Nephrotic syndrome‐associated hypercoagulopathy is alleviated by both pioglitazone and glucocorticoid which target two different nuclear receptors
Background Thrombosis is a potentially life‐threatening nephrotic syndrome (NS) complication. We have previously demonstrated that hypercoagulopathy is proportional to NS severity in rat models and that pioglitazone (Pio) reduces proteinuria both independently and in combination with methylprednisol...
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Published in | Physiological reports Vol. 8; no. 15; pp. e14515 - n/a |
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Main Authors | , , , , , , , , , , , , , , , , , |
Format | Journal Article |
Language | English |
Published |
United States
John Wiley & Sons, Inc
01.08.2020
John Wiley and Sons Inc Wiley |
Subjects | |
Online Access | Get full text |
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Summary: | Background
Thrombosis is a potentially life‐threatening nephrotic syndrome (NS) complication. We have previously demonstrated that hypercoagulopathy is proportional to NS severity in rat models and that pioglitazone (Pio) reduces proteinuria both independently and in combination with methylprednisolone (MP), a glucocorticoid (GC). However, the effect of these treatments on NS‐associated hypercoagulopathy remains unknown. We thus sought to determine the ability of Pio and GC to alleviate NS‐associated hypercoagulopathy.
Methods
Puromycin aminonucleoside‐induced rat NS was treated with sham, Low‐ or High‐dose MP, Pio, or combination (Pio + Low‐MP) and plasma was collected at day 11. Plasma samples were collected from children with steroid‐sensitive NS (SSNS) and steroid‐resistant NS (SRNS) upon presentation and after 7 weeks of GC therapy. Plasma endogenous thrombin potential (ETP), antithrombin (AT) activity, and albumin (Alb) were measured using thrombin generation, amidolytic, and colorimetric assays, respectively.
Results
In a rat model of NS, both High‐MP and Pio improved proteinuria and corrected hypoalbuminemia, ETP and AT activity (p < .05). Proteinuria (p = .005) and hypoalbuminemia (p < .001) were correlated with ETP. In childhood NS, while ETP was not different at presentation, GC therapy improved proteinuria, hypoalbuminemia, and ETP in children with SSNS (p < .001) but not SRNS (p = .330).
Conclusions
Both Pio and GC diminish proteinuria and significantly alleviate hypercoagulopathy. Both Pio and MP improved hypercoagulopathy in rats, and successful GC therapy (SSNS) also improved hypercoagulopathy in childhood NS. These data suggest that even a partial reduction in proteinuria may reduce NS‐associated thrombotic risk.
Acquired hypercoagulopathy contributes to thrombotic‐risk in patients with nephrotic syndrome. Here we show that treatments directed at reversing the glomerular filtration defect effectively reduce hypercoagulopathy in both animal models and childhood nephrosis. These data imply that effective treatment for nephrotic syndrome may simultaneously reduce thrombotic risk. |
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Bibliography: | Pediatric Nephrology Research Consortium Investigators are listed in the Acknowledgments ObjectType-Article-1 SourceType-Scholarly Journals-1 ObjectType-Feature-2 content type line 23 |
ISSN: | 2051-817X 2051-817X |
DOI: | 10.14814/phy2.14515 |