Biomarker studies
Table 2 Multivariable Cox regression analysis
Whole cohort (N=65)* Time to subsequent LN flare‡
Variables at time of urine collection (24months±3months from the LN flare)†
Sustained 30% decline in eGFR§
P value††
HR (95%CI)
P value††
HR (95%CI)
<0.001
CD163 (pg/mmol) MCP-1 (pg/mmol)
1.03 (0.96 to 1.11) 1.12 (1.03 to 1.21) 1.06 (1.02 to 1.10) 1.03 (0.98 to 1.07) 1.01 (0.92 to 1.09) 1.00 (0.99 to 1.00) 0.92 (0.82 to 1.02) 1.00 (0.97 to 1.00) 0.07 (0.01 to 0.32) 0.63 (0.02 to 2.51)
0.43
1.09 (1.05 to 1.14) 1.14 (1.05 to 1.24) 1.07 (1.02 to 1.12) 1.07 (1.01 to 1.12) 1.10 (1.03 to 1.18) 1.58 (1.26 to 1.97) 0.97 (0.78 to 1.19) 1.27 (0.84 to 1.94) 0.73 (0.41 to 1.30) 1.88 (0.34 to 10.2) 2.02 (1.36 to 3.02) 1.16 (1.02 to 1.32) 1.33 (1.01 to 1.74) 2.67 (1.68 to 4.26) 1.04 (0.96 to 1.12) 1.14 (1.04 to 1.25) 1.37 (0.67 to 2.80) 0.85 (0.65 to 1.11) 1.99 (0.86 to 4.19) 0.63 (0.28 to 1.40) 1.18 (0.11 to 12.32) 2.02 (1.19 to 3.44)
0.008 0.002
0.001 0.004
Adiponectin (pg/mmol) sVCAM (pg/mmol) PF4 (pg/mmol) Proteinuria (mg) Serum albumin (g/L) Serum creatinine (umol/L)
0.01
0.19 0.88 0.99 0.12 0.55
0.004
<0.001
0.86 0.24 0.29 0.46
0.001
C3 (g/L) C4 (g/L)
0.93 0.02
1.49 (1.25 to 1.75) <0.001 Subcohort of patients who achieved PERR 24±3months after the LN flare (N=47)* Time to subsequent LN flare¶ Sustained 30% decline in eGFR** HR (95%CI) P value HR (95%CI) P value
Anti-dsDNA Ab (IU/L)
0.01
0.02 0.04
CD163 (pg/mmol) MCP-1 (pg/mmol)
1.14 (1.00 to 1.38) 1.40 (1.11 to 1.76) 1.32 (0.88 to 1.96) 1.04 (1.00 to 1.07) 1.02 (1.93 to 1.11) 1.52 (0.98 to 2.34) 0.85 (0.71 to 1.02) 1.23 (0.67 to 2.27) 0.54 (0.30 to 0.94) 1.30 (0.38 to 4.46) 1.75 (1.40 to 2.42)
0.004
<0.001
Adiponectin (pg/mmol) sVCAM (pg/mmol) PF4 (pg/mmol) Proteinuria (mg) Serum albumin (g/L) Serum creatinine (umol/L)
0.18 0.05 0.75
0.26
0.002
0.052
0.38 0.22 0.10 0.26 0.88
0.09 0.49 0.03 0.66
C3 (g/L) C4 (g/L)
<0.001
0.009
Anti-dsDNA Ab (IU/L)
Predictors of adverse renal outcomes. *Four patients who did not have enough urine to process urinary creatinine were excluded from analysis. Whole cohort: 33 (50.8%) analysed patients experienced a subsequent LN flare and 23 (35.3%) developed a 30% decline in eGFR. PERR cohort: 25 (55%) analysed patients experienced a subsequent LN flare and 10 (20%) patients developed a 30% decline in eGFR. †HRs expressed are for every increase in: 131 pg/mmol of CD163 levels, 27.7 pg/mmol of MCP-1 levels, 1019 pg/mmol of adiponectin levels, 1449 pg/mmol of sVCAM-1 levels, 9.2 pg/mmol of PF4 levels, 200 mg of proteinuria, 2 g/L of serum albumin, 30 µmol/L of serum creatinine, 0.3g/L of C3 and C4 and 25IU/L of anti-dsDNA abs. The value increase in UB was determined by its median value in the subcohort of patients who achieved PERR. ‡Cox regression analysis was adjusted for age, self-reported race, the presence of a prior LN flare, 24-hour protein excretion at the time of the urine collection and serum creatinine at the time of the urine collection. The development of end-stage renal disease (eGFR ≤15) was used as a competing risk for this analysis. §Cox regression analysis was adjusted for age, self-reported race, 24-hour protein excretion and serum creatinine at the time of the urine collection, to avoid overfitting. ¶Cox regression analysis was adjusted for age and self-reported race, to avoid overfitting. **Cox regression analysis was only adjusted for age to avoid overfitting. †† Bold values are significant at p<0.05. anti-dsDNA abs, anti-double-stranded DNA antibodies; CD163, cluster of differentiation 163; eGFR, estimated glomerular filtration rate; LN, lupus nephritis; MCP-1, monocyte chemoattractant protein-1; PERR, primary efficacy renal response; PF4, platelet factor 4; sVCAM-1, soluble vascular cell adhesion molecule-1; UB, urinary biomarker.
of the UBs with an AUC of 0.82 (95% CI 0.68 to 0.95), whereas CD163, which had an AUC of 0.65 (95% CI 0.45 to 0.85) demonstrated only a fair discriminative ability. Of
the conventional biomarkers, anti-dsDNA abs exhibited the highest AUC (0.77, 95% CI 0.66 to 0.81) for detecting patients at risk of developing a subsequent LN flare and
7
Baker R, et al . Lupus Science & Medicine 2026; 13 :e001724. doi:10.1136/lupus-2025-001724
Powered by FlippingBook