# Kidney Transplantation Improves Survival in Antineutrophil Cytoplasmic Antibody–Associated Vasculitides With End-Stage Kidney Disease

Benoît Brilland, Jean-François Augusto, Thomas Jouve, Noémie Jourde-Chiche, Cécile Couchoud

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Benoît Brilland, Jean-François Augusto, Thomas Jouve, Noémie Jourde-Chiche, Cécile Couchoud. Kidney Transplantation Improves Survival in Antineutrophil Cytoplasmic Antibody–Associated Vasculitides With End-Stage Kidney Disease. Kidney International Reports, 2025, 10 (5), pp.1415 - 1427. 10.1016/j.ekir.2025.02.001. hal-05163461

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# Kidney Transplantation Improves Survival in Antineutrophil Cytoplasmic Antibody-Associated Vasculitides With End-Stage Kidney Disease

<figure><img src="image_2.png" /></figure>

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Benoît Brilland<fnref n="1" />,², Jean-François Augusto<fnref n="1" />,², Thomas Jouve³, Noémie Jourde-Chiche⁴ and Cécile Couchoud⁵; on behalf of the Renal Epidemiology and Information Network (REIN) registry⁶

**Introduction:** Antineutrophil cytoplasmic antibody (ANCA)-associated vasculitis (AAV) frequently leads to end-stage kidney disease (ESKD). Although kidney transplantation (KT) is considered the optimal treatment for ESKD, its survival benefit in patients with AAV remains understudied. This study aimed to determine the impact of KT on survival in waitlisted patients with AAV-induced ESKD (AAV-ESKD).

**Methods:** We conducted a retrospective analysis of patients with AAV-ESKD registered in the French Renal Epidemiology and Information Network (REIN) registry and waitlisted for KT between 2002 and 2022. KT was treated as a time-dependent variable to avoid immortal time bias. Survival was assessed using Kaplan-Meier analysis and Cox proportional hazards models, adjusting for key demographic and clinical factors. Subgroup analyses were conducted based on vasculitis type, age, sex, and year of ESKD onset.

**Results:** Of 1165 patients with AAV-ESKD, 468 (40%) were waitlisted, and 318 of these (68%) received a transplant. After a median follow-up of 61 months after waitlisting, KT was associated with a 53% reduction in mortality risk (adjusted hazard ratio [HR] = 0.47 [0.31–0.73], *P* < 0.001). This benefit was consistent across subgroups. Patient survival at 10 years was 72% for transplant recipients versus 28% for nontransplanted patients (*P* < 0.001). Sensitivity analyses, after excluding recipients of living donors and patients removed from the waitlist supported the robustness of these findings. Within 2 years from ESKD onset, 24% of waitlisted patients were transplanted. Graft failure probability was 22% at 10 years posttransplant.

**Conclusion:** KT is associated with a significant survival benefit in waitlisted patients with AAV-ESKD compared with waiting on dialysis. These findings emphasize the importance of timely transplant evaluation and improved access to KT for this population.

Kidney Int Rep (2025) 10, 1415–1427; https://doi.org/10.1016/j.ekir.2025.02.001

KEYWORDS: ANCA; death; glomerulonephritis; kidney transplantation; survival; 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/).

Autoimmune diseases affecting the kidneys are typically characterized by glomerulonephritis (GN), which can lead to a rapid decline in renal function and result in ESKD. Considering all causes

combined, GN accounts for up to 20% of chronic kidney diseases in industrialized countries, representing a major burden on healthcare systems.<fnref n="1" />

AAV are among the most aggressive forms of GN.² Kidney involvement, characterized by necrotizing crescentic GN, is the most frequent organ involvement in granulomatosis with polyangiitis (GPA) and microscopic polyangiitis (MPA)—the 2 main AAV phenotypes— affecting up to 80% to 95% of patients.³⁻⁵ AAV-associated GN (AAV-GN) has a major impact on renal and global survival⁶,⁷; around 25% of patients will require kidney replacement therapy within 5 years

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

⁶Members of the Renal Epidemiology and Information Network Registry are listed in the Appendix

Received 22 November 2024; revised 30 January 2025; accepted 3 February 2025; published online 7 February 2025

<footnote n="1">¹Service de Néphrologie-Dialyse-Transplantation, CHU Angers, Angers, France; ²CRCI2NA, SFR ICAT, Univ Angers, Nantes Université, Inserm, CNRS, Angers, France; ³Nephrology, Hemodialysis, Apheresis and Kidney Transplantation Department, University Hospital Grenoble, Grenoble, France; ⁴Centre de recherche en CardioVasculaire et Nutrition (C2VN), Aix-Marseille Université, INSERM, INRAE, AP-HM Centre de Néphrologie et Transplantation Rénale, Marseille, France; and ⁵Coordination nationale REIN, Agence de la biomédecine, Saint-Denis-La Plaine, France</footnote>
from diagnosis,⁶,⁸ and the estimated excess mortality is 2 to 3 times higher than that of the general population, conferring a risk of death of 20–40% at 5 years.⁹

KT has been found to be safe and successful in the AAV-GN population with ESKD.¹⁰,¹¹ Although the overall patient and graft survival appear similar for these patients when compared with other transplant recipients,¹²⁻¹⁴ they may have a heightened risk for some posttransplant complications, such as infections, cancer, and cardiovascular events, all of which are partly attributed to extensive pretransplant immunosuppression. Moreover, though the risk of AAV relapse decreases after dialysis initiation¹⁵⁻¹⁷ and transplantation,¹⁸⁻²¹ it is not fully suppressed. These factors make it difficult to extrapolate the results of transplantation seen in all nephropathies to this specific population.

Indeed, as in other nephropathies, KT is considered the best option for overall survival compared with patients with AAV maintained on dialysis. However, the survival benefit of KT among patients with AAV-GN-induced ESKD has not been well-studied.¹⁹,²² In line with the results of the main studies performed in the all-cause ESKD population, demonstrating the survival benefit of transplantation,²³,²⁴ a previous study found that KT was associated with a 70% reduction in the risk of death among patients with GPA with ESKD waitlisted for a KT.²² Here, we used a national registry of patients with AAV-ESKD to determine the impact of KT on survival.

# METHODS

## Data Collection

REIN is a comprehensive national registry of patients who start kidney replacement therapy in France.²⁵,²⁶ Data are collected locally by each medical center and are updated prospectively annually with the help of research assistants. The collection of data was initiated in 2002, and patients were followed-up until KT, death, loss of follow-up, recovery of kidney function, or end of the study in December 2022, whichever occurred first.

## Selection of Patients

To assess the impact of transplantation on survival, this national multicenter study included all patients who fulfilled the following criteria: (i) ESKD attributed to AAV (whether GPA or MPA); (ii) initiated hemodialysis or peritoneal dialysis (or were preemptively transplanted) between January 1, 2002, and December 31, 2022; and (iii) waitlisted for a renal transplant between January 1, 2002, and December 31, 2022. Other small vessel vasculitides, such as antiglomerular basement membrane disease, eosinophilic GPA (Churg-Strauss

syndrome), and IgA vasculitis (Henoch-Schoenlein purpura) were excluded. Only the first transplant event was considered.

