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RU38486 prolongs survival in murine congenital polycystic kidney disease
M R Ogborn1, J F Crocker, S C McCarthy
1Department of Pediatrics, Faculty of Medicine, Dalhousie University, Halifax, Nova Scotia, Canada.
Abstract:
The cpk/cpk mutant mouse develops a lethal infantile polycystic kidney disease that is associated with disregulation of post natal glucocorticoid production. To establish if the observed endocrine abnormality is involved in the pathophysiology of polycystic kidney disease, blockade of glucocorticoid action during the immediate post-natal period was attempted. The steroid antagonist, RU38486, when administered from day 3 to day 12 of post-natal life, prolonged survival in affected animals. This finding supports a role for steroid hormones in the pathogenesis of this form of polycystic kidney disease.
Insights
Glucocorticoid hormones contribute to infantile polycystic kidney disease (CPK) in mice. Blocking glucocorticoid action prolonged survival in CPK mice, suggesting a therapeutic target.
Area of Science:
- Endocrinology
- Nephrology
- Developmental Biology
Background:
- The cpk/cpk mutant mouse model exhibits lethal infantile polycystic kidney disease (CPK).
- This condition is linked to dysregulated postnatal glucocorticoid production.
Purpose of the Study:
- To investigate the role of endocrine abnormalities in the pathophysiology of polycystic kidney disease.
- To determine if blocking glucocorticoid action impacts CPK progression.
Main Methods:
- Administration of the steroid antagonist RU38486 to cpk/cpk mice.
- Treatment occurred during the critical early postnatal period (days 3-12).
Main Results:
- RU38486 administration significantly prolonged the survival of affected cpk/cpk mice.
- This indicates that blocking glucocorticoid action has a beneficial effect on the disease course.
Conclusions:
- Glucocorticoid hormones play a significant role in the pathogenesis of this form of polycystic kidney disease.
- Targeting steroid hormone action presents a potential therapeutic strategy for infantile polycystic kidney disease.