# Outcomes After Kidney Transplantation in Antiglomerular Basement Membrane Disease

Priscille Traversat, Marine Dekervel, Christophe Masset, Dominique Bertrand, Léonard Golbin, Philippe Gatault, Antoine Thierry, Emilie Cornec-Le Gall, Maïté Jaureguy, Cyrille Garrouste, et al.

► To cite this version:

Priscille Traversat, Marine Dekervel, Christophe Masset, Dominique Bertrand, Léonard Golbin, et al. Outcomes After Kidney Transplantation in Antiglomerular Basement Membrane Disease. Kidney International Reports, 2025, 10 (9), pp.3150 - 3163. 10.1016/j.ekir.2025.06.021. hal-05319769

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# Outcomes After Kidney Transplantation in Antiglomerular Basement Membrane Disease

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Priscille Traversat<fnref n="1" />,¹⁵, Marine Dekervel<fnref n="1" />,¹⁵, Christophe Masset², Dominique Bertrand³,
Léonard Golbin⁴, Philippe Gatault⁵, Antoine Thierry⁶, Emilie Cornec-Le Gall⁷,
Maïté Jaureguy⁸, Cyrille Garrouste⁹, Dany Anglicheau¹⁰, Valérie Chatelet¹¹,
Sophie Caillard¹², Anna Duval¹², Jean-Philippe Rerolle¹³, Martin Planchais<fnref n="1" />, Agnès Duveau<fnref n="1" />,
Fabien Duthe⁶, Jean-François Augusto<fnref n="1" />,¹⁴ and Benoît Brillard<fnref n="1" />,¹⁴

**Introduction:** Goodpasture disease, or antiglomerular basement membrane (anti-GBM) disease, is a rare autoimmune disorder that often leads to end-stage kidney disease (ESKD). Although kidney transplantation (KT) is the preferred treatment, concerns exist about disease recurrence and graft outcomes in patients with GBM-associated glomerulonephritis (GBM-GN). This study aimed to evaluate posttransplant outcomes in patients with GBM-GN compared with matched controls.

**Methods:** This retrospective, multicenter study included 100 patients with anti-GBM who received KT between 2005 and 2023 in 13 French transplant centers, matched with 200 control recipients. We compared the incidence of delayed graft function (DGF), graft failure, relapse, acute rejection, and death between groups and analyzed risk factors using multivariable models.

**Results:** No significant differences in DGF incidence (22% vs. 19%, *P* = 0.5), graft survival (87% vs. 88% at 5 years, *P* = 0.4), or patient survival (93% vs. 89% at 5 years, *P* = 0.4) were found between patients with GBM-GN and controls. Patients with GBM-GN tended to have lower risk of acute rejection (hazard ratio [HR] = 0.51, 95% confidence interval: 0.25–1.02, *P* = 0.055). Only 1 patient with GBM-GN (1%) experienced disease relapse. Although patients with GBM-GN were waitlisted and transplanted later than controls, specific transplant timing was not associated with improved outcomes.

**Conclusion:** KT in patients with GBM-GN offers comparable outcomes to other nephropathies in the current era. Disease relapse is rare, even in the few patients with detectable antibodies pretransplantation. The lower incidence of acute rejection in the GBM-GN group warrants further investigation. These findings support KT as a viable option in patients with GBM-GN, though specific pre- and posttransplant monitoring is advised.

Kidney Int Rep (2025) **10**, 3150–3163; https://doi.org/10.1016/j.ekir.2025.06.021

KEYWORDS: GBM; glomerulonephritis; Goodpasture; kidney transplantation; outcomes; vasculitis

© 2025 International Society of Nephrology. Published by Elsevier Inc. This is an open access article under the CC BY license (http://creativecommons.org/licenses/by/4.0/).

**Correspondence:** Benoît Brillard, Service de Néphrologie-Dialyse-Transplantation, CHU Angers, 4 rue Larrey, 49000 Angers, France.
E-mail: benoit.brillard@chu-angers.fr

¹⁵PT and MD contributed equally.

Received 24 March 2025; revised 3 June 2025; accepted 9 June 2025; published online 18 June 2025

Goodpasture disease, also known as anti-GBM disease, is a rare autoimmune disorder characterized by the presence of circulating anti-GBM antibodies that target the basement membranes of kidneys and lungs. Clinically, it presents with rapidly progressive GN (GBM-GN), often accompanied by pulmonary hemorrhage. Kidney involvement is present in

<footnote n="1">¹Service de Néphrologie-Dialyse-Transplantation, CHU Angers, Angers, France; ²Institut de Transplantation-Urologie-Néphrologie, Nantes University Hospital, Nantes, France; ³Service de Néphrologie-Dialyse-Transplantation, CHU de Rouen, Rouen, France; ⁴Service de Néphrologie-Dialyse-Transplantation, CHU de Rennes, Rennes, France; ⁵Service de Néphrologie-Dialyse-Transplantation, CHU de Tours, Tours, France; ⁶Service de Néphrologie-Dialyse-Transplantation, CHU de Poitiers, Poitiers, France; ⁷Université de Brest, Inserm, UMR 1078, GGB, CHU Brest, Centre de référence MARHEA, Brest, France; ⁸Service de Néphrologie-Dialyse-Transplantation, CHU d'Amiens, Amiens, France; ⁹Service de Néphrologie-Dialyse-Transplantation, CHU de Clermont-Ferrand, Clermont-Ferrand, France; ¹⁰Service des Maladies du rein et du métabolisme, Hôpital Necker, Assistance Publique-Hôpitaux de Paris, Paris, France; ¹¹Service de Néphrologie-Dialyse-Transplantation, CHU de Caen, Caen, France; ¹²Service de Néphrologie-Dialyse-Transplantation, CHU de Strasbourg, Strasbourg, France; ¹³Service de Néphrologie-Dialyse-Transplantation, CHU de Limoges, Limoges, France; and ¹⁴Univ Angers, Nantes Université, Inserm, CNRS, CRCI2NA, SFR ICAT, Angers, France</footnote>
approximately 80% to 90% of cases,¹ manifesting as hematuria, proteinuria, and progressive kidney failure. GBM-GN can then lead to significant morbidity, with 50% to 70% of patients progressing to ESKD despite early intervention, and particularly if the diagnosis is delayed or if renal function is severely impaired at presentation.²,³ The prognosis for renal recovery is largely determined by the severity of kidney injury and the promptness of treatment initiation.³

As in other kidney diseases, KT has emerged as the preferred treatment option for patients with GBM-GN with ESKD and is considered to offer superior overall survival and quality of life compared with maintenance dialysis, in analogy with other nephropathies, but without specific data. In the context of Goodpasture disease, transplantation carries specific risks as follows: antibodies can reemerge, and the disease can relapse; in addition, pretransplantation immunosuppression carries its specific long-term effects that adds up to those of posttransplantation regimens.

Despite the importance of optimal timing for KT in patients with GBM-GN, current guidelines are limited. Based on multiple reports of disease recurrence (up to 50%) in patients who have detectable anti-GBM antibodies at the time of KT, Kidney Disease: Improving Global Outcomes⁴ and the Canadian Society of Transplantation⁵ recommend a minimum of 6 months of complete serological remission before considering KT. There is currently no European recommendation on the management of these patients before or after transplantation. Although patient and graft survivals previously appeared similar for patients with GBM-GN when compared with other transplant recipients,⁶⁻⁹ optimal timing for KT and factors associated with posttransplant outcomes (relapse, rejection, graft survival, and patient survival) have been poorly studied, mostly on small-scale studies (or macroscopic registry studies), conducted in an earlier era, and with controversial results. To address these critical knowledge gaps, we conducted an observational, retrospective, multicenter study, in the era of modern immunosuppressive regimens, in which we aimed to describe the incidence of DGF, graft failure, relapse, acute rejection, and death of patients with GBM-GN compared with a control group, and to investigate the risk factors associated with these events.

# METHODS

## Selection of Patients

This retrospective study included adult patients who received a kidney transplant in 13 French transplant centers as follows: 12 centers (Spiesser Group) that share a common transplant database (ASTRE)¹⁰,¹¹ and 1

additional center (Nantes DIVAT¹² [Données Informatisées et VAlidées en Transplantation] cohort collaborators). These databases were used to identify patients who received a kidney transplant between 2005 and 2023, for whom ESKD was caused by GBM-GN (cases) or other reasons (controls).

## Selection of Cases

In native kidney, GBM-GN diagnosis was based on active renal involvement (active urine sediment with hematuria, proteinuria and/or impaired renal function) and often associated with pulmonary involvement (intraalveolar hemorrhage), and/or anti-GBM antibodies in serum. In most cases, it was confirmed by a renal biopsy showing GN with linear deposition of anti-GBM antibodies. When kidney biopsy was not performed, anti-GBM positivity was mandatory. One case was included twice because the patient received 2 transplants over time.

## Selection of Controls

Each GBM-GN case was systematically matched with 2 controls of the same center. Controls were selected from the same databases (ASTRE and DIVAT) among all patients who received a kidney transplant during the study period (2005–2023) for ESKD because of any cause other than GBM-GN. The matching process prioritized the following criteria in hierarchical order: (i) same transplant center (mandatory), (ii) same sex when possible, (iii) recipient's age within ±5 years when possible, and (iv) transplant period within ±5 years when possible (Supplementary Figure S1). When multiple potential controls met these criteria, selection was performed by minimizing differences of age and period as much as possible. This matching strategy ensured that controls were representative of the general kidney transplant population at each center during the study period.

## Data Collection

For all patients, cases or controls, pre- and posttransplant clinical, biological, histological, and treatment data (Table 1) were manually retrieved from individual medical records. Glomerular filtration rate was estimated using the Chronic Kidney Disease Epidemiology Collaboration research group equation.¹³ For kidney function evaluation after transplantation, patients returned to dialysis were assigned a creatinine of 500 µmol/l and an estimated glomerular filtration rate of 5 ml/min. For cases, anti-GBM antibodies were assessed in indirect immunofluorescence and/or quantitative enzyme immunoassay.