## Covariates and Definitions

The following information was extracted from the REIN registry²⁷ and used as covariates, exposures, or outcomes: type of vasculitis (GPA or MPA); demographics (age, sex); body mass index; calculated panel reactive antibody; cardiovascular comorbidities (i.e., heart failure, heart rhythm disorders, peripheral arterial disease, abdominal aorta aneurysm, coronary artery disease, and stroke); other relevant comorbidities (i.e., diabetes, respiratory insufficiency, or cancer); initial kidney replacement therapy modality (hemodialysis or peritoneal dialysis); waitlisting date (as well as removal from the waitlist and its underlying cause when applicable); transplant status; date and type (live or deceased donor) of kidney transplant; status at the end of follow-up, and when applicable, the date and cause of death. Kidney allograft survival was also assessed, and causes of allograft loss were retrieved. Given the various numbers of cardiovascular comorbidities, they were grouped together, and the patients were stratified into 3 subgroups (no cardiovascular comorbidity, only 1, and at least 2).

## Statistical Analysis

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

Our primary outcome was all-cause mortality. The exposure of interest was the first kidney transplant. The date on which the patient was first waitlisted for a kidney transplant was used as the start of follow-up. If waitlisting occurred before dialysis started, this latter timepoint was considered as the start of follow-up.

We assessed transplantation as a time-dependent exposure, allocating time spent before a renal transplant to the group that did not have transplants and time spent after to the group that did.²²,²⁸ This time-dependent approach avoids immortal time bias.²⁹ Transplanted patients who experienced graft failure were censored at the time of return to dialysis. Kaplan-Meier analysis was performed to estimate patient survival, and survival curves were compared using the log-rank test. Mortality rates (per 1000 patient-years) were determined by dividing the number of events during the total follow-up by the total follow-up (in years) × 1000. Mortality rate comparisons and 95%
confidence intervals were estimated using the Poisson method.

Cox proportional hazards regression analysis was
performed to examine factors associated with the
occurrence of death. Multivariate Cox regression analysis
included all parameters with *P* < 0.1 in the univariate
analysis. To simplify the multivariable models, the
number of variables in the multivariate Cox analysis was
limited using manual step-by-step backward selection
with a removal criterion of *P* > 0.1. HR with 95% con-
fidence intervals were reported. In addition, to assess the
evolution of relative risk over time, we employed a cu-
mulative time-window analysis approach. Separate Cox
models were fit for cumulative 3-month increases in
follow-up (e.g., baseline to month 3, baseline to month 6,
etc.) over a total period of 15 years. Follow-up time
beyond each time point was censored. This method
provides a dynamic estimation of the HR, thus reflecting
potential variations in the association of transplantation
with the risk of death over time. Again, 95% confidence
intervals were calculated for each estimate.

Lastly, to assess differential results across sub-
groups, we calculated P-values for interaction. Sub-
group analyses were performed to evaluate differences
in all-cause mortality with and without transplantation
according to sex, type of vasculitis (GPA or MPA), age
group at ESKD onset (below or above 60 years) and year
of ESKD onset (before or after 2012, year corresponding
to the median of total follow-up in waitlisted cohort).

The probabilities of access to the waitlist, access to
transplantation, and graft failure were evaluated with
death as a competing event, using the cumulative
incidence competing risk method.³⁰ Cumulative inci-
dence curves were compared using Gray's test.

No imputation of missing data was performed. Sta-
tistical analyses were performed using R v4.3 with the
survival, survminer and tidycmrsk packages. All tests
were 2-sided, and a *P*-value < 0.05 was considered
statistically significant.

Ethical Issues

The national ethics committee (Commission National Informatique et Liberté) approved the data collection conducted by REIN, and this study was approved by the scientific committee of REIN. No informed consent was required to participate in the REIN registry. Data collection is ruled with an implicit consent with a drop-out option. It was conducted according to the principles of the Declaration of Helsinki and its amendments. The clinical and research activities reported are consistent with the Principles of the Declaration of Istanbul as outlined in the 'Declaration of Istanbul on Organ Trafficking and Transplant Tourism.

RESULTS

Baseline Characteristics of all Patients With
AAV-ESKD

Between January 1, 2002 and December 31, 2022, 1165 patients were diagnosed with ESKD attributed to AAV and registered in the REIN Registry as follows: 619 (53%) GPA and 546 (47%) MPA. Overall, 468 of 1165 (40%) were waitlisted for a kidney transplant during the study period, among whom 318 of 468 (68%) subsequently underwent KT during follow-up (Figure 1). Patients with AAV-ESKD were mainly male (60%) with a mean age of 67 ± 14 years at dialysis initiation, most of them being enrolled in hemodialysis (91%) rather than peritoneal dialysis (7.5%) or pre-emptive transplantation (1.4%).

Compared with patients with AAV-ESKD who were
not waitlisted, waitlisted patients were younger (aged
57 ± 13 vs. 74 ± 11 years at dialysis initiation) and had
fewer comorbidities (Table 1). Specific data regarding
each vasculitis subtype is shown in Supplementary
Table S1.

Baseline Characteristics of Waitlisted Patients
With AAV

Most waitlisted patients were male (65%) with a mean age of 58 ± 13 years at the time of waitlisting for KT. The median duration of dialysis before waitlisting was 13 (5–23) months. Regarding the comorbidities, 23% of patients had at least 1 cardiovascular comorbidity, 15% were diabetic, and 11% had respiratory insufficiency. Most patients could walk alone (98%), and many had albumin levels below 30 g/l (37%). Lastly, 43% had a body mass index > 25 kg/m² and 7% below 18.5 kg/m².

Compared with waitlisted patients who were not
transplanted during the study period, patients who
received a kidney transplant were younger (57 ± 14 vs.
61 ± 10 years old at the time of transplantation), with
fewer comorbidities. Most transplanted patients were
male (64%) and GPA (55%) with a mean age at the time
of KT of 59 ± 14 years. The median waitlist duration
was 15 (6-27) months. Transplanted patients tended to
have lower calculated panel reactive antibody(12 ± 25
vs. 18 ± 32). Deceased donor transplantation was
performed in most cases (89%). During follow-up, 34
patients (23%) were removed from the waitlist before
being transplanted (Table 1). Their characteristics are
described in Supplementary Table S2; they were older
and more likely to be diabetic. Reasons for waitlist
removal are detailed in Supplementary Table S3). Spe-
cific data regarding each vasculitis subtype is shown in
Supplementary Table S1.
a

<figure><img src="image_3.png" /></figure>

b

<figure><img src="image_4.png" /><figcaption>**Figure 1.** Study participants. (a) Flowchart of the study. (b) Distribution of the number of ESKD, waitlisted, and transplanted patients considering all vasculitis subtypes or each one separately. The percentages above the bars for the "waitlisted" and "transplanted" categories indicate the proportion of patients relative to the previous category (waitlisted among ESKD; transplanted among waitlisted). AAV, ANCA-associated vasculitides; ANCA, antineutrophil cytoplasmic antibody; ESKD, end-stage kidney disease; GPA, granulomatosis with polyangiitis; MPA, microscopic polyangiitis.</figcaption></figure>

## Causes of Death in AAV Waitlisted Patients

After a median follow-up of 61 (26–107) months since waitlisting, 148 patients (32%) died, the details are as follows: 86 (27%) who received a kidney transplant (including 63 [76%] during the transplant period and 23 [27%] after return to dialysis) and 62 (41%) who did not (including 44 [71%] during the waitlisted period and 18 [29%] after being removed from the waitlist) (Table 1). The cause of death was not known in 26 patients (18%) and labelled as “others causes” in 26 patients (18%). The proportion of death from infectious causes was similar in both groups (26% vs. 27% in the nontransplanted vs. transplanted group), the

proportion of death from cancer causes was not significantly higher in the transplanted group (19% vs. 15%), and the proportion of death from cardiovascular causes was not significantly lower in the transplanted group (12 vs. 15%) (Supplementary Table S4). Causes of death for nonwaitlisted patients and according to the moment of death in waitlisted patients are also available in Supplementary Table S4).

