# Kidney Transplantation Improves Survival in Lupus Nephritis With End-Stage Kidney Disease

Benoît Brilland, Jean-François Augusto, Pierre-Antoine Michel, Noémie Jourde-Chiche, Cécile Couchoud

► To cite this version:

Benoît Brilland, Jean-François Augusto, Pierre-Antoine Michel, Noémie Jourde-Chiche, Cécile Couchoud. Kidney Transplantation Improves Survival in Lupus Nephritis With End-Stage Kidney Disease. Kidney International Reports, 2025, 10 (4), pp.1163 - 1174. 10.1016/j.ekir.2025.01.034. hal-05240653

HAL Id: hal-05240653

https://hal.science/hal-05240653v1

Submitted on 4 Sep 2025

HAL is a multi-disciplinary open access
archive for the deposit and dissemination of sci-
entific research documents, whether they are pub-
lished or not. The documents may come from
teaching and research institutions in France or
abroad, or from public or private research centers.

L'archive ouverte pluridisciplinaire HAL, est
destinée au dépôt et à la diffusion de documents
scientifiques de niveau recherche, publiés ou non,
émanant des établissements d'enseignement et de
recherche français ou étrangers, des laboratoires
publics ou privés.

<figure><img src="image_1.png" /></figure>

Distributed under a Creative Commons Attribution 4.0 International License
# Kidney Transplantation Improves Survival in Lupus Nephritis With End-Stage Kidney Disease

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

Check for updates

Benoît Brillard¹,², Jean-François Augusto¹,², Pierre-Antoine Michel³, Noémie Jourde-Chiche⁴ and Cécile Couchoud⁵; on behalf of the Renal Epidemiology and Information Network (REIN) registry⁶

¹Service de Néphrologie-Dialyse-Transplantation, CHU Angers, Angers, France; ²Centre de Recherche en Cancérologie et Immunologie Intégrée Nantes Angers, Inserm, CNRS, Université Angers, Nantes Université, SFR ICAT, Nantes, France; ³Néphrologie et Dialyses, Département de Néphrologie, Hôpital Tenon, Assistance Publique - Hôpitaux de Paris, Paris, France; ⁴Aix-Marseille Université, Centre de recherche en Cardiovasculaire et Nutrition (C2VN), Institut national de la santé des de la recherche médicale (INSERM), Institut national de recherche pour l'agriculture, l'alimentation et l'environnement (INRAE), APHM Centre de Néphrologie et Transplantation Rénale, Marseille, France; and ⁵Coordination nationale REIN, Agence de la biomédecine, Saint-Denis-La Plaine, France

**Introduction:** Lupus nephritis (LN) is a severe complication of systemic lupus erythematosus (SLE) and is associated with high morbidity and mortality rates. Although kidney transplantation (KT) is considered the optimal treatment for end-stage kidney disease (ESKD), its survival benefit, specifically in patients with LN-induced ESKD (LN-ESKD), is not well-established. This study aimed to determine the effects of KT on the survival of a national cohort of patients with LN-ESKD.

**Methods:** We retrospectively analyzed patients with LN-ESKD registered in the French Renal Epidemiology and Information Network (REIN) registry, who were waitlisted for KT between 2002 and 2022. KT was treated as a time-dependent variable to avoid an immortal time bias. The primary outcome was all-cause mortality, which was assessed using Kaplan-Meier analysis and adjusted Cox proportional hazards models.

**Results:** Of the 882 patients with LN-ESKD, 636 (72%) were waitlisted for KT, and 470 (74%) received a transplant. After a median follow-up of 80 months, KT was associated with a 60% reduction in the risk of death compared with remaining on dialysis (hazard ratio [HR]: 0.40, 95% confidence interval [CI]: 0.240–0.67, *P* < 0.001), with consistent benefits across subgroups. Patient survival at 10 years was 83% for transplant recipients and 60% for nontransplant recipients (*P* < 0.001). Sensitivity analyses, after excluding recipients of living donors and patients who were inactivated from the waitlist, supported these findings. Two years after the onset of ESKD, 38% of the waitlisted patients under went transplantation. The probability of graft failure was 23% at 10 years posttransplant.

**Conclusion:** Compared with patients who remain on dialysis, KT is associated with improved survival in patients with LN-ESKD. Early evaluation of transplant eligibility and timely referral to transplant centers are crucial for optimizing outcomes.

Kidney Int Rep (2025) 10, 1163–1174; https://doi.org/10.1016/j.ekir.2025.01.034

KEYWORDS: death; ESKD; kidney transplantation; lupus; nephritis; survival

© 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/).

SLE has been reported to affect more than 3.4 million people worldwide and is newly diagnosed in 400,000 people each year.¹,² Although

there is significant variation between studies, partly because of ethnic diversity, it is estimated that approximately 40% of people with SLE will develop LN over the disease course, and about 10% to 20% of people with LN will develop ESKD after 10 years.²,³ LN is an early or initial manifestation of SLE in approximately 70% to 80% of affected patients with LN.⁴ Beyond its impact on renal survival, LN compromises overall survival, with an estimated excess of mortality 3 to 26 times higher than that of the general population.⁴,⁵

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

⁶Members of the Renal Epidemiology and Information Network (REIN) registry are listed in the Appendix

Received 10 October 2024; revised 6 January 2025; accepted 28 January 2025; published online 3 February 2025
KT has been found to be safe and successful in pa-
tients with LN-ESKD.⁶⁻¹¹ In several studies, patient and
graft survival rates were comparable to those of other
transplant recipients,⁶⁻⁸,¹⁰⁻¹³ although some reports
suggest lower survival outcomes in this population.¹²,¹³
Patients with LN-ESKD face higher risks of posttrans-
plant complications, such as infections, cancer,
thrombosis, and cardiovascular events. These risks are
partly attributed to extensive pretransplant immuno-
suppression and, in some cases, to the presence of
antiphospholipid syndrome. Furthermore, although the
risk of lupus relapse decreases after transplantation, it
is not entirely eliminated.¹⁴,¹⁵ These factors challenge
the generalizability of transplantation outcomes from
broader nephropathy populations to patients with LN-
ESKD.

Despite these hurdles, KT remains the preferred
treatment for improving overall survival in patients
with LN, compared with dialysis. However, specific
survival benefits of LN-ESKD remain unclear. Although
small-scale studies have suggested improved survival
in patients with SLE undergoing KT compared with
those on dialysis<sup>16-18</sup>; these findings are often biased by
healthier candidates being more likely to undergo
transplantation. Consistent with broader studies in all-
cause ESKD populations,<sup>19,20</sup> the only large-scale study
with a robust methodology demonstrated a 70%
reduction in mortality risk for patients with LN-ESKD
receiving KT compared with those on the waitlist.<sup>21</sup>In
this study, we aimed to evaluate the impact of KT on
survival in patients with LN, using data from the
French National Registry of ESKD.

METHODS

Data Collection

The REIN is a comprehensive national registry of pa-
tients who start kidney replacement therapy in
France.²²,²³ Data are collected locally by each medical
center and are updated prospectively annually with the
help of research assistants. Data collection began in
2002 and patient follow-up continued until the earliest
occurrence of KT, death, loss to follow-up, renal
function recovery, or termination of the study in
December 2022.

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
LN; (ii) initiated hemodialysis or peritoneal dialysis (or
were preemptively transplanted) between January 1,
2002 and December 31, 2022; and (3) waitlisted for a
renal transplant between January 1, 2002 and

December 31, 2022. Only the first transplantation event
was considered.