## Definitions and Outcomes of Interest

Posttransplant outcomes were defined as follows:
<table><caption>**Table 1. Description of patients**</caption><thead><tr><th>Characteristics</th><th>n</th><th>Overall, N = 300</th><th>CTRL, n = 200</th><th>GBM-GN, n = 100</th><th>P-value</th></tr></thead><tbody><tr><td>Baseline characteristics</td><td></td><td></td><td></td><td></td><td></td></tr><tr><td>Male sex, n (%)</td><td>300</td><td>170 (57%)</td><td>112 (56%)</td><td>58 (58%)</td><td>0.7</td></tr><tr><td>BMI (kg/m<sup>2</sup>)</td><td>298</td><td>24.4 (4.4)</td><td>24.9 (4.6)</td><td>23.5 (4.0)</td><td>0.008</td></tr><tr><td>Hyperension, n (%)</td><td>288</td><td>243 (84%)</td><td>166 (88%)</td><td>77 (77%)</td><td>0.012</td></tr><tr><td>Diabetes, n (%)</td><td>298</td><td>42 (14%)</td><td>33 (17%)</td><td>9 (9.0%)</td><td>0.072</td></tr><tr><td>Kidney disease, n (%)</td><td>300</td><td></td><td></td><td></td><td></td></tr><tr><td>GBM-GN</td><td></td><td>-</td><td>-</td><td>100 (100%)</td><td></td></tr><tr><td>ADPKD</td><td></td><td>-</td><td>39 (20%)</td><td>-</td><td></td></tr><tr><td>Immunological (not GBM disease)</td><td></td><td>-</td><td>38 (19%)</td><td>-</td><td></td></tr><tr><td>Genetic (not ADPKD)</td><td></td><td>-</td><td>26 (13%)</td><td>-</td><td></td></tr><tr><td>Diabetic</td><td></td><td>-</td><td>16 (8.0%)</td><td>-</td><td></td></tr><tr><td>Urologic</td><td></td><td>-</td><td>12 (6.0%)</td><td>-</td><td></td></tr><tr><td>Vascular</td><td></td><td>-</td><td>14 (7.0%)</td><td>-</td><td></td></tr><tr><td>Others</td><td></td><td>-</td><td>14 (7.0%)</td><td>-</td><td></td></tr><tr><td>Unknown</td><td></td><td>-</td><td>41 (21%)</td><td>-</td><td></td></tr><tr><td>Presentation at vasculitis diagnosis</td><td></td><td></td><td></td><td></td><td></td></tr><tr><td>Age (yrs)</td><td>97</td><td>-</td><td>-</td><td>43 (18)</td><td></td></tr><tr><td>Kidney involvement, n (%)</td><td>100</td><td>-</td><td>-</td><td>100 (100%)</td><td></td></tr><tr><td>Creatinine (µmol/l)</td><td>63</td><td>-</td><td>-</td><td>956 (555)</td><td></td></tr><tr><td>Need for KRT within 30 d, n (%)</td><td>87</td><td>-</td><td>-</td><td>74 (85%)</td><td></td></tr><tr><td>Proteinuria (g/g)</td><td>49</td><td>-</td><td>-</td><td>3.12 (3.75)</td><td></td></tr><tr><td>Hematuria, n (%)</td><td>47</td><td>-</td><td>-</td><td>46 (98%)</td><td></td></tr><tr><td>Kidney biopsy, n (%)</td><td>198</td><td>106 (54%)</td><td>31 (26%)</td><td>75 (93%)</td><td>&lt;0.001</td></tr><tr><td>Lung involvement, n (%)</td><td>81</td><td>-</td><td>-</td><td>32 (40%)</td><td></td></tr><tr><td>Immunological findings</td><td></td><td></td><td></td><td></td><td></td></tr><tr><td>Presence of anti-GBM abs, n (%)</td><td>84</td><td>-</td><td>-</td><td>75 (89%)</td><td></td></tr><tr><td>Presence of ANCA (IIF or EIA), n (%)</td><td>66</td><td>-</td><td>-</td><td>14 (21%)</td><td></td></tr><tr><td>Anti-PR3</td><td>56</td><td>-</td><td>-</td><td>2 (3.6%)</td><td></td></tr><tr><td>Anti-MPO</td><td>56</td><td>-</td><td>-</td><td>5 (8.9%)</td><td></td></tr><tr><td>Therapeutic management</td><td></td><td></td><td></td><td></td><td></td></tr><tr><td>Induction remission therapy</td><td></td><td></td><td></td><td></td><td></td></tr><tr><td>Plasma exchange, n (%)</td><td>90</td><td>-</td><td>-</td><td>73 (81%)</td><td></td></tr><tr><td>Methylprednisolone pulses, n (%)</td><td>93</td><td>-</td><td>-</td><td>86 (92%)</td><td></td></tr><tr><td>Prednisone, n (%)</td><td>92</td><td>-</td><td>-</td><td>83 (90%)</td><td></td></tr><tr><td>Cyclophosphamide, n (%)</td><td>93</td><td>-</td><td>-</td><td>77 (83%)</td><td></td></tr><tr><td>Rituximab, n (%)</td><td>92</td><td>-</td><td>-</td><td>3 (3.3%)</td><td></td></tr><tr><td>Maintenance therapy</td><td></td><td></td><td></td><td></td><td></td></tr><tr><td>Prednisone, n (%)</td><td>71</td><td>-</td><td>-</td><td>48 (68%)</td><td></td></tr><tr><td>Cyclophosphamide, n (%)</td><td>75</td><td>-</td><td>-</td><td>10 (13%)</td><td></td></tr><tr><td>Rituximab, n (%)</td><td>75</td><td>-</td><td>-</td><td>1 (1.3%)</td><td></td></tr><tr><td>Azathioprine, n (%)</td><td>76</td><td>-</td><td>-</td><td>8 (11%)</td><td></td></tr><tr><td>Mycophenolic acid, n (%)</td><td>75</td><td>-</td><td>-</td><td>7 (9.3%)</td><td></td></tr><tr><td>Outcomes before KT</td><td></td><td></td><td></td><td></td><td></td></tr><tr><td>Relapse</td><td>90</td><td>-</td><td>-</td><td>2 (2.2%)</td><td></td></tr><tr><td>Preemptive transplantation</td><td>300</td><td>39 (13%)</td><td>34 (17%)</td><td>5 (5.0%)</td><td>0.004</td></tr><tr><td>Kidney transplantation</td><td></td><td></td><td></td><td></td><td></td></tr><tr><td>Status at KT</td><td></td><td></td><td></td><td></td><td></td></tr><tr><td>Age (yrs)</td><td>300</td><td>50 (16)</td><td>51 (16)</td><td>50 (16)</td><td>0.5</td></tr><tr><td>First transplantation</td><td>299</td><td>250 (84%)</td><td>166 (83%)</td><td>84 (84%)</td><td>0.9</td></tr><tr><td>Calculated PRA</td><td>206</td><td>25 (36)</td><td>24 (35)</td><td>27 (38)</td><td>0.5</td></tr><tr><td>Serological status</td><td></td><td></td><td></td><td></td><td></td></tr><tr><td>Anti-GBM abs positive (considering IIF+ or EIA+), n (%)</td><td>49</td><td>-</td><td>-</td><td>3 (6.1%)</td><td></td></tr><tr><td>Anti-GBM abs positive (considering IIF only), n (%)</td><td>43</td><td>-</td><td>-</td><td>3 (7.0%)</td><td></td></tr><tr><td>Anti-GBM abs positive (considering EIA only), n (%)</td><td>42</td><td>-</td><td>-</td><td>2 (4.8%)</td><td></td></tr><tr><td>Transplantation procedure</td><td></td><td></td><td></td><td></td><td></td></tr><tr><td>Donor age (yrs)</td><td>282</td><td>53 (17)</td><td>54 (17)</td><td>51 (18)</td><td>0.3</td></tr><tr><td>Deceased donor, n (%)</td><td>297</td><td>259 (87%)</td><td>169 (86%)</td><td>90 (90%)</td><td>0.3</td></tr><tr><td>ABO incompatibility, n (%)</td><td>262</td><td>4 (1.5%)</td><td>3 (1.7%)</td><td>1 (1.1%)</td><td>&gt;0.9</td></tr><tr><td>Donor creatinine (µmol/l)</td><td>262</td><td>82 (45)</td><td>83 (48)</td><td>80 (38)</td><td>0.6</td></tr></tbody></table>

(Continued on following page)
<table><caption>**Table 1. (Continued) Description of patients**</caption><thead><tr><th>Characteristics</th><th>n</th><th>Overall, N = 300</th><th>CTRL, n = 200</th><th>GBM-GN, n = 100</th><th>P-value</th></tr></thead><tbody><tr><td>Cold ischemia time (h)</td><td>293</td><td>15 (8)</td><td>15 (8)</td><td>14 (7)</td><td>0.5</td></tr><tr><td>HLA-mismatches (total)</td><td>296</td><td>4.19 (1.66)</td><td>4.16 (1.67)</td><td>4.26 (1.66)</td><td>0.6</td></tr><tr><td>HLA-A</td><td>296</td><td>1.15 (0.66)</td><td>1.13 (0.67)</td><td>1.17 (0.64)</td><td>0.6</td></tr><tr><td>HLA-B</td><td>296</td><td>1.39 (0.66)</td><td>1.37 (0.66)</td><td>1.43 (0.66)</td><td>0.5</td></tr><tr><td>HLA-DR</td><td>296</td><td>0.95 (0.69)</td><td>0.95 (0.69)</td><td>0.95 (0.71)</td><td>&gt;0.9</td></tr><tr><td>HLA-DQ</td><td>247</td><td>0.84 (0.69)</td><td>0.85 (0.71)</td><td>0.83 (0.64)</td><td>0.9</td></tr><tr><td>Immunosuppressive regimen</td><td></td><td></td><td></td><td></td><td></td></tr><tr><td>Induction therapy</td><td></td><td></td><td></td><td></td><td></td></tr><tr><td>Antithymocyte globulin, n (%)</td><td>298</td><td>103 (35%)</td><td>62 (31%)</td><td>41 (41%)</td><td>0.10</td></tr><tr><td>Basiliximab, n (%)</td><td>297</td><td>184 (62%)</td><td>129 (65%)</td><td>55 (55%)</td><td>0.079</td></tr><tr><td>Prednisone, n (%)</td><td>297</td><td>276 (93%)</td><td>185 (93%)</td><td>91 (93%)</td><td>&gt;0.9</td></tr><tr><td>Maintenance regimen</td><td></td><td></td><td></td><td></td><td></td></tr><tr><td>Calcineurin inhibitors, n (%)</td><td>299</td><td>296 (99%)</td><td>196 (98%)</td><td>100 (100%)</td><td>0.6</td></tr><tr><td>Mycophenolic acid, n (%)</td><td>298</td><td>290 (97%)</td><td>191 (96%)</td><td>99 (99%)</td><td>0.3</td></tr><tr><td>Prednisone, n (%)</td><td>282</td><td>210 (74%)</td><td>131 (70%)</td><td>79 (82%)</td><td>0.030</td></tr><tr><td>mTOR inhibitors, n (%)</td><td>294</td><td>41 (14%)</td><td>26 (13%)</td><td>15 (15%)</td><td>0.6</td></tr><tr><td>Azathioprine, n (%)</td><td>293</td><td>19 (6.5%)</td><td>12 (6.2%)</td><td>7 (7.1%)</td><td>0.7</td></tr><tr><td>Outcomes after KT</td><td></td><td></td><td></td><td></td><td></td></tr><tr><td>Follow-up duration (mo)</td><td>300</td><td>86 (43, 132)</td><td>76 (42, 123)</td><td>97 (46, 145)</td><td>0.14</td></tr><tr><td>DGF, n (%)</td><td>286</td><td>56 (20%)</td><td>35 (19%)</td><td>21 (22%)</td><td>0.5</td></tr><tr><td>Allograft failure, n (%)</td><td>299</td><td>54 (18%)</td><td>37 (19%)</td><td>17 (17%)</td><td>0.7</td></tr><tr><td>Relapses</td><td></td><td></td><td></td><td></td><td></td></tr><tr><td>All, n (%)</td><td>299</td><td>-</td><td>-</td><td>1 (1.0%)</td><td>-</td></tr><tr><td>With kidney involvement, n (%)</td><td>299</td><td>-</td><td>-</td><td>1 (1.0%)</td><td>-</td></tr><tr><td>Rejection, n (%)</td><td>294</td><td>56 (19%)</td><td>43 (22%)</td><td>13 (13%)</td><td>0.074</td></tr><tr><td>Acute rejection (AR), n (%)</td><td>294</td><td>45 (15%)</td><td>34 (17%)</td><td>11 (11%)</td><td>0.2</td></tr><tr><td>TCMR, n (%)</td><td>294</td><td>29 (9.9%)</td><td>22 (11%)</td><td>7 (7.1%)</td><td>0.3</td></tr><tr><td>ABMR, n (%)</td><td>293</td><td>17 (5.8%)</td><td>14 (7.2%)</td><td>3 (3.1%)</td><td>0.2</td></tr><tr><td>Mixed AR, n (%)</td><td>300</td><td>8 (2.7%)</td><td>6 (3.0%)</td><td>2 (2.0%)</td><td>0.7</td></tr><tr><td>Chronic rejection</td><td>291</td><td>16 (5.5%)</td><td>14 (7.2%)</td><td>2 (2.1%)</td><td>0.069</td></tr><tr><td>Death</td><td>300</td><td>49 (16%)</td><td>30 (15%)</td><td>19 (19%)</td><td>0.4</td></tr></tbody></table>

