Kidney Week

Abstract: FR-PO0640

Characteristics and Progression of Glomerular Disease in Patients with APOL1-Associated Kidney Disease

Session Information

• Glomerular Diseases: Clinical, Outcomes, and Therapeutics Research - ANCA/FSGS
  October 23, 2026 | Location: Exhibit Hall A, Convention Center
  Abstract Time: 10:00 AM - 12:00 PM

Category: Glomerular Diseases

• 1402 Glomerular Diseases: Clinical, Outcomes, and Therapeutics

Authors

• Helmuth, Margaret, University of Michigan Michigan Medicine, Ann Arbor, Michigan, United States

Margaret Helmuth, MA

• Demas, Caroline, University of Michigan Michigan Medicine, Ann Arbor, Michigan, United States

Caroline Demas, MPH

• Chen, Dhruti P., The University of North Carolina at Chapel Hill, Chapel Hill, North Carolina, United States

Dhruti P. Chen, MD, FASN

• Fischman, Clara, University of Pennsylvania, Philadelphia, Pennsylvania, United States

Clara Fischman, MD, MS

• Vasquez-Rios, George, Renal Medicine Associates, Albuquerque, New Mexico, United States

George Vasquez-Rios, MD, MSCR, FASN

• Gibson, Keisha L., The University of North Carolina at Chapel Hill, Chapel Hill, North Carolina, United States

Keisha L. Gibson, MD, MPH, FASN

• Parekh, Rulan S., Women's College Hospital, Toronto, Ontario, Canada

Rulan S. Parekh, MD, MS, FASN

• Mariani, Laura H., University of Michigan Michigan Medicine, Ann Arbor, Michigan, United States

Laura H. Mariani, MD, MS, FASN

• Smith, Abigail R., Northwestern University, Evanston, Illinois, United States

Abigail R. Smith, PhD

Background

Apolipoprotein L1 (APOL1) kidney disease (AKD) is a major cause of kidney failure (KF) in individuals of African ancestry, driven by high-risk genotypes that increase susceptibility to progressive glomerular injury. Emerging evidence also suggests CKD risk may vary by APOL1 allelic dose and specific haplotypes, with possible risk even from a single risk allele.

Methods

Patients from the Cure Glomerulonephropathy Network (CureGN) and Nephrotic Syndrome Study Network (NEPTUNE) with at least 1 APOL1 risk allele (RA), UPCR ≥0.5g/g or eGFR between 25-90mL/min/1.73m² (index), 12 months (m) of follow-up, and ≥1 UPCR/eGFR measurement 12-24m post index were included. Change in eGFR across 24m was assessed using linear mixed models. Time to 40% eGFR decline and KF was assessed using Cox regression models.

Results

251 patients were included; 122 (49%) and 129 (51%) with 2 and 1 RAs, respectively were followed for a median (IQR) of 69m (37,99). Median age at index was 29 (15,49) years, 35% were <18 years old, and 49% were male. Glomerular disease diagnoses were 19% MCD, 55% FSGS, 18% MN and 8% IgA. Median (IQR) eGFR and UPCR at index were 68 (41,83) mL/min/1.73m² and 3.1 (1.3,6.2) g/g, respectively. Mean eGFR decline over 24m was -4.1 (-6.1, -2.0) mL/min/1.73m²/yr overall and was faster among patients with 2 RAs vs 1 RA (-7.1 [-9.8, -4.5]) vs (-1.3 [-4.4, 1.7]). Probability of 40% eGFR decline at 24 and 60m were 0.30 (0.24, 0.36) and 0.47 (0.40, 0.54), respectively; estimates were higher among patients with 2 vs 1 RA at both 24m (0.44 vs 0.26) and 60m (0.56 vs 0.38). Among 203 patients who did not progress to KF within 24m, 55 (27%) achieved complete remission (CR; UPCR <0.3 g/g), 21% vs 33% of 2 vs 1 RA respectively. CR or ≥50% reduction in UPCR was achieved by 126 patients (62%), with similar rates across RA groups (63% and 61%). Median UPCR reduction over 24m was 67% and similar between groups. Achieving CR was associated with an 83% lower hazard of KF (HR=0.17 [0.05,0.54]); 75% in patients with 2 RAs (HR =0.25 [0.06,1.03]). Achieving CR or ≥50% reduction in UPCR was associated with a 67% lower KF hazard overall (HR=0.33 [0.18,0.59]) and 48% (HR=0.52 [0.26,1.06]) in patients with 2 RAs.

Conclusion

Proteinuria remission or significant reduction is strongly associated with improved kidney outcomes in AKD patients with 1 and 2 RAs, suggesting its potential role as a key prognostic marker and treatment target.

Funding

• NIDDK Support