## All-Cause Mortality in Waitlisted Patients With AAV

The mortality rate among those who received a kidney transplant was 38.6 (29.1–48.1) per 1000 patient-years,
<table><caption>Table 1. Baseline characteristics and outcomes of patients with AAV-ESKD</caption><thead><tr><th>Characteristics</th><th>ESKD n = 1165</th><th>ESKD not waitlisted n = 697</th><th>ESKD waitlisted n = 468</th><th>p-value<sup>a</sup></th><th>Waitlisted not transplanted N = 150</th><th>Waitlisted transplanted N = 318</th><th>Missing values</th><th>P-value<sup>b</sup></th></tr></thead><tbody><tr><td>Baseline characteristics, n (%)</td><td></td><td></td><td></td><td></td><td></td><td></td><td></td><td></td></tr><tr><td>Vasculitis subtype</td><td></td><td></td><td></td><td>0.4</td><td></td><td></td><td>0 (0%)</td><td>0.022</td></tr><tr><td>GPA</td><td>619 (53%)</td><td>377 (54%)</td><td>242 (52%)</td><td></td><td>66 (44%)</td><td>176 (55%)</td><td></td><td></td></tr><tr><td>MPA</td><td>546 (47%)</td><td>320 (46%)</td><td>226 (48%)</td><td></td><td>84 (56%)</td><td>142 (45%)</td><td></td><td></td></tr><tr><td>Male</td><td>703 (60%)</td><td>397 (57%)</td><td>306 (65%)</td><td>0.004</td><td>103 (69%)</td><td>203 (64%)</td><td>0 (0%)</td><td>0.3</td></tr><tr><td>Age</td><td></td><td></td><td></td><td></td><td></td><td></td><td></td><td></td></tr><tr><td>at ESKD (yrs)</td><td>67 (14)</td><td>74 (11)</td><td>57 (13)</td><td>&lt;0.001</td><td>60 (10)</td><td>56 (14)</td><td>0 (0%)</td><td>&lt;0.001</td></tr><tr><td>at waitlisting (yrs)</td><td>58 (13)</td><td>-</td><td>58 (13)</td><td></td><td>61 (10)</td><td>57 (14)</td><td>0 (0%)</td><td>&lt;0.001</td></tr><tr><td>at transplantation (yrs)</td><td>59 (14)</td><td>-</td><td>59 (14)</td><td></td><td>-</td><td>59 (14)</td><td>0 (0%)</td><td></td></tr><tr><td>First modality</td><td></td><td></td><td></td><td>&lt;0.001</td><td></td><td></td><td>0 (0%)</td><td>0.014</td></tr><tr><td>Hemodialysis</td><td>1,062 (91%)</td><td>657 (94%)</td><td>405 (87%)</td><td></td><td>137 (91%)</td><td>268 (84%)</td><td></td><td></td></tr><tr><td>Peritoneal dialysis</td><td>87 (7.5%)</td><td>40 (5.7%)</td><td>47 (10%)</td><td></td><td>13 (8.7%)</td><td>34 (11%)</td><td></td><td></td></tr><tr><td>Preemptive transplantation</td><td>16 (1.4%)</td><td>0 (0%)</td><td>16 (3.4%)</td><td></td><td>0 (0%)</td><td>16 (5.0%)</td><td></td><td></td></tr><tr><td>Calculated Panel Reactive Antibody (%)</td><td>-</td><td>-</td><td>14 (28)</td><td></td><td>18 (32)</td><td>12 (25)</td><td>65 (14%)</td><td>0.086</td></tr><tr><td>Comorbidities</td><td></td><td></td><td></td><td></td><td></td><td></td><td></td><td></td></tr><tr><td>Not able to walk alone</td><td>122 (12%)</td><td>114 (18%)</td><td>8 (1.9%)</td><td>&lt;0.001</td><td>3 (2.2%)</td><td>5 (1.8%)</td><td>48 (10%)</td><td>0.7</td></tr><tr><td>Albumin level &lt; 30 g/l</td><td>417 (42%)</td><td>270 (45%)</td><td>147 (37%)</td><td>0.011</td><td>53 (40%)</td><td>94 (35%)</td><td>68 (15%)</td><td>0.4</td></tr><tr><td>Albumin level &lt; 36 g/l</td><td>766 (76%)</td><td>497 (83%)</td><td>269 (67%)</td><td>&lt;0.001</td><td>99 (74%)</td><td>170 (64%)</td><td>68 (15%)</td><td>0.045</td></tr><tr><td>BMI</td><td></td><td></td><td></td><td>0.013</td><td></td><td></td><td>48 (10%)</td><td>0.081</td></tr><tr><td>&lt; 18.5 kg/m<sup>2</sup></td><td>84 (8.4%)</td><td>53 (9.1%)</td><td>31 (7.4%)</td><td></td><td>11 (8.2%)</td><td>20 (7.0%)</td><td></td><td></td></tr><tr><td>18.5–25 kg/m<sup>2</sup></td><td>542 (54%)</td><td>333 (57%)</td><td>209 (50%)</td><td></td><td>56 (42%)</td><td>153 (53%)</td><td></td><td></td></tr><tr><td>&gt; 25 kg/m<sup>2</sup></td><td>377 (38%)</td><td>197 (34%)</td><td>180 (43%)</td><td></td><td>67 (50%)</td><td>113 (40%)</td><td></td><td></td></tr><tr><td>Diabetes mellitus</td><td>227 (20%)</td><td>157 (23%)</td><td>70 (15%)</td><td>0.002</td><td>34 (23%)</td><td>36 (12%)</td><td>8 (1.7%)</td><td>0.001</td></tr><tr><td>Cardiovascular comorbidities</td><td></td><td></td><td></td><td>&lt;0.001</td><td></td><td></td><td>10 (2.1%)</td><td>0.029</td></tr><tr><td>None</td><td>696 (61%)</td><td>343 (50%)</td><td>353 (77%)</td><td></td><td>103 (70%)</td><td>250 (80%)</td><td></td><td></td></tr><tr><td>Only 1</td><td>287 (25%)</td><td>208 (30%)</td><td>79 (17%)</td><td></td><td>31 (21%)</td><td>48 (15%)</td><td></td><td></td></tr><tr><td>At least 2</td><td>163 (14%)</td><td>137 (20%)</td><td>26 (5.7%)</td><td></td><td>13 (8.8%)</td><td>13 (4.2%)</td><td></td><td></td></tr><tr><td>Respiratory insufficiency</td><td>195 (17%)</td><td>143 (21%)</td><td>52 (11%)</td><td>&lt;0.001</td><td>28 (19%)</td><td>24 (7.7%)</td><td>11 (2.4%)</td><td>&lt;0.001</td></tr><tr><td>Cancer</td><td>66 (5.9%)</td><td>50 (7.4%)</td><td>16 (3.6%)</td><td>0.01</td><td>5 (3.4%)</td><td>11 (3.7%)</td><td>28 (6.0%)</td><td>0.9</td></tr><tr><td>Timings and delays<sup>c</sup></td><td></td><td></td><td></td><td></td><td></td><td></td><td></td><td></td></tr><tr><td>Time from dialysis to waitlisting (mo)</td><td>-</td><td>-</td><td>13 (5, 23)</td><td>-</td><td>15 (7, 26)</td><td>13 (4, 21)</td><td>0 (0%)</td><td>0.047</td></tr><tr><td>Time from dialysis to KT (mo)</td><td>-</td><td>-</td><td>32 (19, 47)</td><td>-</td><td>-</td><td>32 (19, 47)</td><td>0 (0%)</td><td>-</td></tr><tr><td>Time from waitlisting to KT (mo)</td><td>-</td><td>-</td><td>15 (6, 27)</td><td>-</td><td>-</td><td>15 (6, 27)</td><td>0 (0%)</td><td>-</td></tr><tr><td>Follow-up since dialysis initiation (mo)</td><td>51 (20, 95)</td><td>35 (11, 71)</td><td>80 (43, 123)</td><td>&lt;0.001</td><td>42 (21, 68)</td><td>102 (62, 143)</td><td>0 (0%)</td><td>&lt;0.001</td></tr><tr><td>Follow-up since waitlisting (mo)</td><td>-</td><td>-</td><td>61 (26, 107)</td><td>-</td><td>20 (4, 46)</td><td>83 (49, 126)</td><td>0 (0%)</td><td>&lt;0.001</td></tr><tr><td>Follow-up since transplantation (mo)</td><td>-</td><td>-</td><td>63 (20, 108)</td><td>-</td><td>-</td><td>63 (20, 108)</td><td>0 (0%)</td><td>-</td></tr><tr><td>Transplantation</td><td></td><td></td><td></td><td></td><td></td><td></td><td></td><td></td></tr><tr><td>Donor type</td><td></td><td></td><td></td><td></td><td></td><td></td><td>0 (0%)</td><td>-</td></tr><tr><td>None</td><td>-</td><td>697 (100%)</td><td>150 (32%)</td><td></td><td>150 (100%)</td><td>-</td><td></td><td></td></tr><tr><td>Deceased donor</td><td>-</td><td>-</td><td>282 (60%)</td><td></td><td>-</td><td>282 (89%)</td><td></td><td></td></tr><tr><td>Living donor<sup>d</sup></td><td>-</td><td>-</td><td>36 (7.7%)</td><td></td><td>-</td><td>36 (11%)</td><td></td><td></td></tr><tr><td>Waitlist removal<sup>d</sup></td><td>-</td><td>-</td><td>34 (7.3%)</td><td>-</td><td>34 (23%)</td><td>-</td><td>0 (0%)</td><td>-</td></tr><tr><td>Outcomes</td><td></td><td></td><td></td><td></td><td></td><td></td><td></td><td></td></tr><tr><td>Graft failure</td><td>50 (16%)</td><td>-</td><td>50 (16%)</td><td>-</td><td>-</td><td>50 (16%)</td><td>0 (0%)</td><td>-</td></tr><tr><td>Death</td><td>656 (56%)</td><td>508 (73%)</td><td>148 (32%)</td><td>&lt;0.001</td><td>62 (41%)</td><td>86 (27%)</td><td>0 (0%)</td><td>0.002</td></tr><tr><td>During waitlisted period</td><td>-</td><td>-</td><td>-</td><td>-</td><td>44 (71%)</td><td>-</td><td>0 (0%)</td><td>-</td></tr><tr><td>After waitlist removal<sup>d</sup></td><td>-</td><td>-</td><td>-</td><td>-</td><td>18 (29%)</td><td>-</td><td>0 (0%)</td><td>-</td></tr><tr><td>During transplant period</td><td>-</td><td>-</td><td>-</td><td>-</td><td>-</td><td>63 (73%)</td><td>0 (0%)</td><td>-</td></tr><tr><td>After return to dialysis<sup>d</sup></td><td>-</td><td>-</td><td>-</td><td>-</td><td>-</td><td>23 (27%)</td><td>0 (0%)</td><td>-</td></tr></tbody></table>

