Abstract | BACKGROUND: METHODS: Sprague-Dawley rats received CsA alone (15 mg/kg/d p.o.), CsA and EPL (approximately 100 mg/kg/day p.o.) or vehicle (control) for 12 weeks. At 11 weeks, chronic indwelling arterial and venous catheters were implanted for continuous measurements of arterial blood pressure (BP) and GFR ( inulin clearance) in conscious, freely moving animals. Plasma was sampled for analysis and kidney tissue was fixed for quantitative stereological analyses. RESULTS: Compared to controls, CsA-treatment reduced relative tubular volume (0.73 ± 0.03 vs. 0.85 ± 0.01, p<0.05) and increased relative interstitial volume (0.080 ± 0.004 vs. 0.045 ± 0.003, p<0.05); EPL attenuated these changes (0.82 ± 0.02, p<0.05, and 0.060 ± 0.006, p<0.05, respectively). CsA-treated rats had more sclerotic glomeruli and a higher degree of vascular depositions in arterioles; both were significantly reduced in CsA+EPL-treated animals. CsA increased BP and reduced body weight gain and GFR. In CsA+EPL rats, weight gain, GFR and BP at rest (daytime) were normalized; however, BP during activity (night) remained elevated. Plasma sodium and potassium concentrations, kidney-to- body weight ratios and CsA whole blood concentration were similar in CsA and CsA+EPL rats. CONCLUSIONS: It is concluded that in the chronic cyclosporine rat nephropathy model, EPL reduces renal tissue injury, hypofiltration, hypertension, and growth impairment. MR antagonists should be tested for their renoprotective potential in patients treated with calcineurin inhibitors.
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Authors | Finn Thomsen Nielsen, Boye L Jensen, Pernille B L Hansen, Niels Marcussen, Peter Bie |
Journal | BMC nephrology
(BMC Nephrol)
Vol. 14
Pg. 42
(Feb 20 2013)
ISSN: 1471-2369 [Electronic] England |
PMID | 23425330
(Publication Type: Journal Article, Research Support, Non-U.S. Gov't)
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Chemical References |
- Immunosuppressive Agents
- Mineralocorticoid Receptor Antagonists
- Spironolactone
- Eplerenone
- Cyclosporine
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Topics |
- Animals
- Cyclosporine
(adverse effects)
- Drug Interactions
- Eplerenone
- Fibrosis
(chemically induced, diagnosis, drug therapy)
- Immunosuppressive Agents
(adverse effects)
- Kidney
(drug effects, pathology)
- Longitudinal Studies
- Male
- Mineralocorticoid Receptor Antagonists
(administration & dosage)
- Nephritis, Interstitial
(chemically induced, diagnosis, prevention & control)
- Rats
- Rats, Sprague-Dawley
- Spironolactone
(administration & dosage, analogs & derivatives)
- Treatment Outcome
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