. [Google Scholar] [CrossRef]
- Australian and New Zealand Dialysis and Transplant Registry. 40th Report. Chapter 1: Incidence of End Stage Kidney Disease; Australia and New Zealand Dialysis and Transplant Registry: Adelaide, SA, Australian, 2018. [Google Scholar]
- United States Renal Data System. USRDS Annual Data Report: Epidemiology of Kidney Disease in the United States; Chapter 1: Incidence, Prevalence, Patient Characteristics and Treatment Modalities; National Institutes of Health, National Institutes of Diabetes and Digestive and Kidney Disease: Bethesda, MD, USA, 2018. [Google Scholar]
- O′Shaughnessy, M.M.; Montez-Rath, M.E.; Lafayette, R.A.; Winkelmayer, W.C. Patient characteristics and outcomes by GN subtype in ESRD. Clin. J. Am. Soc. Nephrol. 2015, 10, 1170–1178. [Google Scholar] [CrossRef] [PubMed]
- An, J.N.; Lee, J.P.; Oh, Y.J.; Oh, Y.K.; Ha, J.W.; Chae, D.W.; Kim, Y.S.; Lim, C.S. Incidence of post-transplant glomerulonephritis and its impact on graft outcome. Kidney Res. Clin. Pract. 2012, 31, 219–226. [Google Scholar] [CrossRef]
- Berthoux, F.; El Deeb, S.; Mariat, C.; Diconne, E.; Laurent, B.; Thibaudin, L. Antithymocyte globulin (ATG) induction therapy and disease recurrence in renal transplant recipients with primary IgA nephropathy. Transplantation 2008, 85, 1505–1507. [Google Scholar] [CrossRef] [PubMed]
- Choy, B.Y.; Chan, T.M.; Lai, K.N. Recurrent glomerulonephritis after kidney transplantation. Am. J. Transplant. 2006, 6, 2535–2542. [Google Scholar] [CrossRef]
- Sprangers, B.; Kuypers, D.R. Recurrence of glomerulonephritis after renal transplantation. Transplant. Rev. 2013, 27, 126–134. [Google Scholar] [CrossRef]
- Lim, W.H.; Shingde, M.; Wong, G. Recurrent and de novo Glomerulonephritis After Kidney Transplantation. Front. Immunol. 2019, 10, 1944. [Google Scholar] [CrossRef]
- Garnier, A.S.; Duveau, A.; Demiselle, J.; Croué, A.; Subra, J.F.; Sayegh, J.; Augusto, J.F. Early post-transplant serum IgA level is associated with IgA nephropathy recurrence after kidney transplantation. PLoS ONE. 2018, 13, e0196101. [Google Scholar] [CrossRef]
- Berthelot, L.; Robert, T.; Vuiblet, V.; Tabary, T.; Braconnier, A.; Dramé, M.; Toupance, O.; Rieu, P.; Monteiro, R.C.; Touré, F. Recurrent IgA nephropathy is predicted by altered glycosylated IgA, autoantibodies and soluble CD89 complexes. Kidney Int. 2015, 88, 815–822. [Google Scholar] [CrossRef]
- Berthoux, F.; Suzuki, H.; Mohey, H.; Maillard, N.; Mariat, C.; Novak, J.; Julian, B.A. Prognostic Value of Serum Biomarkers of Autoimmunity for Recurrence of IgA Nephropathy after Kidney Transplantation. J. Am. Soc. Nephrol. 2017, 28, 1943–1950. [Google Scholar] [CrossRef] [PubMed]
- Martin Penagos, L.; Benito Hernandez, A.; Martin, J.; Gomez Roman, J.; San Segundo, D.; Lopez Hoyos, M. April serum levels relate to recurrence of IgA nephropathy. Transplantation 2018, 102, S10. [Google Scholar] [CrossRef]
- Lee, S.; Kin, D.; Kim, J.; Jeon, H. Identification of urinary biomarkers for recurrence of IgA nephropathy after kidney transplantation using proteomic methods. Transplantation 2018, 102, S80. [Google Scholar] [CrossRef]