Covariates and Definitions

Demographic data (age and sex); body mass index (BMI); calculated panel reactive antibody; comorbidities at baseline, including cardiovascular comorbidities (i.e., heart failure, heart rhythm disorders, peripheral arterial disease, abdominal aorta aneurysm, coronary artery disease, and stroke) and other relevant comorbidities (diabetes, respiratory insufficiency, and 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, date and cause of death were extracted from the REIN registry<sup>23,24</sup> and used as covariates, exposures, or outcomes. Kidney allograft survival was assessed, and the causes of allograft loss were identified. Owing to the varying number of cardiovascular comorbidities, these were grouped together and the patients were categorized into subgroups, namely no cardiovascular comorbidity, only 1, or 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 as counts and percentages. Data were
compared using *t* tests for continuous variables and χ²
test (or Fisher exact test, if necessary) for categorical
variables.

The primary outcome measure was the all-cause
mortality. The exposure of interest was the first KT.
The date on which the patient was first waitlisted for
KT was used as the start of follow-up. If waitlisting
occurred before dialysis was started, the latter time-
point was considered the start of the follow-up.

We assessed transplantation as a time-dependent
exposure, allocating the time spent before a renal
transplant to the group that did not have transplants
and the time spent after transplantation to the group
that did.¹⁹,²⁵ This time-dependent approach avoids
immortal time bias.²⁶ Kaplan Meier analysis was per-
formed to estimate patient survival, and survival
curves were compared using a log-rank test. Mortality
rates per 1000 patient-years were calculated by
dividing the number of deaths by the total follow-up
time in years and multiplying by 1000. The 95% CI
for mortality rates were estimated using Poisson's
method.
Cox proportional hazards regression analysis was conducted to identify the factors associated with mortality. Multivariate Cox regression analysis included all parameters (*P* < 0.1 in the univariate analysis). HR with 95% CI are reported. In addition, to assess the evolution of relative risk over time, we employed a cumulative time-window analysis approach. Separate Cox models were fit for cumulative 3-month increases in follow-up (e.g., baseline to month 3 and baseline to month 6, etc.) over a total period of 15 years. The follow-up period beyond each time point was censored. This method provides a dynamic estimation of the HR, thus reflecting potential variations in the effect of transplantation on the risk of death over time. Again, the 95% CI was calculated for each estimate.

Finally, to assess the differential effects across the subgroups, we calculated the *P*-values for the interaction. Subgroup analyses were performed to evaluate differences in all-cause mortality with and without transplantation according to sex, age at ESKD onset (aged < or > 40 years), year of ESKD onset (before or after 2011, the year corresponding to the median of total follow-up in the waitlisted cohort), waitlisting before or after dialysis initiation, and region of transplantation (categorized into 3 main regions).

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.²⁷ Cumulative incidence curves were compared using Gray's test.

No imputation of missing data was performed. Statistical analyses were performed using R v4.3 with the *survival*, *survminer*, and *tidycmprsk* 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. The study was conducted in accordance with the principles of the Declaration of Helsinki and its amendments. Informed consent was not required to participate in the registry. Data collection was ruled out with implicit consent and with a drop-out option.

# RESULTS

## Baseline Characteristics of All Patients With LN-ESKD

Between January 1, 2002 and December 31, 2022, 882 patients were diagnosed with LN-ESKD and registered in the French REIN Registry. Overall, 636 of 882 patients (72%) were waitlisted for KT during the study

<figure><img src="image_3.png" /><figcaption>**Figure 1.** Flowchart of the study. ESKD, end-stage kidney disease; LN, lupus nephritis.</figcaption></figure>

period, of whom 470 of 636 (74%) subsequently underwent KT during follow-up (Figure 1). The patients with LN-ESKD were mainly female (79%), with a mean age of 45 ± 16 years at dialysis initiation. Most patients were enrolled for hemodialysis (81%), with fewer receiving peritoneal dialysis (13%) or preemptive transplantation (6%).

In comparison to patients with LN-ESKD who were not waitlisted, waitlisted patients were younger (aged 41 ± 13 vs. 55 ± 18 years at dialysis initiation) and had fewer comorbidities (Table 1).

## Baseline Characteristics of Waitlisted Patients With LN-ESKD

Most waitlisted patients were female (81%), with a mean age of 42 ± 13 years when they were waitlisted for KT and a median duration of dialysis before waiting of 6 (0–15) months. Twenty percent of the patients had at least 1 cardiovascular comorbidity, 7% had diabetes, and 4% had respiratory insufficiency. Whereas 98% of the participants could walk independently, 37% had low albumin levels (< 30 g/l). In addition, 10% had a BMI > 30 kg/m² and 58% were > 23 kg/m².

Compared with waitlisted patients who did not receive transplants during the study period, transplanted patients were younger (aged 40 ± 12 vs. 47 ± 13 years at waitlisting) and had fewer comorbidities. Transplanted patients had lower calculated panel reactive antibody(27 ± 34 vs. 37 ± 38). Deceased donor transplantation was the predominant method (77%), and a small proportion of patients were excluded from the waitlist (n = 23, 14%) (Table 1). The reasons for waitlist removal are detailed in Supplementary Table S2.

## Causes of Death in Waitlisted Patients With LN

After a median follow-up of 80 (38–133) months since waitlisting, 121 patients (19%) died: 70 (15%) received a kidney transplant (including 47 [67%] during the transplant period and 23 [33%] after returning to dialysis), and 51 (31%) did not (including 46 [90%] during the waitlisted period and 5 [10%] after being
removed from the waitlist) (Table 1). The cause of death was unknown in 21 patients (17%) and was classified as “other” in 22 patients (18%). The proportion of deaths because of infectious causes (21% vs. 18%),

cardiovascular causes (16% vs. 20%), and cancer (16% vs. 4%) were not significantly different between the transplanted and nontransplanted groups (Supplementary Table S2).

