Salt Loading Promotes Kidney Injury via Fibrosis in Young Female Ren2 Rats.
OBJECTIVE
It is increasingly recognized that there is sexual dimorphism in kidney disease progression; however, this disparity is lost in the presence of diabetes where women progress at a similar rate to men. The renin-angiotensin-aldosterone system (RAAS) is known to regulate diabetes-induced kidney injury, and recent literature would suggest that gender differences exist in RAAS-dependent responses in the kidney. In this regard, these gender differences may be overcome by excessive salt intake. Thereby, we hypothesized that salt would promote proteinuria in transgenic female rats under conditions of excess tissue angiotensin (Ang) II and circulating aldosterone.


METHODS
We utilized young female transgenic (mRen2)27 (Ren2) rats and Sprague-Dawley (SD) littermates and fed a high-salt diet (4%) over 3 weeks.


RESULTS
Compared to SD and Ren2 controls, female Ren2 rats fed a high-salt diet displayed increases in proteinuria, periarterial and interstitial fibrosis as well as ultrastructural evidence of basement membrane thickening, loss of mitochondrial elongation, mitochondrial fragmentation and attenuation of basilar canalicular infoldings. These findings occurred temporally with increases in transforming growth factor-β but not indices of oxidant stress.


CONCLUSIONS
Our current data suggest that a diet high in salt promotes progressive kidney injury as measured by proteinuria and fibrosis associated with transforming growth factor-β under conditions of excess tissue Ang II and circulating aldosterone.
Diabetes and Cardiovascular Center, University of Missouri-Columbia School of Medicine, Columbia, Mo., USA ; Department of Medicine, University of Missouri-Columbia School of Medicine, Columbia, Mo., USA ; Division of Endocrinology and Metabolism, University of Missouri-Columbia School of Medicine, Columbia, Mo., USA ; Division of Research Service, Harry S. Truman Memorial Veterans' Hospital, Columbia, Mo., USA.
Javad
J
Habibi
Diabetes and Cardiovascular Center, University of Missouri-Columbia School of Medicine, Columbia, Mo., USA ; Department of Medicine, University of Missouri-Columbia School of Medicine, Columbia, Mo., USA ; Division of Endocrinology and Metabolism, University of Missouri-Columbia School of Medicine, Columbia, Mo., USA.
Melvin R
MR
Hayden
Division of Wake Forest University School of Medicine, Winston-Salem, N.C., USA.
Carlos M
CM
Ferrario
Diabetes and Cardiovascular Center, University of Missouri-Columbia School of Medicine, Columbia, Mo., USA ; Department of Medicine, University of Missouri-Columbia School of Medicine, Columbia, Mo., USA ; Department of Medical Pharmacology and Physiology, University of Missouri-Columbia School of Medicine, Columbia, Mo., USA ; Division of Endocrinology and Metabolism, University of Missouri-Columbia School of Medicine, Columbia, Mo., USA ; Division of Research Service, Harry S. Truman Memorial Veterans' Hospital, Columbia, Mo., USA.
James R
JR
Sowers
Diabetes and Cardiovascular Center, University of Missouri-Columbia School of Medicine, Columbia, Mo., USA ; Department of Medicine, University of Missouri-Columbia School of Medicine, Columbia, Mo., USA ; Division of Endocrinology and Metabolism, University of Missouri-Columbia School of Medicine, Columbia, Mo., USA ; Division of Nephrology and Hypertension, University of Missouri-Columbia School of Medicine, Columbia, Mo., USA ; Division of Research Service, Harry S. Truman Memorial Veterans' Hospital, Columbia, Mo., USA.
Adam T
AT
Whaley-Connell
Angiotensin II; Fibrosis; Proteinuria; Reactive oxygen species; Transgenic (mRen2)27 rat