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Analyses of Proteinuria, Renal Infiltration of Leukocytes, and Renal Deposition of Proteins in Lupus-prone MRL/lpr Mice
Published on: June 8, 2022
Combined cyclosporine A and urolithin A therapy ameliorates murine lupus nephritis
R Ganugula1,2,3,4, K T Babalola1,2, M Arora1,2,3,4
1The Center for Convergent Bioscience and Medicine (CCBM), The University of Alabama, Tuscaloosa, Alabama, 35487, United States.
Abstract:
Monotherapies for lupus nephritis (LN) often fail to fully control the disease's hallmark, renal inflammation and immune complex deposition. This study investigates a novel combination therapeutic strategy using urolithin A (UA), a multifaceted anti-inflammatory and antioxidant agent, with cyclosporine A (CsA), an established immunosuppressant. The combination therapy's superior efficacy is evidenced by a robust reduction in immunoglobulin G (IgG) anti-dsDNA levels, with markedly improved renal function. The treatment also effectively mitigated immune complex deposition and multiple inflammatory chemokines, including I309, IL-16, and MIP-3. This alleviated kidney damage and suppressed lymphocyte infiltration. We found that CsA alone was ineffective across the analyzed markers, while UA alone produced only a modest effect, highlighting the complementary action of their combination. These findings underscore the potent anti-inflammatory and antioxidant properties of UA and suggest that combining it with CsA offers a more robust strategy for controlling inflammation and preserving renal integrity in LN. Given the FDA-approved status of CsA and UA's "generally recognized as safe" (GRAS) classification, this combination therapy presents a promising and practical clinical pathway for the treatment of lupus nephritis.
Insights
This study shows that combining urolithin A (UA) with cyclosporine A (CsA) effectively treats lupus nephritis (LN). The combination significantly reduces kidney inflammation and improves renal function, outperforming either drug alone.
Area of Science:
- Nephrology
- Immunology
- Pharmacology
Background:
- Monotherapies for lupus nephritis (LN) often fail to fully control renal inflammation and immune complex deposition.
- Urolithin A (UA) is a potent anti-inflammatory and antioxidant agent, while cyclosporine A (CsA) is an established immunosuppressant.
Purpose of the Study:
- To investigate the efficacy of a combination therapy using UA and CsA for treating lupus nephritis.
- To evaluate the impact of this combination on renal function, inflammation, and immune markers.
Main Methods:
- Assessed the effects of UA and CsA monotherapies versus their combination on key markers in lupus nephritis.
- Measured immunoglobulin G (IgG) anti-dsDNA levels, renal function, immune complex deposition, and inflammatory chemokines (I309, IL-16, MIP-3).
- Evaluated lymphocyte infiltration and kidney damage.
Main Results:
- The combination of UA and CsA demonstrated superior efficacy compared to monotherapies.
- Marked improvement in renal function and significant reduction in IgG anti-dsDNA levels were observed.
- Effective mitigation of immune complex deposition, inflammatory chemokines, lymphocyte infiltration, and kidney damage.
Conclusions:
- UA and CsA combination therapy offers a robust strategy for controlling inflammation and preserving renal integrity in lupus nephritis.
- UA's anti-inflammatory and antioxidant properties complement CsA's immunosuppressive action.
- This combination presents a promising and practical clinical approach for LN treatment, leveraging FDA-approved CsA and GRAS-classified UA.
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