ABMR, antibody-mediated rejection; abs, antibodies; ADPKD, autosomal dominant polycystic kidney disease; ANCA, antineutrophil cytoplasmic autoantibodies; anti-MPO, antymeloperoxidase, antymeloperoxisae antibodies; Anti-PR3, antiproteinase 3 antibodies; AR, acute rejection; BMI, body mass index; CTRL, controls; DGF, delayed graft function; EIA, enzyme immunoassays; GBM, glomerular basement membrane; GBM-GN, glomerular basement membrane disease-associated glomerulonephritis; HLA, human leukocyte antigen; IIF, indirect immunofluorescence; KRT, kidney replacement therapy; KT, kidney transplantation; mTOR, mammalian target of rapamycin; PRA, panel reactive antibody; TCMR, T-cell-mediated rejection.

1. DGF was defined as previously¹⁴: requirement for ≥ 1 dialysis session within 7 days of transplantation.

2. Kidney allograft failure (ESKD) was defined by return to dialysis or retransplantation.

3. GBM disease relapse was defined as previously¹⁵: renal flares were diagnosed based on biopsy evidence of necrotizing crescentic GN with linear IgG deposition along the GBM in indirect immunofluorescence and increased serum creatinine associated with nephritic urinary sediment, in the absence of other causes of renal allograft dysfunction. Extra-renal flares were diagnosed based on an episode of pulmonary hemorrhage without evidence of infection. In the control group, recurrence of initial nephropathy was not considered.

4. Acute rejection was defined as in Banff classification,¹⁶ acute antibody-mediated rejection and acute T-cell-medicated rejection were recorded but considered together for subsequent analyses.

Borderline rejections were considered as part of acute T-cell-medicated rejection. Chronic rejection events were also recorded.

## Statistical Analysis

Continuous variables were described with mean ± SD, except for delays between events, presented as median (1st–3rd quartiles). Categorical variables were described with counts and percentages. Data were compared using the *t* test for continuous variables, and $\chi^2$ test (or Fisher exact test if necessary) for categorical variables.

For the estimation of patient survival, Kaplan–Meier analyses were performed, and survival curves were compared with a log-rank test. The cumulative incidence of the above-mentioned outcomes of interest were evaluated with death as a competing event using the cumulative incidence competing risk method.¹⁷ Cumulative incidence curves were compared using Gray’s test.
Cox regression analyses were used for the following: (i) adjust event-free survival when comparing cases and controls and (ii) perform multi-variable analyses to examine factors associated with outcomes in the GBM-GN group. Multivariate Cox regression analysis included all parameters with *P* < 0.1 in the univariable analysis. To simplify the multivariable models, the number of variables was limited using manual step-by-step backward selection with a removal criterion of *P* > 0.1. HR with 95% confidence intervals were reported. A logistic regression analysis was performed to examine factors associated with DGF in the GBM-GN group. Multivariable analysis was carried out as described above. Odds ratios with 95% confidence intervals were reported. No imputation of missing data was performed. Statistical analyses were performed using R version 4.0. All tests were 2-sided, and a *P*-value < 0.05 was considered statistically significant.

## Ethical Issues

Our cohort has been declared and authorized by the "Commission Nationale Informatique et Libertés" (agreement number 202200131 / ar23-0077v0). This study was approved by the local ethics committee of Angers University Hospital (2022-175). Owing to the nature of the study and in accordance with French law, the patients' written consent was not mandatory.

# RESULTS

## Description of GBM-GN Cases

A total of 100 patients received a KT for ESKD secondary to GBM-GN. Patients' characteristics are summarized in Table 1. Patients with GBM-GN were diagnosed between 1985 and 2021. The mean age at diagnosis was 43 ± 18 years, two-thirds of patients (58/100, 58%) were males, and mostly (75/84, 89%) found with anti-GBM antibodies at diagnosis. Most of them (75/81, 93%) had a biopsy proven GBM-GN. All of them had anti-GBM antibodies and/or biopsy proven GBM-GN. A fifth of them (14/66, 21%) also had coexistence of antineutrophil cytoplasmic autoantibodies (ANCA). Before KT, nearly none (2/90, 2.2%) of them had relapsed. The mean age at KT was 50 ± 16 years, and patients were transplanted after a median waiting time of 11 (4–21) months. Five patients (5/100, 5%) were transplanted preemptively, and the median time in dialysis before KT was 31 (22–45) months for the others (Supplementary Figure S2). Donor source was mostly deceased donor (90/100, 90%). There was 1 ABO (1/91, 1.1%) incompatible transplantation; the mean calculated panel reactive antibody was 27% ± 38%. At the time of transplantation, anti-GBM antibodies status (indirect immunofluorescence or enzyme

immunoassay) was evaluated in 49 patients (49/100, 49%). It was positive in at least 1 technique for 3 of them (3/49, 6.1%), without specific pretransplant therapeutic intervention. Median follow-up after KT was 97 (46–145) months.

## Description of Control Patients

Characteristics of the 200 controls included in the study are summarized in Table 1. Overall, 100%, 91%, 84%, and 78% of cases were well-matched with controls regarding transplant center, year of transplantation, sex, and recipient age, respectively (Supplementary Figure S1).

Mean age at KT was 51 ± 16 years. Thirty-four patients (34/200, 17%) were transplanted preemptively, and the median time in dialysis before KT was 19 (6–36) months for the other patients (Supplementary Figure S2). Donor source was mostly deceased donors (169/197, 86%). There were 3 cases (1.7%) of ABO incompatibility; the mean calculated panel reactive antibody was 24% ± 35%. Causes of ESKD before KT were mostly led by autosomal dominant polycystic kidney disease (39/200, 20%), immunological causes (38/200, 18%), other genetic causes (26/200, 13%), and unknown causes (41/200, 21%). Median follow-up after KT was 76 ([42–123] months).

## Kidney Function and Survival

### DGF and Kidney Function Evolution

There was no significant difference in the incidence of DGF between groups, involving 21/97 (22%) and 35/189 (19%) patients in the GBM-GN and control group, respectively (*P* = 0.5, Table 1). Factors associated with the occurrence of DGF, in the GBM-GN group, in univariable analysis are described in Supplementary Table S1. In multivariable analysis, donor age (odds ratio = 1.04 [1.01–1.08], *P* = 0.022) and cold ischemia time (odds ratio = 1.12 [1.03–1.23], *P* = 0.013) were the sole factors associated with DGF (Supplementary Table S1).

There was no significant difference in kidney function evolution over time; when considering the whole cohort, creatinine levels were 150 ± 75 and 158 ± 88 µmol/l at 6 months and 1 year, respectively; and estimated glomerular filtration rate levels were 51 ± 21 and 53 ± 24 ml/min at 6 months and 1 year, respectively. Similar values of estimated glomerular filtration rate were observed over the first 5 years of follow-up in both groups (Figure 1).

### Graft Survival

A total of 54 graft failures occurred during follow-up as follows: 17/100 (17%) and 37/199 (19%) in GBM-GN and control group, respectively. In univariable analysis, there was no significant difference in the cumulative
<figure><img src="image_3.png" /><figcaption>**Figure 1.** eGFR evolution after kidney transplantation. Data are represented as mean ± SD. eGFR, estimated glomerular filtration rate; GBM-GN, glomerular basement membrane disease-associated glomerulonephritis.</figcaption></figure>

incidence of graft loss when comparing the GBM-GN group with the control group (3.0% vs. 4.6% at 1 year, 10% vs. 9.4% at 5 years, and 16% vs. 22% at 10 years, *P* = 0.4, Figure 2a). After adjustment, no difference was found in graft survival between these groups (HR = 1.31 [0.49–3.47], *P* = 0.6, Supplementary Table S2).

In the GBM-GN group, in multivariable analysis, donor age (HR = 1.03 [1.00–1.06], *P* = 0.085) and chronic rejection (HR = 16.7 [3.38–82.4], *P* < 0.001) were associated with graft loss (Table 2). Maintenance therapy with mycophenolate mofetil (HR = 0.15 [0.02–1.30], *P* = 0.085) was associated with graft survival.

## Relapses

Only 1 patient with GBM-GN (11/99, 1%) relapsed after transplantation (Figure 2b). This case was challenging, because the patient was negative for anti-GBM antibodies at the time of diagnosis (biopsy proven), transplantation, and relapse. Relapse occurred 22 months after KT, it was both renal (biopsy proven) and extrarenal (diffuse alveolar hemorrhage) and the patient rapidly required dialysis. This case has been extensively reported elsewhere.¹⁸

Interestingly, 3 patients (of the 49 with available antibody assessment: 6.1%) were transplanted with detectable anti-GBM antibodies, none of them relapsed after a follow-up duration of 12, 84, and 173 months,

respectively. Given the small number of antibody-positive patients, this subgroup analysis should be interpreted with caution.