- Wei, C.; El Hindi, S.; Li, J.; Fornoni, A.; Goes, N.; Sageshima, J.; Maiguel, D.; Karumanchi, S.A.; Yap, H.K.; Saleem, M.; et al. Circulating urokinase receptor as a cause of focal segmental glomerulosclerosis. Nat. Med. 2011, 17, 952–960. [Google Scholar] [CrossRef]
- Huang, J.; Liu, G.; Zhang, Y.M.; Cui, Z.; Wang, F.; Liu, X.J.; Chu, R.; Zhao, M.H. Urinary soluble urokinase receptor levels are elevated and pathogenic in patients with primary focal segmental glomerulosclerosis. BMC Med. 2014, 12, 81. [Google Scholar] [CrossRef]
- Delville, M.; Sigdel, T.K.; Wei, C.; Li, J.; Hsieh, S.C.; Fornoni, A.; Burke, G.W.; Bruneval, P.; Naesens, M.; Jackson, A.; et al. A circulating antibody panel for pretransplant prediction of FSGS recurrence after kidney transplantation. Sci. Transl. Med. 2014, 6, 256ra136. [Google Scholar] [CrossRef]
- Lopez-Hellin, J.; Cantarell, C.; Jimeno, L.; Sanchez-Fructuoso, A.; Puig-Gay, N.; Guirado, L.; Vilariño, N.; Gonzalez-Roncero, F.M.; Mazuecos, A.; Lauzurica, R.; et al. A form of apolipoprotein a-I is found specifically in relapses of focal segmental glomerulosclerosis following transplantation. Am. J. Transplant. 2013, 13, 493–500. [Google Scholar] [CrossRef]
- Puig-Gay, N.; Jacobs-Cacha, C.; Sellarès, J.; Guirado, L.; González Roncero, F.; Jiménez, C.; Zárraga, S.; Paul, J.; Lauzurica, R.; Alonso, Á.; et al. Apolipoprotein A-Ib as a biomarker of focal segmental glomerulosclerosis recurrence after kidney transplantation: Diagnostic performance and assessment of its prognostic value—A multi-centre cohort study. Transpl. Int. 2019, 32, 313–322. [Google Scholar] [CrossRef]
- Pérez, V.; Ibernón, M.; López, D.; Pastor, M.C.; Navarro, M.; Navarro-Muñoz, M.; Bonet, J.; Romero, R. Urinary peptide profiling to differentiate between minimal change disease and focal segmental glomerulosclerosis. PLoS ONE 2014, 9, e87731. [Google Scholar] [CrossRef]
- McCarthy, E.T.; Sharma, M.; Savin, V.J. Circulating permeability factors in idiopathic nephrotic syndrome and focal segmental glomerulosclerosis. Clin. J. Am. Soc. Nephrol. 2010, 5, 2115–2121. [Google Scholar] [CrossRef]
- Quintana, L.F.; Blasco, M.; Seras, M.; Pérez, N.S.; López-Hoyos, M.; Villarroel, P.; Rodrigo, E.; Viñas, O.; Ercilla, G.; Diekmann, F.; et al. Antiphospholipase A2 Receptor Antibody Levels Predict the Risk of Posttransplantation Recurrence of Membranous Nephropathy. Transplantation 2015, 99, 1709–1714. [Google Scholar] [CrossRef]
- Tomas, N.M.; Beck, L.H., Jr.; Meyer-Schwesinger, C.; Seitz-Polski, B.; Ma, H.; Zahner, G.; Dolla, G.; Hoxha, E.; Helmchen, U.; Dabert-Gay, A.S.; et al. Thrombospondin type-1 domain-containing 7A in idiopathic membranous nephropathy. N. Engl. J. Med. 2014, 371, 2277–2287. [Google Scholar] [CrossRef] [PubMed]
- Herwig, J.; Skuza, S.; Sachs, W.; Sachs, M.; Failla, A.V.; Rune, G.; Meyer, T.N.; Fester, L.; Meyer-Schwesinger, C. Thrombospondin Type 1 Domain-Containing 7A Localizes to the Slit Diaphragm and Stabilizes Membrane Dynamics of Fully Differentiated Podocytes. J. Am. Soc. Nephrol. 2019, 30, 824–839. [Google Scholar] [CrossRef]
- Murtas, C.; Bruschi, M.; Candiano, G.; Moroni, G.; Magistroni, R.; Magnano, A.; Bruno, F.; Radice, A.; Furci, L.; Argentiero, L.; et al. Coexistence of different circulating anti-podocyte antibodies in membranous nephropathy. Clin. J. Am. Soc. Nephrol. 2012, 7, 1394–1400. [Google Scholar] [CrossRef] [PubMed]