<table><caption>Table 1. Baseline characteristics of patients with LN-ESKD</caption><thead><tr><th>Characteristics</th><th>ESKD<br>N = 882</th><th>ESKD<br>Not waitlisted<br>n = 246</th><th>ESKD<br>Waitlisted<br>n = 636</th><th>P-value<sup>a</sup></th><th>Waitlisted<br>Not transplanted<br>n = 166</th><th>Waitlisted<br>Transplanted<br>n = 470</th><th>P-value<sup>b</sup></th></tr></thead><tbody><tr><td>Baseline characteristics</td><td></td><td></td><td></td><td></td><td></td><td></td><td></td></tr><tr><td>Female sex, n (%)</td><td>701 (79%)</td><td>185 (75%)</td><td>516 (81%)</td><td>0.051</td><td>136 (82%)</td><td>380 (81%)</td><td>0.8</td></tr><tr><td>Age</td><td></td><td></td><td></td><td></td><td></td><td></td><td></td></tr><tr><td>at ESKD (yrs)</td><td>45 (16)</td><td>55 (18)</td><td>41 (13)</td><td>&lt;0.001</td><td>46 (13)</td><td>40 (12)</td><td>&lt; 0.001</td></tr><tr><td>at waitlisting (yrs)</td><td>-</td><td>-</td><td>42 (13)</td><td>-</td><td>47 (13)</td><td>40 (12)</td><td>&lt; 0.001</td></tr><tr><td>at transplantation (yrs)</td><td>-</td><td>-</td><td>42 (12)</td><td>-</td><td>-</td><td>42 (12)</td><td>-</td></tr><tr><td>Waitlisted before dialysis initiation, n (%)</td><td>-</td><td>-</td><td>167 (26%)</td><td>-</td><td>35 (21%)</td><td>132 (28%)</td><td>0.078</td></tr><tr><td>First modality, n (%)</td><td></td><td></td><td></td><td>&lt;0.001</td><td></td><td></td><td>&lt; 0.001</td></tr><tr><td>Hemodialysis</td><td>712 (81%)</td><td>230 (93%)</td><td>482 (76%)</td><td></td><td>145 (87%)</td><td>337 (72%)</td><td></td></tr><tr><td>Peritoneal dialysis</td><td>116 (13%)</td><td>16 (6.5%)</td><td>100 (16%)</td><td></td><td>21 (13%)</td><td>79 (17%)</td><td></td></tr><tr><td>Preemptive transplantation</td><td>54 (6.1%)</td><td>0 (0%)</td><td>54 (8.5%)</td><td></td><td>0 (0%)</td><td>54 (11%)</td><td></td></tr><tr><td>Region of KRT, n (%)</td><td></td><td></td><td></td><td>&lt;0.001</td><td></td><td></td><td>0.5</td></tr><tr><td>Ile-de-France</td><td>204 (23%)</td><td>36 (15%)</td><td>168 (26%)</td><td></td><td>48 (29%)</td><td>120 (26%)</td><td></td></tr><tr><td>North</td><td>287 (33%)</td><td>91 (37%)</td><td>196 (31%)</td><td></td><td>46 (28%)</td><td>150 (32%)</td><td></td></tr><tr><td>South</td><td>391 (44%)</td><td>119 (48%)</td><td>272 (43%)</td><td></td><td>72 (43%)</td><td>200 (43%)</td><td></td></tr><tr><td>Calculated panel reactive antibody (%)</td><td>-</td><td>-</td><td>30 (36)</td><td></td><td>38 (38)</td><td>27 (34)</td><td>0.001</td></tr><tr><td>Comorbidities, n (%)</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>54 (7.4%)</td><td>43 (20%)</td><td>11 (2.1%)</td><td>&lt;0.001</td><td>6 (4.0%)</td><td>5 (1.4%)</td><td>0.088</td></tr><tr><td>Albumin level &lt; 30 g/l</td><td>296 (42%)</td><td>115 (54%)</td><td>181 (37%)</td><td>&lt;0.001</td><td>61 (42%)</td><td>120 (35%)</td><td>0.12</td></tr><tr><td>Albumin level &lt; 36 g/l</td><td>510 (73%)</td><td>175 (82%)</td><td>335 (69%)</td><td>&lt;0.001</td><td>109 (76%)</td><td>226 (66%)</td><td>0.033</td></tr><tr><td>BMI, n (%)</td><td></td><td></td><td></td><td>0.8</td><td></td><td></td><td>&lt; 0.001</td></tr><tr><td>&lt; 23 kg/m<sup>2</sup></td><td>427 (59%)</td><td>120 (61%)</td><td>307 (58%)</td><td></td><td>73 (53%)</td><td>234 (60%)</td><td></td></tr><tr><td>23-30 kg/m<sup>2</sup></td><td>228 (31%)</td><td>58 (29%)</td><td>170 (32%)</td><td></td><td>40 (29%)</td><td>130 (33%)</td><td></td></tr><tr><td>&gt; 30 kg/m<sup>2</sup></td><td>74 (10%)</td><td>20 (10%)</td><td>54 (10%)</td><td></td><td>26 (19%)</td><td>28 (7.1%)</td><td></td></tr><tr><td>Diabetes mellitus, n (%)</td><td>82 (9.5%)</td><td>38 (16%)</td><td>44 (7.0%)</td><td>&lt;0.001</td><td>17 (10%)</td><td>27 (5.9%)</td><td>0.059</td></tr><tr><td>Cardiovascular comorbidities, n (%)</td><td></td><td></td><td></td><td>&lt;0.001</td><td></td><td></td><td>0.027</td></tr><tr><td>None</td><td>622 (73%)</td><td>129 (54%)</td><td>493 (80%)</td><td></td><td>120 (73%)</td><td>373 (82%)</td><td></td></tr><tr><td>Only 1</td><td>145 (17%)</td><td>53 (22%)</td><td>92 (15%)</td><td></td><td>30 (18%)</td><td>62 (14%)</td><td></td></tr><tr><td>At least 2</td><td>88 (10%)</td><td>55 (23%)</td><td>33 (5.3%)</td><td></td><td>14 (8.5%)</td><td>19 (4.2%)</td><td></td></tr><tr><td>Cardiovascular comorbidities (detailed), n (%)</td><td></td><td></td><td></td><td></td><td></td><td></td><td></td></tr><tr><td>Stroke/transient ischemic attack</td><td>71 (8.4%)</td><td>33 (14%)</td><td>38 (6.2%)</td><td>&lt;0.001</td><td>17 (10%)</td><td>21 (4.7%)</td><td>0.009</td></tr><tr><td>Coronary artery disease</td><td>69 (8.2%)</td><td>35 (15%)</td><td>34 (5.6%)</td><td>&lt;0.001</td><td>15 (9.3%)</td><td>19 (4.2%)</td><td>0.016</td></tr><tr><td>Heart failure</td><td>114 (13%)</td><td>57 (24%)</td><td>57 (9.3%)</td><td>&lt;0.001</td><td>19 (12%)</td><td>38 (8.5%)</td><td>0.2</td></tr><tr><td>Rhythm disorders</td><td>56 (6.6%)</td><td>34 (15%)</td><td>22 (3.6%)</td><td>&lt;0.001</td><td>9 (5.5%)</td><td>13 (2.9%)</td><td>0.12</td></tr><tr><td>Abdominal aortic aneurysm</td><td>2 (0.3%)</td><td>2 (1.1%)</td><td>0 (0%)</td><td>0.094</td><td>0 (0%)</td><td>0 (0%)</td><td>&gt; 0.9</td></tr><tr><td>Peripheral artery disease</td><td>44 (5.2%)</td><td>25 (11%)</td><td>19 (3.1%)</td><td>&lt;0.001</td><td>5 (3.1%)</td><td>14 (3.1%)</td><td>&gt; 0.9</td></tr><tr><td>Respiratory insufficiency</td><td>51 (6.0%)</td><td>29 (12%)</td><td>22 (3.6%)</td><td>&lt;0.001</td><td>10 (6.2%)</td><td>12 (2.7%)</td><td>0.039</td></tr><tr><td>Cancer</td><td>26 (3.3%)</td><td>18 (7.7%)</td><td>8 (1.4%)</td><td>&lt;0.001</td><td>4 (2.5%)</td><td>4 (1.0%)</td><td>0.2</td></tr><tr><td>Timings and delays<sup>c</sup>, n (%)</td><td></td><td></td><td></td><td></td><td></td><td></td><td></td></tr><tr><td>Time from dialysis to waitlisting (mos)</td><td>-</td><td>-</td><td>6 (0, 15)</td><td>-</td><td>10 (1, 20)</td><td>6 (0, 14)</td><td>0.008</td></tr><tr><td>Time from dialysis to KT (mos)</td><td>-</td><td>-</td><td>24 (11, 44)</td><td>-</td><td>-</td><td>24 (11, 44)</td><td>-</td></tr><tr><td>Time from waitlisting to KT (mos)</td><td>-</td><td>-</td><td>14 (4, 30)</td><td>-</td><td>-</td><td>14 (4, 30)</td><td>-</td></tr><tr><td>Follow-up since dialysis initiation (mos)</td><td>75 (31-131)</td><td>31 (11-74)</td><td>91 (50-147)</td><td>&lt;0.001</td><td>46 (22-80)</td><td>110 (68-159)</td><td>&lt; 0.001</td></tr><tr><td>Follow-up since waitlisting (mos)</td><td>-</td><td>-</td><td>80 (38, 133)</td><td>-</td><td>34 (10, 61)</td><td>98 (59, 146)</td><td>&lt; 0.001</td></tr><tr><td>Follow-up since transplantation (mos)</td><td>-</td><td>-</td><td>77 (36, 124)</td><td>-</td><td>-</td><td>77 (36, 124)</td><td>-</td></tr><tr><td>Transplantation</td><td></td><td></td><td></td><td></td><td></td><td></td><td></td></tr><tr><td>Donor type, n (%)</td><td></td><td></td><td></td><td></td><td></td><td></td><td></td></tr><tr><td>None</td><td>-</td><td>246 (100%)</td><td>166 (26%)</td><td>-</td><td>166 (100%)</td><td>-</td><td></td></tr><tr><td>Deceased donor</td><td>-</td><td>-</td><td>357 (57%)</td><td>-</td><td>-</td><td>357 (77%)</td><td></td></tr><tr><td>Living donor</td><td>-</td><td>-</td><td>107 (17%)</td><td>-</td><td>-</td><td>107 (23%)</td><td></td></tr><tr><td>Waitlist removal</td><td>-</td><td>-</td><td>23 (3.6%)</td><td>-</td><td>23 (14%)</td><td>-</td><td>-</td></tr></tbody></table>

