THE EFFICACY OF ECULIZUMAB IN LUPUS NEPHRITIS PATIENTS WITH COMPLEMENT-MEDIATED THROMBOTIC MICROANGIOPATHY

 

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THE EFFICACY OF ECULIZUMAB IN LUPUS NEPHRITIS PATIENTS WITH COMPLEMENT-MEDIATED THROMBOTIC MICROANGIOPATHY

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Meng
Tan
Meng Tan coral_tm@163.com Peking University First Hospital Renal department Beijing China *
Huanhuan Wang 1976470328@qq.com Affiliated Hospital of Chengde Medical College Renal department Chengde China -
Ying Tan tanying@bjmu.edu.cn Peking University First Hospital Renal department Beijing China -
Minghui Zhao mhzhao@bjmu.edu.cn Peking University First Hospital Renal department Beijing China -
 
 
 
 
 
 
 
 
 
 
 

Lupus nephritis (LN) complicated with thrombotic microangiopathy (TMA) is associated poor prognosis. Optimal use and timing of complement inhibitors in such patients remain poorly characterised. We evaluated the efficacy of the complement C5 inhibitor eculizumab in patients with LN and complement-mediated TMA

We conducted a retrospective study of 11 patients with LN and TMA who were treated with eculizumab between January 2023 and December 2024 in Peking University First Hospital. A control cohort of 27 contemporaneous patients with LN and TMA who did not receive eculizumab was included for comparison .

All eleven patients treated with eculizumab demonstrated microangiopathic hemolytic anemia (elevated lactate dehydrogenase (LDH), schistocytes) and thrombocytopenia. Ten patients had acute kidney injury (AKI) and recieved renal biopsy, and the rest one was end-stage kidney disease (ESKD) at baseline.The mean follow-up was 50 (34-80) weeks.Eight patients underwent genetic testing. Only one patient had an underlying complement mutation (CFB heterozygous, c.221G>A, p.Arg74His) and anthor one had a heterozygous deletion of CFHR1/4. Ten patients discontinued eculizumab after mean duration of 28 weeks (8-48weeks). All patients achieved hematological response, characterized by improved thrombocytopenia and anemia. Among the eight patients who required dialysis at initiation, four patients (50%) became dialysis-independent, including two patients with delayed initiation of eculizumab. Eculizumab treatment group exhibited a higher rate of renal survival (dialysis free) at follow-up compared to controls (60% vs. 37%). Consider all patients showed severe chonic renal damage (CI ≥6) entered ESKD in both eculizumab and control groups, the subgroup of patients with CI＜6 was analyzed. In the subgroup, patients with eculizumab presented higher rate of renal survival compared with those without eculizumab ((75% vs. 43.5%) detaile in table)

Table,  Baseline characteristics and outcomes of AKI patients treated with eculizumab and control group.

Variable

Eculizumab (n=10)

Control (n=27)

Baseline characteristics

Sex, female

9/10 (90%)

23/27 (85.2%)

Age, years

24.5 (15, 39)

28 (14, 62)

Dialysis at baseline

8/10 (80.0%)

22/27 (81.5%)

SLEDAI

26 (20, 38)

17 (9, 39)

Hgb, g/L

59 (33, 106)

77 (54, 116)

Plt, × 109/L

51 (15, 134)

75 (31, 149)

Scr, μmol/L

624.9 (171, 1470)

342.6 (96.8, 847.2)

C3, g/L

0.44 (0.036, 0.94)

0.383 (0.058, 0.62)

C4, g/L

0.103 (0.010, 0.29)

0.103 (0.025, 0.26)

Pathological LN type and grading

II

1/10 (10.0%)

0/27

III, III+V

3/10 (30.0%)

6/27 (22.2%)

IV, IV+V

6/10 (60.0%)

21/27 (77.8%)

AI

7 (1, 17)

9 (4, 16)

CI

3 (0, 9)

3 (0, 10)

Treatment

Pulse-dosed steroids

8/10 (80.0%)

18/27 (66.7%)

Plasma exchange

7/10 (70.0%)

24/27 (88.9%)

Outcome

Renal survival

6/10 (60.0%)

10/27 (37.0%)

Renal survival in patients with CI <6

6/8 (75.0%)

10/23 (43.5%)

Eculizumab treatment was associated with improved hematological parameters and renal recovery in patients with LN complicated TMA, including some with delayed treatment initiation. A trend toward improved renal survival was observed, particularly in those without severe chronic kidney injury, warranting further investigation in larger prospective studies

Kewords