- Alasfar, S.; Carter-Monroe, N.; Rosenberg, A.Z.; Montgomery, R.A.; Alachkar, N. Membranoproliferative glomerulonephritis recurrence after kidney transplantation: Using the new classification. BMC Nephrol. 2016, 17, 7. [Google Scholar] [CrossRef] [PubMed]
- Lorenz, E.C.; Sethi, S.; Leung, N.; Dispenzieri, A.; Fervenza, F.C.; Cosio, F.G. Recurrent membranoproliferative glomerulonephritis after kidney transplantation. Kidney Int. 2010, 77, 721–728. [Google Scholar] [CrossRef]
- Ponticelli, C.; Glassock, R.J. Posttransplant recurrence of primary glomerulonephritis. Clin. J. Am. Soc. Nephrol. 2010, 5, 2363–2372. [Google Scholar] [CrossRef]
- Odum, J.; Peh, C.A.; Clarkson, A.R.; Bannister, K.M.; Seymour, A.E.; Gillis, D.; Thomas, A.C.; Mathew, T.H.; Woodroffe, A.J. Recurrent mesangial IgA nephritis following renal transplantation. Nephrol. Dial. Transplant. 1994, 9, 309–312. [Google Scholar]
- Moroni, G.; Belingheri, M.; Frontini, G.; Tamborini, F.; Messa, P. Immunoglobulin A Nephropathy. Recurrence After Renal Transplantation. Front. Immunol. 2019, 10, 1332. [Google Scholar] [CrossRef]
- Wyld, M.L.; Chadban, S.J. Recurrent IgA Nephropathy After Kidney Transplantation. Transplantation 2016, 100, 1827–1832. [Google Scholar] [CrossRef]
- Sato, Y.; Ishida, H.; Shimizu, T.; Tanabe, K. Evaluation of tonsillectomy before kidney transplantation in patients with IgA nephropathy. Transpl. Immunol. 2014, 30, 12–17. [Google Scholar] [CrossRef] [PubMed]
- Wang, A.Y.; Lai, F.M.; Yu, A.W.; Lam, P.K.; Chow, K.M.; Choi, P.C.; Lui, S.F.; Li, P.K. Recurrent IgA nephropathy in renal transplant allografts. Am. J. Kidney Dis. 2001, 38, 588–596. [Google Scholar] [CrossRef] [PubMed]
- Clayton, P.; McDonald, S.; Chadban, S. Steroids and recurrent IgA nephropathy after kidney transplantation. Am. J. Transplant. 2011, 11, 1645–1649. [Google Scholar] [CrossRef] [PubMed]
- Uffing, A.; Pérez-Saéz, M.J.; Jouve, T.; Bugnazet, M.; Malvezzi, P.; Muhsin, S.A.; Lafargue, M.C.; Reindl-Schwaighofer, R.; Morlock, A.; Oberbauer, R.; et al. Recurrence of IgA Nephropathy after Kidney Transplantation in Adults. Clin. J. Am. Soc. Nephrol. 2021, 16, 1247–1255. [Google Scholar] [CrossRef]
- Bertelli, R.; Ginevri, F.; Caridi, G.; Dagnino, M.; Sandrini, S.; Di Duca, M.; Emma, F.; Sanna-Cherchi, S.; Scolari, F.; Neri, T.M.; et al. Recurrence of focal segmental glomerulosclerosis after renal transplantation in patients with mutations of podocin. Am. J. Kidney Dis. 2003, 41, 1314–1321. [Google Scholar] [CrossRef]
- Freedman, B.I.; Pastan, S.O.; Israni, A.K.; Schladt, D.; Julian, B.A.; Gautreaux, M.D.; Hauptfeld, V.; Bray, R.A.; Gebel, H.M.; Kirk, A.D.; et al. APOL1 Genotype and Kidney Transplantation Outcomes From Deceased African American Donors. Transplantation 2016, 100, 194–202. [Google Scholar] [CrossRef]
- Lee, B.T.; Kumar, V.; Williams, T.A.; Abdi, R.; Bernhardy, A.; Dyer, C.; Conte, S.; Genovese, G.; Ross, M.D.; Friedman, D.J.; et al. The APOL1 genotype of African American kidney transplant recipients does not impact 5-year allograft survival. Am. J. Transplant. 2012, 12, 1924–1928. [Google Scholar] [CrossRef]