(Continued on following page)
<table><caption>**Table 1.** (Continued) Baseline characteristics of patients with LN-ESKD</caption><thead><tr><th>Characteristics</th><th>ESKD<br>N = 882</th><th>ESKD<br>Not waitlisted<br>n = 246</th><th>ESKD<br>Waitlisted<br>n = 636</th><th>P-value<sup>a</sup></th><th>Waitlisted<br>Not transplanted<br>n = 166</th><th>Waitlisted<br>Transplanted<br>n = 470</th><th>P-value<sup>b</sup></th></tr></thead><tbody><tr><td>Outcomes, n (%)</td><td></td><td></td><td></td><td></td><td></td><td></td><td></td></tr><tr><td>Graft failure</td><td>-</td><td>-</td><td>88 (19%)</td><td>-</td><td>-</td><td>88 (19%)</td><td>-</td></tr><tr><td>Death</td><td>273 (31%)</td><td>152 (62%)</td><td>121 (19%)</td><td>&lt;0.001</td><td>51 (31%)</td><td>70 (15%)</td><td>&lt; 0.001</td></tr><tr><td>During waitlisted period</td><td>-</td><td>-</td><td>-</td><td>-</td><td>46 (90%)</td><td>-</td><td>-</td></tr><tr><td>After waitlist removal</td><td>-</td><td>-</td><td>-</td><td>-</td><td>5 (9.8%)</td><td>-</td><td>-</td></tr><tr><td>During transplant period</td><td>-</td><td>-</td><td>-</td><td>-</td><td>-</td><td>47 (67%)</td><td>-</td></tr><tr><td>After return to dialysis</td><td>-</td><td>-</td><td>-</td><td>-</td><td>-</td><td>23 (33%)</td><td>-</td></tr></tbody></table>

BMI, body mass index; ESKD, end-stage kidney disease; KRT, kidney replacement therapy; KT, kidney transplantation; LN, lupus nephritis.

<sup>a</sup>Comparison between waitlisted and nonwaitlisted patients with ESKD.

<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-third quartile], in opposition to other continuous data, shown as mean (SD).

"-" means not applicable.

## All-Cause Mortality in Waitlisted Patients With LN

The mortality rate among kidney transplant recipients was 16.5 (95% CI: 11.8–21.2) per 1000 patient-years, compared with 36.0 (95% CI: 26.1–46.0) per 1000 patient-years in those who did not receive transplants (P < 0.001, Figure 2a). This reduction in mortality was consistent across all subgroups (Table 2).

Among waitlisted patients with LN, the 5-year survival rates were 93% (90%–96%) for transplant recipients and 83% (77%–89%) for nontransplant patients. At 10 years, the survival rates were 84% (79%–89%) for transplant recipients and 60% (48%–75%) for nontransplant recipients. This improved survival rate was the highest among recipients of living donor transplants compared with the nontransplanted group (P < 0.001, Figure 2b).

## Mortality Risk Among Waitlisted Patients With LN

The factors associated with mortality in the univariate analyses are presented in Table 3. Age at waitlisting, low BMI (< 23 kg/m²) and high BMI (> 30 kg/m²), and cardiovascular comorbidities were associated with mortality. There was a strong association between diabetes and mortality. Albumin levels > 36 g/l and KT were associated with survival.

After adjustments on age at waitlisting, sex, BMI, diabetes, and cardiovascular comorbidities, KT was associated with a 60% reduction in the risk of death (HR = 0.40 [0.24–0.67], P < 0.001) (Tables 2 and 3). When considering donor type, after adjustments on the same variables, living donor KT was associated with a 64% reduction in the risk of death (vs. no transplantation, HR = 0.36 [0.15–0.87], P = 0.023) and deceased donor KT was associated with a 58% reduction (vs. no transplantation, HR = 0.42 [0.24–0.72], P = 0.001).

## Mortality Risk Among Subgroups of Waitlisted Patients With LN

Results were homogeneous across all analyzed subgroups, including sex, age at waitlisting (< or > 40 years), year of ESKD onset (before or after 2011), waitlisting before or after dialysis initiation, and region of transplantation. After adjustments for age at waitlisting, sex, BMI, diabetes, and cardiovascular comorbidities, KT was associated with a reduction in the risk of death, without significant interaction. The strongest effect was found for patients waitlisted before dialysis initiation (HR = 0.22 [0.05–0.9]) and male patients (HR = 0.23 [0.06–0.89]), and the weakest effect was found for younger patients (HR = 0.55 [0.16–1.9]) (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 an increased risk of death in the early posttransplantation period, followed by a decreased risk in the remainder of the study (Supplementary Figure S2).

## Sensitivity Analyses

We conducted 2 sensitivity analyses to validate our primary findings. First, we excluded patients removed from the waitlist (n = 23) to address potential confounding factors such as patients becoming too ill for transplantation (main cause of waitlist removal, 70%; Supplementary Table S1). This did not affect the observed survival benefit (adjusted HR = 0.35 [0.21–0.61], P < 0.001). Second, we censored living donor transplant recipients (n = 107, 17%), and the survival benefit remained consistent (adjusted HR = 0.41 [0.24–0.70], p = 0.001).
<figure><img src="image_4.png" /></figure>