AAV-ESKD, ANCA-associated vasculitis with end-stage kidney disease; ANCA, antineutrophil cytoplasmic antibody; BMI, body mass index; ESKD, end-stage kidney disease; GPA, granulomatosis with polyangiitis; KT, kidney transplantation; MPA, microscopic polyangiitis.

<sup>a</sup>Comparison between patients with ESKD on the waitlist and those not on the waitlist.

<sup>b</sup>Comparison between waitlisted not transplanted and waitlisted transplanted patients.

<sup>c</sup>Timing between events and delays are shown as median [first to third quartile], in opposition to other continuous data, shown as mean (SD).

<sup>d</sup>Patients excluded from the sensitivity analyses.

<sup>e</sup>Patients were censored from subsequent survival analyses.

"-" indicates not applicable.
in contrast to 67.2 (50.5–84.0] per 1000 patient-years among those who did not receive kidney transplant. Such a reduction in mortality was consistent across all subgroups (*P* = 0.002, Table 2).

In the cohort of waitlisted patients with AAV, patient survival was 88% (84%–92%) and 72% (65%–80%) at 5 and 10 years, respectively, in transplant recipients, in contrast to 67% (59%–77%) and 28% (14%–55%) at 5 and 10 years, respectively, in non-transplanted patients. The median patient survival was 13.8 years for transplant recipients versus 5.8 years for nontransplanted patients (*P* < 0.001, Figure 2a). This improved survival was found consistently in GPA (*P* < 0.001, Figure 2b) and MPA (*P* = 0.002, Figure 2c) subgroups. Survival from ESKD onset (start of dialysis) for nonwaitlisted or nontransplanted patients is shown in Supplementary Figure S1).

## Risk of Death in Waitlisted Patients With AAV

Factors associated with death in univariable analyses are presented in Table 3. Age at waitlisting (HR = 1.06 [1.04–1.08] per 1 year increment, *P* < 0.001), MPA vasculitis subtype (vs. GPA, HR = 1.44 [1.01–2.06], *P* = 0.046), inability to walk alone (HR = 3.46 [1.27–9.44], *P* = 0.015), cardiovascular comorbidities (1 vs. none, HR = 1.46 [0.92–2.29, *P* = 0.11; ≥ 2 vs. none, HR = 2.51 [1.33–4.72], *P* = 0.004), and respiratory insufficiency (HR = 3.40 [2.14–5.40], *P* < 0.001) were associated with death. KT (HR = 0.38 [0.25–0.56], *P* < 0.001) was associated with survival.

After adjustment on age at waitlisting, sex (forced in the model), vasculitis subtype (forced in the model), and respiratory and cardiovascular comorbidities, KT was associated with a 53% reduction in the risk of death (HR = 0.47 [0.31–0.73], *P* < 0.001) (Tables 2–3). Of note, patients waitlisted before 2012 (vs. after 2012) were significantly younger, more frequently of GPA subtype, and less frequently diabetic (Supplementary Table S4). No data regarding treatment of vasculitis before waitlisting was available.