- Jungraithmayr, T.C.; Hofer, K.; Cochat, P.; Chernin, G.; Cortina, G.; Fargue, S.; Grimm, P.; Knueppel, T.; Kowarsch, A.; Neuhaus, T.; et al. Screening for NPHS2 mutations may help predict FSGS recurrence after transplantation. J. Am. Soc. Nephrol. 2011, 22, 579–585. [Google Scholar] [CrossRef]
- Machuca, E.; Hummel, A.; Nevo, F.; Dantal, J.; Martinez, F.; Al-Sabban, E.; Baudouin, V.; Abel, L.; Grünfeld, J.P.; Antignac, C. Clinical and epidemiological assessment of steroid-resistant nephrotic syndrome associated with the NPHS2 R229Q variant. Kidney Int. 2009, 75, 727–735. [Google Scholar] [CrossRef]
- Hofstra, J.M.; Lainez, S.; van Kuijk, W.H.; Schoots, J.; Baltissen, M.P.; Hoefsloot, L.H.; Knoers, N.V.; Berden, J.H.; Bindels, R.J.; van der Vlag, J.; et al. New TRPC6 gain-of-function mutation in a non-consanguineous Dutch family with late-onset focal segmental glomerulosclerosis. Nephrol. Dial. Transplant. 2013, 28, 1830–1838. [Google Scholar] [CrossRef]
- Conlon, P.J.; Lynn, K.; Winn, M.P.; Quarles, L.D.; Bembe, M.L.; Pericak-Vance, M.; Speer, M.; Howell, D.N. Spectrum of disease in familial focal and segmental glomerulosclerosis. Kidney Int. 1999, 56, 1863–1871. [Google Scholar] [CrossRef] [PubMed]
- Weber, S.; Gribouval, O.; Esquivel, E.L.; Morinière, V.; Tête, M.J.; Legendre, C.; Niaudet, P.; Antignac, C. NPHS2 mutation analysis shows genetic heterogeneity of steroid-resistant nephrotic syndrome and low post-transplant recurrence. Kidney Int. 2004, 66, 571–579. [Google Scholar] [CrossRef]
- Gipson, D.S.; Trachtman, H.; Kaskel, F.J.; Greene, T.H.; Radeva, M.K.; Gassman, J.J.; Moxey-Mims, M.M.; Hogg, R.J.; Watkins, S.L.; Fine, R.N.; et al. Clinical trial of focal segmental glomerulosclerosis in children and young adults. Kidney Int. 2011, 80, 868–878. [Google Scholar] [CrossRef] [PubMed]
- Trautmann, A.; Bodria, M.; Ozaltin, F.; Gheisari, A.; Melk, A.; Azocar, M.; Anarat, A.; Caliskan, S.; Emma, F.; Gellermann, J.; et al. PodoNet Consortium. Spectrum of steroid-resistant and congenital nephrotic syndrome in children: The PodoNet registry cohort. Clin. J. Am. Soc. Nephrol. 2015, 10, 592–600. [Google Scholar] [CrossRef]
- Canaud, G.; Dion, D.; Zuber, J.; Gubler, M.C.; Sberro, R.; Thervet, E.; Snanoudj, R.; Charbit, M.; Salomon, R.; Martinez, F.; et al. Recurrence of nephrotic syndrome after transplantation in a mixed population of children and adults: Course of glomerular lesions and value of the Columbia classification of histological variants of focal and segmental glomerulosclerosis (FSGS). Nephrol. Dial. Transplant. 2010, 25, 1321–1328. [Google Scholar] [CrossRef] [PubMed]
- Uffing, A.; Pérez-Sáez, M.J.; Mazzali, M.; Manfro, R.C.; Bauer, A.C.; de Sottomaior Drumond, F.; O′Shaughnessy, M.M.; Cheng, X.S.; Chin, K.K.; Ventura, C.G.; et al. Recurrence of FSGS after Kidney Transplantation in Adults. Clin. J. Am. Soc. Nephrol. 2020, 15, 247–256. [Google Scholar] [CrossRef]
- Watts, A.J.B.; Keller, K.H.; Lerner, G.; Rosales, I.; Collins, A.B.; Sekulic, M.; Waikar, S.S.; Chandraker, A.; Riella, L.V.; Alexander, M.P.; et al. Discovery of Autoantibodies Targeting Nephrin in Minimal Change Disease Supports a Novel Autoimmune Etiology. J. Am. Soc. Nephrol. 2022, 33, 238–252. [Google Scholar] [CrossRef]
