Abstract: TH-OR042
Kidney-Specific Four-Protein Index Outperforms Conventional Measures for Detecting Early Kidney Damage in Lupus Nephritis and Diabetic Kidney Disease
Session Information
- Glomerular Precision Nephrology: Novel Mechanisms, Biomarkers, and Therapeutic Targets
November 06, 2025 | Location: Room 310A, Convention Center
Abstract Time: 05:20 PM - 05:30 PM
Category: Glomerular Diseases
- 1402 Glomerular Diseases: Clinical, Outcomes, and Therapeutics
Authors
- Nerenberg, Mike, Exagen Inc, Vista, California, United States
- Taghavi, Sepehr, Exagen Inc, Vista, California, United States
- Silva, Ines A, Exagen Inc, Vista, California, United States
- Matthew Vasquez, Jacob, Exagen Inc, Vista, California, United States
- O'Malley, Tyler, Exagen Inc, Vista, California, United States
- Kyttaris, Vasileios C, Beth Israel Deaconess Medical Center, Boston, Massachusetts, United States
Background
Early detection of kidney damage in diabetic kidney disease (DKD) and lupus nephritis (LN) remains challenging. Conventional markers (creatinine, eGFR, albuminuria) detect damage late. We hypothesized an index of four kidney-specific plasma proteins (UMOD, MIOX, HPSE, AREL1), each reflecting distinct renal pathways, could detect early renal damage better than standard measures.
Methods
UMOD, MIOX, HPSE, AREL1 were measured in plasma from active LN (n=31), early-stage DKD (PERL, n=49, mean eGFR=66), late-stage DKD (FIND, n=50, mean eGFR=21), and matched apparently healthy volunteers (AHV, n=99). Logistic regression-derived DKD and LN indices were compared to eGFR by ROC analysis. Data from PERL and FIND were provided by NIDDK CR.
Results
Indices robustly discriminated DKD (early AUC=0.92, late AUC=0.97) and LN (AUC=1.00) from AHV, significantly outperforming eGFR (DKD early AUC=0.81, late AUC=0.94; LN AUC=0.27). Biomarker indices also surpassed iohexol GFR, albuminuria, and cystatin C in detecting early DKD, and UPCR for early LN.
Conclusion
A biomarker index using UMOD, MIOX, HPSE, AREL1 detects early kidney damage more sensitively than conventional markers, enabling earlier diagnosis, patient stratification, and improved clinical management.
Demographics
| Total (N=291) | AHV (DKD Matched) (N=99) | PERL (Early Disease) (N=49) | FIND (Late Disease) (N=50) | AHV (LN Matched) (N=31) | LN (N=31) | |
| Subject is Female - n(%) | 173 (59.5%) | 47 (47.5%) | 26 (53.1%) | 21 (42.0%) | 26 (83.9%) | 26 (83.9%) |
| Subject is White - n(%) | 137 (47.1%) | 47 (47.5%) | 35 (71.4%) | 12 (24.0%) | 11 (35.5%) | 11 (35.5%) |
| Age - Mean(SD) | 50.0 (14.6) | 56.6 (11.0) | 55.0 (7.8) | 58.1 (13.3) | 34.7 (9.5) | 35.0 (9.8) |
| eGFR - Mean(SD) | 74.6 (35.3) | 86.6 (22.7) | 66.0 (16.0) | 20.6 (29.0) | 88.0 (16.6) | 99.3 (30.5) |
Funding
- Commercial Support – Exagen Inc.