## Acute Rejection-Free Survival

Because there were few heterogenous events (n = 16/291), we did not analyze chronic rejection data and focused on acute rejection events. A total of 45 acute rejection events occurred during the follow-up, considering T-cell–medicated rejection, antibody-mediated rejection, and mixed acute rejection together: 11/99 (11%) and 34/195 (17%) events occurred in the GBM-GN and control groups, respectively (Table 1).

In univariable analysis, there was no significant difference in the cumulative incidence of acute rejection when the GBM-GN group was compared with the control group (8.0% vs. 10% at 1 year, 11% vs. 15% at 5 years, and 13% vs. 17% at 10 years, *P* = 0.3, Figure 2c). However, in multivariable analysis, patients with GBM-GN were at lower risk of acute rejection; that did not reach statistical significance (HR = 0.51 [0.25–1.02], *P* = 0.055, Supplementary Table S3).

In the GBM-GN group, in multivariable analysis, anti-GBM antibody positivity at diagnosis (HR = 0.11 [0.03–0.50], *P* = 0.004) and donor creatinine (HR = 1.71 [0.93–3.13] per 50 µmol/l increments, *P* = 0.084) were the sole factors associated (or tending to be associated) with acute rejection (Table 3).
<figure><img src="image_4.png" /></figure>

<figure><img src="image_5.png" /></figure>

<figure><img src="image_6.png" /></figure>

<figure><img src="image_7.png" /><figcaption>**Figure 2.** Event-free survival after kidney transplantation. (a) Cumulative incidence of ESKD, (b) relapse, and (c) acute rejection. (a and c) Cumulative incidence curves were compared with Gray's test. (d) Overall survival (Kaplan-Meier curves were compared with log-rank test). CTRL, control; ESKD, end-stage kidney disease; GBM-GN, glomerular basement membrane disease-associated glomerulonephritis; HR, hazards ratio.</figcaption></figure>

## Patient Survival

A total of 49 deaths occurred during the follow-up: 19/100 (19%) and 30/200 (15%) in the GBM-GN and control group, respectively. In univariable analysis, there was no significant difference in patient survival when comparing the GBM-GN group with the control group (97% vs. 99% at 1 year, 93% vs. 89% at 5 years, and 77% vs. 85% at 10 years; *P* = 0.4; Figure 2d). After adjustment, no difference was found in GBM-GN and control patients' graft survival (HR = 0.85 [0.46-1.58], *P* = 0.6, Supplementary Table S4).

In the GBM-GN group, in multivariable analysis, age at diagnosis (HR = 1.09 [1.05-1.14], *P* < 0.001), number of total mismatches (HR = 0.64 [0.47-0.86], *P* = 0.004) and allograft failure (HR = 6.17 [1.82-21.0], *P* = 0.004) were associated with death (Table 4).

## Delays Between Events and Association With Outcomes

Although the time between waitlisting and KT was similar between GBM-GN and control patients (11 vs. 14 months, *P* = 0.11), the time between ESKD and KT (31 vs. 19 months, *P* < 0.001), and between ESKD and waitlisting (16 vs. 7 months, *P* < 0.001) was higher for

patients with GBM-GN (Supplementary Figure S1B and C and Supplementary Table S5).

We then studied the impact of delays on the previously described events. When focusing on the GBM-GN group, in univariable analysis, there was no clear trend of an impact of the various considered delays on graft survival, acute rejection-free survival, and patient survival (Supplementary Figure S3). Some analyses were, however, lacking power because of the low number of patients with short delays (< 6 months or < 12 months) between these time points.

## Characteristics and Outcomes of Patients With GBM-GN According to ANCA Status

Among the 66 GBM-GN transplant recipients with known ANCA status at diagnosis, 14 (21%) were ANCA positive. These patients were significantly older both at diagnosis (58 ± 12 vs. 41 ± 17 years; *P* < 0.001) and at transplantation (62 ± 12 vs. 46 ± 16 years; *P* < 0.001) than their ANCA-negative counterparts, and they exhibited pulmonary involvement less often (8.3% vs. 42%; *P* = 0.042). Although limited by the sample size, ANCA-positive patients experienced a trend for lower graft and patient survival (Supplementary Figure S4).
<table><caption>**Table 2.** Factors associated with graft failure (in the GBM-GN cohort)</caption><thead><tr><th rowspan="2">Characteristics</th><th colspan="5">Univariable</th><th colspan="5">Multivariable (simplified)</th></tr><tr><th>N</th><th>Event n</th><th>HR</th><th>95% CI</th><th>P-value</th><th>N</th><th>Event n</th><th>HR</th><th>95% CI</th><th>P-value</th></tr></thead><tbody><tr><td>Baseline characteristics</td><td></td><td></td><td></td><td></td><td></td><td></td><td></td><td></td><td></td><td></td></tr><tr><td>Male sex (vs. female)</td><td>100</td><td>17</td><td>1.54</td><td>0.54-4.40</td><td>0.4</td><td></td><td></td><td></td><td></td><td></td></tr><tr><td>BMI (kg/m<sup>2</sup>)</td><td>99</td><td>16</td><td>1.03</td><td>0.91-1.17</td><td>0.6</td><td></td><td></td><td></td><td></td><td></td></tr><tr><td>Hypertension (vs. no)</td><td>100</td><td>17</td><td>1.04</td><td>0.34-3.21</td><td>&gt;0.9</td><td></td><td></td><td></td><td></td><td></td></tr><tr><td>Diabetes (vs. no)</td><td>100</td><td>17</td><td>1.67</td><td>0.38-7.37</td><td>0.5</td><td></td><td></td><td></td><td></td><td></td></tr><tr><td>Presentation at vasculitis diagnosis</td><td></td><td></td><td></td><td></td><td></td><td></td><td></td><td></td><td></td><td></td></tr><tr><td>Age (yrs)</td><td>97</td><td>17</td><td>1.01</td><td>0.98-1.04</td><td>0.6</td><td></td><td></td><td></td><td></td><td></td></tr><tr><td>Kidney involvement (vs. no)</td><td>100</td><td>17</td><td>Inf.</td><td>Inf.</td><td>-</td><td></td><td></td><td></td><td></td><td></td></tr><tr><td>Lung involvement (vs. no)</td><td>81</td><td>12</td><td>0.62</td><td>0.18-2.09</td><td>0.4</td><td></td><td></td><td></td><td></td><td></td></tr><tr><td>Immunological findings</td><td></td><td></td><td></td><td></td><td></td><td></td><td></td><td></td><td></td><td></td></tr><tr><td>Presence of anti-GBM abs (vs. no)</td><td>84</td><td>11</td><td>0.98</td><td>0.12-7.78</td><td>&gt;0.9</td><td></td><td></td><td></td><td></td><td></td></tr><tr><td>Presence of ANCA (vs. no)</td><td>66</td><td>8</td><td>3.65</td><td>0.79-16.8</td><td>0.1</td><td></td><td></td><td></td><td></td><td></td></tr><tr><td>Therapeutic management</td><td></td><td></td><td></td><td></td><td></td><td></td><td></td><td></td><td></td><td></td></tr><tr><td>Induction remission therapy</td><td></td><td></td><td></td><td></td><td></td><td></td><td></td><td></td><td></td><td></td></tr><tr><td>Plasma exchange (vs. no)</td><td>90</td><td>15</td><td>1.25</td><td>0.28-5.58</td><td>0.8</td><td></td><td></td><td></td><td></td><td></td></tr><tr><td>Methylprednisolone pulses (vs. no)</td><td>93</td><td>15</td><td>Inf.</td><td>Inf.</td><td>-</td><td></td><td></td><td></td><td></td><td></td></tr><tr><td>Prednisone (vs. no)</td><td>92</td><td>15</td><td>Inf.</td><td>Inf.</td><td>-</td><td></td><td></td><td></td><td></td><td></td></tr><tr><td>Cyclophosphamide (vs. no)</td><td>93</td><td>16</td><td>1.25</td><td>0.28-5.53</td><td>0.8</td><td></td><td></td><td></td><td></td><td></td></tr><tr><td>Rituximab (vs. no)</td><td>92</td><td>16</td><td>Inf.</td><td>Inf.</td><td>-</td><td></td><td></td><td></td><td></td><td></td></tr><tr><td>Maintenance therapy</td><td></td><td></td><td></td><td></td><td></td><td></td><td></td><td></td><td></td><td></td></tr><tr><td>Prednisone (vs. no)</td><td>71</td><td>9</td><td>0.55</td><td>0.15-2.05</td><td>0.4</td><td></td><td></td><td></td><td></td><td></td></tr><tr><td>Cyclophosphamide (vs. no)</td><td>75</td><td>9</td><td>0.84</td><td>0.11-6.74</td><td>0.9</td><td></td><td></td><td></td><td></td><td></td></tr><tr><td>Rituximab (vs. no)</td><td>75</td><td>9</td><td>0.00</td><td>0.00-Inf</td><td>&gt;0.9</td><td></td><td></td><td></td><td></td><td></td></tr><tr><td>Azathioprine (vs. no)</td><td>76</td><td>9</td><td>2.12</td><td>0.44-10.3</td><td>0.4</td><td></td><td></td><td></td><td></td><td></td></tr><tr><td>Mycophenolic acid (vs. no)</td><td>75</td><td>9</td><td>Inf.</td><td>Inf.</td><td>-</td><td></td><td></td><td></td><td></td><td></td></tr><tr><td>Kidney transplantation</td><td></td><td></td><td></td><td></td><td></td><td></td><td></td><td></td><td></td><td></td></tr><tr><td>Status at KT</td><td></td><td></td><td></td><td></td><td></td><td></td><td></td><td></td><td></td><td></td></tr><tr><td>Age (yrs)</td><td>100</td><td>17</td><td>1.02</td><td>0.99-1.06</td><td>0.14</td><td></td><td></td><td></td><td></td><td></td></tr><tr><td>First transplantation</td><td>100</td><td>17</td><td>0.41</td><td>0.14-1.16</td><td>0.092</td><td></td><td></td><td></td><td></td><td></td></tr><tr><td>Preemptive transplantation</td><td>100</td><td>17</td><td>1.26</td><td>0.16-9.61</td><td>0.8</td><td></td><td></td><td></td><td></td><td></td></tr><tr><td>Calculated PRA</td><td>69</td><td>9</td><td>1.00</td><td>0.99-1.02</td><td>0.8</td><td></td><td></td><td></td><td></td><td></td></tr><tr><td>Serological status (positive vs. negative)<sup>a</sup></td><td>49</td><td>7</td><td>Inf.</td><td>Inf.</td><td>-</td><td></td><td></td><td></td><td></td><td></td></tr><tr><td>Transplantation procedure</td><td></td><td></td><td></td><td></td><td></td><td></td><td></td><td></td><td></td><td></td></tr><tr><td>Donor age (yrs)</td><td>92</td><td>16</td><td>1.03</td><td>1.00-1.06</td><td>0.081</td><td>89</td><td>16</td><td>1.03</td><td>1.00-1.06</td><td>0.085</td></tr><tr><td>Deceased donor (vs. no)</td><td>100</td><td>17</td><td>1.99</td><td>0.26-15.1</td><td>0.5</td><td></td><td></td><td></td><td></td><td></td></tr><tr><td>Donor creatinine (/50 µmol/l increment)</td><td>90</td><td>14</td><td>0.89</td><td>0.41-1.93</td><td>0.8</td><td></td><td></td><td></td><td></td><td></td></tr><tr><td>Cold ischemia time (h)</td><td>99</td><td>16</td><td>1.09</td><td>1.02-1.18</td><td>0.014</td><td></td><td></td><td></td><td></td><td></td></tr><tr><td>HLA-mismatches (total)</td><td>98</td><td>16</td><td>0.85</td><td>0.63-1.15</td><td>0.3</td><td></td><td></td><td></td><td></td><td></td></tr><tr><td>HLA-A</td><td>98</td><td>16</td><td>0.69</td><td>0.31-1.49</td><td>0.3</td><td></td><td></td><td></td><td></td><td></td></tr><tr><td>HLA-B</td><td>98</td><td>16</td><td>0.64</td><td>0.32-1.28</td><td>0.2</td><td></td><td></td><td></td><td></td><td></td></tr><tr><td>HLA-DR</td><td>98</td><td>16</td><td>0.58</td><td>0.28-1.19</td><td>0.14</td><td></td><td></td><td></td><td></td><td></td></tr><tr><td>HLA-DQ</td><td>83</td><td>15</td><td>1.34</td><td>0.59-3.02</td><td>0.5</td><td></td><td></td><td></td><td></td><td></td></tr><tr><td>Immunosuppressive regimen</td><td></td><td></td><td></td><td></td><td></td><td></td><td></td><td></td><td></td><td></td></tr><tr><td>Induction therapy</td><td></td><td></td><td></td><td></td><td></td><td></td><td></td><td></td><td></td><td></td></tr><tr><td>Anti-thymocyte globulin (vs. no)</td><td>100</td><td>17</td><td>1.35</td><td>0.52-3.50</td><td>0.5</td><td></td><td></td><td></td><td></td><td></td></tr><tr><td>Basiliximab (vs. no)</td><td>100</td><td>17</td><td>0.72</td><td>0.28-1.87</td><td>0.5</td><td></td><td></td><td></td><td></td><td></td></tr><tr><td>Prednisone (vs. no)</td><td>98</td><td>17</td><td>Inf.</td><td>Inf.</td><td>-</td><td></td><td></td><td></td><td></td><td></td></tr><tr><td>Maintenance regimen</td><td></td><td></td><td></td><td></td><td></td><td></td><td></td><td></td><td></td><td></td></tr><tr><td>Calcineurin inhibitors (vs. no)</td><td>100</td><td>17</td><td>Inf.</td><td>Inf.</td><td>-</td><td></td><td></td><td></td><td></td><td></td></tr><tr><td>Mycophenolic acid (vs. no)</td><td>100</td><td>17</td><td>0.11</td><td>0.01-0.87</td><td>0.036</td><td>89</td><td>16</td><td>0.15</td><td>0.02-1.30</td><td>0.085</td></tr><tr><td>Prednisone (vs. no)</td><td>96</td><td>16</td><td>0.57</td><td>0.20-1.65</td><td>0.3</td><td></td><td></td><td></td><td></td><td></td></tr><tr><td>mTOR inhibitors (vs. no)</td><td>98</td><td>16</td><td>1.38</td><td>0.39-4.89</td><td>0.6</td><td></td><td></td><td></td><td></td><td></td></tr><tr><td>Azathioprine (vs. no)</td><td>98</td><td>16</td><td>0.55</td><td>0.07-4.23</td><td>0.6</td><td></td><td></td><td></td><td></td><td></td></tr><tr><td>Outcomes after KT</td><td></td><td></td><td></td><td></td><td></td><td></td><td></td><td></td><td></td><td></td></tr><tr><td>DGF (vs. no)</td><td>97</td><td>16</td><td>2.05</td><td>0.70-6.04</td><td>0.2</td><td></td><td></td><td></td><td></td><td></td></tr><tr><td>Allograft failure (vs. no)</td><td>-</td><td>-</td><td>-</td><td>-</td><td>-</td><td></td><td></td><td></td><td></td><td></td></tr><tr><td>Rejection (vs. no)</td><td>98</td><td>17</td><td>1.99</td><td>0.65-6.13</td><td>0.2</td><td></td><td></td><td></td><td></td><td></td></tr><tr><td>Acute rejection (AR) (vs. no)</td><td>98</td><td>17</td><td>1.71</td><td>0.49-5.97</td><td>0.4</td><td></td><td></td><td></td><td></td><td></td></tr><tr><td>TCMR (vs. no)</td><td>98</td><td>17</td><td>0.64</td><td>0.08-4.81</td><td>0.7</td><td></td><td></td><td></td><td></td><td></td></tr></tbody></table>