- Shirai, Y.; Miura, K.; Ishizuka, K.; Ando, T.; Kanda, S.; Hashimoto, J.; Hamasaki, Y.; Hotta, K.; Ito, N.; Honda, K.; et al. A multi-institutional study found a possible role of anti-nephrin antibodies in post-transplant focal segmental glomerulosclerosis recurrence. Kidney Int. 2024, 105, 608–617. [Google Scholar] [CrossRef]
- Batal, I.; Watts, A.J.B.; Gibier, J.B.; Hamroun, A.; Top, I.; Provot, F.; Keller, K.; Ye, X.; Fernandez, H.E.; Leal, R.; et al. Pre-transplant anti-nephrin antibodies are specific predictors of recurrent diffuse podocytopathy in the kidney allograft. Kidney Int. 2024, 106, 749–752. [Google Scholar] [CrossRef]
- El Ters, M.; Pinto EVairo, F.; Prochnow, C.; Schinstock, C.; Dean, P.; Kemppainen, J.; Lazaridis, K.; Cosio, F.; Fervenza, F.C.; Cornell, L.; et al. Incorporation of Genetic Studies in the Kidney Transplant Evaluation Clinic: The Value of a Multidisciplinary Approach. Transplantation 2023, 107, 952–960. [Google Scholar] [CrossRef]
- Dabade, T.S.; Grande, J.P.; Norby, S.M.; Fervenza, F.C.; Cosio, F.G. Recurrent idiopathic membranous nephropathy after kidney transplantation: A surveillance biopsy study. Am. J. Transplant. 2008, 8, 1318–1322. [Google Scholar] [CrossRef]
- Grupper, A.; Cornell, L.D.; Fervenza, F.C.; Beck, L.H., Jr.; Lorenz, E.; Cosio, F.G. Recurrent Membranous Nephropathy After Kidney Transplantation: Treatment and Long-Term Implications. Transplantation 2016, 100, 2710–2716. [Google Scholar] [CrossRef] [PubMed]
- Cosyns, J.P.; Couchoud, C.; Pouteil-Noble, C.; Squifflet, J.P.; Pirson, Y. Recurrence of membranous nephropathy after renal transplantation: Probability, outcome and risk factors. Clin. Nephrol. 1998, 50, 144–153. [Google Scholar]
- Leon, J.; Pérez-Sáez, M.J.; Batal, I.; Beck, L.H., Jr.; Rennke, H.G.; Canaud, G.; Legendre, C.; Pascual, J.; Riella, L.V. Membranous Nephropathy Posttransplantation: An Update of the Pathophysiology and Management. Transplantation 2019, 103, 1990–2002. [Google Scholar] [CrossRef]
- Beck, L.H., Jr.; Bonegio, R.G.; Lambeau, G.; Beck, D.M.; Powell, D.W.; Cummins, T.D.; Klein, J.B.; Salant, D.J. M-type phospholipase A2 receptor as target antigen in idiopathic membranous nephropathy. N. Engl. J. Med. 2009, 361, 11–21. [Google Scholar] [CrossRef]
- Kattah, A.; Ayalon, R.; Beck, L.H., Jr.; Sethi, S.; Sandor, D.G.; Cosio, F.G.; Gandhi, M.J.; Lorenz, E.C.; Salant, D.J.; Fervenza, F.C. Anti-phospholipase A2 receptor antibodies in recurrent membranous nephropathy. Am. J. Transplant. 2015, 15, 1349–1359. [Google Scholar] [CrossRef] [PubMed]
- Hullekes, F.; Uffing, A.; Verhoeff, R.; Seeger, H.; von Moos, S.; Mansur, J.; Mastroianni-Kirsztajn, G.; Silva, H.T.; Buxeda, A.; Pérez-Sáez, M.J.; et al. Recurrence of membranous nephropathy after kidney transplantation: A multicenter retrospective cohort study. Am. J. Transplant. 2024, 24, 1016–1026. [Google Scholar] [CrossRef]
- Salvadori, M.; Tsalouchos, A. New antigens involved in membranous nephropathy beyond phospholipase A2 receptor. World J. Nephrol. 2022, 11, 115–126. [Google Scholar] [CrossRef] [PubMed]
- Josephson, M.A.; Spargo, B.; Hollandsworth, D.; Thistlethwaite, J.R. The recurrence of recurrent membranous glomerulopathy in a renal transplant recipient: Case report and literature review. Am. J. Kidney Dis. 1994, 24, 873–878. [Google Scholar] [CrossRef]