## Risk of Death in Subgroups of Waitlisted Patients With AAV

Our results were similar across all the subgroups analyzed, including sex, vasculitis type (GPA, or MPA), age at waitlisting (below or above 60 years), and year of ESKD onset (before or after 2012); whether adjusted on age and sex alone, or fully adjusted (age at waitlisting, sex, vasculitis subtype, respiratory and cardiovascular comorbidities), KT was associated with a reduction in the risk of death, without significant interaction. The strongest association was found for younger patients (HR = 0.36) (Table 2 and Supplementary Figure S1).

## Instantaneous Hazard of Death

When analyzing the time-dependent instantaneous hazard, after full adjustment (as described above), KT was associated with a higher risk of death during the first months after transplantation, followed by a lower risk over the remaining study period (Supplementary Figure S2).

## Sensitivity Analyses

We conducted 2 sensitivity analyses to confirm the findings of our primary analysis. First, to better address potential confounding because of the indication (or contraindication) that may arise when patients become too ill (the main cause of waitlist removal, 73.5%, Supplementary Table S2), or otherwise unsuitable for renal transplantation, we excluded patients who were removed from the waitlist during the study period (n = 34). In this analysis, the survival benefit associated with transplantation was diminished (adjusted HR = 0.57 [0.35–0.92], *P* = 0.023), which was anticipated because of the introduction of informative censoring (i.e., censoring related to a factor in the causal pathway between being waitlisted and mortality: those with a higher likelihood of death were selectively removed from the nontransplanted group). Second, because these patients may differ from others on the waitlist with respect to unmeasured confounding factors, we censored living donor transplant recipients (n = 36). This analysis revealed a similar survival benefit for KT as observed in our primary analysis (adjusted HR = 0.49 [0.32–0.76], *P* = 0.001).

## Kidney Allograft Survival

After a median follow-up of 63 (20–108) months since transplantation, 50 patients (16%) experienced graft failure. The main causes of allograft failure were chronic rejection (n = 17, 34%), followed by vascular complications (n = 11, 22%) and vasculitis relapses (n = 4, 8%) (Supplementary Table S5). The cumulative incidence of graft failure, when considering death as a competing event, was 13% (9%–17%) and 22% (16%–28%) by 5 and 10 years, respectively (Figure 3a). There was no difference in kidney allograft survival regarding the vasculitis subgroup, with an incidence of graft failure reaching 20% (12%–28%) in GPA and 24% (15%–34%) in MPA by 10 years (*P* = 0.3, Figure 3b).

## Access to Waitlist and to Transplantation

Lastly, we analyzed the probability of being waitlisted or transplanted, considering death as a competing event (Supplementary Figure 3). Among all patients with ESKD, the rates of waitlisting were 18%, 31%, and 41%, and the rates of transplantation were 4%,
<table><caption>**Table 2.** All-cause mortality according to transplant status among waitlisted patients with AAV-ESKD</caption><thead><tr><th rowspan="2">Characteristics</th><th rowspan="2">n</th><th rowspan="2">Total follow-up (yrs)</th><th rowspan="2">Deaths</th><th rowspan="2">Mortality rate (1000 person-yrs)</th><th rowspan="2">Mortality rate 95% CI</th><th colspan="3">Unadjusted</th><th colspan="3">Adjusted on age/sex</th><th colspan="3">Fully adjusted<sup>a</sup></th></tr><tr><th>HR</th><th>HR 95% CI</th><th>P-value for interaction</th><th>HR</th><th>HR 95% CI</th><th>P-value for interaction</th><th>HR</th><th>HR 95% CI</th><th>P-value for interaction</th></tr></thead><tbody><tr><td>Overall</td><td>786</td><td>2.554</td><td>125</td><td>48.94</td><td>40.36-57.51</td><td></td><td></td><td></td><td></td><td></td><td></td><td></td><td></td><td></td></tr><tr><td>Dialysis, waitlisted</td><td>468</td><td>922</td><td>62</td><td>67.24</td><td>50.50-83.98</td><td>—</td><td>—</td><td></td><td>—</td><td>—</td><td></td><td>—</td><td>—</td><td></td></tr><tr><td>Transplanted</td><td>318</td><td>1.632</td><td>63</td><td>38.59</td><td>29.06-48.13</td><td>0.38</td><td>0.25-0.56</td><td></td><td>0.39</td><td>0.26-0.58</td><td></td><td>0.47</td><td>0.31-0.73</td><td>0.49</td></tr><tr><td>Age (waitlisting)</td><td></td><td></td><td></td><td></td><td></td><td></td><td></td><td>0.50</td><td></td><td></td><td>0.60</td><td></td><td></td><td></td></tr><tr><td>&gt; 60 yrs</td><td>405</td><td>1.153</td><td>82</td><td>71.11</td><td>55.72-86.50</td><td></td><td></td><td></td><td></td><td></td><td></td><td></td><td></td><td></td></tr><tr><td>Dialysis, waitlisted</td><td>249</td><td>483</td><td>42</td><td>86.88</td><td>60.61-113.16</td><td>—</td><td>—</td><td></td><td>—</td><td>—</td><td></td><td>—</td><td>—</td><td></td></tr><tr><td>Transplanted</td><td>156</td><td>670</td><td>40</td><td>59.72</td><td>41.21-78.23</td><td>0.41</td><td>0.24-0.70</td><td></td><td>0.41</td><td>0.24-0.70</td><td></td><td>0.51</td><td>0.30-0.89</td><td></td></tr><tr><td>&le; 