<figure><img src="image_5.png" /><figcaption>**Figure 2.** Patient survival according to transplant status among waitlisted patients with LN-ESKD. (a) All waitlisted patients with lupus nephritis. (b) According to donor type (deceased or living donor). Benjamini-Hochberg-adjusted log-rank *P*-values: deceased donor transplantation versus no transplantation = 0.0072; living donor transplantation versus no transplantation = 0.00055; deceased donor transplantation versus living donor transplantation = 0.16. The total group size was twice that of the transplant group (once for the dialysis period and once for the transplant period).</figcaption></figure>
<table><caption>**Table 2.** All-cause mortality according to transplant status among waitlisted patients with LN-ESKD</caption><thead><tr><th rowspan="2">Subgroup</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>1106</td><td>4266</td><td>98</td><td>22.97</td><td>18.42-27.52</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>636</td><td>1415</td><td>51</td><td>36.04</td><td>26.15-45.93</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>470</td><td>2851</td><td>47</td><td>16.49</td><td>11.77-21.20</td><td>0.41</td><td>0.27-0.63</td><td></td><td>0.46</td><td>0.30-0.71</td><td></td><td>0.40</td><td>0.24-0.67</td><td></td></tr><tr><td>Age (waitlisting)</td><td></td><td></td><td></td><td></td><td></td><td></td><td></td><td>0.92</td><td></td><td></td><td>0.99</td><td></td><td></td><td>0.54</td></tr><tr><td>≤ 40 yrs</td><td>518</td><td>2079</td><td>15</td><td>7.21</td><td>3.56-10.87</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>284</td><td>638</td><td>7</td><td>10.98</td><td>2.85-19.11</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>234</td><td>1441</td><td>8</td><td>5.55</td><td>1.70-9.40</td><td>0.74</td><td>0.26-2.15</td><td></td><td>0.74</td><td>0.25-2.15</td><td></td><td>0.55</td><td>0.16-1.90</td><td></td></tr><tr><td>> 40 yrs</td><td>588</td><td>2187</td><td>83</td><td>37.95</td><td>29.79-46.12</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>352</td><td>778</td><td>44</td><td>56.58</td><td>39.86-73.30</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>236</td><td>1409</td><td>39</td><td>27.67</td><td>18.99-36.36</td><td>0.38</td><td>0.24-0.61</td><td></td><td>0.4</td><td>0.25-0.65</td><td></td><td>0.37</td><td>0.21-0.65</td><td></td></tr><tr><td>Sex</td><td></td><td></td><td></td><td></td><td></td><td></td><td></td><td>0.25</td><td></td><td></td><td>0.39</td><td></td><td></td><td>0.33</td></tr><tr><td>Female</td><td>896</td><td>3437</td><td>81</td><td>23.57</td><td>18.44-28.70</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>516</td><td>1180</td><td>41</td><td>34.75</td><td>24.11-45.38</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>380</td><td>2257</td><td>40</td><td>17.72</td><td>12.23-23.22</td><td>0.46</td><td>0.29-0.73</td><td></td><td>0.5</td><td>0.31-0.80</td><td></td><td>0.45</td><td>0.26-0.78</td><td></td></tr><tr><td>Male</td><td>210</td><td>829</td><td>17</td><td>20.5</td><td>10.75-30.24</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>120</td><td>235</td><td>10</td><td>42.5</td><td>16.16-68.83</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>90</td><td>594</td><td>7</td><td>11.78</td><td>3.05-20.51</td><td>0.25</td><td>0.09-0.71</td><td></td><td>0.29</td><td>0.1-0.83</td><td></td><td>0.23</td><td>0.06-0.89</td><td></td></tr><tr><td>Waitlisted before dialysis initiation</td><td></td><td></td><td></td><td></td><td></td><td></td><td></td><td>0.66</td><td></td><td></td><td>0.77</td><td></td><td></td><td>0.46</td></tr><tr><td>No</td><td>807</td><td>3249</td><td>81</td><td>24.93</td><td>19.50-30.36</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>469</td><td>1166</td><td>43</td><td>36.89</td><td>25.86-47.92</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>338</td><td>2083</td><td>38</td><td>18.24</td><td>12.44-24.04</td><td>0.43</td><td>0.27-0.69</td><td></td><td>0.49</td><td>0.3-0.78</td><td></td><td>0.45</td><td></td><td></td></tr><tr><td>Yes</td><td>299</td><td>1017</td><td>17</td><td>16.71</td><td>8.77-24.66</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>167</td><td>250</td><td>8</td><td>32.05</td><td>9.84-54.26</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>132</td><td>767</td><td>9</td><td>11.73</td><td>4.07-19.39</td><td>0.35</td><td>0.12-1.01</td><td></td><td>0.47</td><td>0.15-1.4</td><td></td><td>0.22</td><td></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>0.7</td><td></td><td></td><td>0.46</td><td></td><td></td><td>0.29</td></tr><tr><td>Before 2011</td><td>385</td><td>2224</td><td>36</td><td>16.19</td><td>10.90-21.48</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>203</td><td>526</td><td>14</td><td>26.61</td><td>12.67-40.54</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>182</td><td>1698</td><td>22</td><td>12.96</td><td>7.54-18.38</td><td>0.44</td><td>0.21-0.91</td><td></td><td>0.44</td><td>0.21-0.92</td><td></td><td>0.33</td><td>0.13-0.82</td><td></td></tr><tr><td>After 20211</td><td>721</td><td>2042</td><td>62</td><td>30.36</td><td>22.80-37.91</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>433</td><td>889</td><td>37</td><td>41.62</td><td>28.21-55.03</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>288</td><td>1153</td><td>25</td><td>21.68</td><td>13.18-30.18</td><td>0.45</td><td>0.26-0.76</td><td></td><td>0.49</td><td>0.29-0.84</td><td></td><td>0.43</td><td>0.23-0.8</td><td></td></tr><tr><td>Region of KRT</td><td></td><td></td><td></td><td></td><td></td><td></td><td></td><td>0.65</td><td></td><td></td><td>0.46</td><td></td><td></td><td>0.75</td></tr><tr><td>Ile-de-France</td><td>288</td><td>1085</td><td>32</td><td>29.49</td><td>19.27-39.70</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>168</td><td>446</td><td>16</td><td>35.9</td><td>18.31-53.49</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>640</td><td>16</td><td>25.02</td><td>12.76-37.28</td><td>0.61</td><td>0.29-1.25</td><td></td><td>0.63</td><td>0.3-1.31</td><td></td><td>0.38</td><td>0.12-1.18</td><td></td></tr><tr><td>North</td><td>346</td><td>1331</td><td>26</td><td>19.54</td><td>12.03-27.05</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>196</td><td>396</td><td>11</td><td>27.75</td><td>11.35-44.15</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>150</td><td>934</td><td>15</td><td>16.06</td><td>7.93-24.18</td><td>0.64</td><td>0.27-1.47</td><td></td><td>0.57</td><td>0.23-1.37</td><td></td><td>0.53</td><td>0.21-1.36</td><td></td></tr></tbody></table>

(Continued on following page)
<table><caption>**Table 2.** (Continued) All-cause mortality according to transplant status among waitlisted patients with LN-ESKD</caption><thead><tr><th rowspan="3">Subgroup</th><th rowspan="3">n</th><th rowspan="3">Total follow-up (yrs)</th><th rowspan="3">Deaths</th><th rowspan="3">Mortality rate (/1000 person- yrs)</th><th colspan="4">Unadjusted</th><th colspan="4">Fully adjusted<sup>a</sup></th></tr><tr><th colspan="2">Mortality rate</th><th colspan="2">Adjusted on age/sex</th><th colspan="2">Mortality rate</th><th colspan="2">Adjusted on age/sex</th><th colspan="2">Mortality rate</th></tr><tr><th>95% CI</th><th>HR</th><th>95% CI</th><th>HR</th><th>95% CI</th><th>95% CI</th><th>HR</th><th>95% CI</th><th>95% CI</th><th>HR</th><th>95% CI</th></tr></thead><tbody><tr><td>South</td><td>472</td><td>1850</td><td>40</td><td>21.62</td><td>14.92-28.32</td><td>—</td><td>—</td><td>—</td><td>—</td><td>—</td><td>—</td><td>—</td><td>—</td></tr><tr><td>Dialysis, waitlisted</td><td>272</td><td>573</td><td>24</td><td>41.88</td><td>25.12-58.63</td><td>—</td><td>—</td><td>—</td><td>—</td><td>—</td><td>—</td><td>—</td><td>—</td></tr><tr><td>Transplanted</td><td>200</td><td>1277</td><td>16</td><td>12.53</td><td>6.39-18.67</td><td>0.24</td><td>0.12-0.48</td><td>0.34</td><td>0.17-0.7</td><td>0.38</td><td>0.18-0.81</td><td>—</td><td>—</td></tr></tbody></table>

BMI, body mass index; CI, confidence interval; ESKD, end-stage kidney disease; HR, hazard ratio; KRT, kidney replacement therapy; LN, lupus nephritis.

<sup>a</sup>Fully adjusted models were adjusted for age at waitlisting, sex, diabetes, BMI, and cardiovascular comorbidities (Supplementary Table S3). The total group size was twice that of the transplant group (once for the dialysis period and once for the transplant period).