- Zand, L.; Lorenz, E.C.; Cosio, F.G.; Fervenza, F.C.; Nasr, S.H.; Gandhi, M.J.; Smith, R.J.; Sethi, S. Clinical findings, pathology, and outcomes of C3GN after kidney transplantation. J. Am. Soc. Nephrol. 2014, 25, 1110–1117. [Google Scholar] [CrossRef]
- Uffing, A.; Hullekes, F.; Riella, L.V.; Hogan, J. Recurrent Glomerular Disease after Kidney Transplantation: Diagnostic and Management Dilemmas. J. Am. Soc. Nephrol. 2021, 16, 1730–1742. [Google Scholar] [CrossRef]
- Caravaca-Fontán, F.; Lucientes, L.; Serra, N.; Cavero, T.; Rodado, R.; Ramos, N.; Gonzalez, F.; Shabaka, A.; Cabello, V.; Huerta, A.; et al. Praga MC3 glomerulopathy associated with monoclonal gammopathy: Impact of chronic histologic lesions and beneficial effects of clone-targeted therapies. Nephrol. Dial. Transplant. 2022, 37, 2128–2137. [Google Scholar] [CrossRef]
- Regunathan-Shenk, R.; Avasare, R.S.; Ahn, W.; Canetta, P.A.; Cohen, D.J.; Appel, G.B.; Bomback, A.S. Kidney Transplantation in C3 Glomerulopathy: A Case Series. Am. J. Kidney. Dis. 2019, 73, 316–323. [Google Scholar] [CrossRef] [PubMed]
- Said, S.M.; Cosio, F.G.; Valeri, A.M.; Leung, N.; Sethi, S.; Salameh, H.; Cornell, L.D.; Fidler, M.E.; Alexander, M.P.; Fervenza, F.C.; et al. Proliferative glomerulonephritis with monoclonal immunoglobulin G deposits is associated with high rate of early recurrence in the allograft. Kidney Int. 2018, 94, 159–169. [Google Scholar] [CrossRef] [PubMed]
- Kennoki, T.; Ishida, H.; Yamaguchi, Y.; Tanabe, K. Proteinuria-reducing effects of tonsillectomy alone in IgA nephropathy recurring after kidney transplantation. Transplantation 2009, 88, 935–941. [Google Scholar] [CrossRef] [PubMed]
- Chancharoenthana, W.; Leelahavanichkul, A.; Ariyanon, W.; Vadcharavivad, S.; Phumratanaprapin, W. Comparative Long-Term Renal Allograft Outcomes of Recurrent Immunoglobulin A with Severe Activity in Kidney Transplant Recipients with and without Rituximab: An Observational Cohort Study. J. Clin. Med. 2021, 10, 3939. [Google Scholar] [CrossRef]
- Sharma, A.; Hariharan, S. Octreotide Delaying the Progression of Recurrent IgA Nephropathy After Kidney Transplantation. Transplant. Direct. 2019, 6, e518. [Google Scholar] [CrossRef]
- Perkovic, V.; Barratt, J.; Rovin, B.; Kashihara, N.; Maes, B.; Zhang, H.; Trimarchi, H.; Kollins, D.; Papachristofi, O.; Jacinto-Sanders, S.; et al. APPLAUSE-IgAN Investigators. Alternative Complement Pathway Inhibition with Iptacopan in IgA Nephropathy. N. Engl. J. Med. 2025, 392, 531–543. [Google Scholar] [CrossRef]
- Mansur, J.B.; Sandes-Freitas, T.V.; Kirsztajn, G.M.; Cristelli, M.P.; Mata, G.F.; de Paula, M.I.; Grenzi, P.C.; Martins, S.B.S.; Felipe, C.R.; Tedesco-Silva, H.; et al. Clinical features and outcomes of kidney transplant recipients with focal segmental glomerulosclerosis recurrence. Nephrology 2019, 24, 1179–1188. [Google Scholar] [CrossRef]
- El Ters, M. PRI-VENT FSGS: Preemptive Rituximab to Prevent Recurrent Focal Segmental Glomerulosclerosis Post-Transplant. Available online: https://clinicaltrials.gov/study/NCT03763643?term=NCT03763643&rank=1. (accessed on 10 February 2025).