60 yrs</td><td>381</td><td>1.401</td><td>43</td><td>30.69</td><td>21.52-39.86</td><td></td><td></td><td></td><td></td><td></td><td></td><td></td><td></td><td></td></tr><tr><td>Dialysis, waitlisted</td><td>219</td><td>439</td><td>20</td><td>45.60</td><td>25.61-65.58</td><td>—</td><td>—</td><td></td><td>—</td><td>—</td><td></td><td>—</td><td>—</td><td></td></tr><tr><td>Transplanted</td><td>162</td><td>963</td><td>23</td><td>23.89</td><td>14.13-33.66</td><td>0.31</td><td>0.16-0.60</td><td></td><td>0.29</td><td>0.14-0.59</td><td></td><td>0.36</td><td>0.17-0.81</td><td></td></tr><tr><td>Sex</td><td></td><td></td><td></td><td></td><td></td><td></td><td></td><td>0.59</td><td></td><td></td><td>0.62</td><td></td><td></td><td>0.56</td></tr><tr><td>Female</td><td>277</td><td>961</td><td>39</td><td>40.58</td><td>27.85-53.32</td><td></td><td></td><td></td><td></td><td></td><td></td><td></td><td></td><td></td></tr><tr><td>Dialysis, waitlisted</td><td>162</td><td>335</td><td>21</td><td>62.69</td><td>35.88-89.50</td><td>—</td><td>—</td><td></td><td>—</td><td>—</td><td></td><td>—</td><td>—</td><td></td></tr><tr><td>Transplanted</td><td>115</td><td>626</td><td>18</td><td>28.75</td><td>15.47-42.04</td><td>0.39</td><td>0.20-0.76</td><td></td><td>0.38</td><td>0.19-0.77</td><td></td><td>0.53</td><td>0.25-1.14</td><td></td></tr><tr><td>Male</td><td>509</td><td>1.593</td><td>86</td><td>53.97</td><td>42.57-65.38</td><td></td><td></td><td></td><td></td><td></td><td></td><td></td><td></td><td></td></tr><tr><td>Dialysis, waitlisted</td><td>306</td><td>587</td><td>41</td><td>69.84</td><td>48.46-91.22</td><td>—</td><td>—</td><td></td><td>—</td><td>—</td><td></td><td>—</td><td>—</td><td></td></tr><tr><td>Transplanted</td><td>203</td><td>1.006</td><td>45</td><td>44.72</td><td>31.65-57.78</td><td>0.33</td><td>0.19-0.55</td><td></td><td>0.36</td><td>0.21-0.61</td><td></td><td>0.47</td><td>0.28-0.81</td><td></td></tr><tr><td>Vasculitis subtype</td><td></td><td></td><td></td><td></td><td></td><td></td><td></td><td>0.99</td><td></td><td></td><td>0.56</td><td></td><td></td><td>0.56</td></tr><tr><td>GPA</td><td>418</td><td>1.507</td><td>66</td><td>43.81</td><td>33.24-54.38</td><td></td><td></td><td></td><td></td><td></td><td></td><td></td><td></td><td></td></tr><tr><td>Dialysis, waitlisted</td><td>242</td><td>470</td><td>28</td><td>59.55</td><td>37.49-81.61</td><td>—</td><td>—</td><td></td><td>—</td><td>—</td><td></td><td>—</td><td>—</td><td></td></tr><tr><td>Transplanted</td><td>176</td><td>1.036</td><td>38</td><td>36.67</td><td>25.01-48.33</td><td>0.37</td><td>0.21-0.64</td><td></td><td>0.36</td><td>0.21-0.65</td><td></td><td>0.42</td><td>0.23-0.77</td><td></td></tr><tr><td>MPA</td><td>368</td><td>1.048</td><td>59</td><td>56.30</td><td>41.94-70.67</td><td></td><td></td><td></td><td></td><td></td><td></td><td></td><td></td><td></td></tr><tr><td>Dialysis, waitlisted</td><td>226</td><td>452</td><td>34</td><td>75.24</td><td>49.95-100.53</td><td>—</td><td>—</td><td></td><td>—</td><td>—</td><td></td><td>—</td><td>—</td><td></td></tr><tr><td>Transplanted</td><td>142</td><td>596</td><td>25</td><td>41.95</td><td>25.50-58.39</td><td>0.41</td><td>0.23-0.72</td><td></td><td>0.47</td><td>0.26-0.83</td><td></td><td>0.53</td><td>0.29-0.97</td><td></td></tr><tr><td>Date of KRT start</td><td></td><td></td><td></td><td></td><td></td><td></td><td></td><td>0.19</td><td></td><td></td><td>0.10</td><td></td><td></td><td>0.19</td></tr><tr><td>Before 2012</td><td>262</td><td>1.309</td><td>63</td><td>48.14</td><td>36.25-60.03</td><td></td><td></td><td></td><td></td><td></td><td></td><td></td><td></td><td></td></tr><tr><td>Dialysis, waitlisted</td><td>142</td><td>274</td><td>22</td><td>80.24</td><td>46.71-113.78</td><td>—</td><td>—</td><td></td><td>—</td><td>—</td><td></td><td>—</td><td>—</td><td></td></tr><tr><td>Transplanted</td><td>120</td><td>1.034</td><td>41</td><td>39.63</td><td>27.50-51.77</td><td>0.34</td><td>0.19-0.60</td><td></td><td>0.31</td><td>0.17-0.57</td><td></td><td>0.41</td><td>0.21-0.82</td><td></td></tr><tr><td>After 2012</td><td>524</td><td>1.246</td><td>62</td><td>49.77</td><td>37.38-62.16</td><td></td><td></td><td></td><td></td><td></td><td></td><td></td><td></td><td></td></tr><tr><td>Dialysis, waitlisted</td><td>326</td><td>648</td><td>40</td><td>61.74</td><td>42.61-80.87</td><td>—</td><td>—</td><td></td><td>—</td><td>—</td><td></td><td>—</td><td>—</td><td></td></tr><tr><td>Transplanted</td><td>198</td><td>598</td><td>22</td><td>36.80</td><td>21.42-52.17</td><td>0.46</td><td>0.27-0.79</td><td></td><td>0.48</td><td>0.28-0.84</td><td></td><td>0.60</td><td>0.34-1.05</td><td></td></tr></tbody></table>

