Biomarker studies
Table 1 Continued
Achieved PERR 24±3months after the LN flare (n=50)
Did not achieve PERR 24±3months after the LN flare (n=19)
Whole cohort (n=69)
P value*
Variables 24±3 months after the LN flare Anti-dsDNA Ab (IU/ml)†
0.01 0.10 0.73 0.03 0.17
25 (5–57)
17 (4–42)
53 (10–101) 0.8 (0.7–1.0) 0.2 (0.1–0.2)
C3, g/L C4, g/L
0.9 (0.8–1.1) 0.2 (0.1–0.2) 65 (57–84)
1.0 (0.8–1.1) 0.2 (0.1–0.2)
Creatinine (µmol/L)
63.5 (53.3–74.3) 108.4 (86.1–128.2) 44.0 (41.0–46.0)
76.0 (62.0–93.0) 90.2 (80.2–122.9) 34.0 (32.0–38.5)
eGFR
105.7 (84.3–128.3) 43.0 (37.0–45.3)
<0.01 <0.01 <0.01
Serum albumin, g/L
24-hour protein excretion (g)
0.4 (0.2–0.7) 8.4 (5.0–12.5)
0.3 (0.2–0.4) 6.2 (4.0–10.0)
1.5 (0.9–2.4)
Prednisone dose (mg)
15.0 (10.0–15.0)
Hydroxychloroquine, n (%) Immunosuppressive, n (%)
62 (89.9) 67 (97.1) 19 (27.5) 45 (65.2)
44 (88)
18 (94.7) 19 (100) 3 (15.8) 13 (68.4) 2 (10.5)
0.79 0.99 0.24 0.78 0.07 0.47 0.89
48 (96.0) 16 (32.0) 32 (64.0)
Azathioprine, n (%) Mycophenolate, n (%)
Cyclophosphamide, n (%) Calcineurin inhibitors, n (%)
2 (2.9) 2 (2.9)
0 (0)
1 (2.0) 33 (66)
1 (5.3)
Renin-angiotensin aldosterone system inhibitors, n (%)
46 (66.6)
13 (68.4)
All values are reported as median (25%, 75%); n (%). *Statistical significance determined through Fisher’s exact test for categorical variables and through the Mann-Whitney test for continuous variables. Bold values are significant at p<0.05. †Reference value for positivity of anti/dsDNA ab defined as >7. Anti-dsDNA ab, anti-double-stranded DNA antibody; eGFR, estimated glomerular filtration rate (measured with CKD-EPI equation); LN, lupus nephritis; PERR, primary efficacy renal response; SLEDAI-2K, SLE Disease Activity Index 2000.
adiponectin: HR 1.06 (1.02–1.10), p=0.002). Further- more, higher levels of all UBs were associated with a 30% decline in eGFR (CD163: HR 1.09 (1.05–1.14), p<0.001; MCP-1: HR 1.14 (1.05–1.24), p=0.001; adiponectin: HR 1.07 (1.02–1.12), p=0.004; sVCAM: HR 1.07 (1.01–1.12), p=0.01; PF4: HR 1.10 (1.03–1.18), p=0.004). In both the univariable and multivariable analysis, anti-dsDNA abs levels measured 24±3 months after the LN flare were associated with the development of a subsequent LN flare (HR 1.49 (1.25–1.75), p=0.02) and a 30% decline in eGFR (HR 2.02 (1.36–3.02), p<0.001). C3 levels meas- ured 24±3 months after the LN flare were also associ- ated with a subsequent LN flare (HR 0.07 (0.01–0.32), p=0.001), but not with a sustained 30% decline in eGFR. Likewise, the proteinuria levels measured 24±3 months after the LN flare were associated with a sustained 30% decline in eGFR (HR 1.58 (1.26–1.97), p=<0.001), but not with subsequent LN flares. In the univariate analysis, serum albumin and serum creatinine were associated with an increased risk of developing a 30% decline in eGFR, but the significance was lost in the multivariable analysis (table 2 and online supplemental table 1). To better determine the utility of the UBs in patients achieving clinical control, we determined the association between the UBs levels 24±3 months after the LN flare and the development of renal outcomes in the subcohort
of patients who achieved PERR. In this subcohort of patients, 27 (54%) (26 (55%) of patients with available corrected UB) experienced a subsequent LN flare with a median time to flare (IQR) of 3.5 (1.67–6.87) years, and 10 (20%) had a 30% decline in eGFR at a median time of 4.38 (3.73–5.33) years after their 24-month urinary sample collection. Univariable and multivariable models showed that patients with higher levels of CD163 and MCP-1 had a higher risk of developing a subsequent renal flare (CD163: HR 1.14 (1.00–1.938, p=0.01; MCP-1: HR 1.40 (1.11–1.76), p=0.004), whereas higher levels of CD163, MCP-1, adiponectin and PF4 were associated with a 30% decline in eGFR (CD163: HR 1.16 (1.02–1.32), p=0.02; MCP-1: HR 1.33 (1.01–1.74), p=0.04; adiponectin: HR 2.67 (1.68–4.26), p<0.001; PF4: HR 1.14 (1.04–1.25), p=0.002). Conventional biomarkers, such as anti- dsDNA abs and C3 levels, were associated with a subse- quent LN flare (HR 1.75 (1.40–2.42), p<0.001 and HR 0.54 (0.30–0.94), p=0.03) and anti-dsDNA abs was also associated with a 30% decline in eGFR (HR 2.02 (1.19– 3.44), p=0.009). 24-hour proteinuria levels showed a non-significant association with the development of a subsequent flare, but were not associated with the risk of a 30% decline in eGFR (table 2 and online supple- mental table 1).
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Baker R, et al . Lupus Science & Medicine 2026; 13 :e001724. doi:10.1136/lupus-2025-001724
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