Abstract: TH-PO0366
Proteinuria Reduction in Nephrotic Syndrome Is Associated with Threshold-Dependent Lipoprotein Changes
Session Information
- Glomerular Diseases: Genetics to Therapeutics
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
- Hwang, Michael, National Institutes of Health, Bethesda, Maryland, United States
- Brown, Rebecca, National Institutes of Health, Bethesda, Maryland, United States
- Auh, Sungyoung, National Institutes of Health, Bethesda, Maryland, United States
- Sampson, Maureen, National Institutes of Health, Bethesda, Maryland, United States
- Howard, Lilian, National Institutes of Health, Bethesda, Maryland, United States
- Waldman, Meryl, National Institutes of Health, Bethesda, Maryland, United States
Background
Dyslipidemia in nephrotic syndrome (NS) contributes to atherosclerotic cardiovascular disease (ASCVD) and is driven by elevations in apolipoprotein B (ApoB)-containing lipoproteins, including low-density lipoproteins (LDLs) and triglyceride-rich lipoproteins (TRLs). It is unclear if reductions in proteinuria lead to continuous improvements in lipids or if a threshold effect exists beyond which further proteinuria reduction confers no additional lipid benefit
Methods
We studied 22 adults (59% male; age 48 ± 12 years) with membranous nephropathy enrolled in a 2-year treatment trial of rituximab plus cyclosporine. All had proteinuria >3.5 g/day at baseline and contributed up to 6 measurements of 24-hour proteinuria and NMR lipoprotein profiles. Segmented mixed-effect models assessed associations between lipids and proteinuria. Proteinuria thresholds were estimated for lipid parameters demonstrating biphasic relationships with proteinuria.
Results
ApoB had a biphasic relationship with proteinuria, with a threshold at 403 mg/day (95% CI 225-721), above which proteinuria was positively associated with ApoB and below which no association was seen (Figure 1). Thresholds varied across lipoprotein particle types: LDL particles 645 mg/day (95% CI 231-1805) and TRL particles 158 mg/day (95% CI 80-311). High-density lipoprotein (HDL) particles and aggregate measures of LDL, TRL, and HDL particle size were not associated with proteinuria.
Conclusion
Proteinuria was associated with threshold-dependent changes in ApoB-containing lipoproteins, beyond which lipid abnormalities may uncouple from proteinuria and reflect residual ASCVD risk independent of NS. These findings may have implications for the management of lipids in patients with NS.
Funding
- NIDDK Support