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5/6th Nephrectomy in Combination with High Salt Diet and Nitric Oxide Synthase Inhibition to Induce Chronic Kidney Disease in the Lewis Rat
Published on: July 3, 2013
Endogenous cardiotonic steroids in chronic renal failure
Elena V Kolmakova1, Steven T Haller, David J Kennedy
1Chronic Dialysis Division, Mechnikov Medical Academy, St. Petersburg, Russia.
Summary
Elevated marinobufagenin (MBG) in chronic kidney disease (CKD) inhibits Na/K-ATPase. This cardiotonic steroid (CTS) may be a therapeutic target for kidney disease.
Area of Science:
- Cardiovascular Physiology
- Nephrology
- Biochemistry
Background:
- Cardiotonic steroids (CTS) are implicated in end-stage renal disease pathogenesis.
- Understanding CTS in chronic kidney disease (CKD) is crucial.
Purpose of the Study:
- Define the nature of CTS in CKD patients and partially nephrectomized (PNx) rats.
- Investigate the role of marinobufagenin (MBG) in CKD pathophysiology.
Main Methods:
- Measured plasma MBG and endogenous ouabain (EO) in CKD patients and controls.
- Assessed erythrocyte Na/K-ATPase activity with and without anti-MBG antibody and Digibind.
- Determined MBG and EO levels in sham-operated and PNx rats.
Main Results:
- CKD patients showed increased plasma MBG and inhibited Na/K-ATPase.
- Anti-MBG antibody restored Na/K-ATPase in CKD erythrocytes.
- PNx rats exhibited elevated MBG levels, similar to CKD patients.
Conclusions:
- Elevated MBG contributes to Na/K-ATPase inhibition in chronic renal failure.
- MBG represents a potential therapeutic target for CKD.
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