Regions were grouped as "North" (Bretagne, Centre-Val de Loire, Normandie, Pays de la Loire, Bourgogne-Franche-Comté, Grand Est, Hauts-de-France, La Réunion et Mayotte), "South" (Auvergne-Rhône-Alpes, Corse, Provence-Alpes-Côte d'Azur, Languedoc-Roussillon, Nouvelle-Aquitaine, Midi-Pyrénées, Guadeloupe, Martinique, Guyane) and "Ile-de-France".

## Kidney Allograft Survival

After a median follow-up of 77 [36–124] months since transplantation, 88 patients (19%) experienced graft failure. The main cause of allograft failure was chronic rejection (n = 37, 42%), followed by other chronic kidney diseases (n = 9, 10%) and vascular complications (n = 9, 10%) (Supplementary Table S3). The cumulative incidence of graft failure, considering death as a competing event, was 10% (7%–13%) and 23% (18%–28%) at 5 and 10 years, respectively (Figure 3a). There was no difference in kidney allograft survival according to the donor type (deceased vs. living donors, P = 0.9; Figure 3b).

## Access to Waitlist and to Transplantation

Finally, we analyzed the probability of being waitlisted or transplanted, considering death as a competing event (Supplementary Figure S3). Among all patients with LN-ESKD, 47%, 63%, and 73% were waitlisted, and 14%, 28%, and 51% were transplanted at 1, 2, and 5 years after ESKD onset, respectively. Considering only waitlisted patients, 65%, 86%, and 98% were waitlisted and 19%, 38%, and 69% were transplanted 1, 2, and 5 years after the onset of ESKD, respectively. In addition, 35%, 51%, and 77% of patients underwent transplantation 1, 2, and 5 years after waitlisting, respectively.

## DISCUSSION

This large population study, spanning 2 decades and encompassing all French patients with LN-ESKD waitlisted for KT, revealed a significant improvement in survival associated with KT. This survival benefit was consistent across the key demographics throughout the study period. However, a considerable number of waitlisted patients died before receiving a transplant, highlighting the urgent need to enhance kidney transplant accessibility for patients with LN-ESKD. Thus, these findings emphasize that early and systematic evaluation of patients with LN for transplant eligibility, ideally before ESKD onset, is critical for improving outcomes.

Our findings corroborate and extend the previous research on patients with LN-ESKD who underwent KT. The survival of patients with LN on chronic dialysis has been shown to be lower than that of other patients on dialysis,<sup>17,18</sup> with a higher mortality rate from infectious and/or cardiovascular causes. Given the additional immunosuppression required, KT may be risky because of the associated risks of infection, diabetes, and hypertension. These factors limit the generalizability of the kidney transplant outcomes from other groups of patients with ESKD to patients with LN-ESKD. Our study confirms that transplantation
<table><caption>**Table 3.** Factors associated with death among waitlisted patients with LN-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>Male sex</td><td>210</td><td>17</td><td>0.87</td><td>0.52-1.47</td><td>0.6</td><td>169</td><td>12</td><td>0.9</td><td>0.48-1.70</td><td>0.8</td></tr><tr><td>Age (per 1 yr 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>1106</td><td>98</td><td>1.07</td><td>1.05-1.09</td><td>&lt;0.001</td><td></td><td></td><td></td><td></td><td></td></tr><tr><td>at waitlisting (yrs)</td><td>1106</td><td>98</td><td>1.07</td><td>1.05-1.09</td><td>&lt;0.001</td><td>895</td><td>75</td><td>1.07</td><td>1.05-1.09</td><td>&lt;0.001</td></tr><tr><td>at transplantation (yrs)</td><td>470</td><td>47</td><td>1.09</td><td>1.06-1.12</td><td>&lt;0.001</td><td></td><td></td><td></td><td></td><td></td></tr><tr><td>Waitlisted before dialysis initiation</td><td>1106</td><td>98</td><td>0.67</td><td>0.40-1.13</td><td>0.13</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>819</td><td>77</td><td>—</td><td>—</td><td></td><td></td><td></td><td></td><td></td><td></td></tr><tr><td>Peritoneal dialysis</td><td>179</td><td>17</td><td>1.04</td><td>0.62-1.77</td><td>0.9</td><td></td><td></td><td></td><td></td><td></td></tr><tr><td>Preemptive transplantation</td><td>108</td><td>4</td><td>0.45</td><td>0.17-1.24</td><td>0.12</td><td></td><td></td><td></td><td></td><td></td></tr><tr><td>Region of KRT</td><td></td><td></td><td></td><td></td><td></td><td></td><td></td><td></td><td></td><td></td></tr><tr><td>Ile-de-France</td><td>288</td><td>32</td><td>—</td><td>—</td><td></td><td></td><td></td><td></td><td></td><td></td></tr><tr><td>North</td><td>346</td><td>26</td><td>0.66</td><td>0.39-1.10</td><td>0.11</td><td></td><td></td><td></td><td></td><td></td></tr><tr><td>South</td><td>472</td><td>40</td><td>0.74</td><td>0.46-1.18</td><td>0.2</td><td></td><td></td><td></td><td></td><td></td></tr><tr><td>cPRA (per 1% increment)</td><td>885</td><td>82</td><td>1</td><td>0.99-1.00</td><td>0.2</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<sup>a</sup></td><td>16</td><td>3</td><td>2.97</td><td>0.93-9.49</td><td>0.066</td><td></td><td></td><td></td><td></td><td></td></tr><tr><td>Albumin level &gt; 30 g/l<sup>a</sup></td><td>529</td><td>42</td><td>0.65</td><td>0.41-1.04</td><td>0.072</td><td></td><td></td><td></td><td></td><td></td></tr><tr><td>Albumin level &gt; 36 g/l<sup>a</sup></td><td>269</td><td>14</td><td>0.44</td><td>0.24-0.78</td><td>0.005</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>23-30 kg/m<sup>2</sup></td><td>300</td><td>20</td><td>—</td><td>—</td><td></td><td>297</td><td>19</td><td>—</td><td>—</td><td></td></tr><tr><td>&lt; 23 kg/m<sup>2</sup></td><td>541</td><td>48</td><td>1.41</td><td>0.84-2.37</td><td>0.2</td><td>518</td><td>47</td><td>2.25</td><td>1.29-3.91</td><td>0.004</td></tr><tr><td>&gt; 30 kg/m<sup>2</sup></td><td>82</td><td>10</td><td>2.61</td><td>1.21-5.59</td><td>0.014</td><td>80</td><td>9</td><td>2.13</td><td>0.92-4.91</td><td>0.077</td></tr><tr><td>Diabetes mellitus</td><td>1086</td><td>95</td><td>1.84</td><td>0.95-3.54</td><td>0.069</td><td>895</td><td>75</td><td>1.57</td><td>0.76-3.22</td><td>0.2</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>866</td><td>67</td><td>—</td><td>—</td><td></td><td>710</td><td>51</td><td>—</td><td>—</td><td></td></tr><tr><td>Only 1</td><td>154</td><td>17</td><td>1.36</td><td>0.80-2.32</td><td>0.3</td><td>135</td><td>16</td><td>1.45</td><td>0.81-2.58</td><td>0.2</td></tr><tr><td>At least 2</td><td>52</td><td>9</td><td>2.32</td><td>1.15-4.65</td><td>0.018</td><td>50</td><td>8</td><td>1.1</td><td>0.50-2.42</td><td>0.8</td></tr><tr><td>Cardiovascular comorbidities (detailed)<sup>b</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>Stroke / transient ischemic attack</td><td>1059</td><td>93</td><td>1.46</td><td>0.71-3.01</td><td>0.3</td><td></td><td></td><td></td><td></td><td></td></tr><tr><td>Coronary artery disease</td><td>1057</td><td>92</td><td>1.89</td><td>0.87-4.10</td><td>0.11</td><td></td><td></td><td></td><td></td><td></td></tr><tr><td>Heart failure</td><td>1062</td><td>93</td><td>1.12</td><td>0.58-2.15</td><td>0.7</td><td></td><td></td><td></td><td></td><td></td></tr><tr><td>Rhythm disorders</td><td>1067</td><td>93</td><td>1.65</td><td>0.67-4.06</td><td>0.3</td><td></td><td></td><td></td><td></td><td></td></tr><tr><td>Abdominal aortic aneurysm</td><td>704</td><td>59</td><td>—</td><td>0.00-Inf</td><td>&gt; 0.9</td><td></td><td></td><td></td><td></td><td></td></tr><tr><td>Peripheral artery disease</td><td>1061</td><td>92</td><td>2.63</td><td>1.22-5.70</td><td>0.014</td><td></td><td></td><td></td><td></td><td></td></tr><tr><td>Respiratory insufficiency</td><td>1064</td><td>94</td><td>1.91</td><td>0.77-4.71</td><td>0.2</td><td></td><td></td><td></td><td></td><td></td></tr><tr><td>Cancer</td><td>968</td><td>91</td><td>—</td><td>0.00-Inf</td><td>&gt; 0.9</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>c</sup></td><td>1106</td><td>98</td><td>1.28</td><td>0.52-3.15</td><td>0.6</td><td></td><td></td><td></td><td></td><td></td></tr><tr><td>Transplantation</td><td>470</td><td>47</td><td>0.41</td><td>0.27-0.63</td><td>&lt; 0.001</td><td>379</td><td>33</td><td>0.4</td><td>0.24-0.67</td><td>&lt;0.001</td></tr><tr><td>Donor type<sup>c</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>636</td><td>51</td><td>—</td><td>—</td><td></td><td></td><td></td><td></td><td></td><td></td></tr><tr><td>Deceased donor</td><td>357</td><td>40</td><td>0.46</td><td>0.30-0.72</td><td>&lt; 0.001</td><td></td><td></td><td></td><td></td><td></td></tr><tr><td>Living donor</td><td>107</td><td>7</td><td>0.26</td><td>0.12-0.59</td><td>0.001</td><td></td><td></td><td></td><td></td><td></td></tr></tbody></table>