(Continued on following page)
<table><caption>**Table 2. (Continued) Factors associated with graft failure (in the GBM-GN cohort)**</caption><thead><tr><th rowspan="2">Characteristics</th><th colspan="5">Univariable</th><th colspan="5">Multivariable (simplified)</th></tr><tr><th>N</th><th>Event n</th><th>HR</th><th>95% CI</th><th>P-value</th><th>N</th><th>Event n</th><th>HR</th><th>95% CI</th><th>P-value</th></tr></thead><tbody><tr><td>Baseline characteristics</td><td></td><td></td><td></td><td></td><td></td><td></td><td></td><td></td><td></td><td></td></tr><tr><td>ABMR (vs. no)</td><td>98</td><td>17</td><td>2.80</td><td>0.37-21.4</td><td>0.3</td><td></td><td></td><td></td><td></td><td></td></tr><tr><td>Mixed AR (vs. no)</td><td>100</td><td>17</td><td>4.55</td><td>0.59-34.9</td><td>0.14</td><td></td><td></td><td></td><td></td><td></td></tr><tr><td>Chronic rejection</td><td>97</td><td>17</td><td>12.1</td><td>2.63-55.3</td><td>0.001</td><td>89</td><td>16</td><td>16.7</td><td>3.38-82.4</td><td>&lt;0.001</td></tr><tr><td>Death</td><td>-</td><td>-</td><td>-</td><td>-</td><td>-</td><td></td><td></td><td></td><td></td><td></td></tr></tbody></table>

ABMR, antibody-mediated rejection; abs, antibodies; ADPKD, autosomal dominant polycystic kidney disease; ANCA, antineutrophil cytoplasmic autoantibodies; AR, acute rejection; BMI, body mass index; CI, confidence interval; DGF, delayed graft function; EIA, enzyme immunoassays; GBM, glomerular basement membrane; GBM-GN, glomerular basement membrane disease-associated glomerulonephritis; HLA, human leukocyte antigen; HR, hazard ratio; IIF, indirect immunofluorescence; KRT, kidney replacement therapy; KT, kidney transplantation; mTOR, mammalian target of rapamycin; PRA, panel reactive antibody; TCMR, T-cell-mediated rejection.

ªAnti-GBM serological status at the time of KT encompasses both IIF and EIA methods.

When there were not enough data in some subgroup, Cox regression model could not converge (result is given as "Inf.").