- Randone, P.; Sanna, E.; Dolla, C.; Gallo, E.; Mingozzi, S.; Tarragoni, R.; Torazza, M.C.; Niarchos, A.; Mella, A.; Manzione, A.M.; et al. Rescue with obinutuzumab and daratumumab as combined B cell/plasma cell targeting approach in severe posttransplant focal segmental glomerulosclerosis recurrence. Am. J. Transplant. 2024, 24, 1896–1900. [Google Scholar] [CrossRef]
- Al-Mousily, M.; Nicoara, O.; Selewski, D.T.; Twombley, K. Liposorber® LA-15 system for LDL apheresis in resistant nephrotic syndrome patients. Pediatr. Nephrol. 2022, 37, 585–592. [Google Scholar] [CrossRef] [PubMed]
- Shoji, J.; Goggins, W.C.; Wellen, J.R.; Cunningham, P.N.; Johnston, O.; Chang, S.S.; Solez, K.; Santos, V.; Larson, T.J.; Takeuchi, M.; et al. Efficacy and Safety of Bleselumab in Preventing the Recurrence of Primary Focal Segmental Glomerulosclerosis in Kidney Transplant Recipients: A Phase 2a, Randomized, Multicenter Study. Transplantation 2024, 108, 1782–1792. [Google Scholar] [CrossRef]
- Angeletti, A.; Bin, S.; Kajana, X.; Spinelli, S.; Bigatti, C.; Caridi, G.; Candiano, G.; Lugani, F.; Verrina, E.E.; La Porta, E.; et al. Combined Rituximab and Daratumumab Treatment in Difficult-to-Treat Nephrotic Syndrome Cases. Kidney Int. Rep. 2024, 9, 1892–1896. [Google Scholar] [CrossRef]
- Sethi, S.; Kumar, S.; Lim, K.; Jordan, S.C. Obinutuzumab is Effective for the Treatment of Refractory Membranous Nephropathy. Kidney Int. Rep. 2020, 5, 1515–1518. [Google Scholar] [CrossRef] [PubMed]
- Gonzalez Suarez, M.L.; Thongprayoon, C.; Hansrivijit, P.; Kovvuru, K.; Kanduri, S.R.; Aeddula, N.R.; Pivovarova, A.I.; Chewcharat, A.; Bathini, T.; Mao, M.A.; et al. Treatment of C3 Glomerulopathy in Adult Kidney Transplant Recipients: A Systematic Review. Med. Sci. 2020, 8, 44. [Google Scholar] [CrossRef]
- Wong, E.; Nester, C.; Cavero, T.; Karras, A.; Le Quintrec, M.; Lightstone, L.; Eisenberger, U.; Soler, M.J.; Kavanagh, D.; Daina, E.; et al. Efficacy and Safety of Iptacopan in Patients with C3 Glomerulopathy. Kidney Int. Rep. 2023, 8, 2754–2764. [Google Scholar] [CrossRef] [PubMed]
- Obata, S.; Vaz de Castro, P.A.S.; Riella, L.V.; Cravedi, P. Recurrent C3 glomerulopathy after kidney transplantation. Transplant. Rev. 2024, 38, 100839. [Google Scholar] [CrossRef]
- Buxeda, A.; Said, S.M.; Nasr, S.H.; Leung, N.; El Ters, M.; Cosio, F.G. Recurrent Proliferative Glomerulonephritis WITH Monoclonal Immunoglobulin Deposits in Kidney Allografts Treated with Anti-CD20 Antibodies. Transplantation 2019, 103, 1477–1485. [Google Scholar] [CrossRef]
Recurrence Prevalence | Overall | IgAN | FSGS | MN | MPGN |
---|---|---|---|---|---|
ANZDATA (1985–2014) | 10.3% | 10% at 10 years | 9% at 10 years | 16% at 10 years | 16% at 10 years |
Mayo/Toronto | 39.5% at 5 years | 42% at 3 years | 31% at 3 years | 45% at 3 years | 41% at 3 years |
British Columbia (1990–2005) | 13% at 10 years | 15.4% | 9.7% | 10% | 4.8% |
Korea (1995–2010) | 17.8% | 14.8% | 6.3% | 0% | 12.5% |
France | NR | 36% at 10 years | NR | NR | NR |
Recurrent Risk | Risk of Graft Loss Due to Recurrence | |
---|---|---|
IgAN | 13–46% | 2–16% |
FSGS | 20–50% | 13–20% |
MPGN | ||
Type 1 | 20–25% | 15% |
Type 2 | 80–100% | 15–30% |