AAV-ESKD, ANCA-associated vasculitis with end-stage kidney disease; ANCA, antineutrophil cytoplasmic antibody; CI, confidence interval; ESKD, end-stage kidney disease; GPA, granulomatosis with polyangiitis; HR, hazard ratio; KRT, kidney replacement therapy; MPA, microscopic polyangiitis.

Total follow-up was computed from time zero (time which patients entered their respective risk groups (not the cohort entry or transplant date)) to end of follow-up. Time spent before kidney transplantation was allocated to the "dialysis, waitlisted" group and time spent after was allocated to the "transplanted" group. This implies that the initial total "dialysis, waitlisted" group size will be equal to the "dialysis, waitlisted" group size + "transplanted" group size.

<footnote><sup>a</sup>Fully adjusted models were adjusted for age at waitlisting, sex (forced), vasculitis type, cardiovascular comorbidity, and respiratory insufficiency (Table 3).</footnote>
<figure><img src="image_5.png" /></figure>

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

<figure><img src="image_7.png" /><figcaption>**Figure 2.** Patient survival according to transplant status among waitlisted patients with AAV-ESKD. (a) All vasculitis subtypes. (b) GPA. (c) MPA. Time zero represents the point at which patients entered their respective risk groups (not the cohort entry or transplant date). Time spent before kidney transplantation was allocated to the “dialysis, waitlisted” group and time spent after was allocated to the “transplanted” group. This implies that the initial total “dialysis, waitlisted” group size will be equal to the “dialysis, waitlisted” group size + “transplanted” group size. GPA, granulomatosis with polyangiitis; MPA, microscopic polyangiitis.</figcaption></figure>
<table><caption>**Table 3.** Factors associated with death among waitlisted patients with AAV-ESKD</caption><thead><tr><th rowspan="2">Characteristics</th><th colspan="5">Univariable analysis</th><th colspan="5">Multivariable analysis</th></tr><tr><th>n</th><th>Deaths</th><th>HR</th><th>95% CI</th><th>P-value</th><th>n</th><th>Deaths</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>Vasculitis subtype</td><td></td><td></td><td></td><td></td><td></td><td></td><td></td><td></td><td></td><td></td></tr><tr><td>GPA</td><td>418</td><td>66</td><td>—</td><td>—</td><td></td><td>404</td><td>62</td><td>—</td><td>—</td><td></td></tr><tr><td>MPA</td><td>368</td><td>59</td><td>1.44</td><td>1.01-2.06</td><td>0.046</td><td>363</td><td>56</td><td>1.32</td><td>0.91-1.93</td><td>0.15</td></tr><tr><td>Males</td><td>509</td><td>86</td><td>1.41</td><td>0.96-2.07</td><td>0.077</td><td>494</td><td>81</td><td>1.30</td><td>0.87-1.92</td><td>0.2</td></tr><tr><td>Age (per 1 year increment)</td><td></td><td></td><td></td><td></td><td></td><td></td><td></td><td></td><td></td><td></td></tr><tr><td>at ESKD (yrs)</td><td>786</td><td>125</td><td>1.06</td><td>1.04-1.08</td><td>&lt;0.001</td><td></td><td></td><td></td><td></td><td></td></tr><tr><td>at waitlisting (yrs)</td><td>786</td><td>125</td><td>1.06</td><td>1.04-1.08</td><td>&lt;0.001</td><td>767</td><td>118</td><td>1.06</td><td>1.03-1.08</td><td>&lt;0.001</td></tr><tr><td>at transplantation (yrs)</td><td>318</td><td>63</td><td>1.07</td><td>1.04-1.10</td><td>&lt;0.001</td><td></td><td></td><td></td><td></td><td></td></tr><tr><td>First modality</td><td></td><td></td><td></td><td></td><td></td><td></td><td></td><td></td><td></td><td></td></tr><tr><td>Hemodialysis</td><td>673</td><td>115</td><td>—</td><td>—</td><td></td><td></td><td></td><td></td><td></td><td></td></tr><tr><td>Peritoneal dialysis</td><td>81</td><td>7</td><td>0.46</td><td>0.21-0.99</td><td>0.046</td><td></td><td></td><td></td><td></td><td></td></tr><tr><td>Preemptive transplantation</td><td>32</td><td>3</td><td>0.53</td><td>0.17-1.67</td><td>0.3</td><td></td><td></td><td></td><td></td><td></td></tr><tr><td>Year of ESKD: before 2012</td><td>262</td><td>63</td><td>0.68</td><td>0.45-1.02</td><td>0.061</td><td></td><td></td><td></td><td></td><td></td></tr><tr><td>cPRA (per 1% increment)</td><td>662</td><td>97</td><td>1</td><td>0.99-1.01</td><td>0.9</td><td></td><td></td><td></td><td></td><td></td></tr><tr><td>Comorbidities</td><td></td><td></td><td></td><td></td><td></td><td></td><td></td><td></td><td></td><td></td></tr><tr><td>Not able to walk alone</td><td>13</td><td>4</td><td>3.46</td><td>1.27-9.44</td><td>0.015</td><td></td><td></td><td></td><td></td><td></td></tr><tr><td>Albumin level &gt; 30 g/l</td><td>425</td><td>58</td><td>0.69</td><td>0.46-1.03</td><td>0.071</td><td></td><td></td><td></td><td></td><td></td></tr><tr><td>Albumin level &gt; 36 g/l</td><td>227</td><td>29</td><td>0.70</td><td>0.46-1.09</td><td>0.11</td><td></td><td></td><td></td><td></td><td></td></tr><tr><td>BMI</td><td></td><td></td><td></td><td></td><td></td><td></td><td></td><td></td><td></td><td></td></tr><tr><td>18.5-25 kg/m²</td><td>362</td><td>48</td><td>—</td><td>—</td><td></td><td></td><td></td><td></td><td></td><td></td></tr><tr><td>&lt; 18.5 kg/m²</td><td>51</td><td>8</td><td>0.84</td><td>0.39-1.79</td><td>0.6</td><td></td><td></td><td></td><td></td><td></td></tr><tr><td>&gt; 25 kg/m²</td><td>293</td><td>50</td><td>1.23</td><td>0.82-1.83</td><td>0.3</td><td></td><td></td><td></td><td></td><td></td></tr><tr><td>Diabetes mellitus</td><td>772</td><td>121</td><td>1.42</td><td>0.84-2.40</td><td>0.2</td><td></td><td></td><td></td><td></td><td></td></tr><tr><td>Cardiovascular comorbidities</td><td></td><td></td><td></td><td></td><td></td><td></td><td></td><td></td><td></td><td></td></tr><tr><td>None</td><td>603</td><td>85</td><td>—</td><td>—</td><td></td><td>601</td><td>83</td><td>—</td><td>—</td><td></td></tr><tr><td>Only 1</td><td>127</td><td>24</td><td>1.46</td><td>0.92-2.29</td><td>0.11</td><td>127</td><td>24</td><td>0.96</td><td>0.60-1.53</td><td>0.9</td></tr><tr><td>At least 2</td><td>39</td><td>11</td><td>2.51</td><td>1.33-4.72</td><td>0.004</td><td>39</td><td>11</td><td>1.55</td><td>0.80-3.00</td><td>0.2</td></tr><tr><td>Respiratory insufficiency</td><td>769</td><td>118</td><td>3.40</td><td>2.14-5.40</td><td>&lt;0.001</td><td>767</td><td>118</td><td>2.34</td><td>1.45-3.78</td><td>&lt;0.001</td></tr><tr><td>Cancer</td><td>734</td><td>116</td><td>1.36</td><td>0.50-3.71</td><td>0.5</td><td></td><td></td><td></td><td></td><td></td></tr><tr><td>Outcomes</td><td></td><td></td><td></td><td></td><td></td><td></td><td></td><td></td><td></td><td></td></tr><tr><td>Waitlist removal<sup>a</sup></td><td>786</td><td>125</td><td>2.77</td><td>1.67-4.61</td><td>&lt;0.001</td><td></td><td></td><td></td><td></td><td></td></tr><tr><td>Transplantation (vs. none)</td><td>318</td><td>63</td><td>0.38</td><td>0.25-0.56</td><td>&lt;0.001</td><td>311</td><td>61</td><td>0.47</td><td>0.31-0.73</td><td>&lt;0.001</td></tr><tr><td>Donor type<sup>a</sup></td><td></td><td></td><td></td><td></td><td></td><td></td><td></td><td></td><td></td><td></td></tr><tr><td>None</td><td>468</td><td>62</td><td>—</td><td>—</td><td></td><td></td><td></td><td></td><td></td><td></td></tr><tr><td>Deceased donor</td><td>282</td><td>59</td><td>0.39</td><td>0.26-0.59</td><td>&lt;0.001</td><td></td><td></td><td></td><td></td><td></td></tr><tr><td>Living donor</td><td>36</td><td>4</td><td>0.23</td><td>0.08-0.63</td><td>0.004</td><td></td><td></td><td></td><td></td><td></td></tr></tbody></table>

AAV-ESKD, ANCA-associated vasculitis with end-stage kidney disease; BMI, body mass index; CI, confidence interval; cPRA, calculated panel reactive antibody; ESKD, end-stage kidney disease; GPA, granulomatosis with polyangiitis; HR, hazard ratio; KT, kidney transplantation; MPA, microscopic polyangiitis.

10%, and 27% by 1, 2, and 5 years from ESKD onset, respectively. Among waitlisted patients, the rates of waitlisting were 43%, 76%, and 97%, and the rates of transplantation were 9%, 24%, and 66% by 1, 2, and 5 years from ESKD onset, respectively. The rates of transplantation were 31%, 52%, and 74% by 1, 2, and 5 years from waitlisting, respectively.

## DISCUSSION

This large population study, spanning 2 decades and encompassing all French patients with AAV-ESKD who were waitlisted for KT, revealed a marked improvement in survival associated with kidney transplant. This survival benefit was consistent across key

demographics, including sex and age groups throughout the study period. Notably, a considerable number of waitlisted patients died before receiving a transplant, highlighting the need to enhance kidney transplant accessibility for patients with AAV-ESKD. In addition, these findings underscore the importance of routinely evaluating patients with AAV with advanced chronic kidney disease for transplant eligibility as part of their standard care.