<table><caption>**Table 3. Factors associated with acute rejection (in the GBM-GN cohort)**</caption><thead><tr><th rowspan="2">Characteristics</th><th colspan="5">Univariable</th><th colspan="5">Multivariable (simplified)</th></tr><tr><th>N</th><th>Event n</th><th>HR</th><th>95% CI</th><th>P-value</th><th>N</th><th>Event n</th><th>HR</th><th>95% CI</th><th>P-value</th></tr></thead><tbody><tr><td>Baseline characteristics</td><td></td><td></td><td></td><td></td><td></td><td></td><td></td><td></td><td></td><td></td></tr><tr><td>Male sex (vs. female)</td><td>97</td><td>11</td><td>3.30</td><td>0.71-15.3</td><td>0.13</td><td></td><td></td><td></td><td></td><td></td></tr><tr><td>BMI (kg/m²)</td><td>96</td><td>11</td><td>1.01</td><td>0.88-1.16</td><td>&gt; 0.9</td><td></td><td></td><td></td><td></td><td></td></tr><tr><td>Hypertension (vs. no)</td><td>97</td><td>11</td><td>0.34</td><td>0.11-1.13</td><td>0.078</td><td></td><td></td><td></td><td></td><td></td></tr><tr><td>Diabetes (vs. no)</td><td>97</td><td>11</td><td>2.31</td><td>0.50-10.7</td><td>0.3</td><td></td><td></td><td></td><td></td><td></td></tr><tr><td>Presentation at vasculitis diagnosis</td><td></td><td></td><td></td><td></td><td></td><td></td><td></td><td></td><td></td><td></td></tr><tr><td>Age (yrs)</td><td>95</td><td>11</td><td>0.98</td><td>0.95-1.01</td><td>0.3</td><td></td><td></td><td></td><td></td><td></td></tr><tr><td>Kidney involvement (vs. no)</td><td>97</td><td>11</td><td>Inf.</td><td>Inf.</td><td>-</td><td></td><td></td><td></td><td></td><td></td></tr><tr><td>Lung involvement (vs. no)</td><td>79</td><td>8</td><td>0.96</td><td>0.23-4.01</td><td>&gt; 0.9</td><td></td><td></td><td></td><td></td><td></td></tr><tr><td>Immunological findings</td><td></td><td></td><td></td><td></td><td></td><td></td><td></td><td></td><td></td><td></td></tr><tr><td>Presence of anti-GBM abs (vs. no)</td><td>82</td><td>8</td><td>0.18</td><td>0.04-0.77</td><td>0.021</td><td>74</td><td>8</td><td>0.11</td><td>0.03-0.50</td><td>0.004</td></tr><tr><td>Presence of ANCA (vs. no)</td><td>65</td><td>7</td><td>0.64</td><td>0.08-5.32</td><td>0.7</td><td></td><td></td><td></td><td></td><td></td></tr><tr><td>Therapeutic management</td><td></td><td></td><td></td><td></td><td></td><td></td><td></td><td></td><td></td><td></td></tr><tr><td>Induction remission therapy</td><td></td><td></td><td></td><td></td><td></td><td></td><td></td><td></td><td></td><td></td></tr><tr><td>Plasma exchange (vs. no)</td><td>88</td><td>9</td><td>0.71</td><td>0.15-3.42</td><td>0.7</td><td></td><td></td><td></td><td></td><td></td></tr><tr><td>Methylprednisolone pulses (vs. no)</td><td>91</td><td>10</td><td>Inf.</td><td>Inf.</td><td>-</td><td></td><td></td><td></td><td></td><td></td></tr><tr><td>Prednisone (vs. no)</td><td>90</td><td>10</td><td>0.87</td><td>0.11-6.89</td><td>0.9</td><td></td><td></td><td></td><td></td><td></td></tr><tr><td>Cyclophosphamide (vs no)</td><td>91</td><td>10</td><td>1.83</td><td>0.23-14.4</td><td>0.6</td><td></td><td></td><td></td><td></td><td></td></tr><tr><td>Rituximab (vs. no)</td><td>90</td><td>10</td><td>Inf.</td><td>Inf.</td><td>-</td><td></td><td></td><td></td><td></td><td></td></tr><tr><td>Maintenance therapy</td><td></td><td></td><td></td><td></td><td></td><td></td><td></td><td></td><td></td><td></td></tr><tr><td>Prednisone (vs. no)</td><td>69</td><td>7</td><td>1.20</td><td>0.23-6.20</td><td>0.8</td><td></td><td></td><td></td><td></td><td></td></tr><tr><td>Cyclophosphamide (vs. no)</td><td>73</td><td>8</td><td>2.54</td><td>0.51-12.6</td><td>0.3</td><td></td><td></td><td></td><td></td><td></td></tr><tr><td>Rituximab (vs. no)</td><td>73</td><td>8</td><td>Inf.</td><td>Inf.</td><td>-</td><td></td><td></td><td></td><td></td><td></td></tr><tr><td>Azathioprine (vs. no)</td><td>74</td><td>8</td><td>2.96</td><td>0.60-14.7</td><td>0.2</td><td></td><td></td><td></td><td></td><td></td></tr><tr><td>Mycophenolic acid (vs. no)</td><td>73</td><td>8</td><td>1.40</td><td>0.17-11.4</td><td>0.8</td><td></td><td></td><td></td><td></td><td></td></tr><tr><td>Kidney transplantation</td><td></td><td></td><td></td><td></td><td></td><td></td><td></td><td></td><td></td><td></td></tr><tr><td>Status at KT</td><td></td><td></td><td></td><td></td><td></td><td></td><td></td><td></td><td></td><td></td></tr><tr><td>Age (yrs)</td><td>97</td><td>11</td><td>0.98</td><td>0.94-1.02</td><td>0.3</td><td></td><td></td><td></td><td></td><td></td></tr><tr><td>First transplantation</td><td>97</td><td>11</td><td>0.88</td><td>0.19-4.07</td><td>0.9</td><td></td><td></td><td></td><td></td><td></td></tr><tr><td>Preemptive transplantation</td><td>97</td><td>11</td><td>2.20</td><td>0.28-17.2</td><td>0.5</td><td></td><td></td><td></td><td></td><td></td></tr><tr><td>Calculated PRA</td><td>68</td><td>7</td><td>1.00</td><td>0.98-1.02</td><td>0.9</td><td></td><td></td><td></td><td></td><td></td></tr><tr><td>Serological status (positive vs. negative)ª</td><td>47</td><td>7</td><td>Inf.</td><td>Inf.</td><td>-</td><td></td><td></td><td></td><td></td><td></td></tr><tr><td>Transplantation procedure</td><td></td><td></td><td></td><td></td><td></td><td></td><td></td><td></td><td></td><td></td></tr><tr><td>Donor age (yrs)</td><td>89</td><td>11</td><td>0.98</td><td>0.95-1.01</td><td>0.2</td><td></td><td></td><td></td><td></td><td></td></tr><tr><td>Deceased donor (vs. no)</td><td>97</td><td>11</td><td>1.14</td><td>0.15-8.93</td><td>0.9</td><td></td><td></td><td></td><td></td><td></td></tr><tr><td>Donor creatinine (per 50 µmol/l increment)</td><td>88</td><td>11</td><td>1.65</td><td>1.03-2.64</td><td>0.038</td><td>74</td><td>8</td><td>1.71</td><td>0.93-3.13</td><td>0.084</td></tr><tr><td>Cold ischemia time (h)</td><td>96</td><td>11</td><td>0.95</td><td>0.87-1.03</td><td>0.2</td><td></td><td></td><td></td><td></td><td></td></tr><tr><td>HLA-mismatches (total)</td><td>96</td><td>11</td><td>0.91</td><td>0.63-1.30</td><td>0.6</td><td></td><td></td><td></td><td></td><td></td></tr><tr><td>HLA-A</td><td>96</td><td>11</td><td>0.42</td><td>0.16-1.06</td><td>0.067</td><td></td><td></td><td></td><td></td><td></td></tr><tr><td>HLA-B</td><td>96</td><td>11</td><td>0.70</td><td>0.30-1.66</td><td>0.4</td><td></td><td></td><td></td><td></td><td></td></tr><tr><td>HLA-DR</td><td>96</td><td>11</td><td>0.99</td><td>0.42-2.34</td><td>&gt;0.9</td><td></td><td></td><td></td><td></td><td></td></tr><tr><td>HLA-DQ</td><td>81</td><td>11</td><td>1.38</td><td>0.53-3.60</td><td>0.5</td><td></td><td></td><td></td><td></td><td></td></tr></tbody></table>

(Continued on following page)
<table><caption>**Table 3. (Continued) Factors associated with acute rejection (in the GBM-GN cohort)**</caption><thead><tr><th rowspan="2">Characteristics</th><th colspan="5">Univariable</th><th colspan="5">Multivariable (simplified)</th></tr><tr><th>N</th><th>Event n</th><th>HR</th><th>95% CI</th><th>P-value</th><th>N</th><th>Event n</th><th>HR</th><th>95% CI</th><th>P-value</th></tr></thead><tbody><tr><td><strong>Baseline characteristics</strong></td><td></td><td></td><td></td><td></td><td></td><td></td><td></td><td></td><td></td><td></td></tr><tr><td>Immunosuppressive regimen</td><td></td><td></td><td></td><td></td><td></td><td></td><td></td><td></td><td></td><td></td></tr><tr><td>Induction therapy</td><td></td><td></td><td></td><td></td><td></td><td></td><td></td><td></td><td></td><td></td></tr><tr><td>Antithymocyte globulin (vs. no)</td><td>97</td><td>11</td><td>0.49</td><td>0.13-1.87</td><td>0.3</td><td></td><td></td><td></td><td></td><td></td></tr><tr><td>Basiliximab (vs. no)</td><td>97</td><td>11</td><td>1.52</td><td>0.45-5.20</td><td>0.5</td><td></td><td></td><td></td><td></td><td></td></tr><tr><td>Prednisone (vs. no)</td><td>96</td><td>10</td><td>0.68</td><td>0.09-5.34</td><td>0.7</td><td></td><td></td><td></td><td></td><td></td></tr><tr><td>Maintenance regimen</td><td></td><td></td><td></td><td></td><td></td><td></td><td></td><td></td><td></td><td></td></tr><tr><td>Calcineurin inhibitors (vs. no)</td><td>97</td><td>11</td><td>Inf.</td><td>Inf.</td><td>-</td><td></td><td></td><td></td><td></td><td></td></tr><tr><td>Mycophenolic acid (vs. no)</td><td>97</td><td>11</td><td>Inf.</td><td>Inf.</td><td>-</td><td></td><td></td><td></td><td></td><td></td></tr><tr><td>Prednisone (vs. no)</td><td>93</td><td>9</td><td>1.84</td><td>0.23-14.7</td><td>0.6</td><td></td><td></td><td></td><td></td><td></td></tr><tr><td>mTOR inhibitors (vs. no)</td><td>95</td><td>10</td><td>1.35</td><td>0.29-6.38</td><td>0.7</td><td></td><td></td><td></td><td></td><td></td></tr><tr><td>Azathioprine (vs. no)</td><td>95</td><td>10</td><td>Inf.</td><td>Inf.</td><td>-</td><td></td><td></td><td></td><td></td><td></td></tr><tr><td>Outcomes after KT</td><td></td><td></td><td></td><td></td><td></td><td></td><td></td><td></td><td></td><td></td></tr><tr><td>DGF (vs. no)</td><td>94</td><td>9</td><td>1.00</td><td>0.21-4.82</td><td>&gt; 0.9</td><td></td><td></td><td></td><td></td><td></td></tr><tr><td>Allograft failure (vs. no)</td><td>97</td><td>11</td><td>1.84</td><td>0.49-6.94</td><td>0.4</td><td></td><td></td><td></td><td></td><td></td></tr><tr><td>Rejection (vs. no)</td><td>-</td><td>-</td><td>-</td><td>-</td><td>-</td><td></td><td></td><td></td><td></td><td></td></tr><tr><td>Acute rejection (AR) (vs. no)</td><td>-</td><td>-</td><td>-</td><td>-</td><td>-</td><td></td><td></td><td></td><td></td><td></td></tr><tr><td>TCMR (vs. no)</td><td>-</td><td>-</td><td>-</td><td>-</td><td>-</td><td></td><td></td><td></td><td></td><td></td></tr><tr><td>ABMR (vs. no)</td><td>-</td><td>-</td><td>-</td><td>-</td><td>-</td><td></td><td></td><td></td><td></td><td></td></tr><tr><td>Mixed AR (vs. no)</td><td>-</td><td>-</td><td>-</td><td>-</td><td>-</td><td></td><td></td><td></td><td></td><td></td></tr><tr><td>Chronic rejection</td><td>-</td><td>-</td><td>-</td><td>-</td><td>-</td><td></td><td></td><td></td><td></td><td></td></tr><tr><td>Death</td><td>-</td><td>-</td><td>-</td><td>-</td><td>-</td><td></td><td></td><td></td><td></td><td></td></tr></tbody></table>

¹, not applicable; ABMR, antibody-mediated rejection; abs, antibodies; ADPKD, autosomal dominant polycystic kidney disease; ANCA, antineutrophil cytoplasmic autoantibodies; AR, acute rejection; BMI, body mass index; CI, confidence interval; DGF, delayed graft function; EIA, enzyme immunoassays; GBM, glomerular basement membrane; GBM-GN, glomerular basement membrane disease-associated glomerulonephritis; HLA, human leukocyte antigen; HR, hazard ratio; IIF, indirect immunofluorescence; KRT, kidney replacement therapy; KT, kidney transplantation; mTOR, mammalian target of rapamycin; PRA, panel reactive antibody; TCMR, T-cell-mediated rejection.