MN | 10–30% | 10–15% |
Disease | Recurrence Rate | |
---|---|---|
Pathological | Clinical–pathological | |
Membranous nephropathy | 7–44% | 10% |
FSGS | 30–50% | 30% |
IgA nephritis | 9–61% | 5% |
MPGN | 27–65% | Depending on type (40%) |
Potential Predictive Biomarkers in GN Subtypes | Clinical Utility | Predict Post-Transplant Recurrence |
---|---|---|
IgA nephropathy | ||
Serum IgA level [21] | ↑ Post-transplant predict recurrence | Yes |
Serum galactose deficient IgA1 [22] | ↑ Pre-transplant predicts post-transplant recurrence | Yes |
Serum IgA-IgG complexes [22] | ↑ Pre-transplant predicts post-transplant recurrence | Yes |
Serum IgA-sCD89 complexes [22] | ↓ Pre-transplant predicts post-transplant recurrence | Yes |
Normalized Gd-IgA1 specific autoantibody [23] | ↑ Pre-transplant predicts post-transplant recurrence | Yes |
Serum APRIL [24] | ↑ Post-transplant predicts recurrence | Yes |
Urine proteomics (SERPINA 1, Transferrin, APOA4 and RBP4) [25] | ↑ Post-transplant predicts recurrence | Yes |
FSGS | ||
Serum suPAR [26] | ↑ Pre-transplant predicts post-transplant recurrence | Yes |
Urine suPAR [27] | ↑ Post-transplant predicts recurrence | Yes |
Anti CD40 autoAb [28] | ↑ Pre-transplant predicts post-transplant recurrence | Yes |
Urine apolipoprotein A-1b [29,30] | ↑ In relapses | No data |
A1AT [31] | Differentiate from other causes | No data |
CLC-1 [32] | ↑ Recurrent disease | No data |
Anti AT1R Ab | ↑ Pre-transplant predicts post-transplant recurrence | Yes |
Membranous GN | ||
PLA2R antibody [33] | ↑ Pre-transplant predicts post-transplant recurrence | Yes |
THSD7A autoantibody [34,35] | ↑ Primary membranous GN | No data |
Autoantigens of AR, SOD2, αENO [36] | ↑ Primary membranous GN | No data |
MPGN | ||
Complement and C3NF [37,38,39] | Possible association with disease recurrence | Uncertain |
Predictors | Multivariate Analysis (HR) | p Value |
---|---|---|
Brazil | 0.45 (0.21–0.98) | 0.05 |
Europe | 0.39 (0.18–0.87) | 0.02 |
Age at diagnosis | 1.37 (1.12–1.68) | 0.002 |
White race | 2.39 (1.16–4.96) | 0.02 |
BMI | 0.89 (0.83–0.96) | 0.002 |
Native kidney nephrectomy | 2.89 (1.09–7.66) | 0.03 |
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Salvadori, M.; Rosso, G. Recurrence of Primary Glomerular Diseases After Kidney Transplantation: Incidence, Predictors, Characteristics and Treatment. Transplantology 2025, 6, 14. https://doi.org/10.3390/transplantology6020014
Salvadori M, Rosso G. Recurrence of Primary Glomerular Diseases After Kidney Transplantation: Incidence, Predictors, Characteristics and Treatment. Transplantology. 2025; 6(2):14. https://doi.org/10.3390/transplantology6020014
Chicago/Turabian StyleSalvadori, Maurizio, and Giuseppina Rosso. 2025. "Recurrence of Primary Glomerular Diseases After Kidney Transplantation: Incidence, Predictors, Characteristics and Treatment" Transplantology 6, no. 2: 14. https://doi.org/10.3390/transplantology6020014
APA StyleSalvadori, M., & Rosso, G. (2025). Recurrence of Primary Glomerular Diseases After Kidney Transplantation: Incidence, Predictors, Characteristics and Treatment. Transplantology, 6(2), 14. https://doi.org/10.3390/transplantology6020014