Abstract: PUB215
Emerging Therapeutic Strategies for APOL1-Mediated Kidney Disease (AMKD)
Session Information
Category: Glomerular Diseases
- 1402 Glomerular Diseases: Clinical, Outcomes, and Therapeutics
Authors
- Rodriguez-Cruz, Zulmarie, Universidad Autonoma de Guadalajara, Zapopan, Jal., Mexico
- Aquino-Dávila, Jean Carlos, Universidad Autonoma de Guadalajara, Zapopan, Jal., Mexico
- Ruiz-Diaz, Juan A, Universidad Autonoma de Guadalajara, Zapopan, Jal., Mexico
- Rivera Rivera, Paola Michelle, Universidad Autonoma de Guadalajara, Zapopan, Jal., Mexico
- Cartagena-Toledo, Alondra Sofia del Coral, Universidad Autonoma de Guadalajara, Zapopan, Jal., Mexico
- Molina-Ortiz, Alondra Marie, Universidad Autonoma de Guadalajara, Zapopan, Jal., Mexico
- Ramirez-Perez, Sergio, Universidad de Guadalajara, Guadalajara, Jal., Mexico
- Nava-Zavala, Arnulfo-Hernán, Universidad Autonoma de Guadalajara, Zapopan, Jal., Mexico
- Romero-García, Patricia Anaid, Universidad Autonoma de Guadalajara, Zapopan, Jal., Mexico
- Aranda, Andres, Universidad Autonoma de Guadalajara, Zapopan, Jal., Mexico
- Alvarez, Lucia E, Universidad Autonoma de Guadalajara, Zapopan, Jal., Mexico
- Ahmad, Kashif A, Universidad Autonoma de Guadalajara, Zapopan, Jal., Mexico
Background
APOL1 Mediated Kidney Disease is a chronic condition linked to two high-risk kidney-expressed genetic variants: G1/G2. These increase kidney injury risk through mechanisms such as mitochondrial dysfunction, potassium depletion, intracellular trafficking disruption, and autophagy failure. Although they are still unclear. Currently, no approved therapies exist for the APOL1 variant effects and prevent kidney damage. We highlight the safety, efficacy, and mechanisms of emerging therapeutic approaches for AMKD.
Methods
A literature review using PubMed identified 12 of 28 articles meeting inclusion criteria. Extracted data included study year, author, type, objectives, sample size, population, methods, key findings, conclusions, and biases. Three therapeutic strategies were identified: small molecule inhibitors, APOL1 antisense oligonucleotides, and JAK/STAT pathway inhibitors.
Results
Small molecule inhibitors, such as Inaxaplin, have demonstrated early efficacy in reducing proteinuria by counteracting APOL1-induced ion dysregulation. APOL1 antisense oligonucleotides have also shown promising potential by suppressing APOL1 expression and decreasing kidney injury in preclinical mouse models. Additionally, JAK-STAT inhibitors, like Baricitinib, may help to reduce inflammation that directly contributes to renal injury.
Conclusion
Emerging APOL1-targeted therapies show promise in slowing disease progression by addressing key molecular mechanisms. With time, these treatments could become the first disease-modifying options for APOL1 kidney disease, while broader factors like genetics and lifestyle also warrant investigation.