²Anti-GBM serological status at the time of KT encompass both IIF and EIA methods.

³When there was not enough data in some subgroup, Cox regression model could not converge (result is given as "Inf.").

No association was found between ANCA status at KT and allograft (HR = 2.39 [0.48-11.8], P = 0.3) or patient (HR = 1.71 [0.47-6.15, P = 0.4]) survival after adjustment on age at transplantation.

## DISCUSSION

This study is, to the best of our knowledge, one of the largest retrospective analyses to date on KT outcomes in patients with GBM-GN compared with a matched control group.⁶⁻⁸,¹⁵ We found no significant difference in kidney function evolution, DGF occurrence, graft survival, or overall survival between GBM-GN and control recipients. There was a trend for a lower acute rejection rate in patients with GBM-GN and we only identified 1 case of relapse. Chronic rejection and donor age were major factors influencing graft survival, whereas positive anti-GBM antibodies at diagnosis seemed protective against acute rejection in the GBM-GN group. Patients with GBM-GN were waitlisted and transplanted later than controls, but no specific transplant timing was associated with improved outcomes. Lastly, no therapeutic strategy, either pre- or posttransplant, was associated with the outcomes studied.

The absence of a significant difference in graft and patient survival between GBM-GN and control groups

suggests that modern immunosuppressive regimens and KT practices can offer outcomes in patients with GBM-GN that are comparable with those of patients with other nephropathies. Despite the initial concerns regarding disease recurrence or specific adverse effects linked to pretransplant immunosuppression, our findings are reassuring. This is in line with previous smaller studies.⁶,⁸,⁹ In our cohort, the 5-year graft and overall survival rate for patients with anti-GBM-GN reached 87% and 93% respectively, congruent with recent studies.⁸,¹⁵

In our cohort, relapse was very rare (1%) and occurred in a patient who was antibody negative at the time of diagnosis, transplantation and relapse. The pathophysiology behind this relapse may involve cryptic or nondetectable low-level antibody production or other immune mechanisms not captured by current diagnostic methods. The low relapse rate in our cohort aligns with recent smaller studies.⁸,¹⁵ Previous studies have reported much higher relapse rates, as high as 50% in patients transplanted with detectable anti-GBM antibodies; however, most of these studies were conducted before the introduction of contemporary immunosuppressive regimens.¹⁹ Without questioning the rationale behind the current recommendations from Kidney Disease: Improving Global Outcomes⁴ and Canadian guidelines,⁵ it is
<table><caption>**Table 4.** Factors associated with death (in the GBM-GN cohort)</caption><thead><tr><th rowspan="2">Characteristics</th><th colspan="5">Univariable</th><th colspan="6">Multivariable (simplified)</th></tr><tr><th>N</th><th>Event n</th><th>HR</th><th>95% CI</th><th>P-value</th><th>N</th><th>Event n</th><th>HR</th><th>95% CI</th><th>P-value</th></tr></thead><tbody><tr><td>Baseline characteristics</td><td></td><td></td><td></td><td></td><td></td><td></td><td></td><td></td><td></td><td></td></tr><tr><td>Male sex (vs. female)</td><td>100</td><td>19</td><td>1.82</td><td>0.65-5.07</td><td>0.3</td><td></td><td></td><td></td><td></td><td></td></tr><tr><td>BMI (kg/m²)</td><td>99</td><td>19</td><td>1.12</td><td>1.01-1.25</td><td>0.030</td><td></td><td></td><td></td><td></td><td></td></tr><tr><td>Hypertension (vs. no)</td><td>100</td><td>19</td><td>1.21</td><td>0.40-3.65</td><td>0.7</td><td></td><td></td><td></td><td></td><td></td></tr><tr><td>Diabetes (vs. no)</td><td>100</td><td>19</td><td>0.57</td><td>0.08-4.26</td><td>0.6</td><td></td><td></td><td></td><td></td><td></td></tr><tr><td>Presentation at vasculitis diagnosis</td><td></td><td></td><td></td><td></td><td></td><td></td><td></td><td></td><td></td><td></td></tr><tr><td>Age (yrs)</td><td>97</td><td>18</td><td>1.06</td><td>1.02-1.09</td><td>&lt; 0.001</td><td>95</td><td>17</td><td>1.09</td><td>1.05-1.14</td><td>&lt;0.001</td></tr><tr><td>Kidney involvement (vs. no)</td><td>100</td><td>19</td><td></td><td></td><td></td><td></td><td></td><td></td><td></td><td></td></tr><tr><td>Lung involvement (vs. no)</td><td>81</td><td>15</td><td>0.31</td><td>0.09-1.12</td><td>0.074</td><td></td><td></td><td></td><td></td><td></td></tr><tr><td>Immunological findings</td><td></td><td></td><td></td><td></td><td></td><td></td><td></td><td></td><td></td><td></td></tr><tr><td>Presence of anti-GBM abs (vs. no)</td><td>84</td><td>15</td><td>0.44</td><td>0.12-1.58</td><td>0.2</td><td></td><td></td><td></td><td></td><td></td></tr><tr><td>Presence of ANCA (vs. no)</td><td>66</td><td>14</td><td>2.84</td><td>0.83-9.70</td><td>0.1</td><td></td><td></td><td></td><td></td><td></td></tr><tr><td>Therapeutic management</td><td></td><td></td><td></td><td></td><td></td><td></td><td></td><td></td><td></td><td></td></tr><tr><td>Induction remission therapy</td><td></td><td></td><td></td><td></td><td></td><td></td><td></td><td></td><td></td><td></td></tr><tr><td>Plasma exchange (vs. no)</td><td>90</td><td>17</td><td>1.44</td><td>0.33-6.33</td><td>0.6</td><td></td><td></td><td></td><td></td><td></td></tr><tr><td>Methylprednisolone pulses (vs. no)</td><td>93</td><td>16</td><td>Inf.</td><td>Inf.</td><td>-</td><td></td><td></td><td></td><td></td><td></td></tr><tr><td>Prednisone (vs. no)</td><td>92</td><td>16</td><td>1.15</td><td>0.15-8.85</td><td>0.9</td><td></td><td></td><td></td><td></td><td></td></tr><tr><td>Cyclophosphamide (vs. no)</td><td>93</td><td>17</td><td>0.81</td><td>0.23-2.84</td><td>0.7</td><td></td><td></td><td></td><td></td><td></td></tr><tr><td>Rituximab (vs. no)</td><td>92</td><td>17</td><td>Inf.</td><td>Inf.</td><td>-</td><td></td><td></td><td></td><td></td><td></td></tr><tr><td>Maintenance therapy</td><td></td><td></td><td></td><td></td><td></td><td></td><td></td><td></td><td></td><td></td></tr><tr><td>Prednisone (vs no)</td><td>71</td><td>15</td><td>0.39</td><td>0.14-1.07</td><td>0.068</td><td></td><td></td><td></td><td></td><td></td></tr><tr><td>Cyclophosphamide (vs no)</td><td>75</td><td>14</td><td>0.38</td><td>0.05-3.10</td><td>0.4</td><td></td><td></td><td></td><td></td><td></td></tr><tr><td>Rituximab (vs no)</td><td>75</td><td>14</td><td>Inf.</td><td>Inf.</td><td>-</td><td></td><td></td><td></td><td></td><td></td></tr><tr><td>Azathioprine (vs no)</td><td>76</td><td>14</td><td>Inf.</td><td>Inf.</td><td>-</td><td></td><td></td><td></td><td></td><td></td></tr><tr><td>Mycophenolic acid (vs no)</td><td>75</td><td>14</td><td>0.72</td><td>0.09-5.55</td><td>0.8</td><td></td><td></td><td></td><td></td><td></td></tr><tr><td>Kidney transplantation</td><td></td><td></td><td></td><td></td><td></td><td></td><td></td><td></td><td></td><td></td></tr><tr><td>Status at KT</td><td></td><td></td><td></td><td></td><td></td><td></td><td></td><td></td><td></td><td></td></tr><tr><td>Age (yrs)</td><td>100</td><td>19</td><td>1.08</td><td>1.04-1.12</td><td>&lt; 0.001</td><td></td><td></td><td></td><td></td><td></td></tr><tr><td>First transplantation</td><td>100</td><td>19</td><td>0.94</td><td>0.27-3.29</td><td>&gt; 0.9</td><td></td><td></td><td></td><td></td><td></td></tr><tr><td>Preemptive transplantation</td><td>100</td><td>19</td><td>Inf.</td><td>Inf.</td><td>-</td><td></td><td></td><td></td><td></td><td></td></tr><tr><td>Calculated PRA</td><td>69</td><td>13</td><td>1.00</td><td>0.99-1.02</td><td>0.9</td><td></td><td></td><td></td><td></td><td></td></tr><tr><td>Serological status (positive vs negative)<sup>a</sup></td><td>49</td><td>9</td><td>Inf.</td><td>Inf.</td><td>-</td><td></td><td></td><td></td><td></td><td></td></tr><tr><td>Transplantation procedure</td><td></td><td></td><td></td><td></td><td></td><td></td><td></td><td></td><td></td><td></td></tr><tr><td>Donor age (yrs)</td><td>92</td><td>18</td><td>1.06</td><td>1.03-1.09</td><td>&lt; 0.001</td><td></td><td></td><td></td><td></td><td></td></tr><tr><td>Deceased donor (vs. no)</td><td>100</td><td>19</td><td>0.47</td><td>0.16-1.42</td><td>0.2</td><td></td><td></td><td></td><td></td><td></td></tr><tr><td>Donor creatinine (per 50 µmol/L increment)</td><td>90</td><td>17</td><td>0.73</td><td>0.31-1.70</td><td>0.5</td><td></td><td></td><td></td><td></td><td></td></tr><tr><td>Cold ischemia time (h)</td><td>99</td><td>18</td><td>1.02</td><td>0.95-1.09</td><td>0.6</td><td></td><td></td><td></td><td></td><td></td></tr><tr><td>HLA-mismatches (total)</td><td>98</td><td>18</td><td>0.77</td><td>0.59-1.01</td><td>0.056</td><td>95</td><td>17</td><td>0.64</td><td>0.47-0.86</td><td>0.004</td></tr><tr><td>HLA-A</td><td>98</td><td>18</td><td>0.46</td><td>0.22-0.94</td><td>0.034</td><td></td><td></td><td></td><td></td><td></td></tr><tr><td>HLA-B</td><td>98</td><td>18</td><td>0.62</td><td>0.32-1.20</td><td>0.2</td><td></td><td></td><td></td><td></td><td></td></tr><tr><td>HLA-DR</td><td>98</td><td>18</td><td>1.01</td><td>0.52-1.97</td><td>&gt;0.9</td><td></td><td></td><td></td><td></td><td></td></tr><tr><td>HLA-DQ</td><td>83</td><td>15</td><td>0.54</td><td>0.22-1.32</td><td>0.2</td><td></td><td></td><td></td><td></td><td></td></tr><tr><td>Immunosuppressive regimen</td><td></td><td></td><td></td><td></td><td></td><td></td><td></td><td></td><td></td><td></td></tr><tr><td>Induction therapy</td><td></td><td></td><td></td><td></td><td></td><td></td><td></td><td></td><td></td><td></td></tr><tr><td>Antithymocyte globulin (vs. no)</td><td>100</td><td>19</td><td>0.79</td><td>0.31-2.03</td><td>0.6</td><td></td><td></td><td></td><td></td><td></td></tr><tr><td>Basiliximab (vs. no)</td><td>100</td><td>19</td><td>1.26</td><td>0.50-3.21</td><td>0.6</td><td></td><td></td><td></td><td></td><td></td></tr><tr><td>Prednisone (vs. no)</td><td>98</td><td>18</td><td>1.26</td><td>0.17-9.53</td><td>0.8</td><td></td><td></td><td></td><td></td><td></td></tr><tr><td>Maintenance regimen</td><td></td><td></td><td></td><td></td><td></td><td></td><td></td><td></td><td></td><td></td></tr><tr><td>Calcineurin inhibitors (vs. no)</td><td>100</td><td>19</td><td></td><td></td><td></td><td></td><td></td><td></td><td></td><td></td></tr><tr><td>Mycophenolic acid (vs. no)</td><td>100</td><td>19</td><td>Inf.</td><td>Inf.</td><td>-</td><td></td><td></td><td></td><td></td><td></td></tr><tr><td>Prednisone (vs. no)</td><td>96</td><td>18</td><td>1.44</td><td>0.42-5.02</td><td>0.6</td><td></td><td></td><td></td><td></td><td></td></tr><tr><td>mTOR inhibitors (vs. no)</td><td>98</td><td>18</td><td>1.37</td><td>0.40-4.75</td><td>0.6</td><td></td><td></td><td></td><td></td><td></td></tr><tr><td>Azathioprine (vs. no)</td><td>98</td><td>18</td><td>Inf.</td><td>Inf.</td><td>-</td><td></td><td></td><td></td><td></td><td></td></tr><tr><td>Outcomes after KT</td><td></td><td></td><td></td><td></td><td></td><td></td><td></td><td></td><td></td><td></td></tr><tr><td>DGF (vs. no)</td><td>97</td><td>19</td><td>2.44</td><td>0.95-6.31</td><td>0.065</td><td></td><td></td><td></td><td></td><td></td></tr><tr><td>Allograft failure (vs. no)</td><td>100</td><td>19</td><td>2.95</td><td>1.16-7.54</td><td>0.023</td><td>95</td><td>17</td><td>6.17</td><td>1.82-21.0</td><td>0.004</td></tr><tr><td>Rejection (vs. no)</td><td>98</td><td>18</td><td>0.59</td><td>0.14-2.57</td><td>0.5</td><td></td><td></td><td></td><td></td><td></td></tr><tr><td>Acute rejection (AR) (vs. no)</td><td>98</td><td>18</td><td>0.37</td><td>0.05-2.76</td><td>0.3</td><td></td><td></td><td></td><td></td><td></td></tr><tr><td>TCMR (vs. no)</td><td>98</td><td>18</td><td>0.48</td><td>0.06-3.65</td><td>0.5</td><td></td><td></td><td></td><td></td><td></td></tr></tbody></table>

