Related Experiment Video
Updated: May 25, 2025
10:37
Comparative Proteomic Analysis of Whole Kidney, Medulla, and Cortical Tubules in Diabetic Pathogenesis of Kidney Injury in Mice
Published on: May 2, 2025
77
APOL1 Dynamics in Diabetic Kidney Disease and Hypertension
Pravin C Singhal1, Karl Skorecki2,3,4
1Department of Medicine, Feinstein Institute for Medical Research, Zucker School of Medicine, Hempstead, NY 11549, USA.
Biomolecules
|February 26, 2025
Summary
APOL1 risk variants cause kidney disease but don't consistently worsen diabetic kidney disease. This may be because high glucose and APOL1 risk variants already maximize kidney injury pathways, making them unresponsive to further damage.
Area of Science:
- Nephrology
- Genetics
- Molecular Biology
Background:
- APOL1 Renal Risk Variants (APOL1RRVs) are linked to chronic kidney disease (CKD) and APOL1-Mediated Kidney Disease (AMKD).
- APOL1RRVs' impact on diabetic kidney disease (DKD) progression is unclear, despite DKD being a leading cause of End-Stage Kidney Disease (ESKD).
- Renin-Angiotensin System (RAS) activation is crucial in DKD and may contribute to AMKD.
Purpose of the Study:
- To investigate the discrepancy in APOL1RRVs' effect on DKD versus other CKD etiologies.
- To explore the mechanistic links between RAS, miR193a, and kidney injury in DKD and AMKD.
- To re-examine the role of hypertension in AMKD progression.
Main Methods:
- Review of in vitro and in vivo studies on RAS activation and kidney cell injury.
- Analysis of podocyte expression of miR193a in high glucose and APOL1RRV models.
- Discussion of clinical reports and genetic data (Mount Sinai BioMe repository) on hypertension and APOL1RRVs.
Main Results:
- Both high glucose and APOL1RRVs increase miR193a, a glomerulosclerosis mediator, potentially saturating injury pathways in DKD.
- The role of hypertension in AMKD progression is debated, with some studies suggesting it's a consequence rather than a cause.
- Genetic data indicates hypertension may precede GFR decline in individuals with APOL1RRVs.
Conclusions:
- The maximal effect of high glucose and APOL1RRVs on miR193a may explain why APOL1RRVs don't consistently worsen DKD.
- Further studies are needed to validate hypothesized models explaining the dissociation between DKD and AMKD and the temporal relationship of hypertension in AMKD.
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