Abstract: FR-PO0632
Baricitinib Reduces Albuminuria in APOL1-Mediated Kidney Disease: A Pilot Randomized Trial
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
- Olabisi, Opeyemi A., Duke University School of Medicine, Durham, North Carolina, United States
- Wolf, Myles, Weill Cornell Medicine, New York, New York, United States
- Barrett, Nadine, Wake Forest University School of Medicine, Winston-Salem, North Carolina, United States
- Chakraborty, Hrishikesh, Duke University School of Medicine, Durham, North Carolina, United States
- Li, Guojie, Duke University School of Medicine, Durham, North Carolina, United States
- Datta, Somenath, Duke University School of Medicine, Durham, North Carolina, United States
Background
APOL1-mediated kidney disease (AMKD) is a leading cause of progressive CKD among individuals of African ancestry and is characterized by albuminuria and limited responsiveness to conventional therapies. Emerging experimental and human data implicate activation of the JAK–STAT signaling pathway as a central mediator of APOL1-induced podocyte injury. We conducted a pilot randomized trial to evaluate whether pharmacologic inhibition of JAK1/2 with baricitinib reduces albuminuria in AMKD.
Methods
JUSTICE was a double-blind, placebo-controlled study in which participants with AMKD—defined by biopsy-proven FSGS or hypertension-attributed CKD (HTN-CKD) with an APOL1 high-risk genotype—were randomized 2:1 to baricitinib or placebo for 6 months. The primary efficacy endpoint was percent change in urinary albumin-to-creatinine ratio (UACR) from baseline to month 6. The primary safety endpoint was hemoglobin decrease ≥1 g/dL. UACR, eGFR, and hemoglobin were assessed longitudinally.
Results
Five participants completed the study (baricitinib, n=4; placebo, n=1). Baricitinib reduced geometric mean UACR by 32.3% at month 6, compared with a 10.9% decrease in the placebo-treated participant. Two of four baricitinib-treated participants achieved UACR reductions ≥30%, with responses ranging from minimal change to >50% reduction. eGFR remained stable during treatment. Hemoglobin decreased by ≥1 g/dL in two baricitinib-treated participants and in none receiving placebo. Among participants with post-treatment follow-up, UACR increased toward pretreatment levels during washout.
Conclusion
In this pilot randomized study, baricitinib reduced albuminuria in AMKD, with evidence of inter-individual heterogeneity in treatment response. The increase in albuminuria after drug withdrawal suggests that JAK–STAT pathway activity contributes to dynamic, reversible disease processes in APOL1-mediated kidney injury. These findings provide clinical support for targeting JAK–STAT signaling in AMKD and highlight the need for larger studies to define predictors of therapeutic response.
Acknowledgment
We thank Leshon Matthews and Maurice Smith, clinical research coordinators, for outstanding coordination of participant recruitment, study visits, regulatory documentation, and data collection for this trial. We also thank Karen Soldano, Akhil Reddy Gogula and Emily Burke, for providing technical support.
Funding
- Other NIH Support – Eli Lilly