BMI, body mass index; CI, confidence interval; cPRA, calculated Panel Reactive Antibody; ESKD, end-stage kidney disease; HR, hazard ratio; inf, infinity; KRT, kidney replacement therapy; KT, kidney transplantation; LN, lupus nephritis.

<sup>a</sup>Albumin level and ability to walk alone were not included in the multivariate model because of an elevated number of missing values (24% and 18%, respectively).

<sup>b</sup>Individual cardiovascular comorbidities were not included in the multivariable analysis (only the grouped variable was).

<sup>c</sup>Not included in the multivariable analysis. See the Sensitivity Analysis section.

The total group size was twice that of the transplant group (once for the dialysis period and once for the transplant period).

significantly improves survival, which is consistent with data from the United States Renal Data System registry,¹⁹ in which deaths from infectious and cardiovascular causes have been reduced. There were no data on relapse risk reduction; however, we can assume that a modern immunosuppressive regimen, limited steroid exposure, and the inflammatory state

associated with SLE also helped reduce the mortality associated with these events. Our cohort did not show a significant reduction in infectious or cardiovascular mortality. However, the increase in cancer-related mortality, which is likely not significant because of inadequate power to detect differences, may be clinically meaningful. It is important to note that
<figure><img src="image_6.png" /></figure>

<figure><img src="image_7.png" /><figcaption>**Figure 3.** Graft survival among transplanted patients with LN-ESKD, computed with death as a competitive event. (a) All transplanted patients with lupus nephritis. (b) According to donor type (deceased or living donor). ESKD, end-stage kidney disease; LN, lupus nephritis.</figcaption></figure>

waitlisted patients face higher infection-related deaths (20% in our LN-ESKD waitlisted cohort vs. 15% in all patients with ESKD regardless of its cause [data from the REIN registry]²²), and transplanted patients face

higher cancer-related deaths (16% in our LN-ESKD transplanted cohort vs. 10% in all patients with ESKD regardless of its cause [data from the REIN registry]²²).
Taken together, these data suggest that all patients with LN 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. Early referral of patients to a kidney transplant center can improve the likelihood of preemptive transplantation, ideally with a living donor. If preemptive transplantation is not feasible, patients will accumulate time on the waitlist, potentially reducing their waiting period after the onset of ESKD. Notably, access to transplantation for all patients with LN-ESKD was very close to the all cause, patients with ESKD who were aged 18 to 59 years included in the REIN registry (2022 annual report results: 51% by 5 years).²²

Subgroup analyses revealed that the survival benefit of transplantation was higher in male patients, who are known to experience more severe disease and higher mortality risk;²⁰,²¹,²⁸,²⁹ higher in patients waitlisted before dialysis initiation, and lower in younger patients (aged < 40 years), likely because of their already low mortality on dialysis. These findings highlight the importance of tailoring strategies to improve access to transplantation, particularly in the high-risk subgroups.

This study has several strengths in terms of the data source and design. First, the REIN registry is a nationwide registry covering all patients with ESKD in France. LN was diagnosed and reported by nephrologists, thereby limiting the risk of false-positive diagnoses. Second, our methodology—time-varying exposure modeling, comorbidity adjustment, and sensitivity analyses—mitigated (but did not eliminate) biases, such as confounding or immortal time bias. In addition, we restricted our analysis to patients on the waiting list to reduce the bias associated with confounding by contraindications (people on the waiting list for KT are generally younger, healthier, and have a higher socioeconomic status²² than those who are not). Although residual confounding factors may still be present, we adjusted our analysis for important factors, including comorbidities, to account for variables known to influence mortality.

Our retrospective study has several limitations. The REIN registry enrolls patients when they reach ESKD, but does not include details on the history of LN. As such, we cannot address how certain factors, such as the time between LN onset, disease remission, transplantation, antibody type and titer at diagnosis or transplantation, associated antiphospholipid antibodies, exposure to immunosuppression, pretransplant events (e.g., infections, cardiovascular events, and relapses), disease activity at the time of waiting, and disease recurrence post-KT may affect outcomes. The ethnicity of patients and the use of

hydroxychloroquine, both known to be associated with SLE outcomes, are unknown. In addition, treatment advances over a 2-decade study period, especially for LN management,²³ may limit generalizability.

In conclusion, this study adds to the existing evidence supporting the significant survival benefit of KT for patients with LN-ESKD. Early referral for transplant evaluation and improved access to transplantation remain critical for improving the outcomes in this high-risk population.

## 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 Renal Epidemiology and Information Network (REIN) is a national registry held by the French Biomedicine Agency. We thank all the nephrologists in France who provided detailed information for the REIN registry and the REIN research assistants in charge of data collection and quality control. Dialysis centers participating in the registry are listed in the REIN annual report (https://www.agence-biomedecine.fr/IMG/pdf/rapport_2022_-_20241128.pdf). All coauthors have read and agreed to the contents of the manuscript. The results presented in this paper have not been published previously in whole or in part, except in abstract format.

