Abstract: TH-PO0412
Environmental Determinants of CKD Progression in African Ancestry with Lupus Nephritis
Session Information
- Glomerular Diseases: Autoimmune Diseases
October 22, 2026 | Location: Exhibit Hall A, Convention Center
Abstract Time: 10:00 AM - 12:00 PM
Category: Glomerular Diseases
- 1401 Glomerular Diseases: Mechanisms, including Podocyte Biology
Authors
- Caster, Dawn J., University of Louisville School of Medicine, Louisville, Kentucky, United States
- Dubbaka, Anjali, University of Louisville School of Medicine, Louisville, Kentucky, United States
- Bridges, Madeline Elizabeth, University of Louisville School of Medicine, Louisville, Kentucky, United States
- Isaacs, Susan M., University of Louisville School of Medicine, Louisville, Kentucky, United States
- Wilkey, Daniel Wade, University of Louisville School of Medicine, Louisville, Kentucky, United States
- Xu, Jianxiang, University of Louisville School of Medicine, Louisville, Kentucky, United States
- Cummins, Timothy, University of Louisville School of Medicine, Louisville, Kentucky, United States
- Powell, David W., University of Louisville School of Medicine, Louisville, Kentucky, United States
- Merchant, Michael, University of Louisville School of Medicine, Louisville, Kentucky, United States
Background
Lupus nephritis (LN), a severe complication of systemic lupus erythematosus, can progress to chronic kidney disease (CKD) and end-stage kidney disease (ESKD). Environmental factors (e.g., air quality; heavy metals) have been implicated in autoimmune diseases and CKD progression, but their role in LN is poorly understood. We hypothesized that heavy metal exposure (a) contributes to CKD progression in LN patients, and (b) accelerates CKD progression in those with genetic risk factors, such as ApoL1 risk variants in individuals of West African descent.
Methods
We identified 20 LN patients of African ancestry from the UofL Glomerular Disease biorepository (IRB 01.0536) for serum and urine metallomics by inductively coupled plasma-mass spectrometry (ICP-MS), targeted proteomics for apolipoprotein L1 (ApoL1) G0, G1, and G2 proteotyping, and discovery serum proteomics. Biospecimens were age-matched between LN CKD patients who progressed to ESKD or ≥50% eGFR decrease (CKD EPI 2021) within 10 years of diagnosis (P, n=10) and those without (NP, n=10). Metal and protein differences were compared by ANOVA with post-hoc t-test (p<0.05). Risk allele differences were compared by Fisher exact tests (p<0.05).
Results
60% of LN patients had ≥1 G1 or G2 risk allele and 15% had two risk alleles. LN progressors were more likely to carry ≥1 G2 allele (p<0.03). Three metals (Cd, Tl, Th) were significantly increased in NP serum (p<0.05); two (V, Sb) were increased in P urine (p<0.05); and one (Th) was increased in NP urine (p<0.001). Of 458 proteins, 25 were differentially abundant (|log2FC|>0.5, p<0.05): 16 increased in P serum and 7 in NP serum. Multivariate adjustment using urine metallomics and genotype enhanced proteomic differences. Hierarchical clustering identified three clades among the 25 proteins associated with future CKD progression.
Conclusion
Future ESKD development in individuals of African descent with LN may be associated with abundant serum proteins and the urine or serum metallome, and influenced by the G2 ApoL1 risk allele. These proteins reflect complement/neutrophil/IgA-IgM function, insulin/adipokine/cytokine signaling, and macrophage activation. Urine metallomics suggest differences in metals regulating macrophage and NFkB signaling. These data support the hypothesis that CKD progression in LN is modified by both environment and genetic background in patients of African descent.
Acknowledgment
We gratefully acknowledge the contributions of the clinical faculty in the UofL Division of Nephrology and Hypertension as well as the patients and their families for their support of translational research. Additional support is acknowledged through: P30ES030283 (MLM, DJC, LC), P20 GM113226 (MLM) and R01 DK126777 (DJC, DWP)
Funding
- NIDDK Support