What is it about?
Our research indicates that inhibiting the mineralocorticoid (MR) signaling can protect against glomerular damage and kidney failure by preventing the pathological activation of parietal epithelial cells. These findings highlight the potential of MR antagonists in these diseases. Furthermore, the use of glucocorticosteroids with minimal mineralocorticoid activity may be preferable in these contexts.
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Why is it important?
The 2021 KDIGO guidelines recommend renin-angiotensin system blockade, optimal blood pressure management, and dietary salt restriction for treating maladaptive FSGS, while primary FSGS should be treated primarily with high-dose oral glucocorticoids. Despite variable relapse rates, these strategies are often insufficient. Additionally, no validated nephroprotective strategies have been added to immunosuppression for the treatment of crescentic glomerulonephritis (CGN). The side effects of immunosuppressive drugs significantly impact patients' life expectancy and quality of life; complementary nephroprotective strategies are needed. Together, our results highlight the common role of MR signaling in the pathophysiology of extra-capillary glomerulopathies, FSGS, and crescentic glomerulonephritis.
Perspectives
This study supports the use of MR antagonists as potential complementary therapeutic agents with original modes of action for these severe kidney diseases. In addition, these data suggest that we have been partially wrong for decades when giving glucocorticoids with mineralocorticoid activity to patients with FSGS or crescentic glomerulonephritis. Prednisone and methylprednisolone are not pure glucocorticoids; they also exhibit mineralocorticoid activity, unlike dexamethasone or betamethasone. Furthermore, we didn’t detect 11β-hydroxysteroid dehydrogenase (11βHSD) in PECs, suggesting that the standard of care could stimulate MR activity in glomerular cells, which is not optimal.
MD, PhD Pierre-Louis Tharaux
Institut de la Santé et de la Recherche Médicale, Inserm
Read the Original
This page is a summary of: Mineralocorticoid receptor inhibition in parietal epithelial cells prevents focal segmental glomerulosclerosis and crescentic glomerulonephritis, Kidney International, September 2025, Elsevier,
DOI: 10.1016/j.kint.2025.07.037.
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