## SUPPLEMENTARY MATERIAL

Supplementary File (PDF)

**Figure S1.** Subgroup analyses regarding the risk of death among waitlisted patients with LN-ESKD.

**Figure S2.** Instantaneous hazard of death over the study period.

**Figure S3.** Probability of being waitlisted or transplanted.

**Table S1.** Causes of waitlist removal in LN-ESKD waitlisted, not transplanted patients.

**Table S2.** Causes of death among waitlisted patients with LN-ESKD.

**Table S3.** Causes of allograft failure in LN-ESKD transplanted patients with LN-ESKD.

## REFERENCES

1. Siegel CH, Sammaritano LR. Systemic lupus erythematosus: A review. JAMA. 2024;331:1480–1491. https://doi.org/10.1001/jama.2024.2315
2. Mok CC, Teng YKO, Saxena R, Tanaka Y. Treatment of lupus nephritis: Consensus, evidence and perspectives. *Nat Rev Rheumatol*. 2023;19:227–238. https://doi.org/10.1038/s41584-023-00925-5

3. Yap DYH, Tang CSO, Ma MKM, Lam MF, Chan TM. Survival analysis and causes of mortality in patients with lupus nephritis. *Nephrol Dial Transplant*. 2012;27:3248–3254. https://doi.org/10.1093/ndt/gfs073

4. Lee YH, Choi SJ, Ji JD, Song GG. Overall and cause-specific mortality in systemic lupus erythematosus: An updated meta-analysis. *Lupus*. 2016;25:727–734. https://doi.org/10.1177/0961203315627202

5. Park ES, Ahn SS, Jung SM, Song JJ, Park YB, Lee SW. Renal outcome after kidney-transplantation in Korean patients with lupus nephritis. *Lupus*. 2018;27:461–467. https://doi.org/10.1177/0961203317725591

6. Horta-Baas G, Camargo-Coronel A, Miranda-Hernández DG, Gómez-Parra LG, Romero-Figueroa MDS, Pérez-Cristóbal M. Renal transplantation in systemic lupus erythematosus: Comparison of graft survival with other causes of end-stage renal disease. *Reumatol Clin (Engl Ed)*. 2019;15:140–145. https://doi.org/10.1016/j.reuma.2017.07.006

7. Ward MM. Outcomes of renal transplantation among patients with end-stage renal disease caused by lupus nephritis. *Kidney Int*. 2000;57:2136–2143. https://doi.org/10.1046/j.1523-1755.2000.00065.x

8. Martínez-López D, Sánchez-Bilbao L, De Cos-Gómez M, et al. Long-term survival of renal transplantation in patients with lupus nephritis: Experience from a single university centre. *Clin Exp Rheumatol*. 2022;40:581–588. https://doi.org/10.55563/clinexprheumatol/ri873i

9. Kim JE, Kim YC, Min SI, et al. Transplant outcomes in kidney recipients with lupus nephritis, and systematic review. *Lupus*. 2020;29:248–255. https://doi.org/10.1177/0961203320902524

10. Jiang W, Xu Y, Yin Q. Graft survival and mortality outcomes after kidney transplant in patients with lupus nephritis: A systematic review and meta-analysis. *Ren Fail*. 2024;46:2296000. https://doi.org/10.1080/0886022X.2023.2296000

11. Derner O, Kramer A, Hruskova Z, et al. Incidence of kidney replacement therapy and subsequent outcomes among patients with systemic lupus erythematosus: Findings from the ERA registry. *Am J Kidney Dis*. 2022;79:635–645. https://doi.org/10.1053/j.ajkd.2021.09.016

12. Gołębiewska J, Dębska-Ślizień A, Bułło-Piontecka B, Rutkowski B. Outcomes in renal transplant recipients with lupus nephritis-A single-center experience and review of the literature. *Transplant Proc*. 2016;48:1489–1493. https://doi.org/10.1016/j.transproceed.2016.02.061

13. Contreras G, Mattiazi A, Guerra G, et al. Recurrence of lupus nephritis after kidney transplantation. *J Am Soc Nephrol*. 2010;21:1200–1207. https://doi.org/10.1681/ASN.2009101093

14. Kang SH, Chung BH, Choi SR, et al. Comparison of clinical outcomes by different renal replacement therapy in patients with end-stage renal disease secondary to lupus nephritis. *Korean J Intern Med*. 2011;26:60–67. https://doi.org/10.3904/kjim.2011.26.1.60

15. Naranjo-Escobar J, Manzi E, Posada JG, et al. Kidney transplantation for end-stage renal disease in lupus nephritis, a very safe procedure: A single Latin American transplant

center experience. *Lupus*. 2017;26:1157–1165. https://doi.org/10.1177/0961203317696591

16. Cairoli E, Sanchez-Marcos C, Espinosa G, et al. Renal transplantation in systemic lupus erythematosus: Outcome and prognostic factors in 50 cases from a single centre. *Biomed Res Int*. 2014;2014:746192. https://doi.org/10.1155/2014/746192

17. Levy B, Couchoud C, Rougier JP, Jourde-Chiche N, Daugas E. Outcome of patients with systemic lupus erythematosus on chronic dialysis: An observational study of incident patients of the French National Registry 2002–2012. *Lupus*. 2015;24:1111–1121. https://doi.org/10.1177/0961203315578763

18. Zhang L, Lee G, Liu X, et al. Long-term outcomes of end-stage kidney disease for patients with lupus nephritis. *Kidney Int*. 2016;89:1337–1345. https://doi.org/10.1016/j.kint.2016.02.014

19. Jorge A, Wallace ZS, Lu N, Zhang Y, Choi HK. Renal transplantation and survival among patients with lupus nephritis: A cohort study. *Ann Intern Med*. 2019;170:240–247. https://doi.org/10.7326/M18-1570

20. Lao C, Van Dantzig P, White D, Rabindranath K, Foxall D, Lawrenson R. Prevalence and outcomes of end-stage kidney disease in patients with systemic lupus erythematosus: A population-based study. *Rheumatol Int*. 2023;44:469–475. https://doi.org/10.1007/s00296-023-05409-z

21. Mahmood SB, Aziz M, Malepati D, et al. Evaluating sex differences in the characteristics and outcomes of lupus nephritis: A systematic review and meta-analysis. *Glomerular Dis*. 2024;4:19–32. https://doi.org/10.1159/000535981

22. Bernède G, Saïd J, Sequeira A, et al. Le systèmed'information de REIN. *Néphrol Ther*. 2022;18:18/5S-e84-18/5S-e86. https://doi.org/10.1016/S1769-7255(22)00577-6

23. Jourde-Chiche N, Béchade C, Couchoud C. REIN : Un outil au service de la recherche. *Néphrol Ther*. 2022;18:18/5S-e60-18/5S-e65. https://doi.org/10.1016/S1769-7255(22)00572-7

24. Caillet A, Mazoué F, Wurtz B, et al. Which data in the French registry for advanced chronic kidney disease for public health and patient care? *Néphrol Ther*. 2022;18:228–236. https://doi.org/10.1016/j.nephro.2022.01.004

25. Wallace ZS, Wallwork R, Zhang Y, et al. Improved survival with renal transplantation for end-stage renal disease due to granulomatosis with polyangiitis: Data from the United States Renal Data System. *Ann Rheum Dis*. 2018;77:1333–1338. https://doi.org/10.1136/annrheumdis-2018-213452

26. Lévesque LE, Hanley JA, Kezouh A, Suissa S. Problem of immortal time bias in cohort studies: Example using statins for preventing progression of diabetes. *BMJ*. 2010;340:b5087. https://doi.org/10.1136/bmj.b5087

27. Noordzij M, Leffondre K, Van Stralen KJ, Zoccali C, Dekker FW, Jager KJ. When do we need competing risks methods for survival analysis in nephrology? *Nephrol Dial Transplant*. 2013;28:2670–2677. https://doi.org/10.1093/ndt/gft355

28. Hödlmoser S, Gehrig T, Antlanger M, et al. Sex differences in kidney transplantation: Austria and the United States, 1978–2018. *Front Med (Lausanne)*. 2022;8:800933. https://doi.org/10.3389/fmed.2021.800933

29. Geroldinger A, Strohmaier S, Kammer M, et al. Sex differences in the survival benefit of kidney transplantation: A retrospective cohort study using target trial emulation. *Nephrol Dial Transplant*. 2023;39:36–44. https://doi.org/10.1093/ndt/gfad137