Lupus Science & Medicine
C3 had a good discriminative ability (AUC 0.75 (95% CI 0.58 to 0.99). Using optimal cut-offs determined by Youden’s index, MCP-1 showed the highest sensitivity (92%) and NPV (96%) for predicting an LN flare within the next 3 years, although its specificity and PPV were relatively low (66% and 48%, respectively). In contrast, C3 levels demon- strated the highest specificity (100%), and PPV (100%); however, the sensitivity was low (55%). Having any two of the four biomarkers elevated (CD163, MCP-1, C3 and anti-dsDNA abs) yielded a sensitivity of 83% and NPV of 94%, and −LR of 0.1. When examining specific combinations of biomarkers, all combinations had excellent specificities (all above 90%), and all except for CD163 + MCP-1 had good to excellent PPVs and had +LR above 10 (tables 3 and 4). Sustained 30% decline in eGFR Four of the UBs assessed (CD163, MCP-1, adiponectin and PF4) and anti-dsDNA abs had a significant associa- tion with a sustained 30% decline in eGFR. MCP-1 had the highest AUC (0.82, 95% CI 0.65 to 0.99), demon- strating an excellent discriminative ability. Adiponectin also had a good discriminative ability AUC (0.80, 95% CI 0.59 to 1.00). Adiponectin showed the best diagnostic accuracy for detecting patients at risk of a sustained 30% decline in eGFR with good sensitivity (80%), excellent NPV (98%) and specificity (95%), and excellent +LR of 16.8. All the biomarkers had excellent NPVs (above 90%) and MCP-1 also had an excellent +LR (10). All of the combinations also had excellent specificities and NPVs, with most achieving excellent +LRs, except for the combinations of CD163 + PF4, MCP-1 + PF4and PF4 + anti-dsDNA Ab, which had +LRs below 10 (tables 3 and 4). DISCUSSION We evaluated whether elevated levels of five UBs— CD163, MCP-1, adiponectin, sVCAM and PF4—meas- ured 24±3 months after an LN flare were associated with adverse long-term renal outcomes, including subsequent LN flares and/or a decline in kidney function. Our find- ings show that among patients who had achieved PERR 2 years after an LN flare, higher levels of CD163 and MCP-1 were associated with an increased risk of experiencing a future LN flare, and elevated levels of CD163, MCP-1, adiponectin and PF4 were associated with a decline in kidney function. Achieving a complete renal response or PERR at 2 years from the LN flare improves long-term renal outcomes. 5 29 30 However, patients who achieve a good clinical response are still at risk of subsequent LN flares 31 and decline in kidney function. 5 6 In the current study, 54% of patients who achieved PERR 2 years after an LN flare experienced a subsequent renal flare, and 20% showed a clinically significant decline in kidney function over the following 5 years, which is similar to what has
been reported previously. 5 6 Underscoring the limitation of using proteinuria as a reliable indicator of treatment success. In recent decades, significant efforts have been made to identify and validate UBs with the ability to reflect kidney histological activity, potentially assisting not only in the detection of LN but also in patient surveillance, thereby guiding therapeutic decisions. CD163, MCP-1, adiponectin, sVCAM and PF4 are UBs that have been *11 (23%) experienced their LN flare within the next 3 years, and 5 (11%) developed this decline in eGFR within the next 5 years. anti-dsDNA Ab, anti-double-stranded DNA antibody; AUC, area under the curve; 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. Table 3 The ability of the predictive biomarkers to discriminate between patients at risk for an adverse renal outcome Predictive biomarkers AUC (95%CI) Development of a subsequent LN flare in the following 3 years* CD163 0.65 (0.45 to 0.85) MCP-1 0.82 (0.68 to 0.95) C3 0.75 (0.58 to 0.99) Anti-dsDNA Ab 0.77 (0.66 to 0.81) CD163 + MCP-1 0.74 (0.55 to 0.93) CD163 + C3 0.76 (0.57 to 0.95) CD163 + anti-dsDNA Ab 0.76 (0.56 to 0.96) MCP-1 + C3 0.80 (0.64 to 0.95) MCP-1 + anti-dsDNA Ab 0.83 (0.67 to 0.98) c3_SU + anti-dsDNA Ab 0.84 (0.68 to 1.00) Development of a sustained 30% decline in eGFR in the following 5 years* CD163 0.73 (0.43 to 1.00) MCP-1 0.82 (0.65 to 0.99) Adiponectin 0.80 (0.59 to 1.00) PF4 0.74 (0.49 to 0.99) Anti-dsDNA Ab 0.77 (0.75 to 0.82) CD163 + adiponectin 0.82 (0.60 to 1.00) CD163 + PF4 0.70 (0.38 to 1.00) CD163 + MCP-1 0.66 (0.33 to 0.99) CD163 + anti-dsDNA Ab 0.82 (0.60 to 1.00) MCP-1 + adiponectin 0.80 (0.66 to 1.00) MCP-1 + PF4 0.69 (0.32 to 1.00) MCP-1 + anti-dsDNA Ab 0.82 (0.59 to 1.00) Adiponectin + PF4 0.80 (0.54 to 1.00) Adiponectin + anti-dsDNA Ab 0.94 (0.85 to 1.00) PF4 + anti-dsDNA Ab 0.96 (0.91 to 1.00) Subcohort of patients who achieved PERR 24±3months after the LN flare (n=47).
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Baker R, et al . Lupus Science & Medicine 2026; 13 :e001724. doi:10.1136/lupus-2025-001724
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