(Continued on following page)
<table><caption>**Table 4. (Continued) Factors associated with death (in the GBM-GN cohort)**</caption><thead><tr><th rowspan="2">Characteristics</th><th colspan="5">Univariable</th><th colspan="5">Multivariable (simplified)</th></tr><tr><th>N</th><th>Event n</th><th>HR</th><th>95% CI</th><th>P-value</th><th>N</th><th>Event n</th><th>HR</th><th>95% CI</th><th>P-value</th></tr></thead><tbody><tr><td>Baseline characteristics</td><td></td><td></td><td></td><td></td><td></td><td></td><td></td><td></td><td></td><td></td></tr><tr><td>ABMR (vs. no)</td><td>98</td><td>18</td><td>0.00</td><td>0.00–Inf</td><td>> 0.9</td><td></td><td></td><td></td><td></td><td></td></tr><tr><td>Mixed AR (vs. no)</td><td>100</td><td>19</td><td>0.00</td><td>0.00–Inf</td><td>> 0.9</td><td></td><td></td><td></td><td></td><td></td></tr><tr><td>Chronic rejection</td><td>97</td><td>18</td><td>2.85</td><td>0.37–21.7</td><td>0.3</td><td></td><td></td><td></td><td></td><td></td></tr><tr><td>Death</td><td>-</td><td>-</td><td>-</td><td>-</td><td>-</td><td></td><td></td><td></td><td></td><td></td></tr></tbody></table>

- not applicable; ABMR, antibody-mediated rejection; abs, antibodies; ADPKD, autosomal dominant polycystic kidney disease; ANCA, antineutrophil cytoplasmic autoantibodies; AR, acute rejection; BMI, body mass index; CI, confidence interval; DGF, delayed graft function; EIA, enzyme immunoassays; GBM, glomerular basement membrane; GBM-GN, glomerular basement membrane disease-associated glomerulonephritis; HLA, human leukocyte antigen; HR, hazard ratio; IIF, indirect immunofluorescence; KRT, kidney replacement therapy; KT, kidney transplantation; mTOR, mammalian target of rapamycin; PRA, panel reactive antibody; TCMR, T-cell mediated rejection.

ªAnti-GBM serological status at the time of KT encompasses both IIF and EIA methods. When there were not enough data in some subgroup, Cox regression model could not converge (result is given as "Inf.").

interesting to note that none of the 3 patients transplanted with positive antibodies at the time of KT relapsed in our cohort. However, this observation should be interpreted with considerable caution, given the following: (i) the small number of patients with available antibody data at transplantation (n = 49); (ii) the even smaller number with positive antibodies (n = 3); and (iii) the fact that current clinical practice, guided by existing guidelines, may have influenced patient selection (e.g., patients with higher antibody titers may have been systematically excluded from transplantation) and timing of transplantation. Therefore, though our data suggest that the actual risk of relapse may be lower than historically reported in the contemporary era, they do not provide sufficient evidence to modify current practices or question existing guidelines.

Surprisingly, our multivariate analysis showed that patients with Goodpasture's disease tended to have a lower risk of acute rejection compared with the control group (HR = 0.51, P = 0.055). In addition, when focusing on the GBM-GN group alone, patients with positive anti-GBM antibody at diagnosis were at lower risk of acute rejection (HR = 0.11, P = 0.004). A possible explanation could be that these patients received more intense immunosuppression (more thy-moglobulin in induction therapy and more steroid in maintenance regimen) because of their underlying autoimmune disease, which might have reduced the risk of rejection. This finding however raises questions about the potential immune tolerance or protective mechanisms developed in some patients with GBM-GN with high initial antibody titers, warranting further investigation.

In our cohort, the interval from ESKD onset to waitlist inscription and to KT was longer among patients with GBM-GN, largely reflecting standard practice of awaiting at least 6 months of serological remission before listing, combined with the often severe, multiorgan course of disease that necessitates prolonged medical optimization. In addition, caution on the part of clinicians and transplant teams—

exacerbated by the rarity of anti-GBM disease—and slower referral pathways may further extend time to waitlisting. Importantly, though limited by the sample size and event number, these delays did not seem to adversely affect graft or patient survival.

Our study has several limitations, mostly due to its retrospective design that may have introduced inherent biases, including selection bias and data availability. However, if the ASTRE database was used to identify patients transplanted with GBM-GN, all data were manually and carefully gathered, on each patient's record on a detailed scale. In addition, only a small rate of GBM-GN relapse after KT, precluding stronger statistical analysis. Another limitation lies in the incomplete antibody data at the time of KT for many patients (half of them), which could have provided a more robust analysis of the relationship between serological remission and outcomes, especially regarding patients with positive anti-GBM antibodies at the time of KT. Further, very few patients received a KT within 12 months, or even within 24 months from GBM-GN diagnosis, precluding any specific analysis on this delay. Finally, this study did not assess the quality of life, an important factor in KT recipients.

Nonetheless, this is the largest French reported experience with KT for GBM-GN, and one of the largest studies on this topic so far. Our study provides valuable insights into the posttransplant outcomes of GBM-GN in the modern era. By including a matched control group and conducting multivariable analyses, we were able to adjust for many potential confounders, providing a comprehensive understanding of the factors influencing graft and patient survival in patients with GBM-GN. In addition, our long-term follow-up allowed us to capture a wide range of clinically significant outcomes, offering a detailed picture of the posttransplant course in this specific patient population.

In conclusion, this study demonstrates that KT in patients with GBM-GN offers graft and patient survival outcomes comparable with those of other nephropathies. Although our findings uphold existing
guidelines mandating serological remission before
transplantation, incomplete titer data prevent firm
conclusions about the predictive power of antibody
levels alone. Accordingly, future studies with
comprehensive antibody monitoring and investigation
of antibody-independent drivers of relapse are war-
ranted. Clinicians can use these results to counsel
patients with GBM-GN more confidently about the
safety and efficacy of KT in the current therapeutic
landscape. Further prospective studies are needed to
refine serological and clinical monitoring strategies
posttransplant.

DISCLOSURE

All the authors declared no competing interests.

ACKNOWLEDGMENTS

The authors sincerely thank the French Spiesser group for
its major contribution to this work. We thank all the ne-
phrologists in France who provide detailed information for
the ASTRE database registry and the research assistants of
ASTRE who update this information.

The authors also thank the French Nantes DIVAT (Don-
nées Informatisées et VAlidées en Transplantation) Cohort
Collaborators for their significant contribution to this work.

SUPPLEMENTARY MATERIAL

Supplementary File (PDF)

**Figure S1.** Matching between GBM-GN cases and control patients.

**Figure S2.** Distribution of delays (time between diagnosis, ESKD, waitlisting and kidney transplantation).

**Figure S3.** Impact of delays on event-free survival after kidney transplantation (in the GBM-GN subgroup).

**Figure S4.** Event-free survival after kidney transplantation according to ANCA status at GBM-GN diagnosis.

**Table S1.** Factors associated with DGF (in the GBM-GN cohort).

**Table S2.** Factors associated with graft failure (in the whole cohort).

**Table S3.** Factors associated with acute rejection (in the whole cohort).

**Table S4.** Factors associated with death (in the whole cohort).

**Table S5.** Distribution of delays between diagnosis, ESKD, waitlisting and kidney transplantation.

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