Our findings align with and expand on existing research on patients with AAV-ESKD and KT. The survival of patients with AAV on chronic dialysis has been shown to be similar to that of other dialysis patients,³¹⁻³³ but with a higher rate of mortality from infectious causes. In addition, though the incidence of

<footnote>aNot included in the multivariate analysis. See sensitivity analysis.</footnote>
a

<figure><img src="image_8.png" /></figure>

b

<figure><img src="image_9.png" /><figcaption>**Figure 3.** Graft survival among transplanted patients with AAV-ESKD. (a) All vasculitis subtypes. (b) According to GPA or MPA. Graft survival was computed with death as a competitive event. AAV, ANCA-associated vasculitides; ANCA, antineutrophil cytoplasmic antibody; ESKD, end-stage kidney disease; GPA, granulomatosis with polyangiitis; MPA, microscopic polyangiitis.</figcaption></figure>

relapse decreases in chronic dialysis, their risk of developing an infectious or cardiovascular complication increases.¹⁵⁻¹⁷ In this context, KT may appear to be a risky option because of the additional immunosuppression required, with its known risk of infection but also diabetes or hypertension, which limits the extrapolation of kidney transplant outcomes from other

ESKD patient groups to those with AAV-ESKD. However, a study conducted in the United States Renal Data System registry, using a methodology similar to ours, showed that the overall survival of patients with ESKD with GPA was better after transplantation than before transplantation (mortality rate decreasing from 65.5–29.3 deaths per 1000 patient-years, 70% reduction in
the risk of death),²² with a benefit close to that seen in the overall ESKD population (68%–82% reduction).²³,²⁴ Death from infectious causes was reduced; however, the beneficial effect was even greater in reducing the risk of cardiovascular mortality. There were no data on relapse risk reduction; however, we can assume that modern immunosuppressive regimen, limiting steroid exposure, and the inflammatory state associated with the vasculitis helped to reduce the mortality associated with these events. In our cohort, we did not find such a significant reduction in death from infectious or cardiovascular causes, but similar rates, suggesting—while limited by our sample size—that prolonged immunosuppression did not increase this risk in transplanted patients when compared with patients waiting for a KT on dialysis. However, it is important to note that waitlisted patients face higher infection-related deaths (26% in our AAV-ESKD waitlisted cohort, vs. 15% in all ESKD regardless of its cause [data from REIN registry]³⁴), and transplanted patients face higher cancer-related deaths (19% in our AAV-ESKD waitlisted cohort, vs. 10% in all ESKD regardless of its cause [data from REIN registry]³⁴).

Notably, overall survival in transplanted patients with AAV previously appeared to be similar to that of other transplant patients,¹²⁻¹⁴ although there are discrepancies between studies, particularly with regard to the choice of reference group.³¹,³³ Similarly, graft survival in patients with AAV appears to be close to that of other transplant recipients,¹²,¹³ again with some discrepancies between studies.¹⁴,³¹,³³

Taken together, these data suggest that all patients with AAV-GN should be evaluated for possible inclusion on the waiting list, as soon as estimated glomerular filtration rate goes below 20 ml/min per 1.73 m², as for other kidney diseases. To optimize the patient's chances of receiving a transplant under good conditions, a thorough evaluation may be necessary (nutritional, muscular, and cardiovascular evaluation, etc.). Even better, referring patients to a kidney transplant center as soon as possible may improve their chance of a preemptive transplantation, ideally with a living donor. In the worst-case scenario, patients will accrue time on the transplantation waiting list to reduce their waiting time.

Interestingly, we noted that the survival benefit associated with transplantation appeared to be higher for patients with AAV-ESKD who started dialysis before 2012 than after. This is probably explained by the fact that the criteria for waitlisting or transplantation have been expanded overtime, both at the donor and recipient level.³⁴ Indeed the patients transplanted more recently in our study were older and more diabetic. In addition, changes in chronic dialysis

practices have improved survival,³⁵ potentially leading ultimately to a decrease in survival benefit in the latest period.

## Limits and Strengths

The strengths of this study are related to our data source and study design. First, the REIN registry is a nationwide registry covering all patients with ESKD in France. The diagnosis of AAV was made and reported by nephrologists, limiting the risk of false-positive diagnoses. We restricted our analysis to patients on the waiting list to reduce bias associated with confounding by contraindication (people on the waiting list for KT are generally younger, healthier, and with higher socioeconomic status³⁶ than those who are not), and we also performed a sensitivity analysis excluding patients who were removed from the waiting list or those receiving from a living donor, and we treated KT as a time-varying exposure to limit immortal time bias. Although residual confounding can still be present, we adjusted our analysis for important factors, including comorbidities and vasculitis subgroup, to account for variables known to have a significant impact on mortality. The generalizability of these findings may be influenced by differences in waitlist criteria, patient demographics, and transplantation practices across countries and healthcare systems. Therefore, caution is needed when extrapolating these results to settings with distinct allocation policies or patient populations, because these factors could modify the observed survival benefit of KT in patients with AAV-ESKD.

Our retrospective study has limitations. First, the REIN registry enrolls patients when they reach ESKD but does not include details on the history of AAV. Therefore, we cannot address how certain factors, such as time between vasculitis onset, vasculitis remission and transplantation, antibody type and titer at diagnosis or transplantation, and exposure to immunosuppression, pretransplant events (e.g., infections, cardiovascular events, relapses) may affect outcomes. Second, during this study of a 2-decade period, substantial treatment advances have been made, especially regarding the use of rituximab for AAV induction and maintenance therapy.³⁷⁻³⁹

## Conclusion

In summary, in this national cohort study of patients with ESKD because of AAV, we found that KT was associated with a significant survival benefit. Timely consideration of kidney transplant should be a part of routine care for patients with AAV-ESKD, and improved access to KT for this population may considerably improve outcomes.
# APPENDIX

## List of Renal Epidemiology and Information Network (REIN)

Dialysis centers participating in the registry are listed in the REIN annual report (https://www.agence-biomedecine.fr/IMG/pdf/rapport_2022_-_20241128.pdf).

# DISCLOSURE

All the authors declared no competing interests.

# ACKNOWLEDGMENTS

The REIN registry is a national registry held by the French Biomedicine Agency. We thank all the nephrologists in France who provide detailed information for the REIN registry and the research assistants of REIN in charge of data collection and quality control. Dialysis centers participating in the registry are listed in REIN annual report (https://www.agencebiomedecine.fr/IMG/pdf/rapport_2022_-_20241128.pdf).

# SUPPLEMENTARY MATERIAL

Supplementary File (PDF)

**Figure S1.** Patient survival according to waitlisted and transplanted status among all patients with AAV-ESKD.

**Figure S2.** Fully adjusted subgroup analyses regarding the risk of death among waitlisted patients with AAV-ESKD.

**Figure S3.** Instantaneous hazard of death over the study period.

**Figure S4.** Cumulative incidence of being waitlisted or transplanted.

**Table S1.** Baseline characteristics of waitlisted patients with AAV-ESKD according to vasculitis subtype.

**Table S2.** Baseline characteristics of waitlisted patients with AAV-ESKD according to removal status during follow-up.

**Table S3.** Causes of waitlist removal in AAV-ESKD waitlisted, not transplanted patients.

**Table S4.** Causes of death in patients with AAV-ESKD.

**Table S5.** Baseline characteristics of waitlisted patients with AAV-ESKD according to date of dialysis initiation (before or after 2012).

**Table S6.** Causes of allograft failure in transplanted patients with AAV-ESKD.

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